Including the 'Spiritual' Within Mental Health Care in the UK, from the Experiences of People with Mental Health Problems.

Spirituality as a dimension of quality of life and well-being has recently begun to be more valued within person-centred treatment approaches to mental health in the UK. The aim of this paper is to provide indicators of the extent to which accessing a spiritual support group may be useful within mental health recovery from the view point of those in receipt of it. The study design was a small-scale exploratory study utilising mixed methods. Quantitative methods were used to map the mental health, general well-being and social networks of the group. These were complimented by a semi-structured open-ended interview which allowed for Interpretative Phenomenological Analysis (IPA) of the life-history accounts of nine individuals with mental health problems who attended a 'spirituality support group'. Data from unstructured open-ended interviews with five faith chaplains and a mental health day centre manager were also analysed using thematic analysis. The views of 15 participants are therefore recounted. Participants reported that the group offered them: an alternative to more formal religious organisations, and an opportunity to settle spiritual confusions/fears. The 'group' was also reported to generally help individual's subjective feelings of mental wellness through social support. Whilst the merits of spiritual care are appealing, convincing services to include it within treatment may still be difficult.

Cord blood Streptococcus pneumoniae-specific cellular immune responses predict early pneumococcal carriage in high-risk infants in Papua New Guinea.

In areas where Streptococcus pneumoniae is highly endemic, infants experience very early pneumococcal colonization of the upper respiratory tract, with carriage often persisting into adulthood. We aimed to explore whether newborns in high-risk areas have pre-existing pneumococcal-specific cellular immune responses that may affect early pneumococcal acquisition. Cord blood mononuclear cells (CBMC) of 84 Papua New Guinean (PNG; high endemic) and 33 Australian (AUS; low endemic) newborns were stimulated in vitro with detoxified pneumolysin (dPly) or pneumococcal surface protein A (PspA; families 1 and 2) and compared for cytokine responses. Within the PNG cohort, associations between CBMC dPly and PspA-induced responses and pneumococcal colonization within the first month of life were studied. Significantly higher PspA-specific interferon (IFN)-γ, tumour necrosis factor (TNF)-α, interleukin (IL)-5, IL-6, IL-10 and IL-13 responses, and lower dPly-IL-6 responses were produced in CBMC cultures of PNG compared to AUS newborns. Higher CBMC PspA-IL-5 and PspA-IL-13 responses correlated with a higher proportion of cord CD4 T cells, and higher dPly-IL-6 responses with a higher frequency of cord antigen-presenting cells. In the PNG cohort, higher PspA-specific IL-5 and IL-6 CBMC responses were associated independently and significantly with increased risk of earlier pneumococcal colonization, while a significant protective effect was found for higher PspA-IL-10 CBMC responses. Pneumococcus-specific cellular immune responses differ between children born in pneumococcal high versus low endemic settings, which may contribute to the higher risk of infants in high endemic settings for early pneumococcal colonization, and hence disease.

Diversity of nontypeable Haemophilus influenzae strains colonizing Australian Aboriginal and non-Aboriginal children.

Nontypeable Haemophilus influenzae (NTHI) strains are responsible for respiratory-related infections which cause a significant burden of disease in Australian children. We previously identified a disparity in NTHI culture-defined carriage rates between Aboriginal and non-Aboriginal children (42% versus 11%). The aim of this study was to use molecular techniques to accurately determine the true NTHI carriage rates (excluding other culture-identical Haemophilus spp.) and assess whether the NTHI strain diversity correlates with the disparity in NTHI carriage rates. NTHI isolates were cultured from 595 nasopharyngeal aspirates collected longitudinally from asymptomatic Aboriginal (n=81) and non-Aboriginal (n=76) children aged 0 to 2 years living in the Kalgoorlie-Boulder region, Western Australia. NTHI-specific 16S rRNA gene PCR and PCR ribotyping were conducted on these isolates. Confirmation of NTHI by 16S rRNA gene PCR corrected the NTHI carriage rates from 42% to 36% in Aboriginal children and from 11% to 9% in non-Aboriginal children. A total of 75 different NTHI ribotypes were identified, with 51% unique to Aboriginal children and 13% unique to non-Aboriginal children (P<0.0001). The strain richness (proportion of different NTHI ribotypes) was similar for Aboriginal (19%, 65/346) and non-Aboriginal children (19%, 37/192) (P=0.909). Persistent carriage of the same ribotype was rare in the two groups, but colonization with multiple NTHI strains was more common in Aboriginal children than in non-Aboriginal children. True NTHI carriage was less than that estimated by culture. The Aboriginal children were more likely to carry unique and multiple NTHI strains, which may contribute to the chronicity of NTHI colonization and subsequent disease.

An agent-based model for cell microenvironment simulation using FLAMEGPU2.

This work presents an advanced agent-based model developed within the FLAMEGPU2 framework, aimed at simulating the intricate dynamics of cell microenvironments. Our primary objective is to showcase FLAMEGPU2's potential in modelling critical features such as cell-cell and cell-ECM interactions, species diffusion, vascularisation, cell migration, and/or cell cycling. By doing so, we provide a versatile template that serves as a foundational platform for researchers to model specific biological mechanisms or processes. We highlight the utility of our approach as a microscale component within multiscale frameworks. Through four example applications, we demonstrate the model's versatility in capturing phenomena such as strain-stiffening behaviour of hydrogels, cell migration patterns within hydrogels, spheroid formation and fibre reorientation, and the simulation of diffusion processes within a vascularised and deformable domain. This work aims to bridge the gap between computational efficiency and biological fidelity, offering a scalable and flexible platform to advance our understanding of tissue biology and engineering.

Safety, tolerability, and effect of a single aural dose of Dornase alfa at the time of ventilation tube surgery for otitis media: A Phase 1b double randomized control trial.

BACKGROUND: One third of children require repeat ventilation tube insertion (VTI) for otitis media. Disease recurrence is associated with persistent middle ear bacterial biofilms. With demonstration that Dornase alfa (a DNase) disrupts middle ear effusion biofilms ex vivo, we identified potential for this as an anti-biofilm therapy to prevent repeat VTI. First, safety and tolerability needed to be measured. METHODS: This was a phase 1B double-blinded randomized control trial conducted in Western Australia. Children between 6 months and 5 years undergoing VTI for bilateral middle ear effusion were recruited between 2012 and 2014 and followed for two years. Children's ears were randomized to receive either Dornase alfa (1 mg/mL) or 0.9 % sodium chloride (placebo) at time of surgery. Children were followed up at 2 weeks post-VTI and at 3-monthly intervals for 2 years. Outcomes assessed were: 1) safety and tolerability, 2) otorrhoea frequency, 3) blocked or extruded ventilation tube (VT) frequency, 4) time to blockage or extrusion, 5) time to infection recurrence and/or need for repeat VTI. RESULTS: Sixty children (mean age 2.3 years) were enrolled with 87 % reaching study endpoint. Treatment did not change otorrhoea frequency. Hearing improved in all children following VTI, with no indication of ototoxicity. Dornase alfa had some effect on increasing time until VT extrusion (p = 0.099); and blockage and/or extrusion (p = 0.122). Frequency of recurrence and time until recurrence were similar. Fourteen children required repeat VTI within the follow-up period. CONCLUSION: A single application of Dornase alfa into the middle ear at time of VTI was safe, non-ototoxic, and well-tolerated. TRIAL REGISTRATION: ACTRN12623000504617.

A multiscale orchestrated computational framework to reveal emergent phenomena in neuroblastoma.

Neuroblastoma is a complex and aggressive type of cancer that affects children. Current treatments involve a combination of surgery, chemotherapy, radiotherapy, and stem cell transplantation. However, treatment outcomes vary due to the heterogeneous nature of the disease. Computational models have been used to analyse data, simulate biological processes, and predict disease progression and treatment outcomes. While continuum cancer models capture the overall behaviour of tumours, and agent-based models represent the complex behaviour of individual cells, multiscale models represent interactions at different organisational levels, providing a more comprehensive understanding of the system. In 2018, the PRIMAGE consortium was formed to build a cloud-based decision support system for neuroblastoma, including a multi-scale model for patient-specific simulations of disease progression. In this work we have developed this multi-scale model that includes data such as patient's tumour geometry, cellularity, vascularization, genetics and type of chemotherapy treatment, and integrated it into an online platform that runs the simulations on a high-performance computation cluster using Onedata and Kubernetes technologies. This infrastructure will allow clinicians to optimise treatment regimens and reduce the number of costly and time-consuming clinical trials. This manuscript outlines the challenging framework's model architecture, data workflow, hypothesis, and resources employed in its development.

Core protocol for the adaptive Platform Trial In COVID-19 Vaccine priming and BOOsting (PICOBOO).

BACKGROUND: The need for coronavirus 2019 (COVID-19) vaccination in different age groups and populations is a subject of great uncertainty and an ongoing global debate. Critical knowledge gaps regarding COVID-19 vaccination include the duration of protection offered by different priming and booster vaccination regimens in different populations, including homologous or heterologous schedules; how vaccination impacts key elements of the immune system; how this is modified by prior or subsequent exposure to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and future variants; and how immune responses correlate with protection against infection and disease, including antibodies and effector and T cell central memory. METHODS: The Platform Trial In COVID-19 priming and BOOsting (PICOBOO) is a multi-site, multi-arm, Bayesian, adaptive, randomised controlled platform trial. PICOBOO will expeditiously generate and translate high-quality evidence of the immunogenicity, reactogenicity and cross-protection of different COVID-19 priming and booster vaccination strategies against SARS-CoV-2 and its variants/subvariants, specific to the Australian context. While the platform is designed to be vaccine agnostic, participants will be randomised to one of three vaccines at trial commencement, including Pfizer's Comirnaty, Moderna's Spikevax or Novavax's Nuvaxovid COVID-19 vaccine. The protocol structure specifying PICOBOO is modular and hierarchical. Here, we describe the Core Protocol, which outlines the trial processes applicable to all study participants included in the platform trial. DISCUSSION: PICOBOO is the first adaptive platform trial evaluating different COVID-19 priming and booster vaccination strategies in Australia, and one of the few established internationally, that is designed to generate high-quality evidence to inform immunisation practice and policy. The modular, hierarchical protocol structure is intended to standardise outcomes, endpoints, data collection and other study processes for nested substudies included in the trial platform and to minimise duplication. It is anticipated that this flexible trial structure will enable investigators to respond with agility to new research questions as they arise, such as the utility of new vaccines (such as bivalent, or SARS-CoV-2 variant-specific vaccines) as they become available for use. TRIAL REGISTRATION: Australian and New Zealand Clinical Trials Registry ACTRN12622000238774. Registered on 10 February 2022.

FBXO11, a regulator of the TGFß pathway, is associated with severe otitis media in Western Australian children.

Otitis media (OM) is a common childhood disease characterised by middle ear inflammation following infection. Susceptibility to recurrent acute OM (rAOM) and chronic OM with effusion (COME) is highly heritable. Two murine mutants, Junbo and Jeff, spontaneously develop severe OM with similar phenotypes to human disease. Fine-mapping of these mutants identified two genes (Evi1 and Fbxo11) that interact with the transforming growth factor ß (TGFß) signalling pathway. We investigated these genes, as well as four Sma- and Mad-related (SMAD) genes of the TGFß pathway, as candidate rAOM/COME susceptibility genes in two predominantly Caucasian populations. Single-nucleotide polymorphisms (SNPs) within FBXO11 (family-based association testing Z-Score=2.61; P(best)=0.009) were associated with severe OM in family-based analysis of 434 families (561 affected individuals) from the Western Australian Family Study of OM. The FBXO11 association was replicated by directed analysis of Illumina 660W-Quad Beadchip data available for 253 cases and 866 controls (OR=1.55 (95% CI 1.28-1.89); P(best)=6.9 × 10(-6)) available within the Western Australian Pregnancy Cohort (Raine) Study. Combined primary and replication results show P(combined)=2.98 × 10(-6). Neither cohort showed an association with EVI1 variants. Family-based associations at SMAD2 (P=0.038) and SMAD4 (P=0.048) were not replicated. Together, these data provide strong evidence for FBXO11 as a susceptibility gene for severe OM.

Emergency department presentation following falls: development of a routine falls surveillance system.

INTRODUCTION: Falls are recognised as a major public health issue, particularly among older people, and have been targeted for attention by national service frameworks and National Institute for Health and Clinical Excellence guidelines in the UK. However, reliable epidemiological data are not easily available, and it remains difficult to monitor the effect of interventions that seek to reduce the public health impact of falls. METHOD: In a 1-year study based in the emergency department (ED) of the University Hospital of Wales all Cardiff residents who described their presentation as following a fall were identified. From a catchment population of 305,353 people a total of 86,031 such ED presentations were recorded, 20,154 (23.4%) of which followed a fall. RESULTS: This gives an overall falls incidence of 66/1000 population per year, meaning that in just a year one resident in 15 attended the ED following a fall. The impact of falls was greatest in the oldest age groups, and in women aged over 75 years the falls incidence of 139/1000 per year was significantly higher than the figure of 99/1000 per year observed in men of the same age. CONCLUSIONS: This study describes a simple way for ED to establish routine falls surveillance. It offers the first estimate of the impact of falls on ED in the UK, suggesting that such services are dealing with 4 million falls-related attendances every year.

A neonatal pneumococcal conjugate vaccine trial in Papua New guinea: study population, methods and operational challenges.

Infants in Papua New Guinea (PNG) are at a high risk of invasive pneumococcal disease, and a substantial burden of this falls on children less than six months old. PNG is planning to introduce a pneumococcal conjugate vaccine for infants in the near future, but to make the maximum impact neonatal immunization will have to be considered. To provide evidence on safety and immunogenicity for neonatal and early infant immunization, we undertook an open randomized controlled trial of 7-valent pneumococcal conjugate vaccine (7vPCV). 318 children received 7vPCV at ages 0, 1 and 2 months or at 1, 2 and 3 months or not at all. All children received 23-valent pneumococcal polysaccharide vaccine at age 9 months. This was a large and complex trial: village reporters visited participants weekly during the first year and fortnightly for a further 6 months and nurses monitored self-reported morbidity and collected many thousands of biological samples. The study team was remarkably successful in achieving the study aims, with 18-month follow-up completed on 77% of enrolled children and over 80% of scheduled samples collected. While the results of the trial will be reported elsewhere, this paper discusses the design of the study and dissects out some of the main reasons for its successful completion. Strong community engagement was an essential factor in success and the principles of equitable partnership and service provision led to a strong research partnership. A two-stage consent process, comprising primary assent followed by later informed consent, led to a high drop-out before initial enrolment, but an outstanding retention of those enrolled in the study. We conclude that factors such as strong community participation, reciprocity and a good relationship between the study team and participants are just as important as the technical elements of laboratory testing and data handling in ensuring the success of a vaccine trial in PNG.

Panel 7 - Pathogenesis of otitis media - a review of the literature between 2015 and 2019.

OBJECTIVE: To perform a comprehensive review of the literature from July 2015 to June 2019 on the pathogenesis of otitis media. Bacteria, viruses and the role of the microbiome as well as the host response are discussed. Directions for future research are also suggested. DATA SOURCES: PubMed database of the National Library of Medicine. REVIEW METHODS: PubMed was searched for any papers pertaining to OM pathogenesis between July 2015 and June 2019. If in English, abstracts were assessed individually for their relevance and included in the report. Members of the panel drafted the report based on these searches and on new data presented at the 20th International Symposium on Recent Advances in Otitis Media. CONCLUSIONS: The main themes that arose in OM pathogenesis were around the need for symptomatic viral infections to develop disease. Different populations potentially having different mechanisms of pathogenesis. Novel bacterial otopathogens are emerging and need to be monitored. Animal models need to continue to be developed and used to understand disease pathogenesis. IMPLICATIONS FOR PRACTICE: The findings in the pathogenesis panel have several implications for both research and clinical practice. The most urgent areas appear to be to continue monitoring the emergence of novel otopathogens, and the need to develop prevention and preventative therapies that do not rely on antibiotics and protect against the development of the initial OM episode.

SpineCreator: a Graphical User Interface for the Creation of Layered Neural Models.

There is a growing requirement in computational neuroscience for tools that permit collaborative model building, model sharing, combining existing models into a larger system (multi-scale model integration), and are able to simulate models using a variety of simulation engines and hardware platforms. Layered XML model specification formats solve many of these problems, however they are difficult to write and visualise without tools. Here we describe a new graphical software tool, SpineCreator, which facilitates the creation and visualisation of layered models of point spiking neurons or rate coded neurons without requiring the need for programming. We demonstrate the tool through the reproduction and visualisation of published models and show simulation results using code generation interfaced directly into SpineCreator. As a unique application for the graphical creation of neural networks, SpineCreator represents an important step forward for neuronal modelling.

Aberrant E-cadherin and alpha-catenin expression in prostate cancer: correlation with patient survival.

E-cadherin maintains the normal differentiated phenotype in epithelial cells; this function is partly mediated by alpha-catenin, which links E-cadherin to the cell cytoskeleton. Dysfunction of E-cadherin in vitro and in vivo is associated with an invasive phenotype. However, the role of alpha-catenin is largely undetermined. We analyzed the expression of E-cadherin and alpha-catenin in prostate cancer to assess the relationship of abnormal expression to stage, grade and survival. E-cadherin expression was evaluated in 99 prostate cancers. In 79 of those specimens, alpha-catenin was also assessed. In benign prostatic epithelium, both E-cadherin and alpha-catenin were expressed uniformly at the cell membrane. Abnormal E-cadherin expression was found in 56% of cancer specimens, whereas alpha-catenin expression was abnormal in 42%. Abnormal expression of each molecule was significantly correlated with Gleason score (P < 0.0001) and the ratio of resection chippings infiltrated by tumor (P < 0.0001). E-cadherin expression was also associated with the extent of disease on the initial bone scan (P = 0.017). Univariate analysis showed significantly lower survival rate for patients with abnormal E-cadherin (P = 0.0003) or alpha-catenin expression (P = 0.031). Multivariate regression analysis showed that the prognostic value of E-cadherin was independent of tumor grade but not of metastasis. These results suggest that perturbation of cell-cell adhesion is involved in the progression of prostate cancer and that analysis of E-cadherin expression may be clinically useful.

Osteolytica: An automated image analysis software package that rapidly measures cancer-induced osteolytic lesions in in vivo models with greater reproducibility compared to other commonly used methods.

Methods currently used to analyse osteolytic lesions caused by malignancies such as multiple myeloma and metastatic breast cancer vary from basic 2-D X-ray analysis to 2-D images of micro-CT datasets analysed with non-specialised image software such as ImageJ. However, these methods have significant limitations. They do not capture 3-D data, they are time-consuming and they often suffer from inter-user variability. We therefore sought to develop a rapid and reproducible method to analyse 3-D osteolytic lesions in mice with cancer-induced bone disease. To this end, we have developed Osteolytica, an image analysis software method featuring an easy to use, step-by-step interface to measure lytic bone lesions. Osteolytica utilises novel graphics card acceleration (parallel computing) and 3-D rendering to provide rapid reconstruction and analysis of osteolytic lesions. To evaluate the use of Osteolytica we analysed tibial micro-CT datasets from murine models of cancer-induced bone disease and compared the results to those obtained using a standard ImageJ analysis method. Firstly, to assess inter-user variability we deployed four independent researchers to analyse tibial datasets from the U266-NSG murine model of myeloma. Using ImageJ, inter-user variability between the bones was substantial (±19.6%), in contrast to using Osteolytica, which demonstrated minimal variability (±0.5%). Secondly, tibial datasets from U266-bearing NSG mice or BALB/c mice injected with the metastatic breast cancer cell line 4T1 were compared to tibial datasets from aged and sex-matched non-tumour control mice. Analyses by both Osteolytica and ImageJ showed significant increases in bone lesion area in tumour-bearing mice compared to control mice. These results confirm that Osteolytica performs as well as the current 2-D ImageJ osteolytic lesion analysis method. However, Osteolytica is advantageous in that it analyses over the entirety of the bone volume (as opposed to selected 2-D images), it is a more rapid method and it has less user variability.

Comparison of text-messaging to voice telephone interviews for active surveillance of adverse events following immunisation.

OBJECTIVES: In 2013, the Follow-up and Active Surveillance of Trivalent Influenza Vaccine in Mums (FASTMum) program began using short message service (SMS) to collect adverse event information in pregnant women who recently received trivalent influenza vaccine (TIV). This study was designed to compare data collected via SMS and telephone for the purposes of monitoring vaccine safety. METHODS: A number of 344 women who received TIV were randomly assigned to a telephone interview group. They were telephoned seven days post-vaccination and administered a standard survey soliciting any adverse events following immunisation (AEFI) they experienced. They were matched by brand of vaccine, age group, and residence to 344 women who were sent a SMS seven days post-vaccination. The SMS solicited similar information. AEFI reported by SMS and telephone interview were compared by calculating risk ratios. RESULTS: Response rate was higher to SMS compared to telephone interview (90.1% vs. 63.9%). Women who were surveyed by SMS were significantly less likely to report an AEFI compared to women who were surveyed by telephone (RR: 0.41; 95% CI: 0.29-0.59). The greatest discrepancies between SMS and telephone interview were for self-reported injection site reactions (3.1% vs. 16.8%) and unsolicited (or "other") events (11.4% vs. 4.1%). Data collected by SMS was significantly timelier. CONCLUSIONS: Data collection by SMS results in significantly improved response rates and timeliness of vaccine safety data. Systems which incorporate SMS could be used to more rapidly detect safety signals and promote more rapid public health response to vaccine quality issues.

Characterization of a basic helix-loop-helix protein, ABF-1: nuclear localization, transcriptional properties, and interaction with Id-2.

The activated B-cell factor (ABF)-1 cDNA was initially isolated from Epstein-Barr virus (EBV)-infected B cells and codes for a DNA-binding protein belonging to the basic helix-loop-helix (bHLH) family of transcription factors. In this study, we characterized the nuclear localization signal of ABF-1, mapped two distinct transcriptional repression domains, and identified one ABF-1-interacting protein, Id-2. By examining the subcellular location of deletion mutants of ABF-1 fused to green fluorescent protein (GFP), critical regions involved in nuclear localization were determined. Analysis of GFP-tagged ABF-1 deletion mutants revealed two separate regions capable of directing nuclear localization. One region mapped to the N-terminal amino acids 71 to 103, whereas the second region localized to the C-terminal bHLH domain. Transient transfection of ABF-1 deletion mutants demonstrated that the N-terminal amino acids 1 to 40 and the bHLH domain function together to achieve maximum repression of E2A activity. Taken together, these results indicate that ABF-1 is a nuclear transcriptional repressor with two distinct regions that function in a synergistic fashion to attenuate E2A-mediated gene activation.

Meningococcal serogroup C-specific IgG antibody responses and serum bactericidal titres in children following vaccination with a meningococcal A/C polysaccharide vaccine.

In the UK, a co-ordinated series of phase II studies is being undertaken with meningococcal serogroup C conjugate (MCC) vaccines. The use of meningococcal A/C polysaccharide (MACP) vaccines in control arms in young children has been avoided because of the well recognised short comings of these vaccines. Following a cluster of serogroup C disease centred on a day nursery, intervention by MACP vaccination was performed as an outbreak control measure. Using this cohort, serogroup C-specific IgG ELISA and serum bactericidal assays (SBA) were performed using both de-O-acetylated (Oac(-)) and acetylated (Oac(+)) serogroup C antigen, the measurement of primarily high avidity antibody and using baby rabbit or human complement in the SBA. The effect of subject age (either less than or greater than 2 years of age) was assessed for the different assays and significant differences (P<0.05) were found using both antigen sources in the high avidity ELISA and in the rabbit complement SBA but not in the standard ELISA. When assessing results from different studies it is important that methodologies utilised allow such comparisons since the choice of reagents can have a profound influence. The importance of standardised assays is paramount at a time where immunogenicity trials are replacing efficacy trials for the introduction of MCC vaccines.

Intrusion of retinal tacks.

We examined nine patients in whom retinal tacks intruded into the eye and lodged in the subretinal space, preretinal space, vitreous cavity, or anterior chamber. Complications included retinal pigment epithelium atrophy; retinal phlebitis; vitreous hemorrhage; focal corneal, iris, and retinal injury; and corneal edema. The intrusion of the retinal tacks did not apparently cause, but was associated with retinal redetachment in five patients. Factors associated with intrusion of the retinal tacks included absence of a barb at the end of the tack to anchor it to the sclera, absence of a groove in the tack, a short shaft, incomplete penetration of the retina, choroid, and sclera by the tack, self-inflicted trauma to the eye, placing a scleral buckle after inserting the tacks, and reproliferation of periretinal membranes. In four patients the intruded tacks did not cause any complications. In four patients the intruded tacks were removed without complications and in the remaining five patients, they were left in the eye.

Prevalence of conjunctival changes in wearers of hard contact lenses.

The prevalence of elevated papillae more than 0.3 mm in diameter was 10.5% in the conjunctivae of 200 subjects who had successfully worn polymethylmethacrylate hard contact lenses for eight hours or more daily for more than five years. Only three of 500 (0.6%) control subjects who had never worn contact lenses had these papillary changes. The prevalence of papillary changes for those with the so-called normal symptoms of mucus, itching, or both associated with wearing of hard contact lenses was 53% (16 of 21 subjects). The prevalence of these symptoms was 76% among subjects with polymethylmethacrylate contact lenses who had papillary changes and 8% among subjects with polymethylmethacrylate contact lenses who did not have papillary changes. We conclude that changes in the upper tarsal conjunctiva are associated with the wearing of hard contact lenses, occur in a significant percentage of patients wearing hard contact lenses for prolonged periods, and include a spectrum of papillary changes.