Serum heat shock protein concentrations are not associated with amyotrophic lateral sclerosis risk or survival in three European populations.

Introduction: Serum heat shock protein (HSP) concentrations have been reported as potential biomarkers for amyotrophic lateral sclerosis (ALS). Here, we investigate the role of serum HSP70, HSP90, and DNAJC7 as biomarkers for ALS. Methods: Serum samples were collected from ALS patients and volunteer controls from three different clinical cohorts (in Germany, Ireland, and Italy). Serum HSP concentrations were determined using enzyme-linked immunosorbent assay. Descriptive statistics, generalized logistic regression, and Cox proportional hazards models were used to model associations between log serum HSP concentrations and ALS risk. Results: In total, 251 ALS patients and 184 healthy volunteers were included. Logistic regression models failed to find associations between ALS risk and log serum concentration of HSP70 (OR 0.43, 95% CI: 0.10-1.78, p = 0.242), HSP90 (OR 0.95, 95% CI: 0.39-2.37, p = 0.904), or DNAJC7 (OR 1.55, 95% CI: 0.90-2.68, p = 0.118). Survival of ALS patients was not associated with log serum concentration of HSP HSP70 (HR1.06, 95% CI: 0.36-3.14, p = 0.916), HSP90 (HR 1.17, 95% CI: 0.67-2.02, p = 0.584), or DNAJC7 (HR 0.83, 95% CI: 0.57-1.21, p = 0.337). Discussion: We did not replicate previous findings that serum HSP70 and HSP90 concentrations were associated with risk of ALS. DNAJC7 was not associated with ALS risk, and there were no obvious longitudinal patterns in log serum concentrations of HSP70, HSP90, or DNAJC7. In addition, serum HSP concentrations were not associated with ALS survival.

A Germany-wide survey of caregiving professionals on climate change and mental health of children and adolescents - factors influencing their relevance rating of extreme weather event associated mental health impairments.

INTRODUCTION: Climate change presents a significant risk for the mental and physical health of young people. In order to identify and properly care for potential mental health impairments from extreme weather events, the relevance of these impairments must be assessed as high by the professional groups providing care for children and adolescents. This raises the question of which factors influence the individual relevance assessment of caretaking professionals? METHODS: Data was collected creating and conducting a Germany-wide online questionnaire via LimeSurvey. The questionnaire was addressed to professionals providing care for children and adolescents, in this case medical and therapeutic personnel as well as school and pedagogical personnel. Professional associations, chief physicians and school principals were contacted as multipliers and asked to forward the questionnaire to their members and staff. The data was analyzed using the R statistical software, and multiple linear regressions were performed to test the hypotheses. RESULTS: Overall, 648 questionnaires were taken into analysis. Approximately 70% of the participants considered climate change-induced impacts on the mental health of children and adolescents due to extreme weather events as relevant. Experiencing heat, storm, heavy precipitation, flood/flooding, and/or avalanches/mudflows made a modest yet significant contribution to explaining higher relevance assessments. In contrast, there was no evidence to suggest that an urban working environment increases the relevance assessment. CONCLUSION: The described influence of experiencing extreme weather events should not be regarded as the sole factor leading to higher relevance ratings. A more comprehensive understanding of the factors influencing relevance assessments is necessary to address key aspects of risk communication and increase risk awareness.

Pop-up COVID-19 vaccination clinics for vulnerable groups in the Midlands.

INTRODUCTION: Roma, travellers and the homeless suffer from a higher risk of both COVID-19 infection and severe disease relative to the general population. The purpose of this project was to ensure as many members as possible from vulnerable groups in the Midlands availed of COVID-19 vaccines. METHODS: Following on from successful testing of vulnerable populations in the Midlands of Ireland in March/April 2021, a collaboration of HSE Midland's Department of Public Health, Safetynet Primary Care and the HSE Midlands Traveller Health Unit (MTHU) operated pop-up vaccination clinics in June/July 2021, targeting the same populations. Clinics delivered the first dose of the Pfizer/BioNTech COVID-19 vaccine, registering clients for second doses in Community Vaccination Centres (CVCs). RESULTS: Thirteen clinics were hosted between 8 June 2021 and 20 July 2021, resulting in 890 first-dose Pfizer vaccinations delivered to vulnerable populations. DISCUSSION: Trust established months prior with our grassroots testing service resulted in strong vaccine uptake, with the quality service provided seeding further demand over time. This service integrated into the national system and allowed individuals to receive their second doses within the community.

To vaccinate or not to vaccinate? Women's perception of vaccination in pregnancy: a qualitative study.

BACKGROUND: Vaccination against influenza and pertussis in pregnancy can reduce the significant morbidity and mortality associated with these infections. Despite this, there is poor uptake of both vaccines in pregnancy. AIM: To explore women's perception of vaccination in pregnancy and thereby determine the reasons behind such low vaccination rates. DESIGN & SETTING: This is a qualitative study undertaken at a large maternity hospital. METHOD: Seventeen post-partum women completed a semi-structured interview discussing vaccination. They were recruited from a quantitative study looking at vaccination rates in pregnancy. The interview transcripts were discussed among three researchers and underwent thematic analysis. RESULTS: Three themes emerged. The first theme explored the influencing factors that shaped the women's decision to vaccinate in pregnancy. The recommendation of a healthcare provider was the most important influencing factor for this study's cohort of women. The second theme highlighted the deficiency in knowledge women had regarding vaccine safety. The last theme related to the pertussis vaccine, and the reluctance of healthcare providers to discuss and offer this vaccine in pregnancy. CONCLUSION: The qualitative approach gives voice to the thoughts and concerns of women as they make the complex decision to vaccinate in pregnancy. Clinicians must be cognizant of the important role they play in advising women to vaccinate in pregnancy. They must advise women that the vaccine is safe and address any of their concerns. Lastly, a message on vaccine safety should be included in future public health campaigns to promote vaccination in pregnancy.

Influenza vaccination in pregnancy: vaccine uptake, maternal and healthcare providers' knowledge and attitudes. A quantitative study.

BACKGROUND: Influenza during pregnancy is a potentially life threatening illness. There are limited data on influenza vaccination uptake and determinants of uptake in Irish obstetric populations. AIM: To determine the uptake of influenza vaccination during pregnancy; determinants of vaccination uptake; knowledge, attitudes, and concerns of postnatal women; and knowledge and attitudes of healthcare professionals (HCPs) surrounding vaccination. DESIGN & SETTING: A quantitative study of postnatal women attending the Rotunda Hospital, a tertiary referral maternity hospital in Dublin, Ireland. A separate quantitative study conducted by the North Dublin City GP Training Programme surveyed GPs, pharmacists, and Rotunda Hospital clinical staff. METHOD: A paper-based survey was distributed to postnatal women. HCPs completed the survey via the online tool Survey Monkey. RESULTS: 330 patient surveys were disseminated, with a 60.0% response rate. Of 198 responders, 109 (55.1%) were vaccinated against influenza. Non-professionals were less likely to be vaccinated (adjusted odds ratio [aOR] 0.29, 95% confidence interval [CI] = 0.09 to 0.89). Vaccination in previous pregnancy (aOR 5.2, 95% CI = 1.69 to 15.62) and information from an HCP were strongly associated with vaccination (aOR 12.8, 95% CI = 2.65 to 62.5). There was a 20.2% (n = 1180) response rate among HCPs. More GPs felt that it was their role to discuss vaccination (92.9%; n = 676), and offer to vaccinate women (91.7%; n = 666) than any other HCP. CONCLUSION: Provision of information about the importance of vaccination against influenza and pertussis during pregnancy by HCPs and their consistent recommendations in support of vaccination were key determinants of vaccine uptake during pregnancy. The sociodemographic determinants of a woman's vaccination status should be addressed in health promotion campaigns. Education of HCPs may address knowledge gaps surrounding vaccination.

Ethnic Minority Health in Ireland-Co-creating knowledge (EMH-IC): a participatory health research protocol.

INTRODUCTION: International policy recommends continuous, cost-effective monitoring of health data to enable health services to identify and respond to health inequities as experienced by different ethnic groups. However, there is a lack of routinely collected ethnicity data, particularly in primary care, and very little implementation research internationally to understand how ethnic identifiers are introduced, embedded and used in healthcare settings. This paper describes a protocol for a novel participatory health research project with the objective of building the evidence base on ethnic minority health in Ireland. Findings on the participatory appraisal of ethnic identifiers as an intervention to generate useful data about minority and majority ethnic groups will have relevance in other settings and countries. METHODS AND ANALYSIS: This multidisciplinary project is designed as a participatory health research study where all stakeholders, including ethnic minority communities, participate in co-design of the research protocol, project governance, collaborative data interpretation and disseminating findings. A national catalogue of all routinely collected health data repositories will be electronically searched for any repositories that contain information on ethnicity. A secondary quantitative analysis of a population-representative cohort study, Growing Up in Ireland, will be carried out to compare the health of ethnic minority and majority groups. A qualitative case study informed by normalisation process theory will be carried out at three primary care sites to monitor the implementation of an ethnic identifier and identify barriers and levers to implementation. ETHICS AND DISSEMINATION: Ethical approval for the qualitative case study has been granted by the Irish Council for General Practitioners (06/09/17). Permission to access data from Growing Up in Ireland has been granted by the Director General of the Central Statistics Office. Dissemination will be carried out at community events and academic conferences, in peer-reviewed journal publications, and through academic and healthcare provider networks.

Usage of unscheduled hospital care by homeless individuals in Dublin, Ireland: a cross-sectional study.

OBJECTIVES: Homeless people lack a secure, stable place to live and experience higher rates of serious illness than the housed population. Studies, mainly from the USA, have reported increased use of unscheduled healthcare by homeless individuals.We sought to compare the use of unscheduled emergency department (ED) and inpatient care between housed and homeless hospital patients in a high-income European setting in Dublin, Ireland. SETTING: A large university teaching hospital serving the south inner city in Dublin, Ireland. Patient data are collected on an electronic patient record within the hospital. PARTICIPANTS: We carried out an observational cross-sectional study using data on all ED visits (n=47 174) and all unscheduled admissions under the general medical take (n=7031) in 2015. PRIMARY AND SECONDARY OUTCOME MEASURES: The address field of the hospital's electronic patient record was used to identify patients living in emergency accommodation or rough sleeping (hereafter referred to as homeless). Data on demographic details, length of stay and diagnoses were extracted. RESULTS: In comparison with housed individuals in the hospital catchment area, homeless individuals had higher rates of ED attendance (0.16 attendances per person/annum vs 3.0 attendances per person/annum, respectively) and inpatient bed days (0.3 vs 4.4 bed days/person/annum). The rate of leaving ED before assessment was higher in homeless individuals (40% of ED attendances vs 15% of ED attendances in housed individuals). The mean age of homeless medical inpatients was 44.19 years (95% CI 42.98 to 45.40), whereas that of housed patients was 61.20 years (95% CI 60.72 to 61.68). Homeless patients were more likely to terminate an inpatient admission against medical advice (15% of admissions vs 2% of admissions in homeless individuals). CONCLUSION: Homeless patients represent a significant proportion of ED attendees and medical inpatients. In contrast to housed patients, the bulk of usage of unscheduled care by homeless people occurs in individuals aged 25-65 years.

Implementation of a Pediatric Emergency Triage System in Xiamen, China.

BACKGROUND: Pediatric emergency rooms (PERs) in Chinese hospitals are perpetually full of sick and injured children because of the lack of sufficiently developed community hospitals and low access to family physicians. The aim of this study was to evaluate the clinical value of a new five-level Chinese pediatric emergency triage system (CPETS), modeled after the Canadian Triage System and Acuity Scale. METHODS: In this study, we compared CPETS outcomes in our PER relative to those of the prior two-level system. Patients who visited our PER before (January 2013-June 2013) and after (January 2014-June 2014) the CPETS was implemented served as the control and experimental group, respectively. Patient flow, triage rates, triage accuracy, wait times (overall and for severe patients), and patient/family satisfaction were compared between the two groups. RESULTS: Relative to the performance of the former system experienced by the control group, the CPETS experienced by the experimental group was associated with a reduced patient flow through the PER (Cox-Stuart test, t = 0, P < 0.05), a higher triage rate (93.40% vs. 90.75%; χ2 = 801.546, P < 0.001), better triage accuracy (96.32% vs. 85.09%; χ2 = 710.904, P < 0.001), shorter overall wait times (37.30 ± 13.80 min vs. 41.60 ± 15.40 min; t = 11.27, P < 0.001), markedly shorter wait times for severe patients (2.07 [0.65, 4.11] min vs. 3.23 [1.90,4.36] min; z = -2.057, P = 0.040), and higher family satisfaction rates (94.23% vs. 92.21%; χ2 = 321.528, P < 0.001). CONCLUSIONS: Implementing the CPETS improved nurses' abilities to triage severe patients and, thus, to deliver the urgent treatments more quickly. The system shunted nonurgent patients to outpatient care effectively, resulting in improved efficiency of PER health-care delivery.

Users' experiences of cathinones sold in head shops and online.

OBJECTIVE: We describe use and effects of head shop powders among opiate dependant polydrug users and recreational drug users. These powders contain cathinones and were sold as bath salts or plant food via the internet or in head shops. METHOD: As this is a relatively new phenomenon, a qualitative approach using three data sources, in-depth interviews, a focus group (containing 10 opiate users) and a head shop website containing 49 product reviews, was employed. Themes were identified. RESULTS: According to the study population, these powders mimic the effects of cocaine, ecstasy and amphetamines. These substances were snorted, ingested or injected by people and were not used as bath salts or plant food. The users' experience indicates that these powders have the potential for dependence, and exhibit side effects such as insomnia, anxiety and other mental health effects. The users report that the effects of the substances vary over time indicating that the chemical contents of the powders may change. CONCLUSION: Though users' descriptions of effects varied, there were indications of health and dependency effects which were more severe and more common among problematic opiate users, who also experienced increased social vulnerability. In general the recreational drug users considered their side effects to be mild and worth the drug induced experience.

Sharing control: user involvement in general practice based methadone maintenance.

OBJECTIVES: This study assessed patients' views of a methadone programme in a Dublin general practice including the degree to which the patients were 'involved in decisions about their treatment'. METHOD: All patients receiving methadone were asked to participate. A face to face questionnaire, with open and closed questions, was administered. Interviews lasted approximately 30 minutes. Quantitative data were analysed using descriptive statistics and qualitative data were analysed using a thematic approach. RESULTS: Forty one (87%) of the 47 patients attending the general practice methadone service were interviewed. Of the 39 patients who had used heroin on admission, 69% had stopped and 31% reduced heroin use since starting methadone treatment. A total of 71% reported that the doctor either always involved (59%) or sometimes involved (12%) them in decisions about their treatment. Involvement was interpreted as 'being listened to' or 'having a say' in deciding methadone dose. Surprisingly those who reported that they were not involved in treatment decisions were more likely to have stopped heroin use (10/11). A significant majority of patients (81%) expressed the desire to stop taking methadone. CONCLUSION: Most patients receiving methadone in general practice were listened to and had a say in deciding their methadone dose but did not have an opportunity to engage in more structured or contractual forms of involvement in treatment such as written care plans. In line with a patient centred approach, treatment providers should set their sights beyond the safe delivery of methadone, to provide a service which is centred on patient goals, expectations and choice.

Health of the homeless in Dublin: has anything changed in the context of Ireland's economic boom?

BACKGROUND: In the context of the Irish economic boom we assessed the health, service utilisation and risk behaviour of homeless people in north Dublin city and compared findings with a 1997 study. METHODS: A census of homeless adults in north Dublin city was conducted in 2005 using an adapted interviewer-administered questionnaire from the 1997 study. RESULTS: A total of 363 (70%) of the target population participated. Compared to 1997 the population was younger (81% versus 70% under 45 years, P < 0.01) with a higher proportion of women (39% versus 29%, P < 0.05) and long-term homeless (66% versus 44%, P < 0.001). Drug misuse superseded alcohol as the main addiction with a doubling of the proportion reporting past or current drug use (64% versus 32%, P < 0.001). The prevalence of comparable physical chronic conditions was largely unchanged while depression (51% versus 35%, P < 0.01) and anxiety (42% versus 32%, P < 0.05) had increased. There were high rates of blood-borne infections, such as HIV (6%), hepatitis B (5%) and hepatitis C (36%) in 2005 and dental problems (53%) all of which can be associated with drug use. Access to free healthcare had not increased. Similar proportions reported not having medical cards (40% versus 45% NS). Homeless people continued to have higher usage of secondary care services than the general population. CONCLUSIONS: This study shows a changing disease profile among the homeless population consistent with a growing drug using population. It confirms that the homeless population in Dublin in terms of health remain excluded from the benefits of an economic boom despite a government policy aimed at redressing social inclusion.

Presence of p16 hypermethylation and Epstein-Barr virus infection in transplant-associated hematolymphoid neoplasm of the skin.

BACKGROUND: Epstein-Barr virus (EBV) is associated with the malignant transformation of B, T, and NK lymphocytes in humans, especially in immunosuppressed individuals. OBJECTIVE: We describe an unusual case confined to the skin in a 39-year-old African American female following a renal transplant. METHODS: Morphologically and immunophenotypically, the tumor was best classified as a plasmablastic lymphoma; however, the neoplastic population revealed rearrangements of both immunoglobulin heavy chain (IgG) and T cell receptor gamma (TCR-gamma). In situ hybridization demonstrated the presence of Epstein-Barr early RNA species (EBER) in the lymphoma cells, consistent with EBV infection. RESULTS: We have previously demonstrated that EBV-induced reactive oxygen is associated with hypermethylation of the tumor suppressor gene p16 in Burkitt lymphoma, and that p16 hypermethylation is nearly always associated with EBV infection in Burkitt lymphoma. LIMITATIONS: Further studies are needed to determine whether p16 is widely suppressed in immunosuppression-induced lymphoma. CONCLUSION: In this study, we demonstrated high levels of hypermethylation of the tumor suppressor gene p16, thus supporting the role of EBV as a carcinogen in post-transplant lymphoproliferative disease.

Baseline quality of life and anxiety in solid organ transplant recipients: a pilot study.

BACKGROUND: Solid organ transplant recipients on high doses of immunosuppression are at increased risk for the development of nonmelanoma skin cancer (NMSC). OBJECTIVE: The objective was to assess the possible factors impacting quality of life (QOL) in solid organ transplant recipients. METHODS: Patients were seen in a dermatology clinic integrated within the transplant center at a university-based hospital. One anxiety questionnaire and three QOL questionnaires were administered to each patient. A regression model was used to determine possible predictors of anxiety and lower QOL. RESULTS: The baseline scores on the QOL instruments and anxiety questionnaire indicate poor organ-specific and general QOL as well as high levels of anxiety. Time since transplant was predictive of lower QOL as measured by Skindex-16 (p<.01). While not significant, number of NMSCs correlated with higher anxiety as measured by the STAI (p=.055). CONCLUSIONS: While transplant patients enjoy longer survival, the quality of the extended life has room for improvement. Future studies will determine how QOL changes over time as these patients develop more numerous and aggressive skin cancers. Intervention with regular screening may not only lessen morbidity associated with skin cancer but may improve overall QOL in the posttransplant period.

Management of skin cancer in solid organ transplant recipients.

The incidence of catastrophic skin cancer in the solid organ transplant population continues to rise. As transplant patients are living longer, it is likely that dermatologists will be looking after an increasing number of organ transplant recipients. The key to managing this patient population lies in a multidisciplinary approach encompassing patient education, skin screening in the immediate post-transplant period, regular follow-up, and rapid referral to a dermatologist once skin lesions suspicious for skin cancer are diagnosed. Of paramount importance is discussion with transplant physicians to negotiate reduction of immunosuppression in the setting of catastrophic skin cancer. This article defines the scope of the problem of skin cancer in the solid organ transplant population, defines the nature of the lesions commonly presented, and reinforces the benefit of a multidisciplinary approach in the management of these patients.

Regulation of tissue factor in microvascular dermal endothelial cells.

Inflammation is accompanied by activation of the coagulation cascade, manifested by thrombosis and fibrin generation. Whereas endothelial cells normally provide a nonthrombogenic surface, inflammatory mediators may induce the expression of tissue factor, rendering their surface thrombogenic. In order to define the mechanisms regulating the expression of tissue factor in the skin microvasculature, we examined tissue factor expression in human dermal microvascular endothelial cells. Quiescent human dermal microvascular endothelial cells did not constitutively express tissue factor protein, but were induced to express tissue factor by treatment with tumor necrosis factor-alpha in a time- and concentration-dependent fashion. Increased expression of tissue factor protein was accompanied by increases in steady-state mRNA levels. Tumor necrosis factor-alpha treatment resulted in increased expression of tissue factor heterogeneous nuclear RNA without changes in mRNA stability, suggesting that increased mRNA was mediated primarily via increased tissue factor gene transcription. In order to define the pathways regulating tissue factor induction, we examined the effects of MG-132, an inhibitor of nuclear factor-kappaB activation, PD98059, an inhibitor of MEK1 action, and SB203580, an inhibitor of activated p38 activity. MG132 only partially blocked tumor necrosis factor-alpha-induced tissue factor protein expression, despite an almost complete inhibition of tumor necrosis factor-alpha-induced E-selectin expression. In contrast, SB203580, almost completely inhibited tumor necrosis factor-alpha-induced tissue factor expression but inhibition of MEK1 by PD98059 had a minimal effect on tumor necrosis factor-alpha-mediated tissue factor induction in human dermal microvascular endothelial cells. Both SB203580 and MG132 treatment inhibited tumor necrosis factor-alpha-mediated increases in tissue factor mRNA and tissue factor gene transcription as measured by expression of tissue factor heterogeneous nuclear RNA. These data support a transcriptional role for both nuclear factor-kappaB and p38 mitogen-activated protein kinase, but not MEK1 in tissue factor gene expression in human dermal microvascular endothelial cells.

FKBP12 modulation of the binding of the skeletal ryanodine receptor onto the II-III loop of the dihydropyridine receptor.

In skeletal muscle, excitation-contraction coupling involves a functional interaction between the ryanodine receptor (RyR) and the dihydropyridine receptor (DHPR). The domain corresponding to Thr(671)-Leu(690) of the II-III loop of the skeletal DHPR alpha(1)-subunit is able to regulate RyR properties and calcium release from sarcoplasmic reticulum, whereas the domain corresponding to Glu(724)-Pro(760) antagonizes this effect. Two peptides, covering these sequences (peptide A(Sk) and C(Sk), respectively) were immobilized on polystyrene beads. We demonstrate that peptide A(Sk) binds to the skeletal isoform of RyR (RyR1) whereas peptide C(Sk) does not. Using surface plasmon resonance detection, we show that 1) domain Thr(671)-Leu(690) is the only sequence of the II-III loop binding with RyR1 and 2) the interaction of peptide A(Sk) with RyR1 is not modulated by Ca(2+) (pCa 9-2) nor by Mg(2+) (up to 10 mM). In contrast, this interaction is strongly potentiated by the immunophilin FKBP12 (EC(50) = 10 nM) and inhibited by both rapamycin (IC(50) = 5 nM) and FK506. Peptide A(Sk) induces a 300% increase of the opening probability of the RyR1 incorporated in lipid bilayer. Removal of FKBP12 from RyR1 completely abolishes this effect of domain A(Sk) on RyR1 channel behavior. These results demonstrate a direct interaction of the RyR1 with the discrete domain of skeletal DHPR alpha(1)-subunit corresponding to Thr(671)-Leu(690) and show that the association of FKBP12 with RyR1 specifically modulates this interaction.