Genomic Diagnosis of Rare Pediatric Disease in the United Kingdom and Ireland.

BACKGROUND: Pediatric disorders include a range of highly penetrant, genetically heterogeneous conditions amenable to genomewide diagnostic approaches. Finding a molecular diagnosis is challenging but can have profound lifelong benefits. METHODS: We conducted a large-scale sequencing study involving more than 13,500 families with probands with severe, probably monogenic, difficult-to-diagnose developmental disorders from 24 regional genetics services in the United Kingdom and Ireland. Standardized phenotypic data were collected, and exome sequencing and microarray analyses were performed to investigate novel genetic causes. We developed an iterative variant analysis pipeline and reported candidate variants to clinical teams for validation and diagnostic interpretation to inform communication with families. Multiple regression analyses were performed to evaluate factors affecting the probability of diagnosis. RESULTS: A total of 13,449 probands were included in the analyses. On average, we reported 1.0 candidate variant per parent-offspring trio and 2.5 variants per singleton proband. Using clinical and computational approaches to variant classification, we made a diagnosis in approximately 41% of probands (5502 of 13,449). Of 3599 probands in trios who received a diagnosis by clinical assertion, approximately 76% had a pathogenic de novo variant. Another 22% of probands (2997 of 13,449) had variants of uncertain significance in genes that were strongly linked to monogenic developmental disorders. Recruitment in a parent-offspring trio had the largest effect on the probability of diagnosis (odds ratio, 4.70; 95% confidence interval [CI], 4.16 to 5.31). Probands were less likely to receive a diagnosis if they were born extremely prematurely (i.e., 22 to 27 weeks' gestation; odds ratio, 0.39; 95% CI, 0.22 to 0.68), had in utero exposure to antiepileptic medications (odds ratio, 0.44; 95% CI, 0.29 to 0.67), had mothers with diabetes (odds ratio, 0.52; 95% CI, 0.41 to 0.67), or were of African ancestry (odds ratio, 0.51; 95% CI, 0.31 to 0.78). CONCLUSIONS: Among probands with severe, probably monogenic, difficult-to-diagnose developmental disorders, multimodal analysis of genomewide data had good diagnostic power, even after previous attempts at diagnosis. (Funded by the Health Innovation Challenge Fund and Wellcome Sanger Institute.).

Clinical Impact of Serious Respiratory Disease in Children Under the Age of 2 Years During the 2021-2022 Bronchiolitis Season in England, Scotland, and Ireland.

BACKGROUND: Interventions introduced to reduce the spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) led to a widespread reduction in childhood infections. However, from spring 2021 onwards the United Kingdom and Ireland experienced an unusual out-of-season epidemic of respiratory disease. METHODS: We conducted a prospective observational study (BronchStart), enrolling children 0-23 months of age presenting with bronchiolitis, lower respiratory tract infection, or first episode of wheeze to 59 emergency departments across England, Scotland, and Ireland from May 2021 to April 2022. We combined testing data with national admissions datasets to infer the impact of respiratory syncytial virus (RSV) disease. RESULTS: The BronchStart study collected data on 17 899 presentations for 17 164 children. Risk factors for admission and escalation of care included prematurity and congenital heart disease, but most admissions were for previously healthy term-born children. Of those aged 0-11 months who were admitted and tested for RSV, 1907 of 3912 (48.7%) tested positive. We estimate that every year in England and Scotland 28 561 (95% confidence interval, 27 637-29 486) infants are admitted with RSV infection. CONCLUSIONS: RSV infection was the main cause of hospitalizations in this cohort, but 51.3% of admissions in infants were not associated with the virus. The majority of admissions were in previously healthy term-born infants.

SARS-CoV-2 Seropositivity in Urban Population of Wild Fallow Deer, Dublin, Ireland, 2020-2022.

SARS-CoV-2 can infect wildlife, and SARS-CoV-2 variants of concern might expand into novel animal reservoirs, potentially by reverse zoonosis. White-tailed deer and mule deer of North America are the only deer species in which SARS-CoV-2 has been documented, raising the question of whether other reservoir species exist. We report cases of SARS-CoV-2 seropositivity in a fallow deer population located in Dublin, Ireland. Sampled deer were seronegative in 2020 when the Alpha variant was circulating in humans, 1 deer was seropositive for the Delta variant in 2021, and 12/21 (57%) sampled deer were seropositive for the Omicron variant in 2022, suggesting host tropism expansion as new variants emerged in humans. Omicron BA.1 was capable of infecting fallow deer lung type-2 pneumocytes and type-1-like pneumocytes or endothelial cells ex vivo. Ongoing surveillance to identify novel SARS-CoV-2 reservoirs is needed to prevent public health risks during human-animal interactions in periurban settings.

Untangling the association between COVID-19 health literacy, trust in the pandemic response, and mental distress, during the COVID-19 pandemic in Ireland: a repeated cross-sectional study.

BACKGROUND: The impact of the COVID-19 pandemic on rates of mental distress is well described. However, the contribution of poor health literacy and low levels of trust in state institutions to mental distress is less well defined. This study aimed to assess the impact of COVID-19 health literacy and trust in the pandemic response (Trust) on mental distress during the COVID-19 pandemic in Ireland. METHODS: We did this nationally representative cross-sectional survey of adult Irish residents during three study periods: from May 26 to June 17, 2020 (n=947); from July 1 to July 23, 2020 (n=995); and from Sept 5 to Sept 28, 2020 (n=972). Participants were contacted using random-digit-dialling and interviewed by a professional market research organisation (Ipsos MRBI' about 80% via mobile phone, 20% via landline). Mental distress was assessed by the Patient Health Questionnaire Anxiety Depression Scale (PHQ-ADS), for which a score of 10 or higher indicated mental distress. Heath literacy and trust were each assessed with three questions, which defined three categories: low, moderate, and high (appendix). Descriptive analysis and multivariate (MVA) Poisson regression were conducted in STATA17, Incidence Rate Ratios (IRR) are reported. FINDINGS: 2914 participants completed the survey across three study periods (median age 46 years, 1510 [51·8%] women, 1401 [48·1%] men, three [0·1%] non-binary). 804 (27·6%) of 2914 participants experienced mental distress (n=804). More women experienced mental distress than men (508 [34%] of women vs 294 [21%] of men). Mental distress was inversely associated with age (from 43% in those aged <30 years [n=232/539] to 19% in those aged >70 years [n=66/349]). Most participants had high health literacy (n=2,530, 86·8%). While health literacy was positively and significantly associated with trust, it was not associated with mental distress and it was therefore excluded from the MVA. Level of trust was captured for 2693 adults; 42·2% participants reported low trust (n=457) or moderate trust (n=679). The prevalence of mental distress was inversely associated with trust; increasing from 24% in those with high trust (n=374/1557), 30% in those with moderate trust (n=202/679), to 36% in those with low trust (n=166/457). In MVA higher rates of mental distress were associated with low trust (IRR 1·45, 95% CI 1·20-1·75; p=0·000) and moderate trust (IRR 1·24, 1·04-1·47, p=0·016) compared with high trust when adjusted for age, sex, employment status, and income,. INTERPRETATION: In Ireland, low levels of trust in the COVID-19 pandemic response were associated with higher levels of mental distress. Although poor health literacy was associated with low levels of trust, it was not independently associated with mental distress. Inference on the nature and direction of causal effects must be cautious given the cross-sectional study design. FUNDING: Health Research Board.

Associations between parental smoking and teenage alcohol and drug use in the Growing Up in Ireland cohort study: a longitudinal observational study.

BACKGROUND: Children with a parent who smokes are more likely to become substance users than those who do not have a parent who smokes. In this study, we examined whether childhood or early adolescent exposure to primary parent smoking increased the risk of subsequent teenage alcohol and drug use at ages 17-18 years. METHODS: For this longitudinal observational study, we analysed data from 6039 teenagers and their parents from the waves 1-3 of the Growing up in Ireland Cohort 98' Study. Parental smoking was assessed at baseline (9 years) and wave 2 (13 years) with responses coded as yes or no. The primary parent was defined as the person who provided most care and who knew most about the Study Child, usually the mother or mother figure for 98% of study participants. Teenage alcohol and drug use assessed at ages 17-18 years (wave 3) was determined by responses to the question "Have you ever consumed alcohol?" (answers yes or no), drug use was assessed by questions on ever trying aerosols/gas, cannabis, and non-prescribed drugs, with those answering yes being classified as other-drug ever users. We did a logistic regression analysis to examine the associations between parents' smoking on teenage alcohol and drug use, controlling for covariates: gender, education, income, education, region, and household type. Ethics approval for the GUI project was obtained from the Health Research Board. FINDINGS: Of the 6039 teenagers included in our study, 2968 (49%) were female, 3070 (51%) were male, 5351 (89%) ever used alcohol, 5065 (85%) were current users, and 2098 (35%) used other drugs. Rates of primary parent smoking were 31% (n=1883) in wave 1 and 30% (n=1829) in wave 2. After adjusting for other exposures known to be associated with teenage substance use, primary parent smoking at waves 1 and 2 was associated with higher odds of teenage alcohol ever use (adjusted odds ratios [aORs] 1·89 [95% CI 1·44--2·46] at wave 1 and 1·53 [1·20-1·98] at wave 2), current alcohol use (1·88 [1·50-2·36] and 1·59 [1·28-1·97]) and other-drug ever use (1·699 [1·45-1·95] and 1·71 [1·47-1·98]). INTERPRETATION: Teenagers aged 17-18 years exposed at ages 9 and 13 years to parental smoking were more likely to report significantly higher odds of alcohol and drug use at age 17-18 years. The finding that exposure to parent smoking in childhood increases the risk of teenage alcohol and other drug use suggests a need for interventions aimed at parents who smoke Limitations include potential unmeasured or residual confounders and reliance on self-reported teenage substance use behaviours. FUNDING: Royal City of Dublin Hospital Trust, Irish Research Council Government of Ireland Postgraduate Scholarship Programme.

Understanding cardiac events in breast cancer (UCARE): pilot cardio-oncology assessment and surveillance pathway for breast cancer patients.

PURPOSE: In Ireland, over 3000 patients are diagnosed with breast cancer annually, and 1 in 9 Irish women will be diagnosed with breast cancer in their lifetime. There is evidence that female breast cancer survivors are more likely to die of cardiovascular disease than their age-matched counterparts. Specific services for cancer patients suffering from cancer therapy related cardiovascular toxicity have led to a higher incidence of safe anti-cancer treatment completion. Such services are not widely available in our jurisdiction, and the purpose of this trial is to remedy this situation. METHODS: This protocol describes a prospective, single arm, pilot feasibility study implementing a dedicated Cardio-Oncology assessment and surveillance pathway for patients receiving multimodal breast cancer treatment. It incorporates novel biomarker and radiomic surveillance and monitoring approaches for cancer-therapy related cardiac dysfunction into routine care for breast cancer patients undergoing adjuvant systemic chemotherapy. RESULTS: Declaration of results will via peer reviewed academic journals, and communicated directly to key knowledge users both nationally and internationally. This engagement will be critical to enable to healthcare services and policy sector make informed decisions or valuable changes to clinical practice, expenditure and/or systems development to support specialized Cardio-Oncology clinical pathways. All data is to be made available upon request. CONCLUSION: Dedicated cardio-oncology services have been recommended in recent literature to improve patient outcomes. Our protocol describes a feasibility study into the provision of such services for breast cancer.

High-resolution genomics identifies pneumococcal diversity and persistence of vaccine types in children with community-acquired pneumonia in the UK and Ireland.

BACKGROUND: Streptococcus pneumoniae is a global cause of community-acquired pneumonia (CAP) and invasive disease in children. The CAP-IT trial (grant No. 13/88/11; https://www.capitstudy.org.uk/ ) collected nasopharyngeal swabs from children discharged from hospitals with clinically diagnosed CAP, and found no differences in pneumococci susceptibility between higher and lower antibiotic doses and shorter and longer durations of oral amoxicillin treatment. Here, we studied in-depth the genomic epidemiology of pneumococcal (vaccine) serotypes and their antibiotic resistance profiles. METHODS: Three-hundred and ninety pneumococci cultured from 1132 nasopharyngeal swabs from 718 children were whole-genome sequenced (Illumina) and tested for susceptibility to penicillin and amoxicillin. Genome heterogeneity analysis was performed using long-read sequenced isolates (PacBio, n = 10) and publicly available sequences. RESULTS: Among 390 unique pneumococcal isolates, serotypes 15B/C, 11 A, 15 A and 23B1 were most prevalent (n = 145, 37.2%). PCV13 serotypes 3, 19A, and 19F were also identified (n = 25, 6.4%). STs associated with 19A and 19F demonstrated high genome variability, in contrast to serotype 3 (n = 13, 3.3%) that remained highly stable over a 20-year period. Non-susceptibility to penicillin (n = 61, 15.6%) and amoxicillin (n = 10, 2.6%) was low among the pneumococci analysed here and was independent of treatment dosage and duration. However, all 23B1 isolates (n = 27, 6.9%) were penicillin non-susceptible. This serotype was also identified in ST177, which is historically associated with the PCV13 serotype 19F and penicillin susceptibility, indicating a potential capsule-switch event. CONCLUSIONS: Our data suggest that amoxicillin use does not drive pneumococcal serotype prevalence among children in the UK, and prompts consideration of PCVs with additional serotype coverage that are likely to further decrease CAP in this target population. Genotype 23B1 represents the convergence of a non-vaccine genotype with penicillin non-susceptibility and might provide a persistence strategy for ST types historically associated with vaccine serotypes. This highlights the need for continued genomic surveillance.

Molecular epidemiology of human herpesvirus 8 in patients with HHV-8-related diseases in Ireland.

Human Herpesvirus 8 (HHV-8) has been classified by sequence analysis of open reading frame (ORF) K1, ORF K15, and variable sequence loci within the central constant region. The purpose of this study was to examine the molecular epidemiology of HHV-8 in an Irish population. This retrospective study included 30 patients who had HHV-8 DNA detected in plasma. Nested end-point PCR was used to characterise four regions of the HHV-8 genome, K1, T0.7 (K12), ORF 75, and K15. Sequencing data were obtained for 23 specimens from 19 patients. Phylogenetic analysis of ORF K1 demonstrated that subtypes A, B, C and F were present in 37%, 11%, 47% and 5%, respectively. For T0.7 and ORF 75, sequencing data were obtained for 12 patients. For T0.7, subtypes A/C, J, B, R and Q were present in 58%, 17%, 8%, 8%, and 8%, respectively. For ORF 75, subtypes A, B, C and D were present in 58%, 8%, 25%, and 8%, respectively. K15 sequences were determined for 13 patients. 69% had the P allele and 31% had the M allele. The data generated by this study demonstrate that a broad variety of HHV-8 subtypes are represented in patients exhibiting HHV-8-related disease in Ireland, a low prevalence country. The predominance of C and A K1 subtypes was as expected for a Western European population. The 31% prevalence for K15 subtype M was higher than expected for a Western European population. This may represent the changing and evolving epidemiology in Ireland due to altered migration patterns.

Mastitis and Mammary Abscess Management Audit (MAMMA) in the UK and Ireland.

BACKGROUND: The aim of this multicentre prospective audit was to describe the current practice in the management of mastitis and breast abscesses in the UK and Ireland, with a specific focus on rates of surgical intervention. METHODS: This audit was conducted in two phases from August 2020 to August 2021; a phase 1 practice survey and a phase 2 prospective audit. Primary outcome measurements for phase 2 included patient management pathway characteristics and treatment type (medical/radiological/surgical). RESULTS: A total of 69 hospitals participated in phase 2 (1312 patients). The key findings were a high overall rate of incision and drainage (21.0 per cent) and a lower than anticipated proportion of ultrasound-guided aspiration of breast abscesses (61.0 per cent). Significant variations were observed regarding the rate of incision and drainage (range 0-100 per cent; P < 0.001) and the rate of needle aspiration (range 12.5-100 per cent; P < 0.001) between individual units. Overall, 22.5 per cent of patients were admitted for inpatient treatment, out of whom which 72.9 per cent were commenced on intravenous antibiotics. The odds of undergoing incision and drainage for a breast abscess or being admitted for inpatient treatment were significantly higher if patients presented at the weekend compared with a weekday (P ≤ 0.023). Breast specialists reviewed 40.9 per cent of all patients directly, despite the majority of patients (74.2 per cent) presenting within working hours on weekdays. CONCLUSIONS: Variation in practice exists in the management of mastitis and breast abscesses, with high rates of incision and drainage in certain regions of the UK. There is an urgent need for a national best-practice toolbox to minimize practice variation and standardize patient care.

Mastitis and breast abscess is a painful infection of the breast. It is an extremely common breast problem. One in three women can get this condition at some stage in their life. To treat a breast abscess, the pus inside should be drained out of the body. This can be done either by cutting into the breast using surgery or by inserting a fine needle using an ultrasonography scan (which uses ultrasound). Fine-needle drainage has the benefit that it does not require admission to hospital. Surgery can cause the breast to look misshapen. It is unknown which method is used more often in the UK and Ireland. The aim of this study was to describe how mastitis and breast abscesses are treated in the UK and Ireland. This study involved a survey of practice (phase 1) and collection of data, which are routinely recorded for these patients (phase 2). This study involved 69 hospitals and 1312 patient records. One in five women had an operation for a breast abscess. This was higher than expected. Six in 10 women had a pus drainage using a fine needle. The chance of having an operation depended on the hospital. Women that came to hospital at the weekend were almost twice as likely to have an operation. One in five women were admitted to hospital. The chances of that more than doubled if a woman came to hospital at the weekend. There are differences in treatment of mastitis and breast abscesses across the UK and Ireland. Changes need to be put in place to make access to treatment more equal.

Factors influencing participation in an online national diabetes prevention programme: A qualitative study with attenders and educators.

AIM: To explore factors affecting participation in the pilot of the synchronous online national diabetes prevention programme (NDPP) in Ireland from the perspectives of those who attended and the educators who recruited for and delivered the programme. METHODS: A qualitative study involving semi-structured interviews and focus groups with NDPP attenders (attended the assessment and at least one session) and educators (dietitians) on the programme. The Framework Method using the Theoretical Domains Framework (TDF) guided the analysis. RESULTS: Thirteen attenders took part in two online focus groups and five online or phone interviews. Eight educators took part. Four themes which cut across the TDF domains were identified as factors influencing participation; (i) lack of awareness of prediabetes and fear of diabetes, relating to attenders' fear of diabetes and lack of knowledge of prediabetes and diabetes prevention; (ii) perceived need for programme support to change health behaviour, concerning attenders' and educators' recognition of the need for the NDPP; (iii) trust in healthcare professionals (HCPs), relating to trust in HCPs to convey the seriousness of prediabetes and the value of diabetes prevention programmes (DPPs) and (iv) practical and personal ease of joining online, relating to the flexibility and accessibility of the synchronous online group format, the IT skills of attenders and educators and apprehension about group education. CONCLUSIONS: Raising awareness of prediabetes and the need for prevention programmes should be a priority for health services and HCPs. The synchronous online group format was seen as less daunting to join than a face-to-face programme and may be a useful option to encourage participation.

Early life adversity and obesity risk in adolescence: a 9-year population-based prospective cohort study.

BACKGROUND: There are few prospective studies of factors that mediate the association between exposure to adverse childhood experiences (ACEs) and obesity in adolescence. Our aim was to address this limitation. METHODS: We used prospective data from the Growing up in Ireland cohort study, with measurements at 9, 13, and 18 years old. The exposures were 14 adverse experiences before age 9. The main outcome was body mass index (BMI) at 18 years. Mediators were daily activity, diet quality, self-image and behavioural difficulties at 13 years. RESULTS: Among the 4561 adolescents in the final cohort, 77.2% experienced any adversity, 50.5% were female and 26.7% were overweight/obese at 18 years. BMI Z was higher at ages 9 (0.54 vs 0.43, p < 0.05, 95% CI of difference: -0.22, -0.01) and 13 years (0.50 vs 0.35, p < 0.05, 95% CI of difference: -0.25, -0.06), in those exposed to an ACE, compared to those unexposed. Structural equation models revealed that behavioural difficulties (ß = 0.01; 95% CI: 0.007-0.018, p < 0.001) and self-concept (ß = 0.0027; 95% CI: 0.0004-0.0050, p = 0.026) indirectly mediate the association between exposure to ACEs and BMI at 18 years. CONCLUSIONS: The association between ACEs and BMI in adolescence is mediated by behavioural difficulties and self-concept. IMPACT: In a previous study, we found modest associations between exposure to a range of adverse childhood experiences and weight gain at 13 years of age. The strength of the association between adverse childhood experiences and weight gain was lower at 18 years of age compared to the association observed at 13 years and was no longer significant after controlling for confounding and including possible mediators. The association between adverse childhood experiences and BMI in adolescence is indirectly mediated by behavioural difficulties and self-concept.

Gabapentinoids in Ireland 2010 to 2020: An observational study of trends in gabapentinoid prescribing, law enforcement drug seizures and postmortem toxicology.

AIMS: We explored trends in gabapentinoid prescribing, drug seizures and postmortem toxicology using a national pharmacy claims database, law enforcement drug seizures data and a population-based postmortem toxicology database. METHODS: Gabapentinoid prescribing rates per 100 000 eligible population (2010-2020), annual number of drug seizures involving gabapentinoids (2012-2020) and gabapentinoid detection (positive) rates per 100 postmortem toxicology case (2013-2020) were calculated. Negative binomial regression models were used to evaluate longitudinal trends for gabapentin and pregabalin separately. RESULTS: Gabapentin (adjusted rate ratio [RR] 1.06, 95% confidence interval [CI] 1.05-1.06, P < .001) and pregabalin (adjusted RR 1.08, 95% CI 1.08-1.09, P < .001) prescribing increased annually, with higher rates of pregabalin (vs. gabapentin) observed every year. Drug seizures involving pregabalin also increased over time (RR 1.54 95% CI 1.25-1.90, P < .0001). Of the 26 317 postmortem toxicology cases, 0.92% tested positive for gabapentin, and 6.37% for pregabalin. Detection rates increased for both gabapentin (RR 1.28, 95% CI 1.11-1.48, P < .001) and pregabalin (RR 1.13, 95% CI 1.11-1.48, P < .001) between 2013 and 2020. A total of 1901 cases (7.2%) tested positive for heroin/methadone; this sub-group had a higher detection rate for pregabalin (n = 528, 27.8%) and gabapentin (n = 41, 2.2%) over the study period, with a high burden of codetections for pregabalin with benzodiazepines (peaking at 37.3% in 2018), and pregabalin with prescription opioids (peaking at 28.9% in 2020). CONCLUSION: This study raises concerns regarding the wide availability of pregabalin in Ireland, including a growing illicit supply, and the potential for serious harm arising from poly drug use involving pregabalin among people who use heroin or methadone.

Female perpetrated sexual assault: a review of attendances to the national sexual assault treatment units in the Republic of Ireland.

BACKGROUND: Female perpetrated sexual assault is under-represented in sexual assault research, and indeed possibly an underreported crime. The aim of this study is to address the lack of comprehensive data in relation to female perpetrated sexual assault attendances to the national sexual assault treatment unit network in the Republic of Ireland. METHODS: This is a cross-sectional study analysing the attendances of female perpetrated sexual assault attendances at the six sexual assault treatment units in the Republic of Ireland between 1 January 2017 and 31 December 2022. RESULTS: There were 95 attendances where the assailant (or one of the assailants) was identified as female. 62% (n=59) of these attendances involved a solo female assailant, 3.2% (n=3) where it was a multiple assailant assault with only female assailants and 34.7% (n=33) cases with male and female assailants. 74.7% (n=71) of victims identified as female, 24.2% (n=23) as male and 1.1% (n=1) as 'other'. The average age of attenders was 27.0 ± 10.7 years old. 54.7% (n=52) of attendances were within 72 hours of the assault. 52.6% (n=50) of these underwent a forensic examination. 30.5% (n=29) of incidents occurred in the assailant's home. 23% of assailants were described as a friend of the victim/survivor. 34.7% (n=33) sustained bodily injuries (genital and/or extra-genital). CONCLUSION: Female perpetrated sexual assault is a distinct entity when analysing attendances to the national sexual assault treatment unit network, representing just under 2% of all attendances. We have shown that those who experience these assaults are likely to be female, be assaulted by a single female perpetrator who is known to them and attend a sexual assault treatment unit within 72 hours of the assault. Awareness of the characteristics of these attendances will ultimately allow us to develop appropriate supports for these victims/survivors and to raise awareness of this type of crime.

The experiences of individuals living with HIV in Ireland attending out-patient physiotherapy.

People living with HIV (PLWH) are living longer and are becoming increasingly susceptible to multi-morbidity resulting in disability. Physiotherapy is an important component in the care of PLWH, increasing functional capacity and quality of life. However, few PLWH access physiotherapy services due to a lack of specialised services, relapses in medical conditions and financial barriers. This study aimed to gather feedback from PLWH in a tertiary infection centre in Ireland attending out-patient physiotherapy on their experiences of physiotherapy. Eleven PLWH completed a semi-structured feedback survey focusing on their expectations and experiences of physiotherapy. Participants reported an overall positive experience of physiotherapy especially in terms of improving movement, confidence, physical activity level and sense of control. In addition, participants highlighted the importance of a physiotherapist with specialist knowledge of HIV. Barriers to participation in physiotherapy included potential relapses in other medical conditions, lack of time due to work and lack of flexibility or availability of physiotherapy appointments. This study highlights the important role of physiotherapy in the care of PLWH, several potential barriers to participation in physiotherapy for PLWH and the importance of the participation of PLWH in the co-design of services.

Delays in Multiple Sclerosis diagnosis (DIMES): protocol for a multicentre, observational study of multiple sclerosis diagnostic pathways in the United Kingdom and Republic of Ireland.

BACKGROUND: Multiple sclerosis (MS) is a leading cause of non-traumatic disability in young adults. Accumulating evidence indicates early diagnosis and early treatment improves long-term outcomes. However, the MS diagnostic pathway is increasingly complex, and delays may occur at several stages. Factors causing delays remain understudied. We aim to quantify the time taken for MS to be diagnosed, and characterise the diagnostic pathway and initial care provided, in the United Kingdom (UK) and Republic of Ireland (ROI). METHODS: Delays In MultiplE Sclerosis diagnosis (DIMES) in the UK and ROI is a multicentre, observational, retrospective study that will be conducted via the Neurology and Neurosurgery Interest Group (NANSIG) collaborative network. Any hospital in the UK and ROI providing an MS diagnostic service is eligible to participate. Data on consecutive individuals newly diagnosed with MS between 1st July 2022 and 31st December 2022 will be collected. The primary outcomes are 1) time from symptoms/signs prompting referral to neurology, to MS diagnosis; and 2) time from referral to neurology for suspected MS, to MS diagnosis. Secondary outcomes include: MS symptoms, referring specialties, investigations performed, neurology appointments, functional status, use of disease modifying treatments, and support at diagnosis including physical activity, and follow up. Demographic characteristics of people newly diagnosed with MS will be summarised, adherence to quality standards summarised as percentages, and time-to-event variables presented with survival curves. Multivariable models will be used to investigate the association of demographic and clinical factors with time to MS diagnosis, as defined in our primary outcomes. DISCUSSION: DIMES aims to be the largest multicentre study of the MS diagnostic pathway in the UK and ROI. The proposed data collection provides insights that cannot be provided from contemporary registries, and the findings will inform approaches to MS services nationally in the future.

Multicomponent perinatal breastfeeding support in women with BMI >25: The Latch On multi-centre randomised trial.

OBJECTIVE: To investigate the effectiveness of a multicomponent breastfeeding support intervention on breastfeeding prevalence at 3 months among women with a body mass index (BMI) >25 kg/m2. DESIGN: Multicentre multicomponent randomised controlled trial. SETTING: Four maternity centres in Ireland. POPULATION: A total of 225 primiparous women and their nominated support partners. Participants were aged 18 years and over, with BMI ≥25 kg/m2, carrying a singleton pregnancy and without contraindication for breastfeeding. METHODS: The intervention included an antenatal group breastfeeding education session for participants and their support partners, followed by a planned postnatal breastfeeding assessment and telephone support for up to 6 weeks by a lactation consultant. MAIN OUTCOME MEASURES: Any breastfeeding at 3 months postpartum. RESULTS: Any breastfeeding prevalence was 68.7% (n = 68) in the intervention group and 62.1% (n = 59) in the control group at 3 months postpartum (odds ratio 1.33, 95% confidence interval 0.72-2.46, p = 0.36). Any and exclusive breastfeeding rates did not significantly differ at any other time point. More women in the control group accessed support from private lactation consultants (intervention 23.5% [n = 12], control 45.3% [n = 24], p = 0.02). CONCLUSIONS: The control group had higher than expected breastfeeding rates, and the study found no evidence of effect on the primary outcome. Providing comprehensive education and support for women intending to breastfeed remains of paramount importance.

Long-term exposure to PM2.5 air pollution and mental health: a retrospective cohort study in Ireland.

BACKGROUND: Mental illness is the leading cause of years lived with disability, and the global disease burden of mental ill-health has increased substantially in the last number of decades. There is now increasing evidence that environmental conditions, and in particular poor air quality, may be associated with mental health and wellbeing. METHODS: This cross-sectional analysis uses data on mental health and wellbeing from The Irish Longitudinal Study on Ageing (TILDA), a nationally representative survey of the population aged 50+ in Ireland. Annual average PM2.5 concentrations at respondents' residential addresses over the period 1998-2014 are used to measure long-term exposure to ambient PM2.5. RESULTS: We find evidence of associations between long-term exposure to ambient PM2.5 and depression and anxiety. The measured associations are strong, and are comparable with effect sizes for variables such as sex. Effects are also evident at relatively low concentrations by international standards. However, we find no evidence of associations between long-term ambient particulate pollution and other indicators of mental health and well-being such as stress, worry and quality of life. CONCLUSIONS: The measured associations are strong, particularly considering the relatively low PM2.5 concentrations prevailing in Ireland compared to many other countries. While it is estimated that over 90 per cent of the world's population lives in areas with annual mean PM2.5 concentrations greater than 10 µg/m3, these results contribute to the increasing evidence that suggests that harmful effects can be detected at even low levels of air pollution.

A multicentre review of the direct-access mammography programme in Ireland for women with breast pain.

AIM: To assess the current use of the direct access mammography pathway for breast pain and the rate of breast cancer detection in this patient cohort. MATERIALS AND METHODS: A retrospective review of general practitioner (GP)-referred mammograms performed during a 12-month period from January to December 2022 across four tertiary referral centres. With the use of medical records and GP referrals, patient demographics, presenting symptoms, family history, and clinical outcomes were recorded. RESULTS: The present study comprised 2,046 patients of which 21.6% did not report breast pain at the time of referral. Thirty-five per cent had a positive family history with 40% of these patients having no breast pain. Twelve per cent were recalled with 30% of these patients requiring biopsy. An overall cancer detection rate (CDR) of 7 per 1000 was determined for women with mastalgia. A CDR of 0 per 1,000 was determined for women <50 years with mastalgia alone and no additional risk factors for malignancy. Fisher's exact test showed no statistically significant association between breast pain and breast cancer. CONCLUSION: There was no statistically significant relationship found between breast pain and breast cancer. This review suggests a low cancer detection rate in women <50 years. In women <50 years with mastalgia without additional symptoms or family history, breast imaging is not required.

Comparing times of self-harm presentations to hospital emergency departments in children, adolescents, young adults and adults: a national registry study 2007-2019.

PURPOSE: The few studies that have explored self-harm presentation times at hospital emergency departments (EDs) - an important factor that can determine if a patient receives a mental health assessment - primarily focus on adult samples. This study examined the times of self-harm presentations to EDs, self-harm methods used, mental health assessments, and admission data across different age-groups. METHODS: Using data from the National Self-Harm Registry Ireland over a 13-year timeframe (2007-2019), this study compared times, days, seasons, methods of self-harm, and admission data for children (8-12 years), adolescents (13-17 years), young adults (18-25 years) and adults (> 25 years). RESULTS: The majority of the 152,474 self-harm presentations (78.6%) for all ages occurred out-of-hours (outside the standard working hours or in-hours times of 09:00-17:00, Monday-Friday). The four hours before midnight had the highest proportions of self-harm presentations for adolescents (27.9%) and adults (23.1%), whereas the four hours after midnight had the highest proportion of self-harm presentations for young adults (22.9%). The 16:00-midnight timeframe had highest proportion of self-harm presentations in children (52.3%). Higher proportions of patients received a mental health assessment in-hours compared to out-of-hours among young adults (78.2% vs. 73.3%) and adults (76.1% vs. 72.0%). Self-harm presentations were lowest during summer months in children and adolescents. DISCUSSION: Hospitals should ensure that adequate resources are available for individuals presenting with self-harm, especially in the case of overcrowded EDs, and protocols need to be designed for those presenting with self-harm due to intoxication. In line with national policy, protocols for patients presenting during out-of-hours should be designed that can incorporate services from allied health multidisciplinary teams, social work, addiction services and counselling organisations. Given the lower rates of self-harm during school holidays for children and adolescents, the school environment must be considered in the context of mental health and self-harm public health prevention interventions.

An investigation of inequalities in exposure to PM2.5 air pollution across small areas in Ireland.

The link between exposure to air pollution and adverse effects on human health is well documented. Yet, in a European context, research on the spatial distribution of air pollution and the characteristics of areas is relatively scarce, and there is a need for research using different spatial scales, a wider variety of socioeconomic indicators (such as ethnicity) and new methodologies to assess these relationships. This study uses comprehensive data on a wide range of demographic and socioeconomic indicators, matched to data on PM2.5 concentrations for small areas in Ireland, to assess the relationship between social vulnerability and PM2.5 air pollution. Examining a wide range of socioeconomic indicators revealed some differentials in PM2.5 concentration levels by measure and by rural and urban classification. However, statistical modelling using concentration curves and concentration indices did not present substantial evidence of inequalities in PM2.5 concentrations across small areas. In common with other western European countries, an overall decline in the levels of PM2.5 between 2011 and 2016 was observed in Ireland, though the data indicates that almost all small areas in Ireland were found to have exceeded the World Health Organization (WHO)'s PM2.5 annual guideline (of 5 µg/m3), calling for greater policy efforts to reduce air pollution in Ireland. The recent Clean Air Strategy contains a commitment to achieve the WHO guideline limits for PM2.5 by 2040, with interim targets at various points over the next two decades. Achieving these targets will require policy measures to decarbonise home heating, promote active travel and the transition to electric vehicles, and further regulations on burning fossil fuels and enforcing environmental regulations more tightly. From a research and information-gathering perspective, installing more monitoring stations at key points could improve the quality and spatial dimension of the data collected and facilitate the assessment of the implementation of the measures in the Clean Air Strategy.