Background: Clinical trials with elexacaftor/tezacaftor/ivacaftor (ETI) in people with cystic fibrosis were associated with significant improvements in % predicted forced expiratory volume in 1 s (FEV1 % pred), sweat chloride, weight and quality of life in the respiratory domain from the cystic fibrosis questionnaire revised (CFQ-R). Limited data exist on its effect on structural lung disease and inflammatory cytokines. Methods: In a real-world setting with 61 people with cystic fibrosis, we prospectively recorded FEV1, sweat chloride, body mass index (BMI) and CFQ-R at baseline, 3 and 6 months after commencement of ETI. In addition, changes in ultra-low-dose (ULD) computed tomography (CT) Bhalla score, peripheral-blood and sputum inflammatory cytokines and patient-reported outcome measures (PROMs), including sino-nasal outcomes test-22 (SNOT-22) and fatigue scale (FACIT-Fatigue). Results: Significant improvements in FEV1 % pred (p=0.0001), sweat chloride (p<0.0001) and BMI (p=0.0147) after ETI treatment were noted. ULD-CT scores demonstrated reductions in peri-bronchial thickening, mucus plugging and total Bhalla score (p<0.001), and improvements in emphysema extent (p<0.0027). Improvements in systemic inflammatory status were seen with a reduction in interleukin (IL)-1 beta (p=0.0049), IL-6 and IL-8 (p<0.0001), and increasing IL-10 (p=0.004). Sputum cytokine analysis was not performed as only four of 61 patients spontaneously expectorated sputum after ETI. PROMs improved significantly for the SNOT-22 (p<0.0001), FACIT-Fatigue score (p=0.0001) and CFQ-R domains, including respiratory (p<0.0001), physical (p=0.007), vitality (p=0.0004), treatment burden (p=0.0028), health (p=0.0007), social (p=0.0073), weight (p=0.0068) and role/school domain (p=0.0018). Conclusion: ETI responders, demonstrate significant improvements in CT imaging, circulating cytokines and PROMs, which may be of further use evaluating cystic fibrosis transmembrane conductance regulator modulation treatment response.

BACKGROUND:Registry-based randomised controlled trials (rRCTs) have been described as pragmatic studies utilising patient data embedded in large-scale registries to facilitate key clinical trial procedures including recruitment, randomisation and the collection of outcome data. Whilst the practice of utilising registries to support the conduct of randomised trials is increasing, the use of the registries within rRCTs is inconsistent. The purpose of this systematic review is to explore the conduct of rRCTs using a patient registry to facilitate trial recruitment and the collection of outcome data, and to discuss the advantages and challenges of rRCTs.METHODS:A systematic search of the literature was conducted using five databases from inception to June 2020: PubMed, Embase (through Ovid), CINAHL, Scopus and the Cochrane Controlled Register of Trials (CENTRAL). The search strategy comprised of MESH terms and key words related to rRCTs. Study selection was performed independently by two reviewers. A risk of bias for each study was completed. A narrative synthesis was conducted.RESULTS:A total 47,862 titles were screened and 24 rRCTs were included. Eleven rRCTs (45.8%) used more than one registry to facilitate trial conduct. Six rRCTs (25%) randomised participants via a specific randomisation module embedded within a registry. Recruitment ranged between 209 to 106,000 participants. Advantages of rRCTs are recruitment efficiency, shorter trial times, cost effectiveness, outcome data completeness, smaller carbon footprint, lower participant burden and the ability to conduct multiple trials from the same registry. Challenges are data collection/management, quality assurance issues and the timing of informed consent.CONCLUSIONS:Optimising the design of rRCTs is dependent on the capabilities of the registry. New registries should be designed and existing registries reviewed to enable the conduct of rRCTs. At all times, data management and quality assurance of all registry data should be given key consideration. We suggest the inclusion of the term 'registry-based' in the title of all rRCT manuscripts and a clear simple breakdown of the registry-based conduct of the trial in the abstract to facilitate indexing in the major databases.

Abstract Background and Aims Acute interstitial nephritis (AIN) is a common cause of acute kidney injury (AKI), histologically characterized by an interstitial inflammatory cell infiltrate. Data regarding long term kidney outcomes is lacking. We performed a retrospective cohort study to evaluate the long-term kidney and mortality outcomes in patients with biopsy-proven AIN between 2011-2018. Method We serve as a tertiary referral centre and sole nephrology provider for a population of over 650,000 people. We identified biopsy-proven AIN cases from the years 2011-2018 from our pathology database. Demographic data, creatinine, eGFR (calculated using CKD-EPI 2021 formula), dialysis and mortality data were collected from our electronic medical record. Ethical approval was obtained. Results Between 2011 – 2018, 576 native kidney biopsies were performed in our centre. 66 (11.5%) cases had pathologically confirmed AIN as the primary kidney diagnosis. Long-term outcome data was available for 90.9% (60). The median age at time of biopsy was 52.5 years (IQR 41.5 - 68.3). 68% of patients were male. The aetiology of AIN was medication in 42%, autoimmune in 15% and infection-associated in 3%. Of the cases of drug-induced AIN the predominant culprits agents were non-steroidal anti-inflammatories 28%, proton pump inhibitors in 24%, antibiotics 20%, with other medications in 8%. The median eGFR at the time of biopsy was 13.6 (IQR 7.9 -25.4) mls/min/1.73 m2. The median eGFR at year 1 was 47.8 (IQR 30.7 - 72.7) mls/min/1.73 m2, 54.4 (IQR 31.2 -79.6) mls/min/1.73 m2 at year 5 and 69.4 (IQR 19.9 - 86.1) mls/min/1.73 m2 at year 10. See Table 1 for results. At one year 64.3% of cases had eGFR < 60 mls/min/1.73 m2 (CKD III or higher). Interestingly the rate of CKD was lower at years 5 and 10 (54.7% and 50% respectively). GFR <30 mls/min (CKD IV or higher) were present in 25% at year 1, 26% at year 5 and 37% at year 10. 23% (14/60) people had dialysis-requiring AKI at the time of biopsy. Of these 21.4% (3) remained dialysis dependent at one year. In this group, no additional cases of ESKD were seen between years 1 through 5, one additional case of ESKD occurred by year 10. A composite outcome of kidney failure (GFR <15, dialysis or kidney transplantation) occurred in 48.2% at year 1, 54.7% at year 5 and 56.2% at year 10. Mortality data was available on 58 patients. 18.9% (11) people had died at 10 years follow-up. 8 out of the 11 deaths were within 5 years, 2 of which were within 1 year of diagnosis. Conclusion In this single centre study, kidney failure occurred in 48% of people at 10 years of follow up. 78% of dialysis-requiring cases recover independent renal function.

Immunoglobulins play a vital role in host immune response and in the pathogenesis of conditions like asthma. Therapeutic agents such as monoclonal antibodies target specific elements of the asthmatic inflammatory cascade. Decisions to utilize these medications are often based on systemic inflammatory profiling without direct insight into the airway inflammatory profile. We sought to investigate the relationship between immunoglobulin and cytokine profiles in the airway and systemic immune compartments of adult asthmatics. Blood sampling and bronchoscopy with bronchoalveolar lavage (BAL) were performed in 76 well-defined adult asthmatics. Antibody and cytokine profiles were measured in both BAL and serum using ELISA and quantibody arrays. There was no relationship between BAL and serum levels of IgE. This is of significance in an asthma population. For some analytes, correlation analysis was significant (P < 0.05) indicating representativeness of our cohort and experimental setup in those cases. Nevertheless, the predictive power (r2) of the BAL-to-serum comparisons was mostly low except for TNF-α (r2 = 0.73) when assuming a simple (linear) relationship. This study highlights the importance of sample site when investigating the roles of immunoglobulins and cytokines in disease pathogenesis and suggests that both localized and systemic immune responses are at play. The prescription of asthma monoclonal therapy is generally based on systemic evaluation of cytokine and immunoglobulin levels. Our research suggests that this approach may not fully reflect the pathophysiology of the disease and may provide insight into why some patients respond to these targeted therapies while others do not.

Uncontrolled arterial hypertension is a major global health issue. Catheter-based renal denervation has shown to lower blood pressure in sham-controlled trials and represents a device-based, complementary treatment option for hypertension. In this situation assessment, the authors, who are practicing experts in hypertension, nephrology, general practice and cardiology in the Republic of Ireland, discuss the current evidence base for the BP-lowering efficacy and safety of catheter-based renal denervation with different modalities. Although important questions remain regarding the identification of responders, and long-term efficacy and safety of the intervention, renal denervation has the potential to provide much-needed help to address hypertension and its adverse consequences. The therapeutic approach needs to be multidisciplinary and personalised to take into account the perspective of patients and healthcare professionals in a shared decision-making process.

The psychological impact of COVID-19 on Health Care Workers (HCWs) has been widely reported. Few studies have sought to examine HCWs personal models of COVID-19 utilising an established theoretical framework. We undertook a mixed methods study of beliefs about COVID-19 held by HCWs in the Mid-West and South of Ireland during the first and third waves of COVID-19. Template analysis was undertaken on the free text responses of 408 HCWs about their perceptions of the Cause of COVID-19 as assessed by the Brief Illness Perception Questionnaire (B-IPQ). Responses were re-examined in the same cohort for stability at 3 months follow-up (n = 100). This analytic template was subsequently examined in a new cohort (n = 253) of HCWs in the third wave. Female HCWs perceived greater emotional impact of COVID-19 than men (t = -4.31, df405, p < 0.01). Differences between occupational groups were evident in relation to Timeline (F4,401 = 3.47, p < 0.01), Treatment Control (F4,401 = 5.64, p < 0.001) and Concerns about COVID-19 (F4,401 = 3.68, p < 0.01). Administration staff believed that treatment would be significantly more helpful and that COVID-19 would last a shorter amount of time than medical/nursing staff and HSCP. However, administration staff were significantly more concerned than HSCP about COVID-19. Template analysis on 1059 responses to the Cause items of the B-IPQ identified ten higher order categories of perceived Cause of COVID-19. The top two Causes identified at both Waves were 'individual behavioural factors' and 'overseas travel'. This study has progressed our understanding of the models HCWs hold about COVID-19 over time, and has highlighted the utility of the template analysis approach in analysing free-text questionnaire data. We suggest that group and individual occupational identities of HCWs may be of importance in shaping HCWs responses to working through COVID-19.

Objectives We sought to examine healthcare workers (HCWs) utilisation of formal and informal psychological support resources in the workplace during the first and third waves of the COVID-19 pandemic in Ireland. Methods A convergent mixed methods approach was undertaken. Four hundred and thirty HCWs in the Mid West and South of Ireland responded to an online survey in terms of their use of psychological support resources during Wave 1 (April/May 2020) of COVID-19. Thirty-nine HCWs undertook in depth interviews at Wave 3 (January/February 2021), and a further quantitative survey was distributed and completed by 278 HCWs at this time. Quantitative data arising at Wave 1 and Wave 3, were synthesised with Qualitative data collected at Wave 3. A Pillar Integration Process (PIP) was utilised in the analysis of the quantitative and qualitative data. Results Five pillars were identified from the integration of results. These were: a) the primacy of peer support, b) the importance of psychologically informed management, c) a need to develop the organisational well-being ethos, d) support for all HCWs, and e) HCWs ideas for developing the well-being path. These pillars encapsulated a strong emphasis on collegial support, an emphasis on the need to support managers, a questioning of the current supports provided within the healthcare organisations and critical reflections on what HCWs viewed as most helpful for their future support needs. Conclusions HCWs who utilised supportive resources indicated ‘in house’ supports, primarily collegial resources, were the most frequently used and perceived as most helpful. While formal psychological supports were important, the mechanism by which such psychological support is made available, through utilising peer support structures and moving towards psychologically informed supervisors and workplaces is likely to be more sustainable and perceived more positively by HCWs.

Purpose Clostridium difficile has been reported to occur in the gastrointestinal tract of 50% of Cystic Fibrosis (CF) subjects, however, clinical C. difficile infection (CDI) is a rare occurrence in this cohort despite the presence of toxigenic and hypervirulent ribotypes. Here, we present the first longitudinal, multicentre analysis of C. difficile prevalence among adult CF subjects. Methodology Faecal samples were collected from adults with CF (selected based on confirmed Pseudomonas aeruginosa pulmonary colonisation) from Ireland, UK and Belgium as part of the CFMATTERS clinical research trial (grant No. 603038) and from non-CF controls. Faecal samples were collected on enrolment, at three monthly intervals, during pulmonary exacerbation and three months post exacerbation. C. difficile was isolated from faecal samples by ethanol shocking followed by culturing on cycloserine cefoxitin egg yolk agar. Isolates were characterised in terms of ribotype, toxin type and antibiotic susceptibility to antibiotics routinely used in the treatment of CDI (metronidazole and vancomycin) and those implicated in induction of CDI (ciprofloxacin and moxifloxacin). Results Prevalence of C. difficile among CF subjects in the three sites was similar ranging from 47% to 50% at baseline, while the healthy control cohort had a carriage rate of 7.1%. Including subjects who were positive for C. difficile at any time point there was a higher carriage rate of 71.4%, 66.7% and 63.2% in Ireland, UK, and Belgium, respectively. Ribotyping of 80 isolates from 45 CF persons, over multiple time points revealed 23 distinct ribotypes with two ribotypes (046 and 078) shared by all centres. The proportion of toxigenic isolates varied across the sites, ranging from 66.7% in Ireland to 52.9% in Belgium and 100% in the UK. Antibiotic susceptibility rates to vancomycin, metronidazole, ciprofloxacin and moxifloxacin was 100%, 97.5%, 1.3% and 63.8%, respectively. Conclusions This study demonstrates the highest carriage rate of C. difficile to date in a CF cohort. Longitudinal data show that C. difficile can be a transient inhabitant of the CF gut, changing both in terms of strain and excretion rates.

Background. Dyspnea is a common symptom in patients with end-stage kidney disease being treated with dialysis. This study aimed to ascertain the level of respiratory disability in patients after kidney transplantation through assessing a cohort of kidney allograft recipients for respiratory compromise and thereby identifying a potential target for therapeutic intervention. Methods. Kidney transplant recipients who were under active observation in a single tertiary referral center were invited to take part in this prevalence study at the time of clinic follow-up. All patients agreed to take part in the study, which involved completing a Medical Research Council (MRC) dyspnea scale, completing the St George's Respiratory Questionnaire, and per-forming basic spirometry. An MRC score of >= 2 and/or a forced expiratory volume in 1 second <90% predicted prompted formal clinical assessment by a respiratory physician. Results. This study enrolled 103 patients; 35% of all patients reported breathlessness, and 56% of all patients warranted formal respiratory medicine review. After completion of their investigations, 33 patients were found to have an underlying condition accounting for their symptoms. Conclusion. Our study highlights the issues of respiratory disability and breathlessness in patients who have undergone kidney transplantation. Although extensive cardiologic evaluation is performed routinely and can rule out many causes of dyspnea, respiratory assessment is not a preoperative prerequisite. This study could suggest that a formal pulmonological evaluation and basic spirometry should be part of the pretransplant evaluation of the kidney transplant recipient.

We summarize how practicing dietitians combined available evidence with clinical experience, to define revised dietary recommendations for phosphorus in chronic kidney disease G3-5D. As well as a review of the evidence base, 4 priority topics were reviewed. These were translated into 3 nutrient level recommendations: the introduction of some plant protein where phosphorus is largely bound by phytate; consideration of protein intake in terms of phosphorus load and the phosphorus to protein ratio; and an increased focus on avoiding phosphate additives. This review summarizes and interprets the available evidence in order to support the development of practical food-based advice for patients with chronic kidney disease.

COVID-19 is an unprecedent occurrence in modern times and individuals who work within healthcare settings, face a broad array of challenges in responding to this worldwide event. Key information on the psychosocial responses of such healthcare workers (HCWs) in the context of COVID-19 is limited and in particular there is a need for studies that utilise longitudinal methods, an overarching theoretical model, and use of a cohort of participants within a defined geographical area across acute and community settings. The work packages making up the current research project use quantitative and qualitative methods to examine the psychological sequelae for HCWs in the context of COVID-19 in geographically adjacent healthcare areas (South and Mid-West of Ireland) across four time points (induction, 3 months, 6 months, and 1 year follow-up). The quantitative arm of the project (WP 1) utilises the Common-Sense Model of Self-Regulation (CSM-SR) and examines a number of key psychological factors pertinent to this model including perceptions about COVID-19 and infection more generally, coping, formal and informal support and a number of impact variables including mood, sleep quality, and perceptions of stigma. The qualitative study (WP 2) will address HCWs experiences of working during the pandemic, ascertain any additional areas of psychological functioning, environmental and workplace factors and resources that may be utilised by HCWs and that are not assessed by the quantitative study protocol, focusing particularly on those staff groups typically underrepresented in previous studies.

Motor neuron disease (MND) is a neurodegenerative disorder which leads to progressive muscle weakness including respiratory muscle decline. The introduction of non-invasive ventilation (NIV) has been shown to improve quality of life, survival and slow the rate of pulmonary function decline. A retrospective chart analysis of patients who attended the MND clinic from 2014 to 2019 at a tertiary-referral, academic, teaching hospital was carried out to evaluate if NIV and greater compliance with NIV was associated with improved survival. 111 patients were included. The mean age at diagnosis was 63.8 years and 61.3% were males. 66.7% of our cohort used NIV and of this 66.7%, 44.1% were compliant. There was a significantly longer survival in those who used NIV (p = 0.002) and in those who used NIV optimally (p = 0.02) when both groups were compared to those who did not use NIV. In the bulbar MND group those who were compliant with NIV survived longer than who those who did not use NIV (p = 0.001). We found a significantly longer survival with the use of NIV, the use of NIV optimally and with use of NIV in those with bulbar onset MND compared to those who did not use NIV.

Background: Treatment with Ivacaftor provides a significant clinical benefit in people with cystic fibrosis (PWCF) with the class III G551D-CFTR mutation. This study determined the effect of CFTR modulation with ivacaftor on the lung microbiota in PWCF. Methods: Using both extended-culture and culture-independent molecular methods, we analysed the lower airway microbiota of 14 PWCF, prior to commencing ivacaftor treatment and at the last available visit within the following year. We determined total bacterial and Pseudomonas aeruginosa densities by both culture and qPCR, assessed ecological parameters and community structure and compared these with biomarkers of inflammation and clinical outcomes. Results: Significant improvement in FEV1, BMI, sweat chloride and levels of circulating inflammatory biomarkers were observed POST-ivacaftor treatment. Extended-culture demonstrated a higher density of strict anaerobic bacteria (p = 0.024), richness (p = 1.59* 10(-4)) and diversity (p = 0.003) POST-treatment. No significant difference in fold change was observed by qPCR for either total bacterial 16S rRNA copy number or P. aeruginosa density for oprL copy number with treatment. Culture-independent (MiSeq) analysis revealed a significant increase in richness (p = 0.03) and a trend towards increased diversity (p = 0.07). Moreover, improvement in lung function, richness and diversity displayed an inverse correlation with the main markers of inflammation (p < 0.05). Conclusions: Following treatment with ivacaftor, significant improvements in clinical parameters were seen. Despite modest changes in overall microbial community composition, there was a shift towards a bacterial ecology associated with less severe CF lung disease. Furthermore, a significant correlation was observed between richness and diversity and levels of circulating inflammatory markers. (C) 2021 European Cystic Fibrosis Society. Published by Elsevier B.V. All rights reserved.

Background: Potential dietary strategies for controlling hyperphosphataemia include the use of protein sources with lower phosphorus bioavailability such as pulses and nuts, focus on phosphorus to protein ratios and the avoidance of all phosphate additives. Methods: We conducted a controlled crossover feeding study in 8 haemodialysis (HD) patients to investigate the acute postprandial effect of a modified versus standard low phosphorus diet for one day on serum phosphate, potassium and intact parathyroid levels in prevalent HD patients. Each participant consumed the modified diet on one day and the standard diet on a second day one week apart. The modified diet included beef and less dairy, with a lower phosphorus to protein ratio, as well as plant-based protein, whole grains, pulses and nuts containing phytates which reduces phosphorus bioavailability. Both diets were tailored for each participant to provide 1.1g protein/kg ideal body weight. Participants provided fasting bloods before breakfast, a pre-prandial sample before the lunch time main meal and samples at one-hour intervals for the four hours after the lunch time main meal, for analysis of phosphate, potassium and intact parathyroid hormone (iPTH). Results: At four hours post the lunch time main meal on each study day, individuals on the modified diet had serum phosphate readings 0.30 mmol/l lower than when on the standard diet (p-value = 0.015, 95% confidence interval [CI] -0.57, -0.04). The corresponding change in serum potassium at four hours was a decrease of 0.675 mmol/l (p-value = 0.011, CI -1.25, -0.10). Conclusions: Decreases in both serum phosphate and serum potassium readings on a modified low phosphorus diet encourage further larger studies to explore the possibility of greater food choice and healthier plant-based diets in HD patients. ClinicalTrials.gov registration: NCT04845724 (15/04/2021).

We summarize how practicing dietitians combined available evidence with clinical experience, to define revised dietary recommendations for phosphorus in chronic kidney disease G3-5D. As well as a review of the evidence base, 4 priority topics were reviewed. These were translated into 3 nutrient level recommendations: the introduction of some plant protein where phosphorus is largely bound by phytate; consideration of protein intake in terms of phosphorus load and the phosphorus to protein ratio; and an increased focus on avoiding phosphate additives. This review summarizes and interprets the available evidence in order to support the development of practical food-based advice for patients with chronic kidney disease.

COVID-19 is an unprecedent occurrence in modern times and individuals who work within healthcare settings, face a broad array of challenges in responding to this worldwide event. Key information on the psychosocial responses of such healthcare workers (HCWs) in the context of COVID-19 is limited and in particular there is a need for studies that utilise longitudinal methods, an overarching theoretical model, and use of a cohort of participants within a defined geographical area across acute and community settings. The work packages making up the current research project use quantitative and qualitative methods to examine the psychological sequelae for HCWs in the context of COVID-19 in geographically adjacent healthcare areas (South and Mid-West of Ireland) across four time points (induction, 3 months, 6 months, and 1 year follow-up). The quantitative arm of the project (WP 1) utilises the Common-Sense Model of Self-Regulation (CSM-SR) and examines a number of key psychological factors pertinent to this model including perceptions about COVID-19 and infection more generally, coping, formal and informal support and a number of impact variables including mood, sleep quality, and perceptions of stigma. The qualitative study (WP 2) will address HCWs experiences of working during the pandemic, ascertain any additional areas of psychological functioning, environmental and workplace factors and resources that may be utilised by HCWs and that are not assessed by the quantitative study protocol, focusing particularly on those staff groups typically underrepresented in previous studies.

This study analysed the effectiveness of plasma treatment on airborne bacteria and surface counts during a 14-day intervention within a four-bedded bay in an adult respiratory ward at Cork University Hospital, Ireland. One-hundred-litre air samples were collected twice daily every weekday for 4 weeks, with settle plates and surface swabs. The plasma treatment did not have an effect on airborne bacteria and fungi that was detectable by culture. However, the possibility that culture-based sampling may be insufficiently sensitive to detect an effect, or that the duration of the study was insufficient for plasma treatment to affect a complex environment, cannot be excluded.

Background Randomised controlled trials (RCTs) are the gold standard for demonstrating efficacy of new therapies. Despite this, nephrology trials, especially of patients with end stage renal disease (ESRD) are much fewer in number than other specialties. Recruitment difficulties are cited as a particular challenge. Using registries to conduct RCTs is a reasonably new practice but is appealing as it combines the benefits of observational studies and clinical trials. There is limited literature on patient motivators, barriers, and consent to these registries. The purpose of our study is to establish this. Methods We conducted a cross-sectional questionnaire-based study. A questionnaire consisting of closed and open-ended questions was collected at a dialysis centre in Southwest Ireland representing a catchment patient population of approximately 430,000. Quantitative data were coded and analysed in SPSS (v16). Descriptive statistics were produced, and open-ended questions were analysed by thematic analysis. Results 87 patients completed the questionnaire. Motivators for participation included personal and altruistic benefits. Barriers/concerns include time requirements, risks (incl. data safety) and side effects along with impacts on current treatment. Though a total of 29.8% of patients ‘strongly agree/agree’ to having concerns regarding their data storage in a registry, 79.3% of patients were ‘very likely/likely’ to consent to participate in the registry. It was important to patients to have their GP (general practitioner) involved in the decision to participate, despite little day-to-day contact with their GP for renal dialysis management. Conclusion Improving patients understanding of clinical trials, emphasising personal and altruistic benefits, and addressing patient’s concerns regarding time and risks of involvement, may improve their likelihood to participate in a registry for RCTs and more broadly speaking, RCTs.