Airway and Systemic Immunoglobulin Profiling and Immune Response in Adult Asthma.

INTRODUCTION: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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.

Translation of Nutrient Level Recommendations to Control Serum Phosphate Into Food-Based Advice.

The control of hyperphosphatemia is key to the management of chronic kidney disease mineral and bone disorder. Dietary restriction of phosphorus is essential to control hyperphosphatemia. Guidelines for chronic kidney disease and end-stage kidney disease generally provide high-level guidance on whether a nutrient should be restricted e.g, restrict dietary phosphorus. Dietitians translate such guidance into nutrient-based strategies and finally into food-based practical dietary advice for patients to follow. The practical aspects of dietary advice are not well described in the literature, neither are the challenges of concurrently altering 1 nutrient e.g., phosphorus while continuing to restrict others e.g., potassium, while maintaining overall nutritional adequacy and quality of life. In this article, we describe how we translated updated nutrient level recommendations into practical dietary advice to be delivered at the bedside.

Revising Dietary Phosphorus Advice in Chronic Kidney Disease G3-5D.

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.

Use of non-invasive ventilation in motor neuron disease - a retrospective cohort analysis.

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.

The presence of Aspergillus fumigatus in asthmatic airways is not clearly related to clinical disease severity.

BACKGROUND: It is suggested that airway fungi, in particular Aspergillus may impinge on clinical phenotype in asthma. Indeed, the term severe asthma with fungal sensitization (SAFS) has been coined. We aimed to ascertain whether the presence of fungi, in particular Aspergillus fumigatus, in the airway correlated with asthma severity and control. Furthermore, we aimed to determine whether traditional markers of Aspergillus sensitization related to the presence of Aspergillus within the airway. METHODS: Sixty-nine patients characterized by asthma severity (GINA) and level of control (ACQ-7) underwent bronchoscopy and bronchoalveolar lavage (BAL). Serum was assessed for A fumigatus-specific IgE and total IgE. Galactomannan and relevant cytokine levels were assessed in serum, plasma and BAL. BAL was analyzed for the presence of A fumigatus. RESULTS: In BAL, fungi were visible by microscopy in 70% and present by qPCR in 86% of patients, while A fumigatus was detectable by qPCR in 46%. Plasma and BAL IL-4, IL-6, IL-10, IL-13 and TNF-α correlated with BAL fungal presence, while plasma IL-17 correlated with BAL fungal presence. Aspergillus positive BAL correlated with increased plasma and BAL IL-6 and BAL IL-13. There was no relationship between fungal airway presence and steroid dose, asthma severity or control. The presence of Aspergillus within the airway did not relate to serum IgE positivity for Aspergillus. CONCLUSIONS: Fungi were present in a large proportion of our asthmatic patients' airways, but their presence was not predicted by traditional markers of sensitization, nor did it appear to be related to measures of disease severity or control.

Prevention of adverse drug reactions in hospitalized older patients with multi-morbidity and polypharmacy: the SENATOR* randomized controlled clinical trial.

BACKGROUND: Multi-morbidity and polypharmacy increase the risk of non-trivial adverse drug reactions (ADRs) in older people during hospitalization. Despite this, there are no established interventions for hospital-acquired ADR prevention. METHODS: We undertook a pragmatic, multi-national, parallel arm prospective randomized open-label, blinded endpoint (PROBE) controlled trial enrolling patients at six European medical centres. We randomized 1,537 older medical and surgical patients with multi-morbidity and polypharmacy on admission in a 1:1 ratio to SENATOR software-guided medication optimization plus standard care (intervention, n = 772, mean number of daily medications = 9.34) or standard care alone (control, n = 765, mean number of daily medications = 9.23) using block randomization stratified by site and admission type. Attending clinicians in the intervention arm received SENATOR-generated advice at a single time point with recommendations they could choose to adopt or not. The primary endpoint was occurrence of probable or certain ADRs within 14 days of randomization. Secondary endpoints were primary endpoint derivatives; tertiary endpoints included all-cause mortality, re-hospitalization, composite healthcare utilization and health-related quality of life. RESULTS: For the primary endpoint, there was no difference between the intervention and control groups (24.5 vs. 24.8%; OR 0.98; 95% CI 0.77-1.24; P = 0.88). Similarly, with secondary and tertiary endpoints, there were no significant differences. Among attending clinicians in the intervention group, implementation of SENATOR software-generated medication advice points was poor (~15%). CONCLUSIONS: In this trial, uptake of software-generated medication advice to minimize ADRs was poor and did not reduce ADR incidence during index hospitalization.

The effect of SENATOR (Software ENgine for the Assessment and optimisation of drug and non-drug Therapy in Older peRsons) on incident adverse drug reactions (ADRs) in an older hospital cohort - Trial Protocol.

BACKGROUND: The aim of this trial is to evaluate the effect of SENATOR software on incident, adverse drug reactions (ADRs) in older, multimorbid, hospitalized patients. The SENATOR software produces a report designed to optimize older patients' current prescriptions by applying the published STOPP and START criteria, highlighting drug-drug and drug-disease interactions and providing non-pharmacological recommendations aimed at reducing the risk of incident delirium. METHODS: We will conduct a multinational, pragmatic, parallel arm Prospective Randomized Open-label, Blinded Endpoint (PROBE) controlled trial. Patients with acute illnesses are screened for recruitment within 48 h of arrival to hospital and enrolled if they meet the relevant entry criteria. Participants' medical history, current prescriptions, select laboratory tests, electrocardiogram, cognitive status and functional status are collected and entered into a dedicated trial database. Patients are individually randomized with equal allocation ratio. Randomization is stratified by site and medical versus surgical admission, and uses random block sizes. Patients randomized to either arm receive standard routine pharmaceutical clinical care as it exists in each site. Additionally, in the intervention arm an individualized SENATOR-generated medication advice report based on the participant's clinical and medication data is placed in their medical record and a senior medical staff member is requested to review it and adopt any of its recommendations that they judge appropriate. The trial's primary outcome is the proportion of patients experiencing at least one adjudicated probable or certain, non-trivial ADR, during the index hospitalization, assessed at 14 days post-randomization or at index hospital discharge if it occurs earlier. Potential ADRs are identified retrospectively by the site researchers who complete a Potential Endpoint Form (one per type of event) that is adjudicated by a blinded, expert committee. All occurrences of 12 pre-specified events, which represent the majority of ADRs, are reported to the committee along with other suspected ADRs. Participants are followed up 12 (+/- 4) weeks post-index hospital discharge to assess medication quality and healthcare utilization. This is the first clinical trial to examine the effectiveness of a software intervention on incident ADRs and associated healthcare costs during hospitalization in older people with multi-morbidity and polypharmacy. TRIAL REGISTRATION NUMBER: Clinicaltrials.gov NCT02097654 , 27 March 2014.

The Effect of Short-Term Vitamin D Supplementation on Calcium Status in Vitamin D Insufficient Renal Transplant Recipients at Risk of Hypercalcemia.

OBJECTIVE: Vitamin D insufficiency is highly prevalent among renal transplant recipients and in observational studies is associated with adverse outcomes. Hypercalcemia, usually due to persistent hyperparathyroidism, also commonly occurs in this population and often coexists with vitamin D insufficiency. However, concern that vitamin D supplementation might exacerbate the pre-existing hypercalcemia often leads clinicians to avoid vitamin D supplementation in such patients. This feasibility study aimed to quantify the effect on serum calcium of short-term low-dose cholecalciferol supplementation in a group of renal transplant recipients with a recent history of serum calcium levels >10 mg/dL. DESIGN: A 2-week, single arm, open-label trial. SETTING: Renal transplant follow-up clinic in an Irish University Hospital. SUBJECTS: Eighteen vitamin D-insufficient adult patients with a functioning renal allograft (estimated glomerular filtration rate > 30 mL/minute/1.73 m2) and a recent history of serum calcium >10 mg/dL. INTERVENTION: Two weeks of treatment with 1,000 IU cholecalciferol/day. MAIN OUTCOME MEASURE: Change in ionized calcium and urine calcium:creatinine ratio at follow-up compared with baseline. RESULTS: Mean (standard deviation [SD]) baseline 25 (OH) vitamin D (25 (OH) D) concentration was 15.9 (5.97) ng/mL and mean (SD) baseline serum calcium was 10.50 (0.6) mg/dL. Following the 2-week intervention, median (interquartile range [IQR]) change in serum calcium from baseline was -0.08 (-3.6 to 0.08) mg/dL, P = .3. Mean (SD) ionized calcium decreased from 5.24 (0.32) mg/dL at baseline to 5.16 (0.28) mg/dL, P = .05. Median (IQR) change in the urinary calcium:creatinine ratio was 0.001 (-0.026 to 0.299) mg/mg, P = .88. Median (IQR) change in 25 (OH) D was 3.6 (2.9-6.2) ng/mL, P < .05. CONCLUSIONS: In vitamin D-insufficient renal transplant recipients at risk of hypercalcemia, low-dose short-term oral cholecalciferol supplementation improves 25 (OH) D concentrations without exacerbating hypercalcemia or increasing the urinary calcium:creatinine ratio.

Randomized placebo controlled trial evaluating the safety and efficacy of single low-dose intracoronary insulin-like growth factor following percutaneous coronary intervention in acute myocardial infarction (RESUS-AMI).

BACKGROUND: Residual and significant postinfarction left ventricular (LV) dysfunction, despite technically successful percutaneous coronary intervention (PCI) for ST-elevation myocardial infarction (STEMI), remains an important clinical issue. In preclinical models, low-dose insulin-like growth factor 1 (IGF1) has potent cytoprotective and positive cardiac remodeling effects. We studied the safety and efficacy of immediate post-PCI low-dose intracoronary IGF1 infusion in STEMI patients. METHODS: Using a double-blind, placebo-controlled, multidose study design, we randomized 47 STEMI patients with significantly reduced (≤40%) LV ejection fraction (LVEF) after successful PCI to single intracoronary infusion of placebo (n = 15), 1.5 ng IGF1 (n = 16), or 15 ng IGF1 (n = 16). All received optimal medical therapy. Safety end points were freedom from hypoglycemia, hypotension, or significant arrhythmias within 1 hour of therapy. The primary efficacy end point was LVEF, and secondary end points were LV volumes, mass, stroke volume, and infarct size at 2-month follow-up, all assessed by magnetic resonance imaging. Treatment effects were estimated by analysis of covariance adjusted for baseline (24 hours) outcome. RESULTS: No significant differences in safety end points occurred between treatment groups out to 30 days (χ2 test, P value = .77). There were no statistically significant differences in baseline (24 hours post STEMI) clinical characteristics or LVEF among groups. LVEF at 2 months, compared to baseline, increased in all groups, with no statistically significant differences related to treatment assignment. However, compared with placebo or 1.5 ng IGF1, treatment with 15 ng IGF1 was associated with a significant improvement in indexed LV end-diastolic volume (P = .018), LV mass (P = .004), and stroke volume (P = .016). Late gadolinium enhancement (±SD) at 2 months was lower in 15 ng IGF1 (34.5 ± 29.6 g) compared to placebo (49.1 ± 19.3 g) or 1.5 ng IGF1 (47.4 ± 22.4 g) treated patients, although the result was not statistically significant (P = .095). CONCLUSIONS: In this pilot trial, low-dose IGF1, given after optimal mechanical reperfusion in STEMI, is safe but does not improve LVEF. However, there is a signal for a dose-dependent benefit on post-MI remodeling that may warrant further study.

Race, Mineral Homeostasis and Mortality in Patients with End-Stage Renal Disease on Dialysis.

BACKGROUND: Abnormalities in mineral homeostasis are ubiquitous in patients on dialysis, and influenced by race. In this study, we determine the race-specific relationship between mineral parameters and mortality in patients initiating hemodialysis. METHODS: We measured the levels of fibroblast growth factor 23 (FGF23) and 25-hydroxyvitamin D (25 D) in 184 African American and 327 non-African American hemodialysis patients who enrolled between 1995 and 1998 in the Choices for Healthy Outcomes in Caring for ESRD Study. Serum calcium, phosphorus, parathyroid hormone (PTH) and total alkaline phosphatase levels were averaged from clinical measurements during the first 4.5 months of dialysis. We evaluated the associated prospective risk of mortality using multivariable Cox proportional hazards models stratified by race. RESULTS: PTH and total alkaline phosphatase levels were higher, whereas calcium, phosphorus, FGF23 and 25 D levels were lower in African Americans compared to those of non-African Americans. Higher serum phosphorus and FGF23 levels were associated with greater mortality risk overall; however, phosphorus was only associated with risk among African Americans (HR 5.38, 95% CI 2.14-13.55 for quartile 4 vs. 1), but not among non-African Americans (p-interaction = 0.04). FGF23 was associated with mortality in both groups, but more strongly in African Americans (HR 3.91, 95% CI 1.74-8.82 for quartiles 4 vs. 1; p-interaction = 0.09). Serum calcium, PTH, and 25 D levels were not consistently associated with mortality. The lowest and highest quartiles of total alkaline phosphatase were associated with higher mortality risk, but this did not differ by race (p-interaction = 0.97). CONCLUSIONS: Aberrant phosphorus homeostasis, reflected by higher phosphorus and FGF23, may be a risk factor for mortality in patients initiating hemodialysis, particularly among African Americans.

Differing coagulation profiles of patients with monoclonal gammopathy of undetermined significance and multiple myeloma.

The link between myeloma and thrombosis is well established. Monoclonal gammopathy of undetermined significance (MGUS) has also been associated with an increased risk of thrombosis. It was recently demonstrated that patients with myeloma display changes in thromboelastometry that may indicate a prothrombotic state. There is little data with regard to changes in thromboelastography in patients with myeloma or MGUS. The aim of this study was to investigate the differing coagulation profiles of patients of patients with myeloma and MGUS by means of conventional coagulation tests and thromboelastography. Blood was taken by direct venepuncture from patients with myeloma, MGUS and normal controls. Routine coagulation tests were performed in an accredited hospital laboratory. Thromboelastography (TEG(®)) was performed as per the manufacturer's protocol. Eight patients were recruited in each group. Patients with myeloma had a significantly lower mean haemoglobin level than patients with MGUS or normal controls (p < 0.001). Patients with myeloma had a significantly more prolonged mean prothrombin time than normal controls (p = 0.018) but not patients with MGUS. Patients with myeloma had significantly higher median D-dimer levels than normal controls (p = 0.025), as did patients with MGUS (p = 0.017). Patients with myeloma had a significantly higher mean factor VIII level than normal controls (p = 0.009) and there was a non-significant trend towards patients with MGUS having higher factor VIII levels than normal controls (p = 0.059). There was no significant difference in thromboelastographic parameters between the three groups. Patients with MGUS appear to have a distinct coagulation profile which is intermediate between patients with myeloma and normal controls.

Comparison of single CT scan assessment of bone mineral density, vascular calcification and fat mass with standard clinical measurements in renal transplant subjects: the ABC HeART study.

BACKGROUND: Despite limitations of routine methods, Clinical Practice Guidelines support the assessment of bone mineral density (BMD) and vascular calcification in renal transplant recipients. Changes in fat mass also occur post-transplantation, although they are traditionally difficult to measure accurately. We report the feasibility, convenience and accuracy of measuring the above 3 parameters using a novel CT protocol. METHODS: We conducted a cross-sectional study of 64 first renal allograft recipients (eGFR > 30 ml/min/1.73 m(2)). Quantitative CT (QCT) BMD analysis was conducted using CT lumbar spine (GE Medical Systems Lightspeed VCT & Mindways QCT Pro Bone Mineral Densitometry System Version 4.2.3) to calculate spinal volumetric BMD and compared with standard DXA calculated areal BMD at the spine, hip and distal forearm. Abdominal aortic calcification was assessed by semi-quantitative Aortic Calcification Index (ACI) method and compared with lateral lumbar x-ray Kappuila score and pulse wave velocity (PWV). Visceral and subcutaneous adipose tissue volume (Osirix 16 Ver 3.7.1) was compared with BMI. RESULTS: Participants were 61 % male, had a mean age of 47 years, median ESKD duration of 5.4 years and a mean eGFR of 54 ml/min. iDXA median T-score at proximal femur was -1.2 and at lumbar spine was -0.2. Median QCT Trabecular T-score at lumbar spine was -1.2. The percent of subjects with a T-score of < 2.5 by site and method was DXA Proximal Femur: 7 %, DXA distal radius: 17 %, DXA spine: 9 %, QCT (American College of Radiology cutoffs): 9 %. CT derived ACI correlated with PWV (r = 0.29, p = 0.02), pulse wave pressure (r = 0.51, p < 0.001), QCT Trabecular (-0.31, p = 0.01) and cortical volumetric BMD and history of cardiovascular events (Mann-Whitney U, p = 0.02). Both visceral and subcutaneous adipose tissue correlated with BMI (r = 0.63 & 0.64, p < 0.001). CONCLUSIONS: Single CT scan triple assessment of BMD, vascular calcification and body composition is an efficient, accurate and convenient method of risk factor monitoring post renal transplantation.

Attention! A good bedside test for delirium?

BACKGROUND: Routine delirium screening could improve delirium detection, but it remains unclear as to which screening tool is most suitable. We tested the diagnostic accuracy of the following screening methods (either individually or in combination) in the detection of delirium: MOTYB (months of the year backwards); SSF (Spatial Span Forwards); evidence of subjective or objective 'confusion'. METHODS: We performed a cross-sectional study of general hospital adult inpatients in a large tertiary referral hospital. Screening tests were performed by junior medical trainees. Subsequently, two independent formal delirium assessments were performed: first, the Confusion Assessment Method (CAM) followed by the Delirium Rating Scale-Revised 98 (DRS-R98). DSM-IV (Diagnostic and Statistical Manual of Mental Disorders, fourth edition) criteria were used to assign delirium diagnosis. Sensitivity and specificity ratios with 95% CIs were calculated for each screening method. RESULTS: 265 patients were included. The most precise screening method overall was achieved by simultaneously performing MOTYB and assessing for subjective/objective confusion (sensitivity 93.8%, 95% CI 82.8 to 98.6; specificity 84.7%, 95% CI 79.2 to 89.2). In older patients, MOTYB alone was most accurate, whereas in younger patients, a simultaneous combination of SSF (cut-off 4) with either MOTYB or assessment of subjective/objective confusion was best. In every case, addition of the CAM as a second-line screening step to improve specificity resulted in considerable loss in sensitivity. CONCLUSIONS: Our results suggest that simple attention tests may be useful in delirium screening. MOTYB used alone was the most accurate screening test in older people.

Registry-based randomised controlled trials: conduct, advantages and challenges-a systematic review.

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.

ROCK STUDY in CF: sustained anti-inflammatory effects of lumacaftor-ivacaftor in sputum and peripheral blood samples of adult patients with cystic fibrosis-an observational study.

BACKGROUND: Previous studies showed that the combination of Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) corrector and potentiator, lumacaftor-ivacaftor (LUMA-IVA) provides meaningful clinical benefits in patients with cystic fibrosis who are homozygous for the Phe508del CFTR mutation. However, little is known about the effect of LUMA-IVA on Proinflammatory Cytokines (PICs). OBJECTIVES: To investigate the impact of LUMA-IVA CFTR modulation on circulatory and airway cytokines before and after 12 months of LUMA-IVA treatment in a real-world setting. METHODS: We assessed both plasma and sputum PICs, as well as standard clinical outcomes including Forced Expiratory Volume in one second (FEV1) %predicted, Body Mass Index (BMI), sweat chloride and pulmonary exacerbations at baseline and prospectively for one year post commencement of LUMA-IVA in 44 patients with cystic fibrosis aged 16 years and older homozygous for the Phe508del CFTR mutation. RESULTS: Significant reduction in plasma cytokines including interleukin (IL)-8 (p<0.05), tumour necrosis factor (TNF)-α (p<0.001), IL-1ß (p<0.001) levels were observed while plasma IL-6 showed no significant change (p=0.599) post-LUMA-IVA therapy. Significant reduction in sputum IL-6 (p<0.05), IL-8 (p<0.01), IL-1ß (p<0.001) and TNF-α (p<0.001) levels were observed after LUMA-IVA therapy. No significant change was noted in anti-inflammatory cytokine IL-10 levels in both plasma and sputum (p=0.305) and (p=0.585) respectively. Clinically significant improvements in FEV1 %predicted (mean+3.38%, p=0.002), BMI (mean+0.8 kg/m2, p<0.001), sweat chloride (mean -19 mmol/L, p<0.001), as well as reduction in intravenous antibiotics usage (mean -0.73, p<0.001) and hospitalisation (mean -0.38, p=0.002) were observed after initiation of LUMA-IVA therapy. CONCLUSION: This real-world study demonstrates that LUMA-IVA has significant and sustained beneficial effects on both circulatory and airway inflammation. Our findings suggest that LUMA-IVA may improve inflammatory responses, which could potentially contribute to improved standard clinical outcomes.

Renal Denervation as a Complementary Treatment Option for Uncontrolled Arterial Hypertension: A Situation Assessment.

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.

Cumulative ionizing radiation exposure in patients with end stage kidney disease: a 6-year retrospective analysis.

OBJECTIVE: To quantify cumulative exposure to ionizing radiation in patients with end stage kidney disease (ESKD). To investigate factors which may be independently associated with risk of high cumulative effective dose (CED). MATERIALS AND METHODS: The study had local institutional review board ethical approval. We conducted a retrospective study of 394 period prevalent ESKD patients attending a single tertiary referral centre between 2004 and 2009. Patient demographics were obtained from case records. Details of radiological investigations were obtained from the institutional radiology computerized database. CED was calculated using standard procedure specific radiation levels. High exposure was defined as CED > 50 mSv, an exposure which has been reported to increase cancer mortality by 5%. Data were compared using Pearson χ(2) and Mann-Whitney U test or Kruskal-Wallis tests. RESULTS: 394 patients were followed for a median of 4 years (1518 patient years follow-up). Of these 63% were male. Seventeen percent of patients had a CED of >50 mSv. Computed tomography (CT) accounted for 9% of total radiological studies/procedures while contributing 61.4% of total study dose. Median cumulative dose and median dose per patient year were significantly higher in the hemodialysis (HD) group (15.13 and 5.79 mSv, respectively) compared to the post-transplant group (2.9 and 0.52 mSv, respectively) (P < 0.001). CONCLUSION: ESKD patients are at risk of cumulative exposure to significant levels of diagnostic radiation. The majority of this exposure is imparted as a result of CT examinations to patients in the HD group.

Prevalence of diminished kidney function in a representative sample of middle and older age adults in the Irish population.

BACKGROUND: The prevalence of chronic kidney disease (CKD) using available estimating equations with the Republic of Ireland is unknown. METHODS: A randomly selected population based cross-sectional study of 1,098 adults aged 45 years and older was conducted using data from the 2007 Survey of Lifestyle, Attitudes and Nutrition (SLÁN). Estimated Glomerular Filtration Rate (eGFR) was calculated from a single IDMS aligned serum creatinine using the CKD-EPI and the MDRD equations, and albumin to creatinine ratio was based on a single random urine sample. RESULTS: The sample clinical characteristics and demography was similar to middle and older age adults in the general Irish population, though with an underrepresentation of subjects >75 years and of males. All results are based on subjects with available blood and urine samples. Applying weighting to obtain survey based population estimates, using Irish population census data, the estimated weighted prevalence of CKD-EPI eGFR<60 mL/min/1.73m2 was 11.6%, (95% confidence interval; 9.0, 14.2%), 12.0% ( 9.0, 14.2%) of men and 11.2% (7.3, 15.2%) of women. Unweighted prevalence estimates were similar at 11.8% (9.9, 13.8%). Albuminuria increased with lower CKD-EPI eGFR category. 10.1% of all subjects had albuminuria and an eGFR≥60 mL/min/1.73 m2 giving an overall weighted estimated prevalence of National Kidney Foundation (NKF) defined CKD 21.3% (18.0, 24.6%), with the unadjusted estimate of 21.9% (19.5, 24.4%). MDRD related estimates for eGFR <60 mL/min/1.73 m2, and NFK defined CKD were higher than CKD-EPI and differences were greater in younger and female subjects. CONCLUSIONS: CKD is highly prevalent in middle and older aged adults within the Republic of Ireland. In this population, there is poor agreement between CKD-EPI and MDRD equations especially at higher GFRs. CKD is associated with lower educational status and poor self rated health.

Neuropathy in the hemodialysis population: a review of neurophysiology referrals in a tertiary center.

This was a retrospective observational study of neurophysiology referrals over 8 years from a tertiary referral center in Ireland. A total of 68 of the 73 referrals yielded one or more abnormalities. Thirty-nine (53%) patients had one or more mononeuropathies; iatrogenic mononeuropathies believed to be associated with arterio-venous fistula creation occurred in 15 patients. Polyneuropathy was identified in 43 patients (59%). Access to an experienced neurophysiology department offers valuable insight into dialysis-associated neuropathies, especially when associated with arterio-venous fistulae.