Surgical Management of Ebstein Anomaly: The Australia and New Zealand Experience.

BACKGROUND: Ebstein anomaly is a rare congenital anomaly of the tricuspid valve which presents challenges to cardiac surgeons due to the spectrum of the disease and the technical difficulty of valve repair. The natural history of the anomaly differs between patients presenting in the neonatal period to those presenting in adulthood. METHODS: A retrospective review of all patients >15 years of age with Ebstein anomaly, undergoing surgery on the tricuspid valve at 6 centers across Australia and New Zealand was performed. Patients from 1985 to 2019 were included in the study. RESULTS: A total of 125 patients were included in the study, 76 patients (60%) undergoing tricuspid valve repair, of which 23 patients underwent a Cone repair and 49 (40%) had a tricuspid valve replacement. The mean follow-up was 7.9 ± 7.3 years. Postoperatively, early mortality was 3 patients (2%) and 10-year survival was 91.5%. A postoperative pacemaker was required in 24 patients (19%). Reoperation was required in 21 patients (17%). There was no statistically significant difference in survival or reoperation between patients who underwent repair or replacement of the tricuspid valve; however, with a small number of patients in long-term follow-up. CONCLUSION: Older children and adult patients undergoing surgery for Ebstein anomaly in Australia and New Zealand experience good medium-term postoperative survival. Repair of the valve is achieved in a significant proportion of patients with increasing use and success with the Cone repair technique.

A randomized, double-blind pilot study of analgesic and anti-inflammatory effects of naproxen sodium and acetaminophen following dental implant placement surgery.

Introduction: Post-surgical pain following dental implant placement surgery is typically managed with non-opioid analgesics, including non-steroidal anti-inflammatory drugs (NSAIDs) and acetaminophen. However, the comparative analgesic efficacy of over-the-counter doses of non-steroidal anti-inflammatory drugs and acetaminophen in implant patients is unknown. Therefore, we compared the analgesic and anti-inflammatory effects of naproxen sodium and acetaminophen after surgical placement of one or two dental implants. Methods: Adult patients were treated with naproxen sodium (440 mg loading dose +220 mg q8h, n = 15) or acetaminophen (1,000 mg q6h-max daily dose 3,000 mg, n = 15) for 3 days after implant placement in a randomized, double-blind design. Pain was assessed on a 0-10 scale every 20 min for 6 h after study medication treatment. Tramadol (50 mg) was available as a rescue medication. Plasma and gingival crevicular fluid (GCF) were collected prior to the surgery and 0, 1, 2, 4, 6, 24, and 72 h after surgery for quantification of interleukin (IL)-6, IL-8, and IL-1ß levels. Results: Pain scores were significantly lower in patients treated with naproxen sodium compared to those treated with acetaminophen. Inflammatory mediator levels in plasma and gingival crevicular fluid increased after surgery and returned to near baseline levels by 72 h. Plasma IL-6 levels were significantly lower 6 h after surgery in patients treated with naproxen sodium compared to acetaminophen. No differences in inflammatory mediator concentrations in gingival crevicular fluid were observed between the treatment groups. The number of implants placed and body mass index (BMI) influenced inflammatory mediator concentrations in plasma and gingival crevicular fluid, respectively. Discussion: Naproxen sodium was more effective than acetaminophen in reducing post-operative pain and systemic inflammation following surgical placement of one or two dental implants. Further studies are needed to determine whether these findings are applicable to more complex implant cases and how they affect clinical outcomes following implant placement. Clinical Trial Registration: ClinicalTrials.gov, identifier NCT04694300.

Anomalous Right Coronary Artery Originating From the Pulmonary Artery (ARCAPA): A Rare Presentation in the Fifth Decade.

Presented is a case report of a 54-year-old male Jehovah's Witness diagnosed with an anomalous right coronary artery originating from the main pulmonary artery with the initial presentation with a history of episodic fatigue, chest pain, palpitation, and bodily weakness. The patient was managed with reimplantation of the anomalous coronary artery onto the ascending aorta.

Biogeographical survey of soil microbiomes across sub-Saharan Africa: structure, drivers, and predicted climate-driven changes.

BACKGROUND: Top-soil microbiomes make a vital contribution to the Earth's ecology and harbor an extraordinarily high biodiversity. They are also key players in many ecosystem services, particularly in arid regions of the globe such as the African continent. While several recent studies have documented patterns in global soil microbial ecology, these are largely biased towards widely studied regions and rely on models to interpolate the microbial diversity of other regions where there is low data coverage. This is the case for sub-Saharan Africa, where the number of regional microbial studies is very low in comparison to other continents. RESULTS: The aim of this study was to conduct an extensive biogeographical survey of sub-Saharan Africa's top-soil microbiomes, with a specific focus on investigating the environmental drivers of microbial ecology across the region. In this study, we sampled 810 sample sites across 9 sub-Saharan African countries and used taxonomic barcoding to profile the microbial ecology of these regions. Our results showed that the sub-Saharan nations included in the study harbor qualitatively distinguishable soil microbiomes. In addition, using soil chemistry and climatic data extracted from the same sites, we demonstrated that the top-soil microbiome is shaped by a broad range of environmental factors, most notably pH, precipitation, and temperature. Through the use of structural equation modeling, we also developed a model to predict how soil microbial biodiversity in sub-Saharan Africa might be affected by future climate change scenarios. This model predicted that the soil microbial biodiversity of countries such as Kenya will be negatively affected by increased temperatures and decreased precipitation, while the fungal biodiversity of Benin will benefit from the increase in annual precipitation. CONCLUSION: This study represents the most extensive biogeographical survey of sub-Saharan top-soil microbiomes to date. Importantly, this study has allowed us to identify countries in sub-Saharan Africa that might be particularly vulnerable to losses in soil microbial ecology and productivity due to climate change. Considering the reliance of many economies in the region on rain-fed agriculture, this study provides crucial information to support conservation efforts in the countries that will be most heavily impacted by climate change. Video Abstract.

A Comparison of Community-Acquired and Hospital-Acquired Hypernatraemia in Patients who are Acutely Admitted to Hospital.

Background Hypernatraemia is associated with a short-term mortality of 20-60%. Age-related physiological changes predispose patients to hypernatraemia. This study reviewed acutely admitted patients comparing those with community-acquired (CAH) and hospital-acquired hypernatraemia (HAH). Methods A retrospective study of 102 consecutive acute medical in-patients with serum [Na]>145 mmol/L was conducted. Baseline characteristics, clinical presentation, laboratory values, monitoring, management and outcomes were compared between CAH and HAH groups. Results Patients were exclusively older (>69 years). Forty patients (39.2%) had CAH and sixty-two (61.8%) had HAH. Those with CAH were more likely to be NH residents, have dementia and reduced mobility. Most HAH patients had mild hypernatraemia initially (75.8%, n=47), and higher rates of acute kidney injury (27% (n=11) vs 8% (n=3)/p=0.02) were observed. Monitoring was inadequate and no patient had a free water deficit documented. Medication review and intravenous fluid prescribing was similar between groups. The median length of stay of discharged HAH patients was longer (22.5 vs 8 days/p=0.005). Mortality rates were similar (47% (n=29) vs 37% (n=15)/p=0.416). Time from admission to death was higher in HAH patients (16 vs 8 days/p=0.008). Conclusions Both CAH and HAH present similarly, however, older patients with cognitive/physical impairments are at an increased risk. Early identification of high-risk patients and adherence to best practice guidelines is required.

Chimeric antigen receptor T cell therapy comes to clinical practice.

Adoptive cellular therapy with chimeric antigen receptor T cells (car-ts) has recently received approval from Health Canada and the U.S. Food and Drug Administration after remarkable and durable remissions were seen in children with recurrent or refractory leukemia and adults with non-Hodgkin lymphoma-responses that were so impressive that a shift in the paradigm of care has now occurred for children with acute lymphoblastic leukemia. The concept behind car-t immunotherapy is that modification of a patient's own T cells to facilitate their localization to the cancer cell, with subsequent activation of the T cell effector mechanism and proliferation, will result in targeted killing of cancer cells. The car-ts are a novel drug in that the starting material for the manufacture of the car-t product comes from the patient, whose viable T cells are then genetically modified. Thus, collaboration is needed between the pharmaceutical companies, which must meet good manufacturing standards for each patient's unique product, and the treating sites. For regulators and health authorities, this new class of drugs requires new paradigms for assessment and approval. Treatments with car-ts require that institutions address unique logistics requirements and management of novel toxicities. The Hospital for Sick Children has had early experience with both the licensing of clinical trials and the introduction of the first commercial product. Here, we provide an overview of basic concepts and treatment, with caveats drawn from what we have learned thus far in bringing this new therapy to the clinical front line.

Nitrogen fertilisers with urease inhibitors reduce nitrous oxide and ammonia losses, while retaining yield in temperate grassland.

Nitrogen fertilisation, although a cornerstone of modern agricultural production, negatively impacts the environment through gaseous losses of nitrous oxide (N2O), a potent greenhouse gas (GHG), and ammonia (NH3), a known air pollutant. The aim of this work was to assess the feasibility of urea treated with urease inhibitors to reduce gaseous N losses in temperate grassland, while maintaining or improving productivity compared to conventional fertiliser formulations. Urease inhibitors were N-(n-butyl)-thiophosphoric triamide (NBPT) (urea + NBPT) and N-(n-propyl)-thiophosphoric triamide (NPPT) (urea+ NBPT + NPPT), while conventional fertilisers were urea and calcium ammonium nitrate (CAN). N2O emission factors were 0.06%, 0.07%, 0.09% and 0.58% from urea + NBPT, urea, urea + NBPT + NPPT and CAN, respectively, with CAN significantly higher than all the urea formulations, which were not significantly different from each other. Ammonia loss measured over one fertiliser application was significantly larger from urea, at 43%, compared with other formulations at 13.9%, 13.8% and 5.2% from urea + NBPT, urea + NBPT + NPPT and CAN, respectively. Changing fertiliser formulation had no significant impact on grass yield or N uptake in four out of five harvests. In the last harvest urea + NBPT significantly out-yielded urea, but not CAN or urea + NBPT + NPPT. Overall, urea treated with either one or both urease inhibitors significantly reduced emissions of N2O and NH3, while preserving yield quantity and quality. Therefore, changing fertiliser formulation to these products should be encouraged as a strategy to reduce GHG and air pollution from agricultural practices in temperate climate.

TREatment of ATopic eczema (TREAT) Registry Taskforce: protocol for a European safety study of dupilumab and other systemic therapies in patients with atopic eczema.

BACKGROUND: A long-term prospective observational safety study is essential to characterize fully the safety profile of systemic immunomodulating therapies for patients with atopic eczema. The TREatment of ATopic eczema (TREAT) Registry Taskforce offers a large platform to conduct such research using national registries that collect the same data using a predefined core dataset. OBJECTIVES: To present a protocol for a safety study comparing dupilumab with other systemic immunomodulating therapies in children and adults with moderate-to-severe atopic eczema, to assess the long-term safety risk of these therapies in a routine clinical care setting. METHODS: We describe a registry-embedded international observational prospective cohort study. Adult and paediatric patients who start treatment with dupilumab or another systemic immunomodulating agent for their atopic eczema will be included. The primary end point is the incidence of malignancies (excluding nonmelanoma skin cancer) compared between the treatment groups. Secondary end points include other serious adverse events and adverse events of special interest, such as eye disorders and eosinophilia. CONCLUSIONS: This protocol delineates a safety study for dupilumab in adult and paediatric patients with atopic eczema, using a standardized methodological approach across several national registries. The protocol could also be used for other novel systemic immunomodulating therapies, and could provide licensing and reimbursement authorities, pharmaceutical companies and clinicians with safety evidence from a routine clinical care setting. What's already known about this topic? There is a need for long-term data on the safety of systemic immunomodulating therapies in patients with atopic eczema. Regulatory bodies, such as the European Medicines Agency, increasingly stipulate the collection of such data as part of the licensing agreement for new treatments, to assess the new agent's long-term safety profile against established therapies. Large numbers of patients with a long duration of follow-up are necessary in order to detect rare events like malignancies. What does this study add? The TREAT Registry Taskforce offers a platform to conduct such research with a network of multiple national atopic eczema research registries. We present a protocol for an investigator-initiated multicentre safety study comparing dupilumab with other systemic immunomodulating therapies in adults and subsequently adolescents and children with moderate-to-severe atopic eczema. This protocol can be used as a framework for similar studies for other novel systemic immunomodulating therapies across both adult and paediatric populations.

Scenarios to limit environmental nitrogen losses from dairy expansion.

Increased global demand for dairy produce and the abolition of EU milk quotas have resulted in expansion in dairy production across Europe and particularly in Ireland. Simultaneously, there is increasing pressure to reduce the impact of nitrogen (N) losses to air and groundwater on the environment. In order to develop grassland management strategies for grazing systems that meet environmental targets and are economically sustainable, it is imperative that individual mitigation measures for N efficiency are assessed at farm system level. To this end, we developed an excel-based N flow model simulating an Irish grass-based dairy farm, to evaluate the effect of farm management on N efficiency, N losses, production and economic performance. The model was applied to assess the effect of different strategies to achieve the increased production goals on N utilization, N loss pathways and economic performance at farm level. The three strategies investigated included increased milk production through increased grass production, through increased concentrate feeding and by applying a high profit grass-based system. Additionally, three mitigation measures; low ammonia emission slurry application, the use of urease and nitrification inhibitors and the combination of both were applied to the three strategies. Absolute N emissions were higher for all intensification scenarios (up to 124 kg N ha-1) compared to the baseline (80 kg N ha-1) due to increased animal numbers and higher feed and/or fertiliser inputs. However, some intensification strategies showed the potential to reduce the emissions per ton milk produced for some of the N-loss pathways. The model showed that the assessed mitigation measures can play an important role in ameliorating the increased emissions associated with intensification, but may not be adequate to entirely offset absolute increases. Further improvements in farm N use efficiency and alternatives to mineral fertilisers will be required to decouple production from reactive N emissions.

TREatment of ATopic eczema (TREAT) Registry Taskforce: consensus on how and when to measure the core dataset for atopic eczema treatment research registries.

BACKGROUND: Comparative, real-life and long-term evidence on the effectiveness and safety of phototherapy and systemic therapy in moderate-to-severe atopic eczema (AE) is limited. Such data must come from well-designed prospective patient registries. Standardization of data collection is needed for direct comparisons and data pooling. OBJECTIVES: To reach a consensus on how and when to measure the previously defined domain items of the TREatment of ATopic eczema (TREAT) Registry Taskforce core dataset for research registries for paediatric and adult patients with AE. METHODS: Proposals for the measurement instruments were based on recommendations of the Harmonising Outcome Measures for Eczema (HOME) initiative, the existing AE database of TREATgermany, systematic reviews of the literature and expert opinions. The proposals were discussed at three face-to-face consensus meetings, one teleconference and via e-mail. The frequency of follow-up visits was determined by an expert survey. RESULTS: A total of 16 experts from seven countries participated in the 'how to measure' consensus process and 12 external experts were consulted. A consensus was reached for all domain items on how they should be measured by assigning measurement instruments. A minimum follow-up frequency of initially 4 weeks after commencing treatment, then every 3 months while on treatment and every 6 months while off treatment was defined. CONCLUSIONS: This core dataset for national AE research registries will aid in the comparability and pooling of data across centres and country borders, and enables international collaboration to assess the long-term effectiveness and safety of phototherapy and systemic therapy used in patients with AE. What's already known about this topic? Comparable, real-life and long-term data on the effectiveness and safety of phototherapy and systemic therapy in patients with atopic eczema (AE) are needed. There is a high diversity of outcomes and instruments used in AE research, which require harmonization to enhance comparability and allow data pooling. What does this study add? Our taskforce has reached international consensus on how and when to measure core domain items for national AE research registries. This core dataset is now available for use by researchers worldwide and will aid in the collection of unified data. What are the clinical implications of this work? The data collected through this core dataset will help to gain better insights into the long-term effectiveness and safety of phototherapy and systemic therapy in AE and will provide important information for clinical practice. Standardization of such data collection at the national level will also allow direct data comparisons and pooling across country borders (e.g. in the analysis of treatment-related adverse events that require large patient numbers).

TREatment of ATopic eczema (TREAT) Registry Taskforce: an international Delphi exercise to identify a core set of domains and domain items for national atopic eczema photo- and systemic therapy registries.

BACKGROUND: Evidence of immunomodulatory therapies to guide clinical management of atopic eczema (AE) is scarce, despite frequent and often off-label use. Patient registries provide valuable evidence for the effects of treatments under real-world conditions that can inform treatment guidelines, give the opportunity for health economic evaluation and the evaluation of quality of care, as well as pharmacogenetic and dynamic research, which cannot be adequately addressed in clinical trials. OBJECTIVES: The TREatment of ATopic eczema (TREAT) Registry Taskforce aims to seek international consensus on a core set of domains and items ('what to measure') for AE research registries, using a Delphi approach. METHODS: Participants from six stakeholder groups were included: doctors, nurses, nonclinical researchers, patients, industry and regulatory body representatives. The eDelphi comprised three sequential online rounds, requesting participants to rate the importance of each proposed domain item. Participants could add domain items to the proposed list in round 1. A final consensus meeting was held to ratify the core set. RESULTS: Participants (n = 479) from 36 countries accessed the eDelphi platform, of whom 86%, 79% and 74% completed rounds 1, 2 and 3, respectively. At the face-to-face consensus meeting attended by 42 participants the final core set was established containing 19 domains with 69 domain items (49 baseline and 20 follow-up items). CONCLUSIONS: This core set of domains and items to be captured by national AE systemic therapy registries will standardize data collection and thereby allow direct comparability across registries and facilitate data pooling between countries. Ultimately, it will provide greater insight into the effectiveness, safety and cost-effectiveness of photo- and systemic immunomodulatory therapies.

Soil biological responses to, and feedbacks on, trophic rewilding.

Trophic rewilding-the (re)introduction of missing large herbivores and/or their predators-is increasingly proposed to restore biodiversity and biotic interactions, but its effects on soils have been largely neglected. The high diversity of soil organisms and the ecological functions they perform mean that the full impact of rewilding on ecosystems cannot be assessed considering only above-ground food webs. Here we outline current understanding on how animal species of rewilding interest affect soil structure, processes and communities, and how in turn soil biota may affect species above ground. We highlight considerable uncertainty in soil responses to and feedbacks on above-ground consumers, with potentially large implications for rewilding interactions with global change. For example, the impact of large herbivores on soil decomposers and plant-soil interactions could lead to reduced carbon sequestration, whereas herbivore interactions with keystone biota such as mycorrhizal fungi, dung beetles and bioturbators could promote native plants and ecosystem heterogeneity. Moreover, (re)inoculation of keystone soil biota could be considered as a strategy to meet some of the objectives of trophic rewilding. Overall, we call for the rewilding research community to engage more with soil ecology experts and consider above-ground-below-ground linkages as integral to assess potential benefits as well as pitfalls.This article is part of the theme issue 'Trophic rewilding: consequences for ecosystems under global change'.

Observed trends of soil fauna in the Antarctic Dry Valleys: early signs of shifts predicted under climate change.

Long-term observations of ecological communities are necessary for generating and testing predictions of ecosystem responses to climate change. We investigated temporal trends and spatial patterns of soil fauna along similar environmental gradients in three sites of the McMurdo Dry Valleys, Antarctica, spanning two distinct climatic phases: a decadal cooling trend from the early 1990s through the austral summer of February 2001, followed by a shift to the current trend of warming summers and more frequent discrete warming events. After February 2001, we observed a decline in the dominant species (the nematode Scottnema lindsayae) and increased abundance and expanded distribution of less common taxa (rotifers, tardigrades, and other nematode species). Such diverging responses have resulted in slightly greater evenness and spatial homogeneity of taxa. However, total abundance of soil fauna appears to be declining, as positive trends of the less common species so far have not compensated for the declining numbers of the dominant species. Interannual variation in the proportion of juveniles in the dominant species was consistent across sites, whereas trends in abundance varied more. Structural equation modeling supports the hypothesis that the observed biological trends arose from dissimilar responses by dominant and less common species to pulses of water availability resulting from enhanced ice melt. No direct effects of mean summer temperature were found, but there is evidence of indirect effects via its weak but significant positive relationship with soil moisture. Our findings show that combining an understanding of species responses to environmental change with long-term observations in the field can provide a context for validating and refining predictions of ecological trends in the abundance and diversity of soil fauna.

Associations between glycaemic control and activation of the renin-angiotensin-aldosterone system in participants with type 2 diabetes mellitus and hypertension.

Introduction Hyperglycaemia increases succinate concentrations and succinate receptor activation in the kidney resulting in renin release. The aim of our study was to determine if there is an association between glycaemic control as evidenced by glycated haemoglobin values and activation of the renin-angiotensin-aldosterone system in patients with type 2 diabetes mellitus and hypertension. Methods A cross-sectional study was conducted at Galway University Hospitals between December 2014 and March 2015. Participants ( n = 66) were identified following interrogation of the electronic database for patients with type 2 diabetes mellitus. Baseline clinical demographics, aldosterone, plasma renin activity, direct renin concentration, urea and electrolytes, glycated haemoglobin, cholesterol, urine sodium and albumin creatinine ratio were recorded. Results There was a significant positive linear correlation between glycated haemoglobin and renin (both plasma renin activity [ P = 0.002] and direct renin concentration [ P = 0.008]) and between serum creatinine and aldosterone measured using both radioimmunoassay ( P = 0.008) and immunochemiluminometric assay ( P = 0.008). A significant negative linear correlation was demonstrated between serum sodium and plasma renin activity ( P = 0.005) and direct renin concentration ( P = 0.015) and between estimated glomerular filtration rate and aldosterone measured using radioimmunoassay ( P = 0.02) and immunochemiluminometric assay ( P = 0.016). A significant negative linear correlation existed between urine sodium and plasma renin activity ( P = 0.04) and aldosterone measured using radioimmunoassay ( P = 0.045). Conclusions There is a direct positive association between glycaemic control and renin. We advocate for renin measurement to be part of the diabetologist's armamentarium to assess, guide and optimize therapeutic strategies in patients with diabetes.

Linking Inuit Knowledge and Public Health for Improved Child and Youth Oral Health in NunatuKavut.

The oral health of Inuit children in Canada has been identified as a public health crisis. Although efforts are being made to identify and address ways to deal with this crisis, current policy and program approaches are largely entrenched within the prevailing paradigm of dental science to the exclusion of Indigenous people's understandings of health. This article reports qualitative findings of a larger study aimed at identifying, understanding, and addressing rates of oral disease among children living in NunatuKavut, a cluster of small, coastal Inuit communities located in southern Labrador, Canada. Through 18 focus groups with youth (n = 86), caregivers (n = 22), and interviews with key informant (n = 13), this study begins to elucidate southern Inuit understandings of oral health. Theorized using Two-Eyed Seeing, an Indigenous approach to balancing both Indigenous and non-Indigenous understandings of the world, the findings reported here reveal 3 themes, each of which is crosscut by historical and contemporary dimensions: 1) (w)holistic conceptualizations of health are essential to good oral health, 2) achieving optimal oral health is prohibitive for Inuit communities, and 3) community-engaged oral health service delivery is needed. Our recommendations have implications for improved oral public health service delivery for Inuit communities, in that the inclusion of Inuit perspectives on oral health should form an instrumental element of oral public health service delivery. Knowledge Transfer Statement: The results of this study may be used by clinicians and oral health educators to inform approaches to oral health service delivery within the context of Indigenous communities. It may also be used by policymakers to recognize how historical and contemporary issues of colonization relate to the formation of oral health-related policies.

Cross-disciplinarity in the advance of Antarctic ecosystem research.

The biodiversity, ecosystem services and climate variability of the Antarctic continent and the Southern Ocean are major components of the whole Earth system. Antarctic ecosystems are driven more strongly by the physical environment than many other marine and terrestrial ecosystems. As a consequence, to understand ecological functioning, cross-disciplinary studies are especially important in Antarctic research. The conceptual study presented here is based on a workshop initiated by the Research Programme Antarctic Thresholds - Ecosystem Resilience and Adaptation of the Scientific Committee on Antarctic Research, which focussed on challenges in identifying and applying cross-disciplinary approaches in the Antarctic. Novel ideas and first steps in their implementation were clustered into eight themes. These ranged from scale problems, through risk maps, and organism/ecosystem responses to multiple environmental changes and evolutionary processes. Scaling models and data across different spatial and temporal scales were identified as an overarching challenge. Approaches to bridge gaps in Antarctic research programmes included multi-disciplinary monitoring, linking biomolecular findings and simulated physical environments, as well as integrative ecological modelling. The results of advanced cross-disciplinary approaches can contribute significantly to our knowledge of Antarctic and global ecosystem functioning, the consequences of climate change, and to global assessments that ultimately benefit humankind.

Screening for primary aldosteronism using the newly developed IDS-iSYS® automated assay system.

BACKGROUND: The recommended approach to screening for primary aldosteronism (PA) in at-risk populations is to determine the ratio of aldosterone concentration (serum (SAC)/plasma (PAC)) to renin measured in plasma as activity (PRA) or concentration (DRC). However, lack of assay standardisation mandates the need for method-specific decision thresholds and clinical validation in the local population. AIM: The study objective was to establish method-specific aldosterone: renin ratio (ARR) cut-offs for PA in men and women using the IDS-iSYS® assay system (IDS plc). METHODS: A prospective cohort study design was used. PAC and DRC were measured immunochemically in ethylenediamine-tetraacetic acid (EDTA) plasma on the IDS-iSYS® instrument. RESULTS: A total of 437 subjects (218 men, 219 women) were recruited including: healthy normotensive volunteers (n=266) and women taking the oral contraceptive pill (OCP; n=15); patients with essential hypertension (EH; n=128); confirmed PA (n=16); adrenal cortical carcinoma (ACC; n=3); Addison's disease (AD; n=4) and phaeochromocytoma/paraganglioma (PPGL; n=5). In this population, an ARR cut-off at >37.4 pmol/mIU provided 100% diagnostic sensitivity, 96% specificity and positive likelihood ratio for PA of 23:1. When the ARR decision threshold was stratified according to gender, a cut-off of >26.1 pmol/mIU in men and >113.6 pmol/mIU in women resulted in diagnostic sensitivity and specificity of 100%. CONCLUSION: This study demonstrates that decision thresholds for PA should not only be method-specific but also gender-specific. However, given the small number of PA patients (n=16), particularly women (n=4), further validation through a prospective study with a larger PA cohort is required before the thresholds presented here could be recommended for routine clinical use.