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IntroductionChronic kidney disease (CKD) causes significant morbidity and mortality. Medical therapies can reduce the progression of disease by up to 50%. CKD is undiagnosed in the majority of people who have it, resulting in undertreatment. CKD Stewardship (CKD-S) aims to identify hospital inpatients with undiagnosed mid-stage to late-stage CKD with the goal of facilitating diagnosis and initiating guideline-based therapies.Methods and analysisThis prospective, multicentre, cohort study compares two models of care, CKD-S and standard care, for identification and management of CKD, across six public hospitals in metropolitan Sydney, Australia. CKD-S entails active case finding using the electronic medical record, with nephrologist outreach to admitting teams and kidney nurse provided patient education. Adult inpatients with an admission estimated glomerular filtration rate (eGFR)<45 mL/min/1.73 m2 and not known to a nephrologist will be eligible, excluding those with short life expectancy or advanced age (>80 years). Participants will be enrolled between 1 March 2024 and 1 March 2025. Baseline and demographic data will be collected after discharge from the hospital. Participants will be followed up 12 months after discharge using Pharmaceutical Benefits Schedule and Medical Benefits Schedule data, linked via the Australian Institute of Health and Welfare Hub. We will report the proportion of all adults admitted to the hospital who are not already known to a nephrologist, in which a diagnosis of stage 3b–5 CKD is recognised by the CKD-S intervention team, compared with standard care. We will then compare the proportion in each cohort who have an eGFR or urine albumin:creatinine ratio measured, are referred to a nephrologist, and are prescribed guideline-directed therapies over the 12 months following discharge from the hospital.Ethics and disseminationThe study has ethics approval from the Sydney Local Health District’s Ethics Committee (Concord Hospital Zone). The results of the CKD-S study will be published in peer-reviewed journals and presented at academic conferences.Trial registration numberACTRN12624000452594.

For decades, ill-defined autosomal dominant renal diseases have been reported, which originate from tubular cells and lead to tubular atrophy and interstitial fibrosis. These diseases are clinically indistinguishable, but caused by mutations in at least four different genes: UMODHNF1BREN, and, as recently described, MUC1. Affected family members show renal fibrosis in the biopsy and gradually declining renal function, with renal failure usually occurring between the third and sixth decade of life. Here we describe 10 families and define eligibility criteria to consider this type of inherited disease, as well as propose a practicable approach for diagnosis. In contrast to what the frequently used term ‘Medullary Cystic Kidney Disease’ implies, development of (medullary) cysts is neither an early nor a typical feature, as determined by MRI. In addition to Sanger and gene panel sequencing of the four genes, we established SNaPshot minisequencing for the predescribed cytosine duplication within a distinct repeat region of MUC1 causing a frameshift. A mutation was found in 7 of 9 families (3 in UMOD and 4 in MUC1), with one indeterminate (UMOD p.T62P). On the basis of clinical and pathological characteristics we propose the term ‘Autosomal Dominant Tubulointerstitial Kidney Disease’ as an improved terminology. This should enhance recognition and correct diagnosis of affected individuals, facilitate genetic counseling, and stimulate research into the underlying pathophysiology.

IntroductionPregnancy induces significant physiological and cardiometabolic changes, and is associated with alterations in the maternal microbiota. Increasing rates of prepregnancy obesity, metabolic abnormalities and reduced physical activity, all impact negatively on the microbiota causing an imbalance between the commensal microorganisms (termed dysbiosis), which may drive complications, such as gestational diabetes or hypertensive disorders. Considerable work is needed to define the inter-relationships between the microbiome, nutrition, physical activity and pregnancy outcomes. The role of the microbiota during pregnancy remains unclear. The aim of the study is to define microbiota signatures longitudinally throughout pregnancy and the first year post birth, and to identify key clinical and environmental variables that shape the female microbiota profile during and following pregnancy.Methods and analysisThe Microbiome Understanding in Maternity Study (MUMS) is an Australian prospective longitudinal cohort study involving 100 mother–infant pairs. Women are enrolled in their first trimester and followed longitudinally. Assessment occurs at <13+0, 20+0–24+6 and 32+0–36+6 weeks gestation, birth and 6 weeks, 6 months and 12 months postpartum. At each assessment, self-collected oral, vaginal and faecal samples are collected with an additional postpartum skin swab and breastmilk sample. Each infant will have oral, faecal and skin swab samples collected. Measurements include anthropometrics, body composition, blood pressure, serum hormonal and metabolic parameters and vaginal pH. Dietary intake, physical activity and psychological state will be assessed using validated self-report questionnaires, and pregnancy and infant outcomes recorded. Parametric and non-parametric hypothesis tests will be used to test the association between high-risk and low-risk pregnancies and their outcomes.Ethics and disseminationThe study received the following approval: South Eastern Sydney Local Health District Research Ethics Committee (17/293 (HREC/17/POWH/605). Results will be made available to the participants of MUMS, their families and the funding bodies; in the form of a summary document. Results for the greater maternity care community and other researchers will be disseminated through conferences, local, national and international presentations and peer-reviewed publications.Trial registration numberACTRN12618000471280 (prospectively registered).

Hypertensive disorders of pregnancy are common and can result in maternal and fetal morbidity and mortality. Women may have chronic hypertension, or develop hypertension during pregnancy. Management involves close maternal and fetal surveillance. If an antihypertensive drug is needed, prescribe one that is safe in pregnancy. Pre-eclampsia is a hypertensive disorder of pregnancy. Women at high risk of pre-eclampsia should start aspirin 150 mg daily at 12-16 weeks gestation and continue until 36 weeks gestation, to reduce the risk of preterm delivery. There are long-term cardiovascular and mortality risks associated with pregnancies complicated by gestational hypertension and pre-eclampsia. Ongoing cardiovascular and metabolic risk surveillance should be undertaken by the woman's general practitioner.Hypertensive disorders of pregnancy are common and can result in maternal and fetal morbidity and mortality. Women may have chronic hypertension, or develop hypertension during pregnancy. Management involves close maternal and fetal surveillance. If an antihypertensive drug is needed, prescribe one that is safe in pregnancy. Pre-eclampsia is a hypertensive disorder of pregnancy. Women at high risk of pre-eclampsia should start aspirin 150 mg daily at 12-16 weeks gestation and continue until 36 weeks gestation, to reduce the risk of preterm delivery. There are long-term cardiovascular and mortality risks associated with pregnancies complicated by gestational hypertension and pre-eclampsia. Ongoing cardiovascular and metabolic risk surveillance should be undertaken by the woman's general practitioner.

Background Most assessments in health professions education consist of knowledge-based examinations as well as practical and clinical examinations. Among the most challenging aspects of clinical assessments is decision making related to borderline grades assigned by examiners. Borderline grades are commonly used by examiners when they do not have sufficient information to make clear pass/fail decisions. The interpretation of these borderline grades is rarely discussed in the literature. This study reports the application of the Objective Borderline Method (version 2, henceforth: OBM2) to a high stakes Objective Structured Clinical Examination undertaken at the end of the final year of a Medicine program in Australia. Methods The OBM2 uses all examination data to reclassify borderline grades as either pass or fail. Factor analysis was used to estimate the suitability of data for application of OBM2. Student’s t-tests, utilising bootstrapping, were used to compare the OBM2 with ‘traditional’ results. Interclass correlations were used to estimate the association between the grade reclassification and all other grades in this examination. Results The correlations between scores for each station and pass/fail outcomes increased significantly after the mark reclassification, yet the reclassification did not significantly impact on students’ total scores. Examiners, students and program leaders expressed high levels of satisfaction and the Faculty’s Curriculum Development Committee has decided that the OBM2 will be used for all future clinical examinations. Implications of the OBM2 are discussed. Conclusions The OBM2 provides a feasible, defensible and acceptable solution for classification of borderline grades as either pass or fail.

Background. Optimal glycaemic targets following transplantation are unknown. Understanding the impact of DM and posttransplant diabetes mellitus (PTDM) may improve patient and graft survival in transplant recipients. Aim. To determine the perioperative and one-year outcomes after renal transplantation and whether these outcomes are affected by preexisting DM, PTDM, or glycaemia during transplant admission. Method. Adult recipients of renal transplants from a single centre over 5.5 years were retrospectively reviewed. Measured outcomes during transplant admission included glycaemia and complications (infective complications, acute rejection, and return to dialysis) and, at 12 months, glycaemic control and complications (cardiovascular complication, graft failure). Results. Of 148 patients analysed, 29 (19.6%) had DM and 27 (18.2%) developed PTDM. Following transplantation, glucose levels were higher in patients with DM and PTDM. DM patients had a longer hospital stay, had more infections, and were more likely return to dialysis. PTDM patients had increased rates of acute rejection and return to dialysis. At 1 year after transplant, there were more cardiovascular complications in DM patients compared to those without DM. Conclusions. Compared to patients without DM, patients with DM or PTDM are more likely to suffer from complications perioperatively and at 12 months. Perioperative glycaemia is associated with graft function and may be a modifiable risk.

Exogenous cortisol raises blood pressure (BP) in humans and there is accumulating evidence of abnormalities of glucocorticoid activity in essential hypertension. In this study we tested the hypothesis that exogenous cortisol attenuates the cholinergic dilator response in the forearm circulation. Fourteen healthy normotensive men were studied. Using bilateral forearm venous plethysmography, we examined forearm blood flow responses to intra-arterial acetylcholine (ACh) and sodium nitroprusside (SNP) pre- and post- N G -monomethyl- l-arginine (LNMMA) after 2 or 5 days of oral cortisol or placebo in a randomized, double-blind crossover study. Exogenous cortisol increased supine systolic ( P < .05) and standing systolic ( P < .05) BP and produced expected metabolic changes and suppressed serum cortisol concentration ( P < .001). Baseline forearm blood flow did not differ between placebo and cortisol treatments at 2 or 5 days. Cholinergic vasodilatation was impaired after cortisol administration, reaching statistical significance at 5 days ( P < .05). Cortisol did not affect responses to SNP. N G -monomethyl- l-arginine inhibited cholinergic vasodilatation in placebo-treated groups but had no additional effect in the presence of cortisol. These results support our hypothesis and suggest that the mechanism of impaired cholinergic dilatation in glucocorticoid-treated subjects involves abnormalities of the endothelial nitric oxide system.

AbstractObjectiveTo determine whether disrupting the renin angiotensin system with angiotensin receptor blockers will improve clinical outcomes in people with covid-19.DesignCLARITY was a pragmatic, adaptive, multicentre, phase 3, randomised controlled trial.Setting17 hospital sites in India and Australia.ParticipantsParticipants were at least 18 years old, previously untreated with angiotensin receptor blockers, with a laboratory confirmed diagnosis of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection who had been admitted to hospital for management of covid-19.InterventionOral angiotensin receptor blockers (telmisartan in India) or placebo (1:1) for 28 days.Main outcome measuresThe primary endpoint was covid-19 disease severity using a modified World Health Organization Clinical Progression Scale (WHO scale) at day 14. Secondary outcomes were WHO scale scores at day 28, mortality, intensive care unit admission, and respiratory failure. Analyses were evaluated on an ordinal scale in the intention-to-treat population.ResultsBetween 3 May 2020 and 13 November 2021, 2930 people were screened for eligibility, with 393 randomly assigned to angiotensin receptor blockers (of which 388 (98.7%) to telmisartan 40 mg/day) and 394 to the control group. 787 participants were randomised: 778 (98.9%) from India and nine (1.1%) from Australia. The median WHO scale score at day 14 was 1 (interquartile range 1-1) in 384 participants assigned angiotensin receptor blockers and 1 (1-1) in 382 participants assigned placebo (adjusted odds ratio 1.51 (95% credible interval 1.02 to 2.23), probability of an odds ratio of >1 (Pr(OR>1)=0.98). WHO scale scores at day 28 showed little evidence of difference between groups (1.02 (0.55 to 1.87), Pr(OR>1)=0.53). The trial was stopped when a prespecified futility rule was met.ConclusionsIn patients admitted to hospital for covid-19, mostly with mild disease, not requiring oxygen, no evidence of benefit, based on disease severity score, was found for treatment with angiotensin receptor blockers, using predominantly 40 mg/day of telmisartan.Trial registrationClinicalTrials.gov NCT04394117.

Current guidelines do not address the appropriate technique for accurate inpatient blood pressure (BP) measurement. Outpatient data suggest that technique matters for accurate readings. Given the substantial impact of BP treatment decisions, this study explored the relative importance of various factors for accurate inpatient BP measurement. This was a ranking-type Delphi survey conducted in two stages. Stage 1 involved document ratification (single round) where an international panel of 9 hypertension experts reviewed and validated source documents relevant to BP measurement. Stage 2 involved variable ranking across three iterative rounds: Rounds 1 and 2 required panellists to independently rank all 10 variables from most to least important with each variable receiving a unique rank; Round 3 used paired comparisons with forced choices to refine consensus. Binary decisions required > 80% agreement for consensus. Ranked order consensus required Kendall’s coefficient > 0.7. The panel agreed with high consensus on the following 10 variables in order of importance: (1) at least two measurements, (2) correct cuff size, (3) not talking during measurement, (4) correctly fitted cuff, (5) cuff at heart level, (6) seated position, (7) contemporary device calibration, (8) legs uncrossed, (9) bare arm below cuff, and (10) supported back (Kendall’s 0.97, P < 0.001). Understanding of true determinants of accurate inpatient BP measurement is still required. Meanwhile, expert consensus provides an intermediary step for prioritising factors in inpatient BP measurement to assess performance.