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Background: Current hyponatraemia guidelines are divided on the use of tolvaptan in hospitalised patients with moderate to severe hyponatraemia, due to an uncertain risk-benefit ratio. We will conduct a randomised trial to test the hypothesis that early use of tolvaptan improves the rate of serum sodium correction and clinical outcomes compared with current standard first-line therapy, restriction of fluid intake, without increasing the risk of serum sodium overcorrection.Methods: We will enrol hospitalised patients with euvolaemic or hypervolaemic hyponatraemia and serum sodium of 115-130 mmol/L at Austin Health, a tertiary care centre in Melbourne, Australia. Participants will be randomised 1:1 to receive either tolvaptan (initial dose 7.5 mg) or fluid restriction (initial limit 1000 ml per 24 h), with titration of therapy based on serum sodium response according to a pre-determined protocol over a 72-h intervention period. The primary endpoint will be the between-group change in serum sodium over time, from study day 1 to day 4. Secondary endpoints include serum sodium increment in the first 24 and 48 h, proportion of participants with normalised serum sodium, length of hospital stay, requirement for serum sodium re-lowering with intravenous dextrose or desmopressin, cognitive and functional measures (Confusion Assessment Method Short form, Timed Up and Go test, hyponatraemia symptom questionnaire), 30-day readmission rate, treatment satisfaction score and serum sodium 30 days after discharge. The trial will be overseen by an independent Data Safety Monitoring Board. Serum sodium will be monitored every 6-12 h throughout the study period, with pre-specified thresholds for commencing intravenous 5% dextrose if serum sodium rise targets are exceeded.Discussion: We seek to inform future international guidelines with high-quality data regarding the utility and safety of tolvaptan compared to standard therapy fluid restriction in patients with moderate-severe hyponatraemia in hospital. If tolvaptan use in this patient group is endorsed by our findings, we will have established an evidence-based framework for tolvaptan initiation and monitoring to guide its use.Trial Registration: Australia and New Zealand Clinical Trials Registry ACTRN12619001683123 . Registered on December 2 2019. [ABSTRACT FROM AUTHOR]

Objective: Both hyponatremia and hypernatremia have been reported to occur more frequently with higher ambient temperatures, although the underlying mechanisms are not well understood. Global temperatures are rising due to climate change, which may impact the incidence of dysnatremia worldwide. We aimed to identify, collate and critically appraise studies analyzing the relationship between climate measures (outdoor temperature, humidity) and serum sodium concentrations. Design: Systematic review, reported in accordance with PRISMA guidelines. Methods: MEDLINE and Embase were searched with relevant key terms. Studies assessing the effect on serum sodium measurement of elevated temperature or humidity versus a comparator were included. Results: Of 1466 potentially relevant studies, 34 met inclusion criteria, originating from 23 countries spanning all inhabited continents. The majority (30 of 34, 88%) reported a significant association between outdoor temperature and dysnatremia, predominantly lower serum sodium with increased ambient temperature. Humidity had a less consistent effect. Individuals aged above 65 years, children, those taking diuretics and antidepressants, those with chronic renal impairment or those undertaking physical exertion had increased vulnerability to heat‐associated dysnatremia. The risk of bias was assessed to be high in all but four studies. Conclusions: Higher ambient temperature is consistently associated with an increased incidence of hyponatremia. We infer that hyponatremia presentations are likely to rise with increasing global temperatures and the frequency of extreme heat events secondary to climate change. Evidence‐based public health messages, clinician education and reduction in fossil fuel consumption are necessary to reduce the expected burden on healthcare services worldwide. [ABSTRACT FROM AUTHOR]

In 2018, consolidating evidence for renoprotective benefits was seen with respect to sodium-glucose cotransporter 2 inhibitors and glucagon-like peptide 1 agonists, which are currently being incorporated into clinical practice. The focus now turns to novel therapeutic targets to optimize renoprotection as diabetic kidney disease grows to epidemic proportions worldwide. The CANVAS Program reported renal benefits of canagliflozin1; these findings build on evidence from the EMPA-REG OUTCOME trial7 for a renoprotective effect of sodium-glucose cotransporter 2 (SGLT2) inhibitors.The AWARD-7 trial reported renal benefits of dulaglutide2; these results add weight to previous findings of renoprotective effects of glucagon-like peptide 1 (GLP1) agonists.Targeting podocyte histone modification via promotion of H3K27me3 prevented glomerular cell dedifferentiation and loss of renal function in a mouse model of obesity and type 2 diabetes mellitus3.Inhibition of apoptosis signal-regulating kinase 1 (ASK1) prevented oxidative stress and fibrosis and was renoprotective in a mouse model; human trials of ASK1 inhibition in diabetic kidney disease are underway4. [ABSTRACT FROM AUTHOR]

Combined oral contraceptives (OCs) are the most commonly prescribed medication in women of reproductive age, but despite widespread use, their effect on cognitive performance remains controversial. Given strong evidence for the neurological impact of reproductive hormones, a clear rationale for investigation exists. This systematic review sought to identify, collate and critically appraise studies assessing the impact of OCs on cognition in healthy premenopausal women. Ovid MEDLINE, PsychINFO and EMBASE were comprehensively searched using relevant keywords for original peer-reviewed observational studies or randomised trials published after 1960. Of 1289 references screened, 22 studies were eligible for inclusion. Assembled evidence supports a cognitive impact of OCs restricted to specific domains; however, the quality of evidence is poor. The most consistent finding is improved verbal memory with OC use. Evidence is also emerging that differing progestin androgenicity may lead diverse OC formulations to differentially impact certain cognitive domains, such as visuospatial ability. At present, evidence is inconclusive, contradictory and limited by methodological inconsistencies. There is scope for further research in this area to definitively determine the cognitive impact of OCs. [ABSTRACT FROM AUTHOR]

Oral contraceptives (OCs) containing estrogen and progesterone analogues are widely used amongst reproductive-aged women, but their neurocognitive impact is poorly understood. Preliminary studies suggest that OCs improve verbal memory and that OCs with greater androgenic activity may improve visuospatial ability. We sought to explore the cognitive impact of OCs by assessing performance of OC users at different stages of the OC cycle, and comparing this performance between users of different OC formulations according to known androgenic activity. We conducted a prospective, observational trial of OC users, evaluating cognitive performance with CogState software on two occasions: days 7–10 of active hormonal pill phase, and days 3–5 of the inactive pill phase (coinciding with the withdrawal bleed resembling menstruation). Thirty-five OC users (18 taking androgenic formulations, 17 taking anti-androgenic) were assessed. Analysis by androgenic activity showed superior performance by users of androgenic OCs, as compared to anti-androgenic OCs, in visuospatial ability and facial affect discrimination tasks. A growing understanding of cognitive effects of OC progestin androgenicity may have implications in choice of OC formulation for individuals and in future OC development. [ABSTRACT FROM AUTHOR]

The article discusses the importance of pharmacogenomic testing in the field of psychiatry. Topics covered include the use of such testing method to project efficacy and side effects of medications and assess prescribing patterns in patients. Also mentioned is the definition of pharmacogenomics as a field of study that examines the effect of genes on drug therapy.

Background and Aims: A relationship between diabetes, glucose and COVID‐19 outcomes has been reported in international cohorts. This study aimed to assess the relationship between diabetes, hyperglycaemia and patient outcomes in those hospitalised with COVID‐19 during the first year of the Victorian pandemic prior to novel variants and vaccinations. Design, setting: Retrospective cohort study from March to November 2020 across five public health services in Melbourne, Australia. Participants: All consecutive adult patients admitted to acute wards of participating institutions during the study period with a diagnosis of COVID‐19, comprising a large proportion of patients from residential care facilities and following dexamethasone becoming standard‐of‐care. Admissions in patients without known diabetes and without inpatient glucose testing were excluded. Results: The DINGO COVID‐19 cohort comprised 840 admissions. In 438 admissions (52%), there was no known diabetes or in‐hospital hyperglycaemia, in 298 (35%) patients had known diabetes, and in 104 (12%) patients had hyperglycaemia without known diabetes. ICU admission was more common in those with diabetes (20%) and hyperglycaemia without diabetes (49%) than those with neither (11%, P < 0.001 for all comparisons). Mortality was higher in those with diabetes (24%) than those without diabetes or hyperglycaemia (16%, P = 0.02) but no difference between those with in‐hospital hyperglycaemia and either of the other groups. On multivariable analysis, hyperglycaemia was associated with increased ICU admission (adjusted odds ratio (aOR) 6.7, 95% confidence interval (95% CI) 4.0–12, P < 0.001) and longer length of stay (aOR 173, 95% CI 11–2793, P < 0.001), while diabetes was associated with reduced ICU admission (aOR 0.55, 95% CI 0.33–0.94, P = 0.03). Neither diabetes nor hyperglycaemia was independently associated with in‐hospital mortality. Conclusions: During the first year of the COVID‐19 pandemic, in‐hospital hyperglycaemia and known diabetes were not associated with in‐hospital mortality, contrasting with published international experiences. This likely mainly relates to hyperglycaemia indicating receipt of mortality‐reducing dexamethasone therapy. These differences in published experiences underscore the importance of understanding population and clinical treatment factors affecting glycaemia and COVID‐19 morbidity within both local and global contexts. [ABSTRACT FROM AUTHOR]