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The key aim of diabetes management is to prevent complications, which are a major cause of morbidity and mortality. At an individual level, people with diabetes are less likely than they were several decades ago to experience classical macrovascular and microvascular complications as a result of improvements in modifiable cardiovascular risk factors and preventive healthcare. However, a significant burden of diabetes complications persists at a population level because of the increasing incidence of diabetes, as well as longer lifetime exposure to diabetes because of younger diagnosis and increased life expectancy. Trials have shown that the most effective strategy for preventing complications of diabetes is a multifactorial approach focussing simultaneously on the management of diet, exercise, glucose levels, blood pressure and lipids. In addition to the cornerstone strategies of addressing diet, exercise and lifestyle measures, the introduction of newer glucose-lowering agents, including sodium-glucose transport protein 2 inhibitors and glucagon-like peptide-1 agonists, have brought about a paradigm shift in preventing the onset and progression of complications of type 2 diabetes, particularly cardiovascular and renal disease. The improvement in rates of classical complications of diabetes over time has been accompanied by a growing awareness of non-traditional complications, including non-alcoholic fatty liver disease. These emerging complications may not respond to a glycaemic-centred approach alone and highlight the importance of foundational strategies centred on lifestyle measures and supported by pharmaceutical therapy to achieve weight loss and reduce metabolic risk in patients living with diabetes., (© 2024 Royal Australasian College of Physicians.)

Background: Patients with advanced cancer who misunderstand their prognosis and chance of cure tend to overestimate the likely benefits of palliative systemic therapy., Aim: To determine patient perceptions of palliative systemic therapy benefits in advanced cancer., Methods: We surveyed 104 outpatients with advanced cancer receiving systemic anticancer therapy and their treating oncologists. Patients recorded their understanding of treatment impact on chance of cure and symptoms. Life expectancy was estimated by patients and oncologists. A visual analogue scale (0-10) was used to record how patients and oncologists valued quality of life (QOL) and length of life (LOL) (<4 QOL most important; 4-7 QOL and LOL equal; >7 LOL most important). Patient-oncologist discordance was defined as a ≥4-point difference., Results: The main reasons patients selected for receiving treatment were to live longer (54%) and cure their cancer (36%). Most patients reported treatment was very/somewhat likely to prolong life (84%) and improve symptoms (76%), whereas 20% reported treatment was very/somewhat likely to cure their cancer. 42% of patients selected a timeframe for life expectancy (choice of four timeframes between <1 year and ≥5 years); of these, 62% selected a longer timeframe than their oncologist. When making treatment decisions, 71% of patients (52% of oncologists) valued QOL and LOL equally. Patient-oncologist discordance was 21%, mostly because of oncologists valuing QOL more than their patients (70%)., Conclusion: At least 20% of patients receiving systemic therapy for advanced cancer reported an expectation of cure. Most patients and oncologists value QOL and LOL equally when making treatment decisions., (© 2024 The Authors. Internal Medicine Journal published by John Wiley & Sons Australia, Ltd on behalf of Royal Australasian College of Physicians.)

Background: The standard of care in newly diagnosed metastatic non-small cell lung cancer (NSCLC) is to test for aberrations in three genes for driver mutations - ALK, ROS1 and epidermal growth factor receptor (EGFR) - and also for immunohistochemistry to be performed for programmed death-ligand 1 expression level. Next-generation sequencing (NGS), with or without RNA fusion testing, is increasingly used in standard clinical practice to identify patients with potentially actionable mutations. Stratification of NGS mutation tiers is currently based on the European Society of Medical Oncology Scale for Clinical Actionability of Molecular Targets (ESCAT) Tiers I-V and X., Aim: Our aim was to analyse NSCLC tumour samples for the prevalence of Tiers I-V mutations to establish guidance for current and novel treatments in patients with metastatic disease., Methods: NGS was performed employing the Oncomine Precision Assay (without RNA fusion testing) that interrogates DNA hotspot variants across 45 genes to screen 210 NSCLC tissue samples obtained across six Sydney hospitals between June 2021 and March 2022., Results: In our cohort, 161 of 210 (77%) had at least one gene mutation identified, with 41 of 210 (20%) having two or more concurrent mutations. Tier I mutations included 42 of 210 (20%) EGFR mutations (EIA) and five of 210 (3%) MET exon 14 skipping mutations (EIB). Non-Tier I variants included 22 of 210 (11%) KRAS G12C hotspot mutations (EIIB), with a further 47 of 210 (22%) having non-G12C KRAS (EX) mutations. NGS testing revealed an additional 15% of cases with Tier II ESCAT mutations in NSCLC. Forty-six percent of patients also demonstrated potential Tier III and IV mutations that are currently under investigation in early-phase clinical trials., Conclusions: In addition to identifying patients with genomic alterations suitable for clinically proven standard-of-care therapeutic options, the 45-gene NGS panel has significant potential in identifying potentially actionable non-Tier 1 mutations that may become future standard clinical practice in NSCLC., (© 2023 Royal Australasian College of Physicians.)

Background: Heart failure is a major burden in Australia in terms of morbidity, mortality and healthcare expenditure. Multiple evidence-based therapies are recommended for heart failure with reduced ejection fraction (HFrEF), but data on physician adherence to therapy guidelines are limited., Aim: To compare use of HFrEF therapies against current evidence-based guidelines in an Australian hospital inpatient population., Methods: A retrospective review of patients admitted with a principal diagnosis of HFrEF across six metropolitan hospitals in Sydney, Australia, between January 2015 and June 2016. Use of medical and device therapies was compared with guideline recommendations using individual patient indications/contraindications. Readmission and mortality data were collected for a 1-year period following the admission., Results: Of the 1028 HFrEF patients identified, 39 were being managed with palliative intent, leaving 989 patients for the primary analysis. Use of beta-blockers (87.7% actual use/93.6% recommended use) and diuretics (88.4%/99.3%) was high among eligible patients. There were large evidence-practice gaps for angiotensin-converting enzyme inhibitors/angiotensin II receptor blockers (ACEI/ARB; 66.4%/89.0%) and aldosterone antagonists (41.0%/77.1%). In absolute terms, use of these therapies each increased by over 11% from admission. Ivabradine (11.5%/21.2%), automated internal cardiac defibrillators (29.5%/66.1%) and cardiac resynchronisation therapy (13.1%/28.7%) were used in a minority of eligible patients. Over the 1-year follow-up period, the mortality rate was 14.8%, and 44.2% of patients were readmitted to hospital at least once., Conclusion: Hospitalisation is a key mechanism for initiation of HFrEF therapies. The large evidence-practice gaps for ACEI/ARB and aldosterone antagonists represent potential avenues for improved HFrEF management., (© 2022 Royal Australasian College of Physicians.)

The incidence of pulmonary embolism (PE) in the oldest old (persons aged ≥85) is increasing, but there are limited data on its clinical features and diagnosis. We performed a retrospective cohort study of 302 consecutive patients with confirmed PE and compared the oldest old to the young (aged <65) and the younger old (aged 65-84). The most common symptoms in the oldest old were dyspnoea (74.3%) and tachypnoea (71.4%), but the prevalence of chest pain decreased with advancing age. Delayed diagnosis was most common in the oldest old and was associated with increasing age, absence of dyspnoea, presence of cardiorespiratory disease and a higher Charlson Comorbidity index. Better age-specific diagnostic pathways are required in this population., (© 2020 Royal Australasian College of Physicians.)

To share our experience of establishing an acute outreach service to nursing homes and to evaluate the impact of such service on emergency department presentations, data were drawn from a pre-existing database from 2013 to 2017. Of the 986 acute patients treated in 12 nursing homes over a 23-month period, the acute geriatric outreach service was shown to be safe, with few adverse events (one allergic reaction) and 5.3% of patients required transfer to hospital. The acute service decreased emergency department presentation of nursing home patients by 10% compared to the subacute service (incidence rate ratio = 0.90; 95% confidence interval: 0.84-0.96; P = 0.001). Cost-benefit analysis showed for every $1 spent, a saving of $5 was realised., (© 2018 Royal Australasian College of Physicians.)

Changes in serum phosphate during diabetic ketoacidosis (DKA) treatment are not well characterised, although it is known that serum phosphate falls with treatment. We sought to define the nature of these changes and whether the severity of acidosis on admission influenced the severity of subsequent hypophosphataemia. We retrospectively reviewed data on all patients with confirmed DKA presenting to our unit between 2007 and 2010 inclusive. Forty-three patients with 64 episodes of DKA were evaluated. At presentation, 62.5% of patient episodes were hyperphosphataemic. Initial serum phosphate in all patient episodes correlated significantly with the initial serum creatinine (r = 0.694, P < 0.01) and the initial blood glucose (r = 0.593, P < 0.01). Serum phosphate fell during the course of treatment in all episodes (mean absolute fall 1.28 ± 0.77 (SEM) mmol/L). The mean nadir phosphate was 0.58 ± 0.19 mmol/L. Ninety per cent of nadir phosphate levels were hypophosphataemic (<0.8 mmol/L), and 11% were severely hypophosphataemic (<0.32 mmol/L). Mean initial bicarbonate differed significantly between those with nadir phosphates <0.5 mmol/L (9.26 ± 4.55) and those with nadir phosphates >0.5 mmol/L (13.0 ± 4.59, P = 0.0031). Similar significant bicarbonate differences were noted between those with nadir phosphates less than and more than 0.32 mmol/L respectively (7.42 ± 2.44 and 12.2 ± 4.87, P < 0.01). The initial hyperphosphataemia is reflective of intravascular volume depletion and pre-renal renal impairment. The severity of subsequent hypophosphataemia can be predicted by the degree of metabolic acidosis on presentation. As profound hypophosphataemia can be associated with serious complications, clinicians should recognise the likelihood of this biochemical derangement in those DKA patients presenting with profound acidosis., (© 2012 The Authors; Internal Medicine Journal © 2012 Royal Australasian College of Physicians.)

The role of thrombolysis in pulmonary thromboembolism is controversial. We describe a case of life-threatening acute pulmonary embolism where thrombolysis was successfully administered because of extreme refractory hypoxaemia. We suggest that profound refractory hypoxaemia in this clinical setting was due to the combination of severe right ventricular dysfunction and shunting from pulmonary infarction. The shunt was not likely to have resolved in the short term, but right ventricular function and hypoxaemia improved with clot lysis. Similar clinical presentations should prompt active consideration of thrombolysis., (© 2012 The Authors. Internal Medicine Journal © 2012 Royal Australasian College of Physicians.)

We report four cases of rhabdomyolysis and severe, disabling myopathy associated with HMG CoA reductase-inhibitor therapy. Patient developed symptoms following the addition of roxithromycin to combination lipid-lowering therapy with simvastatin and gemfibrozil. Patients 2 and 3 became symptomatic after developing acute on chronic renal impairment while taking simvastatin. The muscle biopsy of patient 3 revealed a necrotizing myopathy and the presence of inclusion bodies. Patient 4 developed symptoms within 4 weeks of starting cerivastatin monotherapy. The four cases illustrate the importance of considering the potential for drug interactions and making appropriate dosage adjustments for renal insufficiency in patients receiving HMG CoA reductase therapy.