Blood pressure elevations in hospital.

Long-term hypertension control in the community significantly reduces cardiovascular risk. However, the benefit of controlling acute elevations of blood pressure in hospitalised patients is unclear. In-hospital elevations of blood pressure are relatively common and might not reflect poorly controlled blood pressure before admission. The measurement of blood pressure in hospital patients significantly differs from the best practice recommended for primary care and outpatients. Recent observational studies suggest that the pharmacological treatment of acute, asymptomatic, in-hospital elevations of blood pressure may have no benefit. However, it may increase the risk of in-hospital and post-discharge complications. Pending the development of robust inpatient measurement protocols, acute blood pressure elevations in hospitalised patients should not routinely require antihypertensive treatment in the absence of symptoms or acute end-organ damage. Rather, such elevations should facilitate follow-up of blood pressure and other cardiovascular risk factors after discharge.

Marfan syndrome resulting from a rare pathogenic FBN1 variant, ascertained through a proband with IgG4-related arteriopathy.

A 57-year-old man with a family history of aortic aneurysm was found, during assessment of unexplained fever, to have an infrarenal aortic aneurysm requiring immediate repair. Dilatation of popliteal and iliac arteries was also present. Progressive aortic root dilatation with aortic regurgitation was documented from 70 years leading to valve-sparing aortic root replacement at 77 years, at which time genetic studies identified a likely pathogenic FBN1 missense variant c.6916C > T (p.Arg2306Cys) in exon 56. The proband's lenses were normally positioned and the Marfan syndrome (MFS) systemic score was 0/20. Cascade genetic testing identified 15 other family members with the FBN1 variant, several of whom had unsuspected aortic root dilatation; none had ectopia lentis or MFS systemic score ≥ 7. Segregation analysis resulted in reclassification of the FBN1 variant as pathogenic. The combination of thoracic aortic aneurysm and dissection (TAAD) and a pathogenic FBN1 variant in multiple family members allowed a diagnosis of MFS using the revised Ghent criteria. At 82 years, the proband's presenting abdominal aortic aneurysm was diagnosed retrospectively to have resulted from IgG4-related inflammatory aortopathy.

Olmesartan-associated duodenal villous atrophy, an emerging clinical issue.

Duodenal villous atrophy with olmesartan was described in 2012, 10 years following registration of olmesartan. Clinical features are severe watery diarrhoea, usually occurring in association with weight loss. Onset is delayed, with a mean duration of prior exposure to olmesartan of 3 years. Diagnosis may be delayed. Symptoms resolve over weeks following cessation of olmesartan. Epidemiological studies suggest increased risk with olmesartan, rather than a class effect of all angiotensin receptor blockers. Post-marketing surveillance for drug safety remains important.

High and variable population prevalence of HLA-B*56:02 in indigenous Australians and relation to phenytoin-associated drug reaction with eosinophilia and systemic symptoms.

Phenytoin drug reaction with eosinophilia and systemic symptoms (DRESS) in 3 Aboriginal Australians positive for HLA-B*56:02 has been previously reported. We report the allele frequency of HLA-B*56:02 in 2 South Australian populations, 1 Aboriginal (4.8%, 95% confidence interval 2.4-7.8%) and the other European (0%). We compared the frequency with publicly available information on HLA-B*56:02 status in other Indigenous Australian (n = 4) and European Australian cohorts (n = 1). In the Indigenous Australian cohorts, HLA-B*56:02 allele frequency ranged from 1.3 to 19%. We also describe an additional case of phenytoin DRESS (RegiSCAR DRESS score 7) in an Aboriginal Australian that was associated with HLA-B*56:02 and with CYP2C9*1/*3 genotype. In Aboriginal Australians, phenytoin DRESS appears distinctly linked to HLA-B*56:02 with an allele carriage rate substantially higher than in Europeans, but also with considerable regional variation. Investigations of human leucocyte antigen and other contributing genes and severe adverse drug reactions in understudied non-European populations are required to optimize safe medication use and inform risk mitigation strategies.

Why maximum tolerated dose?

A long-established approach to the pharmacological treatment of disease has been to start low and go slow. However, clinicians often prescribe up to maximum tolerated dose (MTD), especially when treating acute and more severe disease, without evidence to show that MTD is more likely to improve outcomes. Cardiovascular guidelines for some indications advocate MTD even in prevention, for example hypercholesterolaemia, without compelling evidence of better outcomes. This review explores the origins and potential problems of prescribing medications at MTD. Oral effective dose 50 (ED50) may be a useful guide for balancing efficacy and safety.

Review article: Environmental heatstroke and long-term clinical neurological outcomes: A literature review of case reports and case series 2000-2016.

Global temperatures are rising; extreme environmental heat can result in adverse health effects including heatstroke. Acute effects of heat are well recognised, but there is less understanding of potential long-term adverse outcomes. Our aim was to review recent medical literature for clinical cases of environmental heatstroke with a focus on neurological outcome. Structured search strategies were designed to retrieve publications of heatstroke case reports using Ovid Medline and Embase (2000-2016). One thousand and forty-nine abstracts were identified, and after application of exclusion criteria 71 articles deemed relevant. Ninety cases were identified from 71 articles. 100% presented with acute neurological symptoms; 87.8% presented with non-neurological symptoms. 44.4% patients recovered fully, 23.3% died, 23.3% suffered convalescent or long-term neurological sequelae, and in 8.9% no long-term follow up was available. 57.1% of the patients who died or had a neurological deficit had no documented co-morbidity. Patterns of neurological deficits included 66.7% patients with motor dysfunction, 9.5% cognitive impairment, 19% both motor and cognitive impairment and 4.7% other. In total 71.4% of the impaired patients had long-term cerebellar dysfunction. Adverse long-term neurological outcomes were common in surviving patients presenting with environmental heatstroke. Permanent neurological deficits were present in 34.4% of survivors where outcome was known; many were young, healthy individuals. Cerebellar injury was common suggesting cerebellar structures are vulnerable to heat. These findings highlight that people of all ages and pre-morbid states are at risk of severe heat-related illness. In the face of climate change, effective interventions for heat-related illness, including both treatment and prevention are necessary.

Association of Statin Exposure With Histologically Confirmed Idiopathic Inflammatory Myositis in an Australian Population.

Importance: Statin medications are widely prescribed for cardiovascular risk reduction. Myalgia and rhabdomyolysis are well-recognized adverse effects of statins, and they resolve with the cessation of statin therapy. Idiopathic inflammatory myositis (IIM) is a heterogeneous group of autoimmune myopathies that may also be associated with statin use. Recently, statin-associated autoimmune myopathy has been recognized as a distinct entity with the presence of specific autoantibodies against hydroxymethylglutaryl-coenzyme A reductase, which results in a necrotizing myositis that does not resolve with cessation of statin therapy and requires treatment with immunosuppressive agents. Objective: To examine the association between histologically confirmed IIM and current exposure to statin medications. Design, Setting, and Participants: Population-based case-control study using the South Australian Myositis Database of all histologically confirmed cases of IIM diagnosed between 1990 and 2014 in patients 40 years or older (n = 221) and population-based controls from the North West Adelaide Health Study (n = 662), matched by age and sex in a 3:1 ratio of controls to cases. Data analysis using conditional logistic regression was performed from June 1, 2016, to July 14, 2017. Exposures: Current statin medication use. Main Outcomes and Measures: Unadjusted and adjusted (for diabetes and cardiovascular disease) odds ratios and 95% CIs for likelihood of inflammatory myositis. Results: A total of 221 IIM cases met the inclusion criteria with a mean (SD) age of 62.2 (10.8) years, and 132 (59.7%) were female. Statin exposure at the time of IIM diagnosis was 68 of 221 patients (30.8%) and 142 of 662 matched controls (21.5%) (P = .005). There was an almost 2-fold increased likelihood of statin exposure in patients with IIM compared with controls (adjusted odds ratio, 1.79; 95% CI, 1.23-2.60; P = .001). Similar results were observed when patients with necrotizing myositis were excluded from the analysis (adjusted odds ratio, 1.92; 95% CI, 1.29-2.86; P = .001). Conclusions and Relevance: In this large population-based study, statin exposure was significantly associated with histologically confirmed IIM. Given the increased use of statins worldwide and the severity of IIM, increased awareness and recognition of this potentially rare adverse effect of statin exposure is needed.

Great big meta-analysis of everything: follow-up complete and known, the ultimate paean.

Historically, selected patients or populations have been at the centre of meta-analysis, with consideration of a particular patient, or population group as central to defining the question addressed. More recently, meta-analysis with studies included based on the intervention provided have been published. This paper explores the implications of extending this methodology beyond selected interventions for limited periods of time.

Guideline for the diagnosis and management of hypertension in adults - 2016.

The National Heart Foundation of Australia has updated the Guide to management of hypertension 2008: assessing and managing raised blood pressure in adults (updated December 2010). Main recommendations For patients at low absolute cardiovascular disease risk with persistent blood pressure (BP) ≥ 160/100 mmHg, start antihypertensive therapy. The decision to treat at lower BP levels should consider absolute cardiovascular disease risk and/or evidence of end-organ damage, together with accurate BP assessment. For patients at moderate absolute cardiovascular disease risk with persistent systolic BP ≥ 140 mmHg and/or diastolic BP ≥ 90 mmHg, start antihypertensive therapy. Treat patients with uncomplicated hypertension to a target BP of < 140/90 mmHg or lower if tolerated. Changes in management as a result of the guideline Ambulatory and/or home BP monitoring should be offered if clinic BP is ≥ 140/90 mmHg, as out-of-clinic BP is a stronger predictor of outcome. In selected high cardiovascular risk populations, aiming for a target of < 120 mmHg systolic can improve cardiovascular outcomes. If targeting < 120 mmHg, close follow-up is recommended to identify treatment-related adverse effects including hypotension, syncope, electrolyte abnormalities and acute kidney injury. Why the changes have been made A 2015 meta-analysis of patients with uncomplicated mild hypertension (systolic BP range, 140-169 mmHg) demonstrated that BP-lowering therapy is beneficial (reduced stroke, cardiovascular death and all-cause mortality). A 2015 trial comparing lower with higher blood pressure targets in selected high cardiovascular risk populations found improved cardiovascular outcomes and reduced mortality, with an increase in some treatment-related adverse events.