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.

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.

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.

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.

Multicentre audit of ACE-inhibitor associated angioedema (MAAAA).

BACKGROUND: Angiotensin-converting enzyme (ACE) inhibitors are a commonly used class of medications that are generally well tolerated. However, angioedema, a rare but potentially life-threatening adverse effect, may occur. METHODS: A retrospective audit was performed on patients who presented with angioedema to two emergency departments in Adelaide, Australia. Case notes of patients presenting with angioedema who were using an ACE inhibitor were reviewed. This study examined the clinical features of presentation, treatment and outcomes of the patients. RESULTS: A total of 164 patients were identified as having angioedema across the two emergency departments. Fifty-one (31%; 95% CI = 24-39) were found to be on an ACE inhibitor. The two main presenting symptoms were soft tissue swelling in the head and neck (98%), and respiratory distress (33%), both of which usually developed after several hours. Patients were commonly treated with steroids (70%), antihistamines (65%) and adrenaline (35%). Two patients developed airway obstruction. DISCUSSION: A substantial proportion of emergency department encounters with angioedema in South Australia are from patients who also use an ACE inhibitor. It is important that general practitioners are aware of this problem, to enable rapid recognition and appropriate patient education when prescribing these medications.

Lump in the throat - a case study.

Jack, aged 66 years, presented to his general practitioner with a foreign body sensation in his throat and altered voice, which developed over 30 minutes. He was otherwise well, having no other new symptoms or recent alterations to medication. He had not eaten anything unusual. He had hypertension, type 2 diabetes, stable ischaemic heart disease, urolithiasis and benign prostatic hypertrophy. His regular medication was metformin, rosuvastatin, carvedilol, candesartan (last 5 years) and saxagliptin (last 6 months). He had no allergies but was intolerant of ramipril due to cough. There was no family history of note. On examination he had no itch or rash, or swelling of the tongue, lips, cheek or neck. However, there was oedema of the soft palate and uvula. He was maintaining his airway, saturating at 98%, and his chest was clear. He was afebrile and systemically well.

NPS MedicineWise application in supporting medication adherence in chronic heart failure: an acceptability and feasibility pilot study.

Introduction: Heart failure (HF) is an increasing global concern. Despite evidence-based pharmacotherapy, associated morbidity and mortality remain high. This study aimed to assess the acceptability, feasibility, and value of the NPS MedicineWise dose reminder app in a tiered, pharmacist-led intervention to address medication non-adherence in patients with HF. Methods: This prospective, single-blinded, randomised controlled trial recruited 55 patients with HF between September 2019 and October 2020. Participants were randomly assigned to either the intervention or control arms. Intervention participants used the app which prompted medication administration at each dosing interval. Control participants received standard care and remained blinded to the app throughout the study. Treatment non-adherence prompted a tiered, pharmacist-led intervention. Comparison of the Self-Efficacy for Appropriate Medication Use Scale (SEAMS) at baseline and 6-months measured the app's value in supporting medication adherence. Secondary outcome measures included self-reported medication knowledge, health-related quality of life, psychological wellbeing, and signs and symptoms of HF. Data were analysed using standard statistical tests with significance set at α 0.05. Results: Approximately half of respondents reported managing HF and medications better by using the MedicineWise app (Tier 1). Most respondents expressed satisfaction with the in-app messages (Tier 2) and pharmacists' phone calls (Tier 3). The intervention participants demonstrated a significant improvement in the SEAMS between baseline and 6-months follow-up. Discussion: It is feasible and potentially of value to use the MedicineWise app with a tiered, pharmacist-led intervention to support medication adherence in patients with HF. Our findings provide clinicians with "real-world" information on the practicality and potential value of using mobile health to support treatment adherence in patients with HF. Trial registration number: Australian New Zealand Clinical Trials Registry Clinical trial registration number: ACTRN12619000289112p (http://www.ANZCTR.org.au/ACTRN12619000289112p.aspx).

Acceptability and feasibility of the NPS MedicineWise mobile phone application in supporting medication adherence in patients with chronic heart failure: Protocol for a pilot study.

INTRODUCTION: Heart failure (HF) is an increasing global concern. Despite evidence-based pharmacotherapy, morbidity and mortality remain high in HF. Medication non-adherence is a crucial factor in optimising clinical outcomes. A growing number of smartphone applications (apps) assist management. While evidence support their use to promote treatment adherence, apps alone may not be the solution. The objective of this pilot study is to assess the acceptability and feasibility of a tiered intervention added to the NPS MedicineWise dose reminder app (MedicineWise app) in supporting medication adherence in HF. METHODS AND ANALYSIS: This prospective, single-blinded, randomised controlled trial will recruit 55 Australian patients with HF to be randomly assigned to either intervention (MedicineWise app + usual care) or control (usual care alone) arm. Control participants will remain unaware of the intervention throughout the study. At baseline, intervention participants will be instructed in the MedicineWise app. A reminder will then prompt medication administration at each dosing interval. If non-adherence is suggested from 24 hourly reports (critical medications) or 72 hours (non-critical medications), the individual/s will be escalated through a tiered, pharmacist-led intervention. The primary outcome will be the acceptability and feasibility of this approach in supporting adherence. Between-group comparison of the Self-Efficacy for Appropriate Medication Use Scale (SEAMS) at baseline, 3 and 6 months will be used to measure the app's value in supporting adherence. Secondary outcome measures include self-reported medication adherence and knowledge, health-related quality of life, psychological wellbeing, signs and symptoms of HF, and medication and HF knowledge. ETHICS AND DISSEMINATION: The protocol received ethics approval from Central Adelaide Clinical Human Research Ethics Committee (Protocol number R20190302) and University of South Australia Human Research Ethics Committee (Protocol number 202450). Findings will be disseminated through peer-reviewed journals. TRIAL REGISTRATION NUMBER: Australian New Zealand Clinical Trials Registry Clinical trial number: ACTRN12619000289112p (http://www.ANZCTR.org.au/ACTRN12619000289112p.aspx).

Risky business: a single-centre cross-sectional analysis of calculated cardiovascular risk in patients with primary aldosteronism and essential hypertension.

OBJECTIVES: Primary aldosteronism (PA), the most common endocrine cause of hypertension, is associated with a higher risk of cardiovascular disease (CVD) than blood pressure (BP)-matched essential hypertension (EH). We aimed to compare the calculated risks of CVD in patients who had hypertension with PA or EH using CVD risk calculators, hypothesising that they will fail to recognise the increased CVD risk in PA. DESIGN: Cross-sectional analysis. SETTING: An endocrine hypertension service in Victoria, Australia. PARTICIPANTS: Patients who had hypertension without CVD referred for the investigation of hypertension. OUTCOME MEASURES: Calculated 5-year or 10-year CVD risk as predicted by the National Vascular Disease Prevention Alliance (NVDPA) algorithm, Framingham Risk Score, Pooled Cohort Equations and QRISK3. RESULTS: Those with PA (n=128) and EH (n=133), did not differ significantly in their calculated CVD risks with the NVDPA algorithm (moderate-to-high 5-year risk 36/100 vs 45/99, p=0.17); the Framingham Risk Score (median 10-year risk 7.72% (4.43%-12.95%) vs 6.84% (3.85%-10.50%), p=0.14); the Pooled Cohort Equations (median 10-year risk 9.45% (4.36%-15.37%) vs 7.90% (2.09%-14.73%), p=0.07); and QRISK3 (median 10-year risk 11.31% (7.22%-20.29%) vs 12.47% (5.10%-19.93%), p=0.51). Similarities persisted on regression analyses accounting for systolic BP. CONCLUSIONS: CVD risk algorithms do not reflect the increased risk of CVD in patients with PA, and likely underestimate the true risk of CVD among those with PA. Screening for PA, in addition to using the CVD risk algorithm in patients who had hypertension, may facilitate the targeted treatment of PA and minimisation of cardiovascular risk in affected individuals.