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.Pravik Solanki, Stella May Gwini, Renata Libianto, Genevieve Gabb, Jimmy Shen, Morag J Young, Peter J Fuller, Jun Yan

Efficacy of melatonin with behavioural sleep-wake scheduling for delayed sleep-wake phase disorder: a double-blind, randomised clinical trial

Background: Delayed Sleep-Wake Phase Disorder (DSWPD) is characterised by sleep initiation insomnia when attempting sleep at conventional times and difficulty waking at the required time for daytime commitments. Although there are published therapeutic guidelines for the administration of melatonin for DSWPD, to our knowledge, randomised controlled trials are lacking. This trial tested the efficacy of 0.5 mg melatonin, combined with behavioural sleep-wake scheduling, for improving sleep initiation in clinically diagnosed DSWPD patients with a delayed endogenous melatonin rhythm relative to patient-desired (or -required) bedtime (DBT). Methods: This randomised, placebo-controlled, double-blind clinical trial was conducted in an Australian outpatient DSWPD population. Following 1-wk baseline, clinically diagnosed DSWPD patients with delayed melatonin rhythm relative to DBT (salivary dim light melatonin onset [DLMO] after or within 30 min before DBT) were randomised to 4-wk treatment with 0.5 mg fast-release melatonin or placebo 1 h before DBT for at least 5 consecutive nights per week. All patients received behavioural sleep-wake scheduling, consisting of bedtime scheduled at DBT. The primary outcome was actigraphic sleep onset time. Secondary outcomes were sleep efficiency in the first third of time in bed (SE T1) on treatment nights, subjective sleep-related daytime impairment (Patient Reported Outcomes Measurement Information System [PROMIS]), PROMIS sleep disturbance, measures of daytime sleepiness, clinician-rated change in illness severity, and DLMO time. Findings: Between September 13, 2012 and September 1, 2014, 307 participants were registered; 116 were randomised to treatment (intention-to-treat n = 116; n = 62 males; mean age, 29.0 y). Relative to baseline and compared to placebo, sleep onset occurred 34 min earlier (95% confidence interval [CI] −60 to −8) in the melatonin group. SE T1 increased; PROMIS sleep-related impairment, PROMIS sleep disturbance, insomnia severity, and functional disability decreased; and a greater proportion of patients showed more than minimal clinician-rated improvement following melatonin treatment (52.8%) compared to placebo (24.0%) (P < 0.05). The groups did not differ in the number of nights treatment was taken per protocol. Post-treatment DLMO assessed in a subset of patients (n = 43) was not significantly different between groups. Adverse events included light-headedness, daytime sleepiness, and decreased libido, although rates were similar between treatment groups. The clinical benefits or safety of melatonin with long-term treatment were not assessed, and it remains unknown whether the same treatment regime would benefit patients experiencing DSWPD sleep symptomology without a delay in the endogenous melatonin rhythm. Conclusions: In this study, melatonin treatment 1 h prior to DBT combined with behavioural sleep-wake scheduling was efficacious for improving objective and subjective measures of sleep disturbances and sleep-related impairments in DSWPD patients with delayed circadian phase relative to DBT. Improvements were achieved largely through the sleep-promoting effects of melatonin, combined with behavioural sleep-wake scheduling.Tracey L. Sletten, Michelle Magee, Jade M. Murray, Christopher J. Gordon, Nicole Lovato, David J. Kennaway, Stella M. Gwini, Delwyn J. Bartlett, Steven W. Lockley, Leon C. Lack, Ronald R. Grunstein, Shantha M.W. Rajaratnam, for the Delayed Sleep on Melatonin (DelSoM) Study Grou

May Measurement Month 2018: a pragmatic global screening campaign to raise awareness of blood pressure by the International Society of Hypertension

Aims Raised blood pressure (BP) is the biggest contributor to mortality and disease burden worldwide and fewer than half of those with hypertension are aware of it. May Measurement Month (MMM) is a global campaign set up in 2017, to raise awareness of high BP and as a pragmatic solution to a lack of formal screening worldwide. The 2018 campaign was expanded, aiming to include more participants and countries. Methods and results Eighty-nine countries participated in MMM 2018. Volunteers (≥18 years) were recruited through opportunistic sampling at a variety of screening sites. Each participant had three BP measurements and completed a questionnaire on demographic, lifestyle, and environmental factors. Hypertension was defined as a systolic BP ≥140 mmHg or diastolic BP ≥90 mmHg, or taking antihypertensive medication. In total, 74.9% of screenees provided three BP readings. Multiple imputation using chained equations was used to impute missing readings. 1 504 963 individuals (mean age 45.3 years; 52.4% female) were screened. After multiple imputation, 502 079 (33.4%) individuals had hypertension, of whom 59.5% were aware of their diagnosis and 55.3% were taking antihypertensive medication. Of those on medication, 60.0% were controlled and of all hypertensives, 33.2% were controlled. We detected 224 285 individuals with untreated hypertension and 111 214 individuals with inadequately treated (systolic BP ≥ 140 mmHg or diastolic BP ≥ 90 mmHg) hypertension. Conclusion May Measurement Month expanded significantly compared with 2017, including more participants in more countries. The campaign identified over 335 000 adults with untreated or inadequately treated hypertension. In the absence of systematic screening programmes, MMM was effective at raising awareness at least among these individuals at risk

Do health service staff support the implementation of voluntary assisted dying at their workplace?

Background: On 29 November 2017, the Victorian Parliament passed the Voluntary Assisted Dying (VAD) Act 2017, which came into effect on 19 June 2019. Aims: To investigate whether staff from a large regional health service support the legalisation of VAD and the implementation of VAD at their workplace. Methods: Staff were invited to complete an anonymous online survey comprising both closed- and open-ended questions. Results: Thirty-eight percent of the workforce (n = 1624) responded to the survey. Most participants supported the legalisation of VAD (88%), the provision of eligibility assessment and/or the administration of VAD within the health service (80%). There were negligible differences in support for VAD by role; however, specialist doctors were significantly less supportive (65%). Approximately half of the respondents expressed concern about monitoring (49%) or implementation (53%) of VAD. Concerns were also raised about assessment of eligibility, support for staff involved in VAD and pressure on both patients and staff to participate. Nearly three-quarters (71%) of participants agreed that if the health service offers VAD services, a special unit or facility should be available. Conclusions: This study found that health workers have concerns about the implementation of VAD at their workplace but are generally supportive. This article provides information for health services considering the implementation of VAD, about staff concerns and issues that need to be addressed for the successful introduction of VAD

Comparison of ambulatory blood pressure between patients with primary aldosteronism and other forms of hypertension

OBJECTIVE: Primary aldosteronism (PA) is a potentially curable cause of hypertension associated with worse cardiovascular prognosis than blood pressure-matched essential hypertension (EH). Effective targeted treatment for PA is available with the greatest benefit seen if treatment is started early, prior to the development of end-organ damage. However, PA is currently substantially under-diagnosed. The standard screening test for PA, the aldosterone-to-renin ratio (ARR), is performed infrequently in both primary and tertiary care. In contrast, ambulatory blood pressure monitoring (ABPM) is frequently utilized in the assessment of hypertension. The aim of this study was to compare ABPM parameters in hypertensive patients with and without PA, in order to identify features of ABPM associated with PA that can prompt screening. STUDY DESIGN: Patients with PA (n = 55) were identified from a tertiary clinic specializing in the management of endocrine causes of hypertension whilst the controls (n = 389) were consecutive patients with hypertension but without a known diagnosis of PA who were referred for ABPM. RESULTS: In this study, PA patients were younger and had higher 24-h, day, and night-time blood pressure compared with controls despite similar number of antihypertensive medications. However, there was no significant difference in nocturnal dipping or day-night blood pressure variability between the two groups. CONCLUSIONS: An elevated ambulatory blood pressure in patients on multiple antihypertensives could suggest underlying PA but in the absence of other distinguishing features, ABPM could not reliably differentiate PA from other forms of hypertension. Routine biochemical screening for PA remained the most reliable way of detecting this treatable secondary cause of hypertension

Psychometric properties of the Perceived Stress Scale (PSS-10) in silica-exposed workers from diverse cultural and linguistic backgrounds

Abstract Background The Perceived Stress Scale (PSS-10) has been used in a range of occupational cohorts, but only recently in stone benchtop workers undergoing screening for silicosis. The aim of this study was to compare psychometric properties of the PSS-10 in stone benchtop workers amongst those born overseas or who used an interpreter. Methods Stone benchtop workers in Melbourne, Australia completed the PSS-10 as part of their occupational screening for silicosis. Internal consistency was assessed with Cronbach’s α for the total score and the positive and negative subscales. Validity was assessed using confirmatory factor analysis (CFA). Analysis was performed for the total group and for subgroups according to sex, interpreter use, overseas-born, and language spoken at home. Results The results of 682 workers with complete PSS-10 scores were included in analysis. Most participants were male (93%), with mean age 36.9 years (SD 11.4), with just over half (51.6%) born in Australia, 10.1% using an interpreter, and 17.5% using a language other than English at home. Cronbach’s α for the overall group (α = 0.878) suggested good internal consistency. Discussion CFA analysis for validity testing suggested PSS-10 performance was good for both sexes, moderate for country of birth and language spoken at home categories, but poorer for those who used an interpreter. Whilst professional interpreters provide a range of benefits in the clinical setting, the use of translated and validated instruments are important, particularly in cohorts with large numbers of migrant workers. Conclusion This study describes the psychometric properties of the PSS-10 in a population of stone benchtop workers, with good internal consistency, and mixed performance from validity testing across various subgroups

Cancer Incidence, Mortality, and Blood Lead Levels Among Workers Exposed to Inorganic Lead

Purpose: We aimed to measure mortality and cancer incidence in a cohort of lead-exposed workers by using blood lead levels to assess exposure. Methods: The cohort comprised male lead workers. Subjects were matched to cancer and death registries. Observed death and cancer incidence rates were compared with population rates to obtain standardized mortality ratios (SMR) and standardized incidence ratios (SIR). Results: There were 4114 male subjects with average follow-up time of 16.2 years, and 406 deaths were observed. There were significant results for overall death (SMR, 111; 95% confidence interval [95% CI], 101-123), digestive system deaths (SMR, 167; 95% CI, 110-250), and deaths from external causes (SMR, 135; 95% CI, 105-174). A total of 228 subjects had cancer, with an overall SIR of 83 (95% CI, 73-95); liver cancer SIR of 217 (95% CI, 103-454) and esophageal cancer SIR of 240 (95% CI, 129-447). The latter was seven-fold greater (SIR 755; 95% CI, 314-1813) among those with a blood lead level result above 30 μg/dL compared with population rates. No other increases in cancers were observed. Conclusions: Overall mortality was elevated. Although incidence rates of overall cancer were low, further studies and analysis are required to investigate any biologically plausible associations between inorganic lead and liver or esophageal cancer. © 2012 Elsevier Inc

Ga-68-PSMA-PET screening and transponder-guided salvage radiotherapy to the prostate bed alone for biochemical recurrence following prostatectomy: interim outcomes of a phase II trial

PURPOSE: To evaluate outcomes for men with biochemically recurrent prostate cancer who were selected for transponder-guided salvage radiotherapy (SRT) to the prostate bed alone by 68Ga-labelled prostate-specific membrane antigen positron emission tomography (68Ga-PSMA-PET). METHODS: This is a single-arm, prospective study of men with a prostate-specific antigen (PSA) level rising to 0.1-2.5 ng/mL following radical prostatectomy. Patients were staged with 68Ga-PSMA-PET and those with a negative finding, or a positive finding localised to the prostate bed, continued to SRT only to the prostate bed alone with real-time target-tracking using electromagnetic transponders. The primary endpoint was freedom from biochemical relapse (FFBR, PSA > 0.2 ng/mL from the post-radiotherapy nadir). Secondary endpoints were time to biochemical relapse, toxicity and patient-reported quality of life (QoL). RESULTS: Ninety-two patients (median PSA of 0.18 ng/ml, IQR 0.12-0.36), were screened with 68Ga-PSMA-PET and metastatic disease was found in 20 (21.7%) patients. Sixty-nine of 72 non-metastatic patients elected to proceed with SRT. At the interim (3-year) analysis, 32 (46.4%) patients (95% CI 34.3-58.8%) were FFBR. The median time to biochemical relapse was 16.1 months. The rate of FFBR was 82.4% for ISUP grade-group 2 patients. Rates of grade 2 or higher gastrointestinal and genitourinary toxicity were 0% and 15.2%, respectively. General health and disease-specific QoL remained stable. CONCLUSION: Pre-SRT 68Ga-PSMA-PET scans detect metastatic disease in a proportion of patients at low PSA levels but fail to improve FFBR. Transponder-guided SRT to the prostate bed alone is associated with a favourable toxicity profile and preserved QoL. TRIAL REGISTRATION NUMBER: ACTRN12615001183572, 03/11/2015, retrospectively registered