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

Validity of oral mucosal transudate specimens for HIV testing using enzyme-linked immunosorbent assay in children in Chimanimani district, Zimbabwe

Objective. To assess the validity of oral mucosal transudate (OMT) specimens for HIV testing in children using enzyme-linked immunosorbent assay (ELISA). Methods. A cross-sectional descriptive study was conducted as part of a community-based behavioural and HIV sero-status survey of adults and children in the Chimanimani district of Zimbabwe. Dried blood spot (DBS) and OMT samples were collected from children aged between 2 and 14 years, inclusive. Both samples were tested for HIV using the Vironostika Uniform II plus O kits. The main study outcomes were the sensitivity and specificity of OMT samples, with DBS as the gold-standard specimen. Results. Paired DBS and OMT specimens were available from 1 274 (94.4%) of the 1 350 children enrolled. Using the DBS, HIV prevalence was 3.2%. Overall sensitivity of OMT was 48.8% (95% confidence interval (CI) 33.3 - 64.5), and specificity was 98.5% (95% CI 97.7 - 99.1). Conclusion. The overall sensitivity of OMT specimens for HIV testing in children using ELISA was low. Stratifying the analysis by sector showed that OMT samples are good specimens for HIV testing. It is important to note that factors such as the low HIV prevalence in our study population, quality of the OMT, diet and oral hygiene could have influenced the results

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

Response to letter to the editor by Nicholas S. Kelley, Michael T. Osterholm, and Edward A. Belongia, M.D.

[No abstract available

Financing future fertility: Women\u27s views on funding egg freezing

Like other assisted reproductive technology (ART) procedures, the cost of egg freezing (EF) is significant, presenting a potential barrier to access. Given recent technological advancements and rising demand for EF, it is timely to reassess how EF is funded. An online cross-sectional survey was conducted in Victoria, Australia and was completed by 656 female individuals. Participants were asked their views on funding for both medical and non-medical EF. The median age of participants was 28 years (interquartile range 23–37 years) and most participants were employed (44% full-time, 28% part-time, 33% students). There was very high support for public funding for medical EF (n = 574, 87%), with 302 (46%) participants indicating support for the complete funding of medical EF through the public system. Views about funding for non-medical EF were more divided; 43 (6%) participants supported full public funding, 235 (36%) supported partial public funding, 150 (23%) supported coverage through private health insurance, and 204 (31%) indicated that non-medical EF should be self-funded. If faced with the decision of what to do with surplus eggs, a high proportion of participants indicated that they would consider donation (71% to research, 59% to a known recipient, 52% to a donor programme), indicating that eggs surplus to requirements could be a potential source of donor eggs. This study provides insights that could inform policy review, and suggests revisiting whether the medical/non-medical distinction is a fair criterion to allocate funding to ART

Cancer incidence, mortality, and blood lead levels among workers exposed to inorganic lead

PurposeWe aimed to measure mortality and cancer incidence in a cohort of lead-exposed workers by using blood lead levels to assess exposure.MethodsThe 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).ResultsThere 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.ConclusionsOverall 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.StellaMay Gwini, Ewan MacFarlane, Anthony Del Monaco, Dave McLean, Dino Pisaniello, Geza Paul Benke and Malcolm Ross Si

Cancer incidence, mortality, and blood lead levels among workers exposed to inorganic lead

PurposeWe aimed to measure mortality and cancer incidence in a cohort of lead-exposed workers by using blood lead levels to assess exposure.MethodsThe 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).ResultsThere 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.ConclusionsOverall 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.StellaMay Gwini, Ewan MacFarlane, Anthony Del Monaco, Dave McLean, Dino Pisaniello, Geza Paul Benke and Malcolm Ross Si