Associations of Testosterone and Related Hormones With All-Cause and Cardiovascular Mortality and Incident Cardiovascular Disease in Men : Individual Participant Data Meta-analyses.

BACKGROUND: Whether circulating sex hormones modulate mortality and cardiovascular disease (CVD) risk in aging men is controversial. PURPOSE: To clarify associations of sex hormones with these outcomes. DATA SOURCES: Systematic literature review to July 2019, with bridge searches to March 2024. STUDY SELECTION: Prospective cohort studies of community-dwelling men with sex steroids measured using mass spectrometry and at least 5 years of follow-up. DATA EXTRACTION: Independent variables were testosterone, sex hormone-binding globulin (SHBG), luteinizing hormone (LH), dihydrotestosterone (DHT), and estradiol concentrations. Primary outcomes were all-cause mortality, CVD death, and incident CVD events. Covariates included age, body mass index, marital status, alcohol consumption, smoking, physical activity, hypertension, diabetes, creatinine concentration, ratio of total to high-density lipoprotein cholesterol, and lipid medication use. DATA SYNTHESIS: Nine studies provided individual participant data (IPD) (255 830 participant-years). Eleven studies provided summary estimates (n = 24 109). Two-stage random-effects IPD meta-analyses found that men with baseline testosterone concentrations below 7.4 nmol/L (<213 ng/dL), LH concentrations above 10 IU/L, or estradiol concentrations below 5.1 pmol/L had higher all-cause mortality, and those with testosterone concentrations below 5.3 nmol/L (<153 ng/dL) had higher CVD mortality risk. Lower SHBG concentration was associated with lower all-cause mortality (median for quintile 1 [Q1] vs. Q5, 20.6 vs. 68.3 nmol/L; adjusted hazard ratio [HR], 0.85 [95% CI, 0.77 to 0.95]) and lower CVD mortality (adjusted HR, 0.81 [CI, 0.65 to 1.00]). Men with lower baseline DHT concentrations had higher risk for all-cause mortality (median for Q1 vs. Q5, 0.69 vs. 2.45 nmol/L; adjusted HR, 1.19 [CI, 1.08 to 1.30]) and CVD mortality (adjusted HR, 1.29 [CI, 1.03 to 1.61]), and risk also increased with DHT concentrations above 2.45 nmol/L. Men with DHT concentrations below 0.59 nmol/L had increased risk for incident CVD events. LIMITATIONS: Observational study design, heterogeneity among studies, and imputation of missing data. CONCLUSION: Men with low testosterone, high LH, or very low estradiol concentrations had increased all-cause mortality. SHBG concentration was positively associated and DHT concentration was nonlinearly associated with all-cause and CVD mortality. PRIMARY FUNDING SOURCE: Medical Research Future Fund, Government of Western Australia, and Lawley Pharmaceuticals. (PROSPERO: CRD42019139668).

Hydroxyurea to prevent brain injury in children with sickle cell disease (HU Prevent)-A randomized, placebo-controlled phase II feasibility/pilot study.

Central nervous system (CNS) injury is common in sickle cell disease (SCD) and occurs early in life. Hydroxyurea is safe and efficacious for treatment of SCD, but high-quality evidence from randomized trials to estimate its neuroprotective effect is scant. HU Prevent was a randomized (1:1), double-blind, phase II feasibility/pilot trial of dose-escalated hydroxyurea vs. placebo for the primary prevention of CNS injury in children with HbSS or HbS-ß0-thalassemia subtypes of SCD age 12-48 months with normal neurological examination, MRI of the brain, and cerebral blood flow velocity. We hypothesized that hydroxyurea would reduce by 50% the incidence of CNS injury. Two outcomes were compared: primary-a composite of silent cerebral infarction, elevated cerebral blood flow velocity, transient ischemic attack, or stroke; secondary-a weighted score estimating the risk of suffering the consequences of stroke (the Stroke Consequences Risk Score-SCRS), based on the same outcome events. Six participants were randomized to each group. One participant in the hydroxyurea group had a primary outcome vs. four in the placebo group (incidence rate ratio [90% CI] 0.216 [0.009, 1.66], p = .2914) (~80% reduction in the hydroxyurea group). The mean SCRS score was 0.078 (SD 0.174) in the hydroxyurea group, 0.312 (SD 0.174) in the placebo group, p = .072, below the p-value of .10 often used to justify subsequent phase III investigations. Serious adverse events related to study procedures occurred in 3/41 MRIs performed, all related to sedation. These results suggest that hydroxyurea may have profound neuroprotective effect in children with SCD and support a definitive phase III study to encourage the early use of hydroxyurea in all infants with SCD.

Asbestos exposures associated with the use and handling of drilling mud additives.

This paper summarizes historical asbestos exposure data collected during the handling of short-fiber chrysotile asbestos that was used as an additive to drilling fluid in oil and gas exploration. A total of 1171 industrial hygiene (IH) personal and area air samples were collected and analyzed from more than 20 drilling rigs between 1972 and 1985. The dataset consists of 1097 short-term samples (<240 min) with more than 80% having sample durations less than 30 min. Average airborne fiber concentrations measured during asbestos handling activities ranged from 0.62 f/cc to 3.39 f/cc using phase-contrast microscopy (PCM). An additional 14 samples were considered long-term samples (>240 min) and there were 60 samples with no reported sample duration. Eight-hour time-weighted average (8-h TWA) results, calculated using short-term samples, along with long-term samples greater than 240 min, did not exceed contemporaneous Occupational Safety and Health Administration (OSHA) permissible exposure limits (PELs). This analysis fills a data gap in the evaluation of asbestos exposures from the use of drilling mud additives (DMAs) that contained chrysotile asbestos.

Outcomes of 15 dogs and two cats with metabone fractures treated with fluoroscopically guided normograde metabone pinning.

OBJECTIVE: To report the outcomes of 15 dogs and two cats with metabone fractures treated with fluoroscopically guided normograde metabone pinning (FGNMP). STUDY DESIGN: Retrospective case series. ANIMALS: A total of 15 client owned dogs and two cats with 57 metabone fractures. METHODS: Description of FGNMP and reporting of the following data: signalment, pre- and postoperative radiographs, intramedullary pin diameter used, anesthesia, surgery and coaptation times, duration to normal weightbearing and bone union, postoperative care and complications. RESULTS: Median surgery time was 54 min (range: 26-99), median duration of coaptation was 14 days (range: 1-5 weeks), median time to normal weightbearing was 16 days (range: 2-45) and median time to bone union was 6 weeks (range: 4-12). All cases had at least 12 months of post-surgical follow-up with a median follow-up of 18 months (range: 12-70). No major complications occurred. Mild radiographic changes associated with subchondral bone sclerosis were noted on follow-up radiographs in 13/57 fractures. All cases returned to normal gait and full (15) or acceptable (2) function. CONCLUSION: In this study, FGNMP was an effective and safe technique for metabone fracture repair, requiring only short-term external coaptation in most patients. Time to bone union and return to normal function compared favorably to previously reported techniques. CLINICAL RELEVANCE: Fluoroscopically guided normograde metabone pinning provides an alternative technique for treatment of metabone fractures.

Athletic retirement: factors contributing to sleep and mental health problems.

Introduction: The aim of this investigation was to determine which factors were associated with symptoms of sleep and mental health disorders in former athletes. Methods: Former athletes (N = 173, 50% women) who retired from any competition level within the last 20 years participated in an online survey. The survey consisted of the Athlete Sleep Screening Questionnaire (ASSQ), Personal Wellbeing Index-Adult (PWI-A), Center for Epidemiologic Studies Depression Scale-Revised (CESD-R), and Generalised Anxiety Disorder Assessment (GAD-7). Results: Binary logistic regressions revealed that both age (OR = 0.95 [95% CI:0.92, 0.99], p = 0.007) and gender (OR = 2.28 [95% CI:1.09, 4.79], p = 0.029) were associated with anxiety, with women and younger ex-athletes presenting greater risk of anxiety symptoms. Higher body mass was associated with an increased risk for sleep difficulty (OR = 1.13 [95% CI:1.03, 1.23], p = 0.008), sleep disordered breathing (OR = 1.20 [95% CI:1.10, 1.30], p < 0.001), and compromised wellbeing (OR = 0.89 [95% CI:0.83, 0.96], p = 0.001). Athletes who subjectively placed a lower priority on sport while competing presented greater risk of sleep disordered breathing (OR = 2.00[95% CI:1.05, 3.80], p = 0.035). No associations between recency retirement and any outcome measures were observed. Discussion: Findings suggest potential predictive factors for difficulty transitioning out of sport. Future longitudinal research should consider the interplay between sport re-engagement and the incidence and chronicity of sleep and mental health disorders.

Plant-based and vegetarian diets are associated with reduced obstructive sleep apnoea risk.

Introduction: Obstructive sleep apnoea (OSA) and obesity commonly coexist. Weight loss and exercise are recommended management options for OSA. However, most of the current evidence on diet and OSA is focused on calorie restriction rather than diet quality. The aim of the present study was to determine the association of plant-based dietary indices (PDI) with OSA risk. Methods: Cross-sectional data from 14 210 participants of the National Health and Nutrition Examination Survey who provided dietary information using the 24-hour recall method were used. PDI - including healthy (hPDI), unhealthy (uPDI) and pro-vegetarian diet index (PVDI) - were determined. OSA risk was determined using the STOP-BANG questionnaire. Logistic regression was used to determine the relationship between dietary indices and OSA risk. Results: Higher adherence to PDI (odds ratio (OR)Q5 versus Q1=0.81; 95% confidence interval (CI): 0.66-1.00), hPDI (OR=0.83; 95% CI: 0.69-1.01) and PVDI (OR=0.84; 95% CI: 0.68-1.05) was inversely associated with OSA risk, whereas higher consumption of an unhealthy plant-based diet (OR=1.22; 95% CI: 1.00-1.49) was positively associated with OSA. Sex differences in estimates were observed for PDI in males (OR=0.71; 95% CI: 0.56-0.90) versus females (OR=0.93; 95% CI: 0.68-1.28), hPDI in males (OR=0.90; 95% CI: 0.68-1.18) versus females (OR=0.77; 95% CI: 0.54-1.09) and uPDI in males (OR=1.13; 95% CI: 0.89-1.44) versus females (OR=1.42; 95% CI: 1.03-1.97) but not for PVDI. Conclusions: Higher adherence to a healthy plant-based diet is associated with reduced OSA risk, while an unhealthy plant-based diet has a positive association. The magnitude of these associations differs by sex. Further longitudinal studies are warranted.

Use of exercise tests in screening for pulmonary arterial hypertension in systemic sclerosis: A systematic literature review.

Background and objective: Patients with systemic sclerosis (SSc) and pulmonary arterial hypertension (PAH) have a poor prognosis, accounting for 30% of all SSc-related deaths. Guidelines recommend annual screening for PAH regardless of symptoms, as early treatment improves outcomes. Current protocols include combinations of clinical features, biomarkers, pulmonary function tests, and echocardiography. None include exercise testing, although early-stage PAH may only be evident during exercise. This systematic review assessed the performance of exercise tests in predicting the presence of PAH in patients with SSc, where PAH was confirmed through right heart catheterisation (RHC). Methods: Comprehensive literature searches were performed using MEDLINE, EMBASE, Cochrane Database of Systematic Reviews and Cochrane Central Register of Controlled Trails, CINAHL, Scopus and Web of Science from inception to May 2023. Articles were screened for eligibility by two independent reviewers. Eligibility criteria included the use of a non-invasive exercise test to screen adult patients to detect PAH in a population without a previous diagnosis of PAH, with diagnosis confirmed by RHC. Results: Eight studies met the inclusion criteria, describing at least one of three different non-invasive exercise tests: cardiopulmonary exercise test, six-minute walk test and stress Doppler echocardiography. All studies found that exercise tests had some ability to predict the presence of PAH, with sensitivity between 50% and 100% and specificity from 73% to 91%. Conclusion: Exercise tests are infrequently used for screening for PAH in SSc but can predict the presence of PAH. More data are required to establish which tests are most effective.

Gout Knowledge: A Survey of Australian Outpatients with Gout.

Background: The prevalence of gout has increased in the Western societies due to ageing and increasing BMI. Recently, lifestyle and dietary factors have been linked in epidemiological studies with an alteration of the risk of gout; however, there remains a lack of data on patient knowledge of these factors. The purpose of this survey-based study was to determine the knowledge of gout and its treatment both in the community and specialist care settings. Methods: Participants were recruited from a hospital rheumatology outpatient department, consumer organization and a random sample of participants from a population-based cohort who had self-reported gout in South Australia. Participants completed a survey regarding basic demographics, the Single Item Literacy Screener, use of medication and diet for treatment of their gout and knowledge of gout. Results: Seventy-four people were recruited (87% male) with a mean age of 66 years (range 35-88). The mean duration of gout was 16.6 years (range 0-60). On screening with SILS, 19.0% were identified as having limited reading ability. Most gout was managed by the family practitioner (81.1%) and/or rheumatologist (18.9%). In regard to current gout medications, 52.7% were taking allopurinol, 17.6% colchicine, 9.5% non-steroidal anti-inflammatory drugs, 6.8% prednisolone and 5.4% herbal preparations. For further information regarding gout, participants would most commonly approach their general practitioner (85.1%). Most participants correctly identified certain triggers to gout attacks and almost half of participants (41.9%) reported that they had altered their diet due to gout. Conversely, participants often incorrectly identified common risk or protective factors for gout. Conclusion: Gout remains a common, yet undertreated, chronic condition. Our study highlights a lack of knowledge amongst patients of risk and protective factors in relation to gout. The increasing prevalence of gout within the population indicates a need to improve education and understanding among those with the condition.

Reconsidering screening thresholds in health assessments for obstructive sleep apnea using operational and safety incident data.

The rail industry in Australia screens workers for probable obstructive sleep apnea (OSA) due to known safety risks. However, existing criteria to trigger screening only identify a small proportion of workers with OSA. The current study sought to examine the relationship between OSA risk and rail incidents in real-world data from Australian train drivers, and conducted a proof of concept analysis to determine whether more conservative screening criteria are justified. Health assessment (2016-2018) and subsequent rail incident data (2016-2020) were collected from two passenger rail service providers. Predictors included OSA status (confirmed no OSA with a sleep study, controlled OSA, unknown OSA [no recorded sleep assessment data] and confirmed OSA with no indication of treatment); OSA risk according to the current Standard, and OSA risk according to more conservative clinical markers (BMI threshold and cardiometabolic burden). Coded rail safety incidents involving the train driver were included. Data were analysed using zero-inflated negative binomial models to account for over-dispersion with high 0 counts, and rail safety incidents are reported using Incidence Risk Ratios (IRRs). A total of 751 train drivers, typically middle-aged, overweight to obese and mostly men, were included in analyses. There were 43 (5.7%) drivers with confirmed OSA, 62 (8.2%) with controlled OSA, 13 (1.7%) with confirmed no OSA and 633 (84.4%) drivers with unknown OSA. Of the 633 train drivers with unknown OSA status, 21 (3.3%) met 'at risk' criteria for OSA according to the Standard, and incidents were 61% greater (IRR: 1.61, 95% Confidence Interval (CI) 1.02-2.56) in the years following their health assessment compared to drivers who did not meet 'at risk' criteria. A more conservative OSA risk status using lower BMI threshold and cardiometabolic burden identified an additional 30 'at risk' train drivers who had 46% greater incidents compared to drivers who did not meet risk criteria (IRR (95% CI) 1.46 (1.00-2.13)). Our more conservative OSA risk criteria identified more workers, with greater prospective incidents. These findings suggest that existing validated tools could be considered in future iterations of the Standard in order to more sensitively screen for OSA.

Sleep health primary care clinical resource.

BACKGROUND: Obstructive sleep apnoea (OSA) and insomnia are the two most common sleep disorders and are frequent reasons for presentation in Australian general practice. OBJECTIVE: This article describes the development, content and suggested uses of the online sleep health primary care clinical resource, which provides general practitioners and other primary healthcare professionals with evidence-based information on the aetiology, assessment, management, referral and ongoing care for OSA and chronic insomnia. DISCUSSION: The Royal Australian College of General Practitioners-accepted clinical resource for the management of OSA and chronic insomnia in primary care was developed by the Australian National Centre for Sleep Health Services Research. The resource is designed to be used during consultations (eg following the steps in assessment and management and the use of online questionnaires for the assessment of OSA [Epworth Sleepiness Scale/OSA50/STOP-Bang] and insomnia [Sleep Condition Indicator/and Insomnia Severity Index]) and as an education/training tool (eg evidence on the role of continuous positive airway pressure/mandibular advancement splints for management of OSA and brief behavioural therapy for insomnia/cognitive behavioural therapy for insomnia for the management of insomnia).

Sleep disorder risk, perceived control over sleep, and mental health symptoms in paramedicine students.

Paramedics commonly experience both poor sleep and mental health symptoms. Clarifying whether sleep or mental health symptoms are a challenge prior to commencement of employment is important, as early prevention and intervention initiatives during training could support these workers. Paramedicine students (n=53) were included, with sleep disorder screening (obstructive sleep apnea, insomnia and restless legs syndrome), and mental health outcomes (depressive symptoms: Patient Health Questionnaire-9, and anxiety symptoms: General Anxiety Disorder-7). Data were analysed using robust regression models, adjusted for age, sex, and shift work status. Meeting criteria for a sleep disorder (n=21) was associated with higher scores for anxiety (8.2 [95% CI: 5.9-10.5] v 4.6, [3.4-5.8]) and depressive symptoms (11.1 [8.6-13.6] v 4.4 [3.1-5.7)] compared to those who did not meet the criteria for a sleep disorder (n=32). Depressive symptoms were lower in those with perceived control over sleep (5.2 [3.2-7.2] v 9.8 [7.7-11.8]). There was no interaction between sleep disorder risk and perceived control over sleep on mental health symptoms. Investigation and management of factors contributing to low perceived control over sleep, together with early screening and management of sleep disorders, are likely to be important priorities to support paramedic student wellbeing prior to commencing shift work.

Assessment and management of sleep disorders in shift workers: Challenges and considerations for general practice.

BACKGROUND: Shift work is characterised by displaced sleep opportunities and associated sleep disturbance. Shift workers often report sleepiness and other wake time symptoms associated with poor sleep. However, clinical sleep disorders are also prevalent in shift workers. Although prevalence rates are similar or higher in shift workers compared with the general population, help seeking in shift workers with sleep disorders is low. OBJECTIVE: This article aims to provide general practitioners with a contemporary overview of the prevalence rates for sleep disorders in shift workers, to clarify the existing evidence relating to mental and physical health consequences of sleep disorders in shift workers and to highlight the need to consider undiagnosed sleep disorders before attributing sleep-related symptoms solely to work schedules. DISCUSSION: Symptoms of sleep loss associated with shift work overlap with symptoms experienced by individuals living with sleep disorders. Although >40% of middle-aged Australians live with a sleep disorder that requires investigation and management, symptoms in shift workers are often attributed to the work schedule and, as a result, might not be investigated for appropriate diagnosis and treatment. We argue that screening for sleep disorders in shift workers with sleep complaints should be a priority.

Regular snoring is associated with uncontrolled hypertension.

Snoring may be a risk factor for cardiovascular disease independent of other co-morbidities. However, most prior studies have relied on subjective, self-report, snoring evaluation. This study assessed snoring prevalence objectively over multiple months using in-home monitoring technology, and its association with hypertension prevalence. In this study, 12,287 participants were monitored nightly for approximately six months using under-the-mattress sensor technology to estimate the average percentage of sleep time spent snoring per night and the estimated apnea-hypopnea index (eAHI). Blood pressure cuff measurements from multiple daytime assessments were averaged to define uncontrolled hypertension based on mean systolic blood pressure≥140 mmHg and/or a mean diastolic blood pressure ≥90 mmHg. Associations between snoring and uncontrolled hypertension were examined using logistic regressions controlled for age, body mass index, sex, and eAHI. Participants were middle-aged (mean ± SD; 50 ± 12 y) and most were male (88%). There were 2467 cases (20%) with uncontrolled hypertension. Approximately 29, 14 and 7% of the study population snored for an average of >10, 20, and 30% per night, respectively. A higher proportion of time spent snoring (75th vs. 5th; 12% vs. 0.04%) was associated with a ~1.9-fold increase (OR [95%CI]; 1.87 [1.63, 2.15]) in uncontrolled hypertension independent of sleep apnea. Multi-night objective snoring assessments and repeat daytime blood pressure recordings in a large global consumer sample, indicate that snoring is common and positively associated with hypertension. These findings highlight the potential clinical utility of simple, objective, and noninvasive methods to detect snoring and its potential adverse health consequences.

Content Comparison of Quality-of-Life Instruments Used in Economic Evaluations of Sleep Disorder Interventions: A Systematic Review.

BACKGROUND: Assessment of quality of life (QoL) in people living with sleep disorders using questionnaires is necessary to compare intervention benefits. Knowledge of the content and concepts covered by specific QoL instruments is essential to determine which instruments are best suited for conducting economic evaluations of sleep-related interventions. OBJECTIVES: This review aims to identify the QoL instruments that have been applied in economic evaluations of sleep disorder interventions and compare their conceptual overlap and content coverage using the framework of the International Classification of Functioning, Disability and Health (ICF). METHODS: A systematic review of full economic evaluations in sleep published in peer-reviewed journals from conception to 30 May, 2023 was conducted. MEDLINE, PsychInfo, ProQuest, Cochrane, Scopus, CINAHL, Web of Science and Emcare were searched for eligible studies. Studies incorporating either generic or sleep-specific QoL instruments as the primary or secondary measures of effectiveness within a full economic evaluation were included. Quality appraisal against the JBI Critical Appraisal Checklist for Economic Evaluations and EURONHEED checklists and mapping of QoL items to ICF categories were performed by two reviewers, with a third helping settle any potential differences. RESULTS: Sixteen instruments were identified as having been used in sleep health economic evaluations. The EQ-5D-3L, Epworth Sleepiness Scale, and Insomnia Severity Index were the most widely used, but the latter two are predominantly diagnostic tools and not specifically designed to guide economic evaluations. Other instruments with broader ICF content coverage have been least used, and these include the Sleep Apnea Quality of Life Index, Functional Outcomes of Sleep Questionnaire, 15 Dimensions, Short-Form 6 Dimensions, 12-item Short Form Survey, 36-item Short Form Survey and the GRID Hamilton Rating Scale for Depression. CONCLUSIONS: This study provides an overview of current QoL instruments used in economic evaluations of sleep with respect to their content coverage. A combination of generic and sleep-specific instruments with broader ICF content coverage is recommended for such evaluations.

A circadian-informed lighting intervention accelerates circadian adjustment to a night work schedule in a submarine lighting environment.

STUDY OBJECTIVE: Night work has detrimental impacts on sleep and performance, primarily due to misalignment between sleep-wake schedules and underlying circadian rhythms. This study tested whether circadian-informed lighting accelerated circadian phase delay, and thus adjustment to night work, compared to blue-depleted standard lighting under simulated submariner work conditions. METHODS: Nineteen healthy sleepers (12 males; mean±SD aged 29 ±10 y) participated in two separate 8-day visits approximately one month apart to receive, in random order, circadian-informed lighting (blue-enriched and dim, blue-depleted lighting at specific times) and standard lighting (dim, blue-depleted lighting). After an adaptation night (day 1), salivary dim light melatonin onset (DLMO) assessment was undertaken from 18:00-02:00 on days 2-3. During days 3-7, participants completed simulated night work from 00:00-08:00 and a sleep period from 10:00-19:00. Post-condition DLMO assessment occurred from 21:00-13:00 on days 7-8. Ingestible capsules continuously sampled temperature to estimate daily core body temperature minimum (Tmin) time. Tmin and DLMO circadian delays were compared between conditions using mixed effects models. RESULTS: There were significant condition-by-day interactions in Tmin and DLMO delays (both p<0.001). After four simulated night shifts, circadian-informed lighting produced a mean [95%CI] 4.3 [3.3 to 5.4] h greater delay in Tmin timing and a 4.2 [3 to 5.6] h greater delay in DLMO timing compared to standard lighting. CONCLUSIONS: Circadian-informed lighting accelerates adjustment to shiftwork in a simulated submariner work environment. Circadian lighting interventions warrant consideration in any dimly lit and blue-depleted work environments where circadian adjustment is relevant to help enhance human performance, safety, and health.

DISPLACE study shows poor quality of transcranial doppler ultrasound for stroke risk screening in sickle cell anemia.

ABSTRACT: Children with sickle cell anemia (SCA) are at increased risk of stroke when compared with their age-based counterparts. The Stroke Prevention Trial in Sickle Cell Anemia (STOP) previously demonstrated that with the use of transcranial Doppler ultrasound (TCD; Sickle Stroke Screen) and chronic red cell transfusion, the risk of stroke is reduced by over 90%. The STOP criteria detailed the type and method of measurement required; the time-averaged mean maximum velocity (TAMMV). Unfortunately, it has been difficult to adhere to the appropriate TAMMV measurements. The objectives of this study were to assess the quality of TCD and transcranial Doppler imaging (TCDi) reports to determine the report quality and accuracy. This is a subanalysis of the DISPLACE (Dissemination and Implementation of Stroke Prevention Looking at the Care Environment) study. Over 12 000 TCD/TCDi reports were collected during this study from 28 institutions; 391 TCDs were reviewed for this subanalysis. There were significant variations in the vessels being assessed, the velocities used to define abnormal results, and who was interpreting the scans. In 52% of reports, it was impossible to identify whether the TAMMV was what was measured. Similarly, it was only clear in 42% of reports that the TAMMV was used to interpret the examination as normal/abnormal. Given this inconsistency, we strongly recommend standardization of TCD/TCDi reporting, specialized training for those performing and interpreting the scans in the use of TCD/TCDi in patients with SCA, internal quality assurance, and institutional quality improvement work to ensure appropriate use of this potentially lifesaving technology.

Circadian-informed lighting improves vigilance, sleep, and subjective sleepiness during simulated night shift work.

STUDY OBJECTIVES: Shiftwork is associated with cognitive impairment and reduced sleep time and quality, largely due to circadian misalignment. This study tested if circadian-informed lighting could improve cognitive performance and sleep during simulated night shifts versus dim control lighting. METHODS: Nineteen healthy participants (Mean±SD 29±10 years, 12 males, 7 females) were recruited to a laboratory study consisting of two counterbalanced 8-day lighting conditions (order randomized) 1-month apart: 1) control lighting condition- dim, blue-depleted and 2) circadian-informed lighting condition- blue-enriched and blue-depleted where appropriate. Participants underwent an adaptation night (22:00h - 07:00h), then four nights of simulated nightwork (cognitive testing battery of nine tasks, 00:00h - 08:00h) and sleep during the day (10:00h - 19:00h). Psychomotor vigilance task (PVT) lapses, Karolinska Sleepiness Scale (KSS) scores, and polysomnography-derived sleep outcomes were compared between conditions and across days using mixed models. RESULTS: Significant condition-by-day-by-time of task interaction effects were found for PVT lapses, median reaction time, and reaction speed, with ~50% fewer lapses by the end of simulated shiftwork with circadian-informed lighting versus control (mean±SD 7.4±5.0 vs. 15.6±6.1). KSS was lower around the nightshift midpoints on days 6 and 7 with circadian versus control lighting. Participants slept 52 minutes longer [95% CIs: 27.5, 76.5 mins] by Day 7 with circadian-informed versus control lighting, p<0.001. Effects were inconsistent on other performance tasks. CONCLUSIONS: Circadian-informed lighting improved sleep, sleepiness, and vigilance compared to control lighting. These findings support the potential for lighting interventions to improve sleep and vigilance in night shift workers chronically exposed to dim lighting.

Pharmacological management of co-morbid obstructive sleep apnoea and insomnia.

INTRODUCTION: Clinical presentation of both insomnia and obstructive sleep apnea (COMISA) is common. Approximately 30% of clinical cohorts with OSA have insomnia symptoms and vice versa. The underlying pathophysiology of COMISA is multifactorial. This poses a complex clinical challenge. Currently, there are no clinical guidelines or recommendations outside of continuous positive airway pressure (CPAP) therapy and cognitive behavioral therapy for insomnia (CBTi). Clinically translatable precision medicine approaches to characterize individual causes or endotypes may help optimize future pharmacological management of COMISA. AREAS COVERED: This review article provides an up-to-date account of COMISA and its consequences, the underlying pathophysiology of sleep apnea, insomnia and COMISA, current treatment approaches and limitations, pharmacotherapy targets and future priorities. EXPERT OPINION: There are multiple promising emerging therapies, but clinical trial data specifically in COMISA populations are lacking. This is a priority for future investigation to inform development of evidence-based guidelines. Pharmacotherapies, particularly for insomnia, do not target the underlying causes of the disorder thus, are indicated for short-term use only and should remain second line. Future multidisciplinary research should be directed toward the multifactorial nature of COMISA and the challenges of adapting COMISA treatment in clinical practice and overcoming the practical barriers that health-care providers and consumers encounter.

Brazilian Guidelines for transcranial doppler in children and adolescents with sickle cell disease

BACKGROUND: Sickle cell disease is the most common monogenic hereditary disease in Brazil. Although strokes are one of the main causes of morbidity and mortality in these patients, the use of transcranial Doppler to identify children at risk is not universally used. OBJECTIVE: To develop Brazilian guidelines for the use of transcranial Doppler in sickle cell disease children and adolescents, so that related health policies can be expanded, and thus contribute to reduce morbidity and mortality. METHODS: The guidelines were formulated in a consensus meeting of experts in transcranial Doppler and sickle cell disease. The issues discussed were previously formulated and scientific articles in databases (MEDLINE, SciELO and Cochrane) were carefully analyzed. The consensus for each question was obtained by a vote of experts on the specific theme. RESULTS: Recommendations were made, including indications for the use of transcranial Doppler according to the sickle cell disease genotype and patients age; the necessary conditions to perform the exam and its periodicity depending on exam results; the criteria for the indication of blood transfusions and iron chelation therapy; the indication of hydroxyurea; and the therapeutic approach in cases of conditional transcranial Doppler. CONCLUSION: The Brazilian guidelines on the use of transcranial doppler in sickle cell disease patients may reduce the risk of strokes, and thus reduce the morbidity and mortality and improve the quality of life of sickle cell disease patients.

Stroke in sickle cell anemia

The results of studies of strokes in children who are sickle cell anemia carriers are presented in this work. The roles of transfusions and transcranial Doppler to predict patients with a high risk of having a stroke are emphasized.

Neste relato são apresentados os resultados de estudos de acidente vascular cerebral em crianças portadoras de anemia falciforme. É enfatizado o papel das transfusões e do doppler transcraniano em predizer quais os pacientes que encontram-se sob risco de apresentarem acidente vascular cerebral.