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INTRODUCTION: Recent growth in the functionality and use of technology has prompted an increased interest in the potential for remote or decentralized clinical trials in dementia. There are many potential benefits associated with decentralized medication trials, but we currently lack specific recommendations for their delivery in the dementia field. METHODS: A modified Delphi method engaged an expert panel to develop recommendations for the conduct of decentralized medication trials in dementia prevention. A working group of researchers and clinicians with expertise in dementia trials further refined the recommendations. RESULTS: Overall, the recommendations support the delivery of decentralized trials in dementia prevention provided adequate safety checks and balances are included. A total of 40 recommendations are presented, spanning aspects of decentralized clinical trials, including safety, dispensing, outcome assessment, and data collection. DISCUSSION: These recommendations provide an accessible, pragmatic guide for the design and conduct of remote medication trials for dementia prevention. HIGHLIGHTS: Clinical trials of medication have begun adopting decentralized approaches. Researchers in the field lack guidance on what would be appropriate circumstances and frameworks for what would be appropriate circumstances and frameworks for the use of decentralized trial methods in dementia prevention. The present report provides consensus-based expert recommendations for decentralized clinical trials for dementia prevention.
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Ensaios Clínicos como Assunto , Consenso , Demência , Humanos , Demência/prevenção & controle , Demência/tratamento farmacológico , Técnica Delphi , Projetos de Pesquisa/normasRESUMO
Melatonin is commonly used for sleep and jetlag at low doses. However, there is less documentation on the safety of higher doses, which are being increasingly used for a wide variety of conditions, including more recently COVID-19 prevention and treatment. The aim of this review was to investigate the safety of higher doses of melatonin in adults. Medline, Scopus, Embase and PsycINFO databases from inception until December 2019 with convenience searches until October 2020. Randomised controlled trials investigating high-dose melatonin (≥10 mg) in human adults over 30 years of age were included. Two investigators independently abstracted articles using PRISMA guidelines. Risk of bias was assessed by a committee of three investigators. 79 studies were identified with a total of 3861 participants. Studies included a large range of medical conditions. The meta-analysis was pooled data using a random effects model. The outcomes examined were the number of adverse events (AEs), serious adverse events (SAEs) and withdrawals due to AEs. A total of 29 studies (37%) made no mention of the presence or absence of AEs. Overall, only four studies met the pre-specified low risk of bias criteria for meta-analysis. In that small subset, melatonin did not cause a detectable increase in SAEs (Rate Ratio = 0.88 [0.52, 1.50], p = .64) or withdrawals due to AEs (0.93 [0.24, 3.56], p = .92), but did appear to increase the risk of AEs such as drowsiness, headache and dizziness (1.40 [1.15, 1.69], p < .001). Overall, there has been limited AE reporting from high-dose melatonin studies. Based on this limited evidence, melatonin appears to have a good safety profile. Better safety reporting in future long-term trials is needed to confirm this as our confidence limits were very wide due to the paucity of suitable data.
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COVID-19 , Melatonina , Adulto , Humanos , Melatonina/farmacologia , SARS-CoV-2 , SonoRESUMO
PURPOSE: Consistent predictors of weight loss outcomes with very low-energy diets (VLEDs) in obstructive sleep apnea (OSA) have not been identified. This study aimed to identify variables predictive of weight loss success in obese patients with OSA undertaking an intensive weight loss programme. METHODS: We analysed biological, psychological, and behavioural variables as potential predictors of weight loss in obese patients with OSA after a 2-month VLED followed by one of two 10-month weight loss maintenance diets. Actigraphy, in-lab polysomnography, urinary catecholamines, and various psychological and behavioural variables were measured at baseline, 2, and 12 months. Spearman's correlations analysed baseline variables with 2-month weight loss, and 2-month variables with 2-12 month-weight change. RESULTS: Forty-two patients completed the VLED and thirty-eight completed the maintenance diets. Actigraphy data revealed that late bedtime (rs = - 0.45, p = < 0.01) was correlated with 2-month weight loss. The change in the time that participants got out of bed (rise-time) from baseline to two months was also correlated with 2-month weight loss (rs = 0.36, p = 0.03). The Impact of Weight on Quality of Life-Lite questionnaire (IWQOL) Public Distress domain (rs = - 0.54, p = < 0.01) and total (rs = - 0.38, p = 0.02) scores were correlated with weight loss maintenance from 2 to 12 months. CONCLUSIONS: Results from this small patient sample reveal correlations between actigraphy characteristics and weight loss in obese patients with OSA. We suggest the IWQOL may also be a useful clinical tool to identify OSA patients at risk of weight regain after initial weight loss. CLINICAL TRIAL REGISTRATION: This clinical trial was prospectively registered on 18/02/2013 with the Australia and New Zealand Clinical Trials Registry (ACTRN12613000191796). PUBLIC REGISTRY TITLE: Sleep, Lifestyle, Energy, Eating, Exercise Program for the management of sleep apnea patients indicated for weight loss treatment: A randomised, controlled pilot study. URL: https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=363680.
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Qualidade de Vida , Apneia Obstrutiva do Sono , Humanos , Obesidade/complicações , Polissonografia , Apneia Obstrutiva do Sono/diagnóstico , Apneia Obstrutiva do Sono/terapia , Redução de PesoRESUMO
BACKGROUND AND OBJECTIVE: Use of in-laboratory polysomnography (PSG) to diagnose obstructive sleep apnoea (OSA) is cost and resource intensive. Questionnaires, physical measurements and home monitors have been studied as potential simpler alternatives. This study aimed to develop a diagnostic model for OSA for use in primary care. METHODS: Primary care practitioners were trained to recognize symptoms of sleep apnoea and recruited patients based on the clinical need to investigate OSA. Assessment was by symptom questionnaires, anthropomorphic measurements, digital facial photography, and a single-channel nasal flow monitor (Flow Wizard©, DiagnoseIT, Sydney, Australia) worn at home for 3 nights. The in-laboratory PSG was the reference test, with OSA defined as apnoea-hypopnoea index (AHI) ≥10 events/h. RESULTS: In the model development phase, 25 primary care practitioners studied 315 patients in whom they suspected OSA, of which 57% had AHI≥10 and 22% had AHI≥30. Published OSA questionnaires provided low to moderate prediction of OSA (area under the curve [AUC] 0.53-0.73). The nasal flow monitor alone yielded high accuracy for predicting OSA with AUC of 0.87. Sensitivity was 0.87 and specificity 0.77 at a threshold respiratory event index (REI) of 18 events/h. A model adding age, gender, symptoms and BMI to the nasal flow monitor REI only modestly improved OSA prediction (AUC 0.89), with similar AUC (0.88) confirmed in the validation population of 114 patients. CONCLUSION: Sleep apnoea can be diagnosed in the primary care setting with a combination of clinical judgement and portable monitor test outcomes.
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Síndromes da Apneia do Sono , Apneia Obstrutiva do Sono , Humanos , Polissonografia , Atenção Primária à Saúde , Apneia Obstrutiva do Sono/diagnóstico , Inquéritos e QuestionáriosRESUMO
Impact factors and ranking lists of research journals are very often used to judge our career achievements and progression by employers and granting bodies. However, a comprehensive list for the interdisciplinary field of sleep research does not currently exist because our journals tend to be placed into discipline-specific lists that do not cope well with our historic interdisciplinarity, which embraces many core disciplines. We aimed to build a ranking list specifically for sleep research journals based on the journal impact factor and the google scholar H5 indices. We then searched for all sleep journals given an impact factor by Thomson Reuters from 2005 to 2018 and all journals given a current H5 index by Google Scholar. We provide a ranking list specifically for sleep journals that might be useful for researchers to cite when providing context in their applications for employment, promotion and funding.
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Fator de Impacto de Revistas , Sono/fisiologia , História do Século XXI , HumanosRESUMO
BACKGROUND: Depression is common in older people and is associated with underlying brain change increasing the risk of dementia. Sleep disturbance is frequently reported by those with lifetime depression, however whether circadian misalignment also exists is unclear. We aimed to examine circadian rhythms and sleep associations in older patients with and without lifetime depression. METHODS: Thirty-four older people meeting DSM-IV criteria for lifetime major depression (mean age = 63.9 years), and 30 healthy controls (mean age = 65.7 years) were recruited. Participants underwent 2-weeks of actigraphy followed by a 3-night protocol including dim light melatonin onset (DLMO) assessment and overnight polysomnography (PSG) for sleep architecture. DLMO and phase angle of entrainment were computed. RESULTS: Compared to controls, participants with depression had a significantly longer phase angle of entrainment (6.82 h ± 1.45 vs. 5.87 h ± 1.60, p = 0.02, Cohens-d = 0.62). A small to moderate yet non-significant difference in DLMO times, with earlier DLMO (34 ± 27 min) observed in depression (20:36 ± 1:48 vs. 21:10 ± 1:48, p = 0.22, Cohens-d = 0.32). Individuals with depression had longer sleep latency and latency to rapid eye movement sleep than controls (all p < 0.05). CONCLUSION: Circadian advancement and alterations to the timing of sleep and REM onset are evident in older people with lifetime major depression, despite having only mild residual symptoms. Further research examining the prognostic significance of these changes is warranted as well as chronotherapeutic treatment studies.
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Ritmo Circadiano , Depressão/complicações , Depressão/fisiopatologia , Transtornos do Sono-Vigília/complicações , Transtornos do Sono-Vigília/fisiopatologia , Actigrafia , Idoso , Estudos de Casos e Controles , Feminino , Humanos , Masculino , Melatonina , Pessoa de Meia-Idade , Polissonografia , Latência do Sono , Sono REMRESUMO
OBJECTIVE: Interest in the use of cannabidiol (CBD) is increasing worldwide as its therapeutic effects are established and legal restrictions moderated. Unlike Δ9 -tetrahydrocannabinol (Δ9 -THC), CBD does not appear to cause cognitive or psychomotor impairment. However, further assessment of its effects on cognitively demanding day-to-day activities, such as driving, is warranted. Here, we describe a study investigating the effects of CBD on simulated driving and cognitive performance. METHODS: Thirty healthy individuals will be recruited to participate in this randomised, double-blind, placebo-controlled crossover trial. Participants will complete four research sessions each involving two 30-min simulated driving performance tests completed 45 and 210 min following oral ingestion of placebo or 15, 300, or 1,500 mg CBD. Cognitive function and subjective drug effects will be measured, and blood and oral fluid sampled, at regular intervals. Oral fluid drug testing will be performed using the Securetec DrugWipe® 5S and Dräger DrugTest® 5000 devices to determine whether CBD increases the risk of "false-positive" roadside tests to Δ9 -THC. Noninferiority analyses will test the hypothesis that CBD is no more impairing than placebo. CONCLUSION: This study will clarify the risks involved in driving following CBD use and assist in ensuring the safe use of CBD by drivers.
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Condução de Veículo , Canabidiol/administração & dosagem , Cognição/efeitos dos fármacos , Canabidiol/efeitos adversos , Estudos Cross-Over , Relação Dose-Resposta a Droga , Método Duplo-Cego , Humanos , Fatores de TempoRESUMO
Therapeutic-continuous positive airway pressure seems to increase weight compared with placebo-continuous positive airway pressure. It is not known whether weight gain with therapeutic-continuous positive airway pressure dose is dependent or whether it causes metabolic dysfunction. Data synthesis of three randomised placebo-continuous positive airway pressure-controlled trials (2-3 months) was performed to test whether there is a dose-dependent effect of continuous positive airway pressure on weight. Fasting glucose, insulin, insulin resistance (homeostatic model assessment), lipids and visceral abdominal fat were also tested to determine any effect on metabolic function. Mixed-model analysis of variance was used to quantify these effects. One-hundred and twenty-eight patients were analysed. Overall there was a small increase in weight with therapeutic-continuous positive airway pressure use compared with placebo-continuous positive airway pressure (difference: 1.17 kg; 0.37-1.97, p = 0.005), which was greater with high-use therapeutic-continuous positive airway pressure compared with high-use placebo-continuous positive airway pressure (1.45 kg; 0.10-2.80, p = 0.04). Continuous positive airway pressure use as a continuous variable was also significantly associated with weight change in continuous positive airway pressure users (0.30 kg hr-1 night-1 ; 0.04-0.56, p = 0.001), but not in placebo users (0.04 kg hr-1 night-1 ; -0.22 to 0.26, p = 0.76). Neither therapeutic-continuous positive airway pressure nor the dose of therapeutic-continuous positive airway pressure caused any changes to metabolic outcomes. The weight gain effects of medium-term therapeutic-continuous positive airway pressure appear modest and are not accompanied by any adverse metabolic effects.
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Peso Corporal/fisiologia , Pressão Positiva Contínua nas Vias Aéreas/métodos , Metabolismo/fisiologia , Síndromes da Apneia do Sono/terapia , Aumento de Peso/fisiologia , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Síndromes da Apneia do Sono/complicaçõesRESUMO
RATIONALE: Patients with obstructive sleep apnea (OSA) unable to tolerate standard treatments have few alternatives. They may benefit from weight loss, but the major symptom of daytime performance impairment may remain during weight loss programs. OBJECTIVES: We hypothesized that wakefulness-promoter armodafinil would improve driving task performance over placebo in patients undergoing weight loss. METHODS: This was a placebo-controlled, double-blind, randomized trial of armodafinil versus placebo daily for 6 months in patients who were also randomized to one of two diets for 6 months with follow-up at 1 year in overweight, adult, patients with OSA who had rejected standard treatment and suffered daytime sleepiness. MEASUREMENTS AND MAIN RESULTS: Primary outcome was change in steering deviation in the final 30 minutes of a 90-minute afternoon driving task (AusED) at 6 months. Secondary outcomes were Epworth Sleepiness Scale, Functional Outcomes of Sleep Questionnaire, and fat mass measured by dual-emission X-ray absorptiometry. Armodafinil improved driving task performance over placebo at 3 months (12.9 cm; 95% confidence interval, 4.1-21.7; P = 0.004), but not the primary time point of 6 months (5.5 cm; 95% confidence interval, -3.3 to 14.3; P = 0.223). Patients on armodafinil lost 2.4 kg more fat than those on placebo at 6 months (95% confidence interval, 0.9-4.0; P = 0.002). Other secondary outcomes were not significantly improved. CONCLUSIONS: Armodafinil did not improve driving task performance at the primary endpoint of 6 months. Armodafinil might be a useful adjunctive to weight loss in patients with OSA rejecting conventional treatments but this needs to be directly tested in a specifically designed, properly powered clinical trial. Clinical trial registered with Australian and New Zealand Clinical Trials Registry (ACTRN 12611000847910).
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Condução de Veículo , Dieta Redutora , Modafinila/uso terapêutico , Obesidade/dietoterapia , Síndromes da Apneia do Sono/tratamento farmacológico , Promotores da Vigília/uso terapêutico , Adulto , Austrália , Terapia Combinada , Método Duplo-Cego , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Nova Zelândia , Obesidade/diagnóstico , Valores de Referência , Síndromes da Apneia do Sono/diagnóstico , Análise e Desempenho de Tarefas , Redução de Peso/efeitos dos fármacosRESUMO
Very low energy diets (VLED) appear to be the most efficacious dietary-based obesity reduction treatments in obstructive sleep apnea (OSA); however, effective weight loss maintenance strategies remain untested in this condition. Our study aimed to assess the feasibility, tolerability and efficacy of two common maintenance diets during a 10-month follow-up period after rapid weight loss using a 2-month VLED. In this two-arm, single-centre, open-label pilot trial, obese adult OSA patients received a 2-month VLED before being allocated to either the Australian Guide to Healthy Eating diet (AGHE) or a low glycaemic index high-protein diet (LGHP). Outcomes were measured at 0, 2 and 12 months. We recruited 44 patients [113.1 ± 19.5 kg, body mass index (BMI): 37.2 ± 5.6 kg m-2 , 49.3 ± 9.2 years, 12 females]. Twenty-four patients were on continuous positive airway pressure (CPAP) or mandibular advancement splint (MAS) therapy for OSA. Forty-two patients completed the VLED. The primary outcome of waist circumference was reduced by 10.6 cm at 2 months [95% confidence interval (CI): 9.2-12.1], and patients lost 12.9 kg in total weight (95% CI: 11.2-14.6). There were small but statistically significant regains in waist circumference between 2 and 12 months [AGHE = 3.5 cm (1.3-5.6) and LGHP = 2.8 cm (0.6-5.0]. Other outcomes followed a similar pattern of change. After weight loss with a 2-month VLED in obese patients with OSA, a structured weight loss maintenance programme incorporating commonly used diets was feasible, tolerable and efficacious for 10 months. This programme may be deployed easily within sleep clinics; however, future research should first test its translation within general clinical practice.
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Dieta com Restrição de Carboidratos/tendências , Obesidade/dietoterapia , Obesidade/epidemiologia , Apneia Obstrutiva do Sono/dietoterapia , Apneia Obstrutiva do Sono/epidemiologia , Redução de Peso/fisiologia , Adulto , Austrália/epidemiologia , Índice de Massa Corporal , Peso Corporal/fisiologia , Pressão Positiva Contínua nas Vias Aéreas/tendências , Dieta com Restrição de Carboidratos/métodos , Feminino , Humanos , Masculino , Avanço Mandibular/tendências , Pessoa de Meia-Idade , Obesidade/diagnóstico , Projetos Piloto , Apneia Obstrutiva do Sono/diagnóstico , Fatores de Tempo , Resultado do Tratamento , Circunferência da Cintura/fisiologiaRESUMO
The aim was to investigate whether continuous positive airway pressure treatment could modulate serum vitamin D (25-hydroxyvitamin D) and bone turnover markers (collagen-type 1 cross-linked C-telopeptide, osteocalcin and N-terminal propeptide of type 1 collagen) in secondary analysis from a randomized controlled trial. Sixty-five continuous positive airway pressure-naïve male patients with obstructive sleep apnea (age = 49 ± 12 years, apnea-hypopnea index = 39.9 ± 17.7 events h-1 , body mass index = 31.3 ± 5.2 kg m-2 ) were randomized to receive either real (n = 34) or sham (n = 31) continuous positive airway pressure for 12 weeks. At 12 weeks, all participants received real continuous positive airway pressure for an additional 12 weeks. After 12 weeks of continuous positive airway pressure (real versus sham), there were no between-group differences for any of the main outcomes [Δ25-hydroxyvitamin D: -0.80 ± 5.28 ng mL-1 (mean ± SE) versus 3.08 ± 3.66 ng mL-1 , P = 0.42; Δcollagen-type 1 cross-linked C-telopeptide: 0.011 ± 0.014 ng mL-1 versus -0.004 ± 0.009 ng mL-1 , P = 0.48; Δosteocalcin: 1.13 ± 1.12 ng mL-1 versus 0.46 ± 0.75 ng mL-1 , P = 0.80; ΔN-terminal propeptide of type 1 collagen: 2.07 ± 3.05 µg L-1 versus -1.05 ± 2.13 µg L-1 , P = 0.48]. There were no further differences in subgroup analyses (continuous positive airway pressure-compliant patients, patients with severe obstructive sleep apnea or sleepy patients). However, after 24 weeks irrespective of initial randomization, vitamin D increased in patients with severe obstructive sleep apnea (9.56 ± 5.51 ng mL-1 , P = 0.045) and in sleepy patients (14.0 ± 4.69 ng mL-1 , P = 0.007). Also, there was a significant increase in osteocalcin at 24 weeks (3.27 ± 1.06 ng mL-1 , P = 0.01) in compliant patients. We conclude that 12 weeks of continuous positive airway pressure did not modulate vitamin D or modulate any of the bone turnover markers compared with sham. However, it is plausible that continuous positive airway pressure may have late beneficial effects on vitamin D levels and bone turnover markers in selected groups of patients with obstructive sleep apnea.
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Remodelação Óssea/fisiologia , Pressão Positiva Contínua nas Vias Aéreas/tendências , Apneia Obstrutiva do Sono/sangue , Apneia Obstrutiva do Sono/terapia , Vitamina D/sangue , Adulto , Índice de Massa Corporal , Método Duplo-Cego , Humanos , Masculino , Pessoa de Meia-Idade , Cooperação do Paciente , Apneia Obstrutiva do Sono/fisiopatologiaRESUMO
Obstructive sleep apnoea (OSA) is a common condition characterized by repetitive upper airway obstruction during sleep. OSA promotes wide intrathoracic pressure swings, intermittent hypoxia and sleep fragmentation. Growing evidence derived from animal models mimicking the oxygen profile observed in patients with OSA as well as clinical studies support that this important sleep-disordered breathing is associated with increased cardiovascular risk. Although the precise mechanisms are not fully established, it is conceivable that the metabolic deregulation promoted by the components of OSA may have an important causal role in the poor cardiovascular prognosis. In this review, we summarize the potential role of OSA and its components on cardiometabolic disease. We also summarize evidence evaluating the impact of OSA treatment (notably continuous positive airway pressure) on reversing the metabolic deregulation promoted by OSA. Finally, we discuss the research agenda and perspectives for this important research area.
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Doenças Cardiovasculares/etiologia , Doenças Metabólicas/etiologia , Apneia Obstrutiva do Sono/complicações , Apneia Obstrutiva do Sono/fisiopatologia , Animais , Pressão Positiva Contínua nas Vias Aéreas , Humanos , Hipóxia/etiologia , Fatores de Risco , Apneia Obstrutiva do Sono/terapiaRESUMO
OBJECTIVE: Acutely restricting sleep worsens insulin sensitivity in healthy individuals whose usual sleep is normal in duration and pattern. The effect of recovery or weekend 'catch-up' sleep on insulin sensitivity and metabolically active hormones in individuals with chronic sleep restriction who regularly 'catch-up' on sleep at weekends is as yet unstudied. DESIGN: 19 men (mean ± SEM age 28·6 ± 2·0 years, BMI 26·0 ± 0·8 kg/m(2) ) with at least 6 months' history (5·1 ± 0·9 years) of lifestyle-driven, restricted sleep during the working week (373 ± 6·6 min/night) with regular weekend 'catch-up' sleep (weekend sleep extension 37·4 ± 2·3%) completed an in-laboratory, randomized, crossover study comprising two of three conditions, stratified by age. Conditions were 3 weekend nights of 10 hours, 6 hours or 10 hours time-in-bed with slow wave sleep (SWS) suppression using targeted acoustic stimuli. MEASUREMENTS: Insulin sensitivity was measured in the morning following the 3rd intervention night by minimal modelling of 19 samples collected during a 2-h oral glucose tolerance test. Glucose, insulin, c-peptide, leptin, peptide YY (PYY), ghrelin, cortisol, testosterone and luteinizing hormone (LH) were measured from daily fasting blood samples; HOMA-IR, HOMA-ß and QUICKI were calculated. RESULTS: Insulin sensitivity was higher following three nights of sleep extension compared to sustained sleep restriction. Fasting insulin, c-peptide, HOMA-IR, HOMA-ß, leptin and PYY decreased with 'catch-up' sleep, QUICKI and testosterone increased, while morning cortisol and LH did not change. Targeted acoustic stimuli reduced SWS by 23%, but did not alter insulin sensitivity. CONCLUSIONS: Three nights of 'catch-up' sleep improved insulin sensitivity in men with chronic, repetitive sleep restriction. Methods to improve metabolic health by optimizing sleep are plausible.
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Privação do Sono/sangue , Sono/fisiologia , Adulto , Glicemia/metabolismo , Índice de Massa Corporal , Peptídeo C/sangue , Estudos Cross-Over , Grelina/sangue , Teste de Tolerância a Glucose , Humanos , Hidrocortisona/sangue , Insulina/sangue , Leptina/sangue , Hormônio Luteinizante/sangue , Masculino , Peptídeo YY/sangue , Testosterona/sangueRESUMO
Dyslipidaemia and increased oxidative stress have been reported in severe obstructive sleep apnea, and both may be related to the development of cardiovascular disease. We have previously shown in a randomized crossover study in patients with moderate to severe obstructive sleep apnea that therapeutic continuous positive airway pressure treatment for 8 weeks improved postprandial triglycerides and total cholesterol when compared with sham continuous positive airway pressure. From this study we have now compared the effect of 8 weeks of therapeutic continuous positive airway pressure and sham continuous positive airway pressure on oxidative lipid damage and plasma lipophilic antioxidant levels. Unesterified cholesterol, esterified unsaturated fatty acids (cholesteryl linoleate: C18:2; and cholesteryl arachidonate: C20:4; the major unsaturated and oxidizable lipids in low-density lipoproteins), their corresponding oxidized products [cholesteryl ester-derived lipid hydroperoxides and hydroxides (CE-O(O)H)] and antioxidant vitamin E were assessed at 20:30 hours before sleep, and at 06:00 and 08:30 hours after sleep. Amongst the 29 patients completing the study, three had incomplete or missing [CE-O(O)H] data. The mean apnea -hypopnoea index, age and body mass index were 38 per hour, 49 years and 32 kg m(-2) , respectively. No differences in lipid-based oxidative markers or lipophilic antioxidant levels were observed between the continuous positive airway pressure and sham continuous positive airway pressure arms at any of the three time-points [unesterified cholesterol 0.01 mm, P > 0.05; cholesteryl linoleate: C18:2 0.05 mm, P > 0.05; cholesteryl arachidonate: C20:4 0.02 mm, P = 0.05; CE-O(O)H 2.5 nm, P > 0.05; and lipid-soluble antioxidant vitamin E 0.03 µm, P > 0.05]. In this study, accumulating CE-O(O)H, a marker of lipid oxidation, does not appear to play a role in oxidative stress in obstructive sleep apnea.
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Antioxidantes/análise , Pressão Positiva Contínua nas Vias Aéreas , Lipídeos/sangue , Estresse Oxidativo , Apneia Obstrutiva do Sono/sangue , Apneia Obstrutiva do Sono/terapia , Biomarcadores/sangue , Índice de Massa Corporal , Feminino , Humanos , Lipídeos/química , Masculino , Pessoa de Meia-Idade , Sono/fisiologia , Apneia Obstrutiva do Sono/metabolismo , Apneia Obstrutiva do Sono/fisiopatologia , Fatores de Tempo , Vitamina E/sangueRESUMO
Point-of-collection testing (POCT) devices are widely used in roadside and workplace drug testing to identify recent cannabis use by measuring the presence of Δ9 -tetrahydrocannabinol (THC) in oral fluid (OF). However, the performance of POCT devices with oral medicinal cannabis products remains poorly described. In a randomised, double-blinded, crossover trial, adults with insomnia disorder (n = 20) received a single (2 mL) oral dose of oil containing 10 mg THC + 200 mg cannabidiol, or placebo, prior to sleep. Participants were tested with the Securetec DrugWipe® 5S (10 ng/mL THC cut-off) and Dräger DrugTest® 5000 (25 ng/mL THC cut-off) POCT devices at baseline (pre-treatment) and then at 0.5, 10, and 18 h post-treatment. An OF sample, taken at each time point, was also analysed using liquid chromatography-tandem mass spectrometry. Large individual variability in OF THC concentrations was observed 0.5 h post-treatment (range: 0-425 ng/mL; mean (SD) 48.7 (107.5) ng/mL). Both the Securetec DrugWipe® 5S and DrugTest® 5000 demonstrated poor sensitivity to THC at 0.5 h post-treatment (25% and 50%, respectively). At 10 and 18 h post-treatment, all participant OF THC concentrations were below screening cut-offs, and all test results were negative. These findings highlight the relatively poor sensitivity of both devices in detecting recent use of an oral medicinal cannabis product. They also suggest a low probability of obtaining a positive THC result the morning after ('one-off') use. Further research is required to establish the probability of obtaining a positive THC result with regular medicinal cannabis use.
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This comprehensive review delves into the potential of intranasal insulin delivery for managing Alzheimer's Disease (AD) while exploring the connection between AD and diabetes mellitus (DM). Both conditions share features of insulin signalling dysregulation and oxidative stress that accelerate inflammatory response. Given the physiological barriers to brain drug delivery, including the blood-brain barrier, intranasal administration emerges as a non-invasive alternative. Notably, intranasal insulin has shown neuroprotective effects, impacting Aß clearance, tau phosphorylation, and synaptic plasticity. In preclinical studies and clinical trials, intranasally administered insulin achieved rapid and extensive distribution throughout the brain, with optimal formulations exhibiting minimal systemic circulation. The detailed mechanism of insulin transport through the nose-to-brain pathway is elucidated in the review, emphasizing the role of olfactory and trigeminal nerves. Despite promising prospects, challenges in delivering protein drugs from the nasal cavity to the brain remain, including enzymes, tight junctions, mucociliary clearance, and precise drug deposition, which hinder its translation to clinical settings. The review encompasses a discussion of the strategies to enhance the intranasal delivery of therapeutic proteins, such as tight junction modulators, cell-penetrating peptides, and nano-drug carrier systems. Moreover, successful translation of nose-to-brain drug delivery necessitates a holistic understanding of drug transport mechanisms, brain anatomy, and nasal formulation optimization. To date, no intranasal insulin formulation has received regulatory approval for AD treatment. Future research should address challenges related to drug absorption, nasal deposition, and the long-term effects of intranasal insulin. In this context, the evaluation of administration devices for nose-to-brain drug delivery becomes crucial in ensuring precise drug deposition patterns and enhancing bioavailability.
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Administração Intranasal , Doença de Alzheimer , Encéfalo , Insulina , Humanos , Doença de Alzheimer/tratamento farmacológico , Doença de Alzheimer/metabolismo , Insulina/administração & dosagem , Insulina/farmacocinética , Insulina/uso terapêutico , Animais , Encéfalo/metabolismo , Sistemas de Liberação de Medicamentos , Hipoglicemiantes/administração & dosagem , Hipoglicemiantes/farmacocinética , Hipoglicemiantes/uso terapêutico , Mucosa Nasal/metabolismoRESUMO
BACKGROUND: In mid-later life adults, early-onset and late-onset (i.e., onset ≥50 years) depression appear to be underpinned by different pathophysiology yet have not been examined in relation to autonomic function. Sleep provides an opportunity to examine the autonomic nervous system as the physiology changes across the night. Hence, we aimed to explore if autonomic profile is altered in mid-later life adults with remitted early-onset, late-onset and no history of lifetime depression. METHODS: Participants aged 50-90 years (n = 188) from a specialised clinic underwent a comprehensive clinical assessment and completed an overnight polysomnography study. General Linear Models were used to examine the heart rate variability differences among the three groups for four distinct sleep stages and the wake after sleep onset. All analyses controlled for potential confounders - age, sex, current depressive symptoms and antidepressant usage. RESULTS: For the wake after sleep onset, mid-later life adults with remitted early-onset depression had reduced standard deviation of Normal to Normal intervals (SDNN; p = .014, d = -0.64) and Shannon Entropy (p = .004, d = -0.46,) than those with no history of lifetime depression. Further, the late-onset group showed a reduction in high-frequency heart rate variability (HFn.u.) during non-rapid eye movement sleep stage 2 (N2; p = .005, d = -0.53) and non-rapid eye movement sleep stage 3 (N3; p = .009, d = -0.55) when compared to those with no lifetime history. LIMITATIONS: Causality between heart rate variability and depression cannot be derived in this cross-sectional study. Longitudinal studies are needed to examine the effects remitted depressive episodes on autonomic function. CONCLUSION: The findings suggest differential autonomic profile for remitted early-onset and late-onset mid-later life adults during sleep stages and wake periods. The differences could potentially serve as peripheral biomarkers in conjunction with more disease-specific markers of depression to improve diagnosis and prognosis.
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Idade de Início , Sistema Nervoso Autônomo , Frequência Cardíaca , Polissonografia , Humanos , Frequência Cardíaca/fisiologia , Feminino , Masculino , Pessoa de Meia-Idade , Idoso , Idoso de 80 Anos ou mais , Sistema Nervoso Autônomo/fisiopatologia , Fases do Sono/fisiologia , Sono/fisiologia , Depressão/fisiopatologiaRESUMO
BACKGROUND AND AIMS: This study assessed whether the addition of continuous positive airway pressure (CPAP) during weight loss would enhance cardiometabolic health improvements in patients with obesity and Obstructive Sleep Apnoea (OSA). METHODS AND RESULTS: Patients with overweight or obesity, pre-diabetes and moderatesevere OSA were randomised to receive CPAP therapy with a weight loss programme (CPAP+WL) or a weight loss programme alone (WL alone). PRIMARY OUTCOME: 2-hour glucose assessed by an oral glucose tolerance test. SECONDARY OUTCOMES: 24 hr blood pressure, body composition (DEXA) and fasting blood markers. 17 patients completed 3-month follow-up assessments (8 CPAP+WL and 9 WL alone). Overall, participants in both groups lost â¼12 kg which reduced polysomnography determined OSA severity by â¼45 %. In the CPAP+WL group, CPAP use (compliance 5.29 hrs/night) did not improve any outcome above WL alone. There was no improvement in 2-hour glucose in either group. However, in the pooled (n = 17) analysis there were overall improvements in most outcomes including insulin sensitivity (.000965 units, p = .008), sleep systolic BP (- 16.2 mmHg, p = .0003), sleep diastolic BP (-9.8 mmHg, p = 0.02), wake diastolic BP (- 4.3 mmHg, p = .03) and sleepiness (Epworth Sleepiness Score -3.2, p = .0003). In addition, there were reductions in glucose area under the curve (-230 units, p = .009), total (-0.86 mmol/L, p = 0.006) and LDL cholesterol (-0.58 mmol/L, p = 0.007), triglycerides (-0.75 mmol/L, p = 0.004), fat mass (-7.6 kg, p < .0001) and abdominal fat (-310 cm3, p < .0001). CONCLUSION: Weight loss reduced OSA and improved sleepiness and cardiometabolic health. These improvements were not further enhanced by using CPAP. Results suggest weight loss should be the primary focus of treatment for patients with OSA and obesity.
Assuntos
Glicemia , Pressão Positiva Contínua nas Vias Aéreas , Obesidade , Apneia Obstrutiva do Sono , Redução de Peso , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Glicemia/metabolismo , Pressão Sanguínea , Pressão Positiva Contínua nas Vias Aéreas/métodos , Teste de Tolerância a Glucose , Resistência à Insulina , Obesidade/terapia , Obesidade/complicações , Sobrepeso/terapia , Sobrepeso/complicações , Projetos Piloto , Polissonografia , Apneia Obstrutiva do Sono/terapia , Apneia Obstrutiva do Sono/complicações , Resultado do Tratamento , Programas de Redução de Peso/métodosRESUMO
Obstructive sleep apnoea (OSA) is highly prevalent in mild cognitive impairment (MCI) and Alzheimer's disease (AD). The gold standard treatment for OSA is continuous positive airway pressure (CPAP). Long-term, well-powered efficacy trials are required to understand whether CPAP could slow cognitive decline in individuals with MCI/AD, but its tolerability in this group remains uncertain. The present review investigates CPAP adherence among individuals with OSA and MCI/AD. Electronic searches were performed on 8 databases. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were followed. Six independent studies and four secondary analyses included 278 unique participants (mean age = 72.1 years). In five of the retained studies, around half of participants (45% N = 85 MCI, 56% N = 22 AD) were adherent to CPAP, where ≥4 h use per night was considered adherent. Three of the retained studies also reported average CPAP use to range between 3.2 and 6.3 h/night. CPAP adherence in individuals with MCI and AD is low, albeit similar to the general elderly population. Reporting adherence in future studies as both average duration as well as using a binary cut-off would improve our understanding of the optimum CPAP use in dementia clinical trials and care.