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IMPORTANCE: The symptoms of primary hyperparathyroidism are often subtle, such as fatigue, mood changes, and sleep disturbances. After parathyroidectomy, patients often report improvement in sleep and mood; however, objective data supporting these improvements is lacking. OBJECTIVE: This prospective study uses standard measures to objectively and subjectively assess sleep in patients with primary hyperparathyroidism before and after parathyroidectomy. DESIGN: A longitudinal prospective study was conducted over three one-week-long periods: pre-parathyroidectomy, 1-week post-parathyroidectomy, and three months post-parathyroidectomy. During each time point, patients wore an actigraphy device, recorded a sleep diary, and completed the Pittsburgh Sleep Quality Index (PSQI), Insomnia Severity Index (ISI), and Depression Anxiety Stress Scale (DASS). Statistical analysis was performed using repeated measures models to compare the average measures among the three time points and test for trends over time. SETTING: Single institution, tertiary care center. PARTICIPANTS: Patients with primary hyperparathyroidism from ages 18 to 89 years old. EXPOSURE: Parathyroidectomy between September 2020 and January 2024. MAIN OUTCOMES AND MEASURES: Actigraphy data, consensus sleep diary, Pittsburgh Sleep Quality Index (PSQI), Insomnia Severity Index (ISI), Depression Anxiety Stress Scales - 21 Items (DASS). RESULTS: Thirty-six patients were enrolled, and 34 patients completed the study. Actigraphy data showed a significant negative trend in average sleep latency (p = 0.045) and average time in bed (p = 0.046). Sleep diary data showed additional differences in the number of awakenings (p = 0.002), wake after sleep onset (p < 0.001), sleep quality (p < 0.001), and sleep efficiency (p = 0.02) among the three time points and/or as a significant negative trend. PSQI and ISI scores were significantly different among the three time points (p = 0.002 and p < 0.001, respectively) and also declined significantly over time (p = 0.008 and p = 0.007, respectively). DASS depression, anxiety, and stress scores were significantly different among the three time points (p < 0.001, p = 0.01, and p < 0.001, respectively), and stress also declined significantly over time (p = 0.005). CONCLUSION AND RELEVANCE: This study represents the most extensive prospective study demonstrating objective and subjective sleep and mood improvement in patients with primary hyperparathyroidism after parathyroidectomy.
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Actigrafia , Hiperparatireoidismo Primário , Paratireoidectomia , Humanos , Hiperparatireoidismo Primário/cirurgia , Hiperparatireoidismo Primário/complicações , Hiperparatireoidismo Primário/psicologia , Pessoa de Meia-Idade , Masculino , Feminino , Estudos Prospectivos , Idoso , Adulto , Estudos Longitudinais , Idoso de 80 Anos ou mais , Qualidade do Sono , Adulto Jovem , Adolescente , Depressão/etiologia , Resultado do Tratamento , Sono/fisiologia , Índice de Gravidade de Doença , Distúrbios do Início e da Manutenção do Sono/etiologiaRESUMO
Insomnia nosology has significantly evolved since the Diagnostic and Statistical Manual (DSM)-III-R first distinguished between 'primary' and 'secondary' insomnia. Prior International Classification of Sleep Disorders (ICSD) nosology 'split' diagnostic phenotypes to address insomnia's heterogeneity and the DSM nosology 'lumped' them into primary insomnia, while both systems assumed causality for insomnia secondary to health conditions. In this systematic review, we discuss the historical phenotypes in prior insomnia nosology, present findings for currently proposed insomnia phenotypes based on more robust approaches, and critically appraise the most relevant ones. Electronic databases PsychINFO, PubMED, Web of Science, and references of eligible articles, were accessed to find diagnostic manuals, literature on insomnia phenotypes, including systematic reviews or meta-analysis, and assessments of the reliability or validity of insomnia diagnoses, identifying 184 articles. The data show that previous insomnia diagnoses lacked reliability and validity, leading current DSM-5-TR and ICSD-3 nosology to 'lump' phenotypes into a single diagnosis comorbid with health conditions. However, at least two new, robust insomnia phenotyping approaches were identified. One approach is multidimensional-multimethod and provides evidence for self-reported insomnia with objective short versus normal sleep duration linked to clinically relevant outcomes, while the other is multidimensional and provides evidence for two to five clusters (phenotypes) based on self-reported trait, state, and/or life-history data. Some approaches still need replication to better support whether their findings identify true phenotypes or simply different patterns of symptomatology. Regardless, these phenotyping efforts aim at improving insomnia nosology both as a classification system and as a mechanism to guide treatment.
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Distúrbios do Início e da Manutenção do Sono , Humanos , Classificação Internacional de Doenças , Fenótipo , Reprodutibilidade dos Testes , Autorrelato , Distúrbios do Início e da Manutenção do Sono/diagnósticoRESUMO
About 5.4%-45.7% of the general population has mild-to-moderate obstructive sleep apnea (mmOSA), which is highly comorbid with cardiovascular and/or cerebrovascular diseases (CBVD). We examined the association between mmOSA and all-cause mortality and the modifying effect of age and CBVD. A total of 1681 adults 20-88 years old from the Penn State Adult Cohort (PSAC) (41.9% male) were followed up for 20.1 ± 6.2 years for all-cause mortality. Mild and moderate OSA were defined as an apnea/hypopnea index (AHI) 5-14.9 and 15-29.9 events/hour, respectively. CBVD was defined as a report of a physician diagnosis or treatment for heart disease and/or stroke. Cox proportional hazards regression models were used to estimate all-cause mortality adjusted for confounders. All-cause mortality risk was significantly increased in the mmOSA group in young and middle-aged adults (<60 years) (HR = 1.59, 95%CI 1.08-2.04) but not in older adults (≥60 years) (HR = 1.05, 95%CI 0.80-1.39). A synergistic effect between mmOSA and CBVD was stronger in those <60 years (HR = 3.82, 95%CI 2.25-6.48 in <60 years vs 1.86 95%CI 1.14-3.04 in ≥60 years). There was an additive effect between moderate OSA and hypertension in <60 but not in those ≥60 years. Mild OSA was associated with all-cause mortality only in the presence of CBVD. Mortality risk is increased in young and middle-aged adults with moderate OSA, whereas the mortality risk associated with mild OSA is elevated only, regardless of age, in the presence of comorbid CBVD. AHI cut-offs warranting treatment of mmOSA may need to be adjusted based on age and comorbidities.
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Insomnia with objective short sleep duration has been proposed as the most biologically severe phenotype of the disorder associated with cardiometabolic morbidity in population-based samples. In this study, we investigated the association between insomnia with objective short sleep duration and hypertension in a large clinical sample. We studied 348 patients diagnosed with chronic insomnia disorder based on International Classification of Sleep Disorders Third Edition criteria and 150 normal sleepers. Objective short sleep duration was defined by the median total sleep time of the sample (< 7 hr) measured with 1-night polysomnography. Hypertension was defined based on blood pressure levels, antihypertensive medication use and/or a physician diagnosis. After adjusting for potential confounders, patients with chronic insomnia disorder who slept < 7 hr were associated with 2.8-fold increased odds of hypertension compared with normal sleepers who slept ≥ 7 hr (odds ratio = 2.81, 95% confidence interval = 1.068-7.411) or < 7 hr (odds ratio = 2.75, 95% confidence interval = 1.005-7.542), whereas patients with chronic insomnia disorder who slept ≥ 7 hr (odds ratio = 1.52, 95% confidence interval = 0.537-4.285) or normal sleepers who slept < 7 hr (odds ratio = 1.07, 95% confidence interval = 0.294-3.904) were not significantly associated with increased odds of hypertension compared with normal sleepers who slept ≥ 7 hr. Linear regression analyses showed that, for every hour decrease in total sleep time, systolic and diastolic blood pressure increased by 1.014 mmHg (p = 0.045) and 0.923 mmHg (p = 0.015), respectively, in patients with chronic insomnia disorder but not in normal sleepers. Our findings further support that insomnia with objective short sleep duration is a risk factor for hypertension, and objective short sleep duration may be a useful marker of the biological severity of chronic insomnia disorder in clinical practice.
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Hipertensão , Distúrbios do Início e da Manutenção do Sono , Transtornos do Sono-Vigília , Humanos , Distúrbios do Início e da Manutenção do Sono/complicações , Duração do Sono , Sono/fisiologia , Hipertensão/diagnóstico , Transtornos do Sono-Vigília/complicaçõesRESUMO
BACKGROUND: Both air pollution and poor sleep have been associated with increased risk of cardiovascular diseases. However, the association between air pollution and sleep health, especially among adolescents, is rarely investigated. METHODS: To investigate the association between fine particulate (PM2.5) air pollution and habitual sleep patterns, we analyzed data obtained from 246 adolescents who participated in the Penn State Child Cohort follow-up examination. We collected their individual-level 24-h (short-term) PM2.5 concentration by using a portable monitor. We estimated their residential-level PM2.5 concentration during the 60-day period prior to the examination (intermediate-term) using a kriging approach. Actigraphy was used to measure participants' sleep durations for seven consecutive nights. Habitual sleep duration (HSD) and sleep variability (HSV) were calculated as the mean and SD of the seven-night sleep duration. Multivariable-adjusted linear regression models were used to assess the association between PM2.5 exposures and HSD/HSV. An interaction between short-term and intermediate-term PM2.5 was created to explore their synergistic associations with HSD/HSV. RESULTS: Elevated short-term and intermediate-term PM2.5 exposure were significantly (p < 0.05) associated with higher HSV, but not HSD. Specifically, the mean (95% CI) increase in HSV associated with 1 SD higher 24-h (26.3 µg/m3) and 60-day average (2.2 µg/m3) PM2.5 were 14.6 (9.4, 14.8) and 4.9 (0.5, 9.2) minutes, respectively. In addition, there was a synergistic interaction (p = 0.08) between short-term and intermediate-term PM2.5 exposure on HSV, indicative that the association between intermediate-term PM2.5 and HSV became stronger as short-term PM2.5 increases, and vice versa. CONCLUSION: Short-term individual-level and intermediate-term residential-level PM2.5 exposures are adversely and synergistically associated with increased sleep variability, an indicator of instability of sleep quantity, in adolescents. Through such an association with sleep pattern, PM2.5 air pollution may increase long-term cardiometabolic risks.
Assuntos
Poluentes Atmosféricos , Poluição do Ar , Criança , Humanos , Adolescente , Estudos Transversais , Material Particulado/análise , Poluição do Ar/efeitos adversos , Poluição do Ar/análise , Sono , Poeira , Poluentes Atmosféricos/análise , Exposição Ambiental/análiseRESUMO
Our study is the first using multiple variables to compare concurrent with longitudinal predictors of cognitive disengagement syndrome (CDS). The population-based sample comprised 376 youth (mean baseline age 8.7 and follow-up 16.4 years) rated by parents on the Pediatric Behavior Scale. The baseline CDS score was the strongest predictor of follow-up CDS. Baseline autism and insomnia symptoms also predicted follow-up CDS above and beyond baseline CDS. Autism, insomnia, inattention, somatic complaints, and excessive sleep were concurrently related to CDS at baseline and follow-up. Additionally, follow-up depression was associated with follow-up CDS, and baseline hyperactivity/impulsivity was negatively associated with baseline CDS. Oppositional defiant/conduct problems and anxiety were nonsignificant. Age, sex, race, and parent occupation were unrelated to CDS, and correlations between baseline CDS and 15 IQ, achievement, and neuropsychological test scores were nonsignificant. Results indicate childhood CDS is the strongest risk factor for adolescent CDS, followed by autism and insomnia symptoms.
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BACKGROUND: A high comorbidity between attention-deficit/hyperactivity disorder (ADHD) and obstructive sleep apnea (OSA) as well as similar impairments across neurobehavioral outcomes has been described in children. However, there is a paucity of research examining the comorbidity of these two disorders in adolescents. This study examined the association of OSA with sleep, neurobehavioral, and cardiometabolic outcomes in adolescents with ADHD from the general population. METHODS: 421 adolescents (16.9 ± 2.3 years, 53.9% male) underwent 9-hr polysomnography, neurobehavioral, and physical evaluation. ADHD was ascertained by a parent-or-self-report of a lifetime diagnosis/treatment of ADHD. OSA was defined as an apnea hypopnea index of ≥2 events/hour. Groups of controls (n = 208), OSA-alone (n = 115), ADHD-alone (n = 54), and ADHD+OSA (n = 44) were studied. Multivariable-adjusted general linear models tested group differences in PSG parameters, neurobehavioral, and cardiometabolic outcomes after controlling for sex, race/ethnicity, age, and/or body mass index percentile. RESULTS: The ADHD+OSA group had significantly longer sleep onset latency, shorter total sleep time, lower sleep efficiency, and higher percent of stage 1 sleep, as compared with all other groups, however, these differences were diminished by excluding adolescents on psychoactive medication. The ADHD-alone group showed significantly higher periodic limb movements than controls. The ADHD+OSA and ADHD-alone groups did not significantly differ on any measure of neurocognitive or behavioral functioning. The ADHD+OSA and OSA-alone groups showed significantly worse cardiometabolic and inflammatory biomarkers when compared to controls or the ADHD-alone, but did not significantly differ between each other. CONCLUSIONS: Adolescents with a diagnosis ADHD+OSA showed phenotypic risk factors for OSA (i.e., overweight/obesity, visceral adiposity, metabolic syndrome, and inflammation) but not worse neurobehavioral outcomes when compared with ADHD-alone. While comorbidity is possible, these data support that adolescents with a suspicion of ADHD should be screened for OSA, before a diagnosis is reached and psychoactive medication initiated.
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Transtorno do Deficit de Atenção com Hiperatividade , Doenças Cardiovasculares , Apneia Obstrutiva do Sono , Adolescente , Transtorno do Deficit de Atenção com Hiperatividade/complicações , Transtorno do Deficit de Atenção com Hiperatividade/epidemiologia , Doenças Cardiovasculares/complicações , Doenças Cardiovasculares/epidemiologia , Criança , Feminino , Humanos , Masculino , Polissonografia , Sono , Apneia Obstrutiva do Sono/complicações , Apneia Obstrutiva do Sono/diagnóstico , Apneia Obstrutiva do Sono/epidemiologiaRESUMO
Although insomnia is by far the most common sleep disorder, our understanding of its neurobiology is limited. Insomnia, particularly when associated with objective sleep disturbance, has been associated with activation of the hypothalamic-pituitary-adrenal axis. The objective of this experimental study was to compare the response of the hypothalamic-pituitary-adrenal axis to ovine corticotropin-releasing hormone, a stress test, in men with insomnia versus controls. Circulating adrenocorticotropic hormone and cortisol levels were assayed before (-30 min, -15 min), at (0 min) and after (+5 min, +15 min, +30 min, +60 min, +90 min, +120 min) exogenous ovine corticotropin-releasing hormone administration in 23 men (11 insomnia, 12 controls), who underwent four consecutive nights of in-lab polysomnography. Men with insomnia compared with controls demonstrated markedly and significantly shorter total sleep time (368.4 ± 8.99â min versus 411.61 ± 8.61 min; p < 0.01) and lower sleep efficiency (76.77 ± 1.80% versus 86.04 ± 1.72%; p < 0.01) on polysomnography, and showed decreased adrenocorticotropic hormone and cortisol levels after ovine corticotropin-releasing hormone administration. Adrenocorticotropic hormone levels at 15â min and 30 min were significantly lower in men with insomnia than in controls (p < 0.05). Similarly, the peak levels of cortisol at +60 min, and the total and net area under the curve levels of this hormone were significantly lower in men with insomnia than controls (all p < 0.01). Adrenocorticotropic hormone and cortisol response to ovine corticotropin-releasing hormone administration was attenuated in men with insomnia associated with objective sleep disturbance, suggesting that objectively defined insomnia subtypes have a disrupted hypothalamic-pituitary-adrenal axis function and highlight the need to develop treatments targeting the underlying hypothalamic-pituitary-adrenal axis dysregulation.
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Distúrbios do Início e da Manutenção do Sono , Transtornos do Sono-Vigília , Hormônio Adrenocorticotrópico/metabolismo , Animais , Hormônio Liberador da Corticotropina/farmacologia , Feminino , Humanos , Hidrocortisona , Sistema Hipotálamo-Hipofisário/metabolismo , Masculino , Sistema Hipófise-Suprarrenal/metabolismo , OvinosRESUMO
Trazodone and cognitive-behavioural treatment for insomnia (CBT-I) are widely used to treat patients with chronic insomnia. Although both treatments improve sleep continuity, no study has compared their comparative effectiveness in modifying spectral electroencephalographic (EEG) activity during sleep in humans. In this study, participants included 19 men and women with chronic insomnia who were randomized to either trazodone (n = 8) or CBT-I (n = 11) treatment for 3 months. We examined delta (0.39-3.91 Hz), theta (4.30-7.81 Hz), alpha (8.20-11.72 Hz), sigma (12.11-14.84 Hz), beta (15.23-35.16 Hz) and gamma (35.55-49.61 Hz) relative power during non-rapid eye movement (NREM) sleep at pre-treatment, 3- month post-treatment and 6-month follow-up. This study was registered in Clinical Trials (NCT01348542). We found trazodone but not CBT-I significantly decreased sigma (p = .041, d = 0.88; time × group p = .009) and beta (p = .005, d = 1.41; time × group p = .016) power during NREM sleep at post-treatment. Compared to CBT-I, trazodone increased delta (p = .018) and decreased sigma (p = .013) and beta (p = .023) power during NREM sleep at post-treatment. At follow-up, we did not observe significant changes in relative EEG power during NREM sleep in either the CBT-I or trazodone group compared to pre-treatment. Compared to CBT-I, trazodone decreased alpha (p = .039) and sigma (p = .009) power during NREM sleep at follow-up. In conclusion, trazodone, but not CBT-I, decreased fast-frequency EEG activity during NREM sleep. Compared to CBT-I, trazodone appears to have a stronger impact on cortical and physiological hyperarousal in patients with chronic insomnia.
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Terapia Cognitivo-Comportamental , Distúrbios do Início e da Manutenção do Sono , Sono , Trazodona , Cognição , Eletroencefalografia , Feminino , Humanos , Masculino , Polissonografia , Distúrbios do Início e da Manutenção do Sono/tratamento farmacológico , Trazodona/uso terapêuticoRESUMO
Background: In contrast to pre-sleep cognitive arousal, self-reported pre-sleep somatic arousal is a rather elusive construct for which little validity has been provided. Thus, the clinical significance of somatic symptoms during the pre-sleep period remains unknown. Participants: 248 patients (45.0 ± 16.7 years old, 65.3% female) with a diagnosis of chronic insomnia disorder, out of 388 consecutive patients evaluated at the Behavioral Sleep Medicine (BSM) program of Penn State Hershey Sleep Research & Treatment Center. Methods: Participants completed the Pre-sleep Arousal Scale assessing cognitive (PSAS-C) and somatic (PSAS-S) arousal as well as the Insomnia Severity Index (ISI), Ford Insomnia Response to Stress Test (FIRST), Arousal Predisposition Scale (APS), and Depression Anxiety Stress Scale (DASS). Multivariable stepwise regression assessed which clinical factors were independently associated with greater PSAS-C and PSAS-S scores. Receiver operating characteristic analysis determined the predictive value for identifying sleep reactivity (FIRST≥18) and clinical anxiety (DASS-A ≥ 10) and clinically useful cutoff scores. Results: The strongest correlates of PSAS-S were DASS-A (ß = 0.64) and chronic pain (ß = 0.11), while those of PSAS-C were FIRST (ß = 0.29) and a history of stroke (ß = 0.10). A PSAS-S score of 14.8 (AUC = 0.87, 95%CI = 0.83-0.91) and a PSAS-C score of 24.5 (AUC = 0.82, 95%CI = 0.76-0.88) showed the best balance in specificity and sensitivity to identify clinical anxiety and sleep reactivity, respectively. Conclusions: Self-reported pre-sleep somatic symptoms are a marker of comorbid anxiety and, potentially chronic pain, impacting nighttime sleep. The optimal cutoff scores of 14 and 20 proposed herein can help clinicians with case formulation, with tailoring BSM treatments and their targets.
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Nível de Alerta/fisiologia , Distúrbios do Início e da Manutenção do Sono/terapia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Doença Crônica , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Autorrelato , Inquéritos e Questionários , Adulto JovemRESUMO
BACKGROUND: Insomnia has been associated in cross-sectional studies with increased beta (15-35 Hz) electroencephalogram (EEG) power during nonrapid eye movement (NREM) sleep, an index of cortical hyperarousal. However, it is unknown whether this cortical hyperarousal is present before individuals with insomnia develop the disorder. To fill this gap, we examined the association of childhood sleep high-frequency EEG activity with incident insomnia symptoms (i.e., absence of insomnia symptoms in childhood but presence in adolescence). METHODS: We studied a case-control subsample of 45 children (6-11 years) from the Penn State Child Cohort, a population-based random sample of 421 children, who were followed up after 8 years as adolescents (13-20 years). We examined low-beta (15-25 Hz) and high-beta (25-35 Hz) relative power at central EEG derivations during NREM sleep and, in secondary analyses, during sleep onset latency, sleep onset, and REM sleep. Incident insomnia symptoms were defined as the absence of parent-reported difficulty falling and/or staying asleep during childhood and a self-report of these insomnia symptoms during adolescence. RESULTS: Childhood high-beta power during NREM sleep was significantly increased in children who developed insomnia symptoms in adolescence (n = 25) as compared to normal sleeping controls (n = 20; p = .03). Multivariable-adjusted logistic regression models showed that increased childhood high-beta EEG power during NREM sleep was associated with a threefold increased odds (95% CI = 1.12-7.98) of incident insomnia symptoms in adolescence. No other significant relationships were observed for other sleep/wake states or EEG frequency bands. CONCLUSIONS: Increased childhood high-frequency EEG power during NREM sleep is associated with incident insomnia symptoms in adolescence. This study indicates that cortical hyperarousal during sleep may be a premorbid neurophysiological sign of insomnia, which may mediate the increased risk of psychiatric disorders associated with insomnia.
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Ritmo beta/fisiologia , Eletroencefalografia , Distúrbios do Início e da Manutenção do Sono/diagnóstico , Fases do Sono/fisiologia , Adolescente , Adulto , Estudos de Casos e Controles , Criança , Feminino , Seguimentos , Humanos , Incidência , Masculino , Adulto JovemRESUMO
Self-reported somatic arousal remains a challenging clinical construct, particularly because only a subset of patients report symptoms such as racing heart, palpitations or increased body temperature interfering with their sleep. It is unclear whether self-reported somatic arousal is a marker of hyperarousal or co-morbid clinical anxiety in individuals with insomnia. Participants included 196 young adults aged 20.2â ±â 1.0â years old who were predominantly females (75%). About 39% of the sample reported subthreshold insomnia, and about 8% reported clinically significant insomnia, based on their Insomnia Severity Index. Participants completed the Pre-Sleep Arousal Scale, Beck Anxiety Inventory, Beck Depression Inventory, Arousal Predisposition Scale, and Ford Insomnia Response to Stress Test. Multivariable stepwise regression assessed which factors were independently associated with pre-sleep cognitive (Pre-Sleep Arousal Scale-Cognitive) and somatic (Pre-Sleep Arousal Scale-Somatic) arousal. Receiver-operating characteristic analysis assessed the predictive value to identify clinically significant anxiety (Beck Anxiety Inventoryâ ≥â 20), insomnia (Insomnia Severity Indexâ ≥â 15) and arousability (Arousal Predisposition Scaleâ ≥â 32). Beck Anxiety Inventory (ßâ =â 0.42) was the best single correlate of Pre-Sleep Arousal Scale-Somatic, while Insomnia Severity Index (ßâ =â 0.33) was of Pre-Sleep Arousal Scale-Cognitive. A Pre-Sleep Arousal Scale-Somatic score of 12 or more identified those with clinically significant anxiety with 65% specificity and 65% sensitivity, while a cut-off score of 14 increased its sensitivity (86%). Self-reported pre-sleep somatic arousal may be an index of co-morbid clinical anxiety in individuals with insomnia. These findings aid clinicians with assessment and treatment, particularly in the absence of clinical guidelines indicating when somatically focused relaxation techniques should be included as part of multicomponent cognitive behavioural treatment of insomnia.
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Ansiedade/fisiopatologia , Nível de Alerta/fisiologia , Sono/fisiologia , Vigília/fisiologia , Adulto , Feminino , Humanos , Masculino , Autorrelato , Inquéritos e Questionários , Adulto JovemRESUMO
PURPOSE OF REVIEW: To summarize research from the past 2 years on the association between insomnia, short sleep duration, and hypertension and provide a critical analysis of the evidence and suggestions for future directions in this field. RECENT FINDINGS: Evidence indicates that the association between insomnia and elevated blood pressure (BP) or stage 1 and 2 hypertension is stronger in those with chronic insomnia, as compared to those with isolated insomnia symptoms, and primarily found in those with the insomnia with objective short sleep duration phenotype. There is a key gap in ambulatory BP monitoring across the sleep-wake cycle as well as in randomized clinical trials testing the effectiveness of pharmacological or cognitive-behavioral insomnia therapies in lowering BP. Insomnia is a strong candidate to join the list of risk factors for hypertension along with obstructive sleep apnea. In the meantime, chronic insomnia should become part of the routine assessment of patients with elevated BP and should be a source for referral, diagnostic evaluation, and treatment, rather than regarded as a symptom of the underlying medical disorder.
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Pressão Sanguínea/fisiologia , Gerenciamento Clínico , Hipertensão/prevenção & controle , Distúrbios do Início e da Manutenção do Sono/terapia , Sono/fisiologia , Monitorização Ambulatorial da Pressão Arterial , Humanos , Hipertensão/etiologia , Hipertensão/fisiopatologia , Fatores de Risco , Distúrbios do Início e da Manutenção do Sono/complicações , Distúrbios do Início e da Manutenção do Sono/fisiopatologiaRESUMO
Inflammation has been suggested as a potential pathway by which insomnia and short sleep can affect risk of morbidity in adults. However, few studies have examined the association of insomnia with inflammation in adolescents, despite accumulating evidence that pathophysiologic changes may already occur during this critical developmental period. The present study sought to examine the association of insomnia symptoms with systemic inflammation and the role of objective sleep duration in this association. Participants were 378 adolescents (16.9±2.3y, 45.8% female) from the Penn State Child Cohort, a population-based sample who underwent 9-h polysomnography (PSG) followed by a single fasting blood draw to assess plasma levels of C-reactive protein (CRP) and other inflammatory markers. Insomnia symptoms were defined by a self-report of difficulties falling and/or staying asleep, while objective sleep duration groups were defined as a PSG total sleep time ⩾8, 8-7, and ⩽7h. We assessed the association of insomnia symptoms, objective sleep duration, and their interaction with inflammatory markers, while adjusting for multiple potential confounders. Adolescents reporting insomnia symptoms had significantly higher levels of CRP compared to controls and a significant interaction (p<0.01) showed that objective sleep duration modified this association. Elevated CRP was present in adolescents with insomnia symptoms and ⩽7h of sleep (1.79mg/L) as compared to controls or adolescents with insomnia symptoms and ⩾8h of sleep (0.90mg/L and 0.98mg/L, respectively) or controls with ⩽7h of sleep (0.74mg/L; all p-values <0.01). In sum, insomnia symptoms with objective short sleep duration are associated with systemic inflammation as early as adolescence. This study suggests that chronic low-grade inflammation may be a common final pathway towards morbidity in adulthood in this insomnia phenotype.
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Proteína C-Reativa/análise , Inflamação/sangue , Distúrbios do Início e da Manutenção do Sono/sangue , Sono/fisiologia , Adolescente , Biomarcadores/sangue , Feminino , Humanos , Masculino , Fatores de Risco , Adulto JovemRESUMO
While chronic systemic inflammation in obstructive sleep apnea (OSA) has been traditionally considered a consequence of intermittent hypoxia, several treatment studies targeting inflammation suggest that this process may precede the development of the disorder. A recent cross-sectional study in the Penn State Child Cohort (PSCC) revealed that inflammation largely mediates the association between visceral adiposity and OSA in adolescence. The purpose of this study was to examine for the first time whether, longitudinally, inflammation precedes OSA during this developmental period. A subsample of the PSCC with longitudinal sleep and inflammation data (n=51) was included in this study. Participants underwent 9-h polysomnography (22:00-7:00), physical exam, and fasting morning blood draw at both time points. Plasma C-reactive protein (CRP) was measured via ELISA. At follow-up, visceral, subcutaneous, and total fat area were assessed via dual X-ray absorptiometry. Sex differences in body composition emerged in adolescence, with boys having more visceral adiposity than girls. Longitudinal increases in waist circumference from childhood to adolescence were associated with increases in CRP (ΔCRP) and follow-up CRP in boys, but not girls. Furthermore, in boys, ΔCRP was associated with higher follow-up apnea/hypopnea index (AHI). When ΔCRP was entered into a model predicting follow-up AHI, Δwaist circumference was no longer significant, indicating that inflammation largely explains the association between increasing central obesity and OSA severity. These preliminary findings, in a longitudinal, non-clinical sample of children developing OSA, suggest that inflammation derived from visceral adipose tissue precedes the development of the disorder, suggesting a potential causal mechanism.
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Desenvolvimento Infantil , Inflamação/complicações , Síndromes da Apneia do Sono/complicações , Composição Corporal , Proteína C-Reativa/metabolismo , Criança , Progressão da Doença , Humanos , Inflamação/epidemiologia , Estudos Longitudinais , Masculino , Polissonografia , Caracteres Sexuais , Síndromes da Apneia do Sono/epidemiologiaRESUMO
Only a handful of studies, primarily in clinical samples, have reported an association between obesity, inflammation, and obstructive sleep apnea (OSA) in children and adolescents. No studies, however, have examined the pathogenetic link between visceral adiposity, systemic inflammation, and incident OSA in a large general population sample using objective measures of sleep and body fat. Adolescents (n = 392; mean age 17.0 ± 2.2 yr, 54.0% male) from the Penn State Child Cohort (PSCC) underwent 9-h overnight polysomnography; a DXA scan to assess body fat distribution; and a single fasting blood draw for the assessment of plasma interleukin-6 (IL-6), IL-6 soluble receptor (IL-6 sR), tumor necrosis factor alpha (TNFα), tumor necrosis factor receptor 1A (TNFR1), C-reactive protein (CRP), leptin, and adiponectin levels via ELISA. Visceral fat area was significantly elevated in moderate OSA (AHI ≥ 5), especially in boys. IL-6, CRP, and leptin were highest in adolescents with moderate OSA, even after adjusting for BMI percentile. Mediation analysis revealed that 42% of the association between visceral fat and OSA in adolescents was mediated by IL-6 (p = 0.03), while 82% of the association was mediated by CRP (p = 0.01). These data are consistent with the model of a feed-forward, vicious cycle, in which the release of proinflammatory cytokines by visceral adipocytes largely explains the association between central obesity and OSA; in turn, inflammation is also elevated in OSA independent of BMI. These findings, in a large, representative, non-clinical sample of young people, add to our understanding of the developmental pathogenesis of sleep apnea.
Assuntos
Adipocinas/imunologia , Proteína C-Reativa/imunologia , Citocinas/imunologia , Inflamação , Obesidade Abdominal/imunologia , Receptores de Citocinas/imunologia , Apneia Obstrutiva do Sono/imunologia , Absorciometria de Fóton , Adiponectina/imunologia , Adolescente , Distribuição da Gordura Corporal , Comorbidade , Ensaio de Imunoadsorção Enzimática , Feminino , Humanos , Interleucina-6/imunologia , Leptina/imunologia , Masculino , Obesidade Abdominal/diagnóstico por imagem , Obesidade Abdominal/epidemiologia , Polissonografia , Receptores de Interleucina-6/imunologia , Receptores Tipo I de Fatores de Necrose Tumoral/imunologia , Fatores Sexuais , Apneia Obstrutiva do Sono/diagnóstico , Apneia Obstrutiva do Sono/epidemiologia , Fator de Necrose Tumoral alfa/imunologia , Adulto JovemRESUMO
Previous findings on the association of obstructive sleep apnoea (OSA) and the hypothalamic-pituitary-adrenal (HPA) axis are inconsistent, partly due to the confounding effect of obesity and infrequent sampling. Our goal was to examine whether in a relatively nonobese population, OSA is associated with elevated cortisol levels and to assess the effects of a 2-month placebo-controlled continuous positive airway pressure (sham-CPAP) use.72 subjects (35 middle-aged males and post-menopausal females with OSA, and 37 male and female controls) were studied in the sleep laboratory for four nights. 24-h blood sampling was performed every hour on the fourth day and night in the sleep laboratory at baseline, after sham-CPAP and after CPAP treatment.In both apnoeic men and women, OSA was associated with significantly higher 24-h cortisol levels compared with controls, whereas CPAP lowered cortisol levels significantly, close to those of controls.These results suggest that OSA in nonobese men and slightly obese women is associated with HPA axis activation, similar albeit stronger compared with obese individuals with sleep apnoea. Short-term CPAP use decreased cortisol levels significantly compared with baseline, indicating that CPAP may have a protective effect against comorbidities frequently associated with chronic activation of the HPA axis, e.g. hypertension.
Assuntos
Pressão Positiva Contínua nas Vias Aéreas/métodos , Hidrocortisona/metabolismo , Sistema Hipotálamo-Hipofisário/metabolismo , Sistema Hipófise-Suprarrenal/metabolismo , Apneia Obstrutiva do Sono/terapia , Adulto , Idoso , Ansiedade/metabolismo , Ansiedade/psicologia , Pressão Sanguínea , Estudos de Casos e Controles , Ritmo Circadiano , Estudos Cross-Over , Depressão/metabolismo , Depressão/psicologia , Método Duplo-Cego , Feminino , Humanos , Hipertensão/complicações , Hipertensão/metabolismo , Hipóxia/etiologia , Hipóxia/metabolismo , Masculino , Pessoa de Meia-Idade , Obesidade/complicações , Obesidade/metabolismo , Apneia Obstrutiva do Sono/complicações , Apneia Obstrutiva do Sono/metabolismo , Apneia Obstrutiva do Sono/psicologia , Privação do Sono/etiologia , Privação do Sono/metabolismo , Estresse Psicológico/metabolismo , Estresse Psicológico/psicologia , Resultado do TratamentoRESUMO
Because there is a lack of agreed upon diagnostic criteria, it is critical to understand the natural history of obstructive sleep apnoea (OSA) in children in order to establish treatment strategies based on objective data.The Penn State Child Cohort is a representative, general-population sample of 700 elementary school children at baseline, of whom 421 were reassessed 8â years later, during adolescence.The remission of childhood apnoea-hypopnoea index (AHI) ≥2 events per h in adolescence was 52.9%. Using the higher threshold of AHI ≥5 events per h, remission was 100.0%, with 50.0% partially remitting to AHI 2-â<5 events per h and the other half remitting to AHI <2 events per h. The incidence of adolescent AHI ≥2 events per h in those with childhood AHI <2 events per h was 36.5%, while the incidence of AHI ≥5 events per h in those with childhood AHI <5 events per h was 10.6%. This longitudinal study confirms that prepubertal OSA tends to resolve naturally during the transition to adolescence, and that primary snoring and mild sleep disordered breathing (SDB) do not appear to be strongly associated with progression to more severe SDB.The key risk factors for SDB in adolescence are similar to those found in middle-aged adults (i.e. male sex, older age and obesity). Moreover, consistent with recent studies in adults, this study includes the novel cross-sectional finding that visceral fat is associated with SDB as early as adolescence.
Assuntos
Síndromes da Apneia do Sono/diagnóstico , Apneia Obstrutiva do Sono/diagnóstico , Adolescente , Apneia , Composição Corporal , Índice de Massa Corporal , Criança , Pré-Escolar , Estudos de Coortes , Estudos Transversais , Progressão da Doença , Feminino , Humanos , Incidência , Estudos Longitudinais , Masculino , Obesidade Infantil/complicações , Indução de Remissão , Fatores de Risco , Síndromes da Apneia do Sono/epidemiologia , Síndromes da Apneia do Sono/fisiopatologia , Apneia Obstrutiva do Sono/epidemiologia , Apneia Obstrutiva do Sono/fisiopatologiaRESUMO
PURPOSE OF REVIEW: Sleep plays many roles in maintenance of cardiovascular health. This review summarizes the literature across several areas of sleep and sleep disorders in relation to cardiometabolic disease risk factors. RECENT FINDINGS: Insufficient sleep duration is prevalent in the population and is associated with weight gain and obesity, inflammation, cardiovascular disease, diabetes, and mortality. Insomnia is also highly present and represents an important risk factor for cardiovascular disease, especially when accompanied by short sleep duration. Sleep apnea is a well-characterized risk factor for cardiometabolic disease and cardiovascular mortality. Other issues are relevant as well. For example, sleep disorders in pediatric populations may convey cardiovascular risks. Also, sleep may play an important role in cardiovascular health disparities. SUMMARY: Sleep and sleep disorders are implicated in cardiometabolic disease risk. This review addresses these and other issues, concluding with recommendations for research and clinical practice.
Assuntos
Doenças Cardiovasculares/prevenção & controle , Diabetes Mellitus/prevenção & controle , Obesidade/prevenção & controle , Transtornos do Sono-Vigília/complicações , Sono/fisiologia , Doenças Cardiovasculares/etiologia , Diabetes Mellitus/etiologia , Humanos , Obesidade/etiologia , Fatores de Risco , Transtornos do Sono-Vigília/terapiaRESUMO
Over the last 15years, many studies have established an association of sleep apnea with inflammation and metabolic aberrations. However, no controlled studies have examined potential gender effects in this association. We recruited 120 middle-aged, predominantly non-obese mild-to-moderate sleep apneics and controls (62 males, 58 females). All participants underwent a clinical history, physical examination, and 1-night 8-h polysomnography recording and provided a single fasting blood sample for assessment of interleukin-6 (IL-6), tumor necrosis factor receptor 1 (TNFR1), C-reactive protein (CRP), leptin, and adiponectin levels. Among non-sleep apneics, females had higher levels of TNFR1 (p=0.01), CRP (p=0.005), leptin (p<0.001), and adiponectin (p<0.001) compared to males, independent of age and body mass index. When analyzed separately by gender, sleep apneic men had elevated TNFR1 (p=0.04), CRP (p=0.06) and IL-6 (p=0.11) relative to control men; in sleep apneic females, only CRP was elevated (p=0.04). Furthermore, CRP was associated with apnea severity in a dose-response manner (p-linear=0.04 in both genders) and was independently associated with comorbid hypertension in apnea (p-linear=0.005 for women; p-linear=0.09 for men). In conclusion, although women have naturally higher levels of inflammatory and metabolic markers than men, sleep apneic men appear to have a more severe inflammatory profile compared to women. Our findings suggest that these markers should be analyzed and interpreted separately in men and women, and that a single measure of plasma CRP appears to be a clinically-useful marker of apnea severity and comorbid cardiovascular morbidity.