A longitudinal study of symptom cluster latent profiles in ovarian cancer patients undergoing chemotherapy.

BACKGROUND: This study aimed to identify distinct patterns within the symptom cluster of fatigue, pain, and sleep disturbance among ovarian cancer patients receiving chemotherapy, to determine the factors predicting these patterns and their impact on quality of life. METHODS: The longitudinal study collected data from 151 ovarian cancer patients at three time points: before chemotherapy (T0), after the first chemotherapy cycle (T1), and following the completion of four cycles of chemotherapy (T2). Latent profile analysis and latent transition analysis were used to identify symptom patterns and evaluate changes in symptom patterns. A bias-adjusted three-step approach was utilized to examine predictor variables and distal outcomes associated with latent class membership. RESULTS: Three symptom patterns emerged: "All Low," "Moderate" (T0)/"Low pain and high sleep disturbance" (T1 and T2), and "All High." Patients with lower educational attainment and higher levels of anxiety and depression were found to be at an elevated risk of belonging to the "All High" class. All quality-of-life domains showed significant differences among the three subgroups, following an "All Low" > "All High" pattern (p < 0.05). Membership in three classes remained relatively stable over time, with probabilities of 0.749 staying within their groups from T0 to T2. CONCLUSIONS: This study underscores the existence of a diverse and heterogeneous experience within the symptom cluster of fatigue, pain, and sleep disturbance among ovarian cancer patients. Importantly, these patterns were stable throughout chemotherapy. Recognizing and understanding these patterns can inform the development of targeted interventions to alleviate the burden of symptom clusters in this population.

Sleep dysfunction associated with worse chemotherapy-induced peripheral neurotoxicity functional outcomes.

PURPOSE: Sleep problems are commonly reported by cancer survivors; however, knowledge of the impact of chemotherapy-induced peripheral neurotoxicity (CIPN) on sleep quality remains limited. In this study, we explored the impact of CIPN on sleep quality, as well as identified clinical characteristics associated with poor sleep quality. METHODS: Participants were assessed cross-sectionally post-neurotoxic chemotherapy. CIPN severity was graded using a range of questionnaires that assessed CIPN severity and quality of life, as well as neurological grading scales. Sleep quality was assessed using a self-rated questionnaire (Pittsburgh Sleep Quality Index, PSQI). Participants with poor sleep quality were further grouped according to whether sleep impairment was due to CIPN or other factors. RESULTS: Among 77 participants who reported CIPN, 75% (n = 58) reported poor sleep quality. Of those, 41% (n = 24) reported CIPN as contributing to sleep impairment, while 59% (n = 34) reported other causes. Participants with CIPN-induced sleep impairments had higher CIPN severity across all outcome measures, as well as greater neuropathic pain (all p < 0.05). Furthermore, participants with CIPN-induced sleep impairments reported worse impact of neuropathy on physical and social functioning, as well as emotional well-being (all p < 0.05). CONCLUSIONS: Participants with CIPN-induced poor sleep quality reported worse scores across all CIPN severity measures. This emphasises the negative impacts of CIPN symptoms on quality of life of chemotherapy-treated patients and highlights the importance of sleep quality assessment in cancer survivors.

Neuropsychiatric manifestations and sleep disturbances with dolutegravir-based antiretroviral therapy versus standard of care in children and adolescents: a secondary analysis of the ODYSSEY trial.

BACKGROUND: Cohort studies in adults with HIV showed that dolutegravir was associated with neuropsychiatric adverse events and sleep problems, yet data are scarce in children and adolescents. We aimed to evaluate neuropsychiatric manifestations in children and adolescents treated with dolutegravir-based treatment versus alternative antiretroviral therapy. METHODS: This is a secondary analysis of ODYSSEY, an open-label, multicentre, randomised, non-inferiority trial, in which adolescents and children initiating first-line or second-line antiretroviral therapy were randomly assigned 1:1 to dolutegravir-based treatment or standard-of-care treatment. We assessed neuropsychiatric adverse events (reported by clinicians) and responses to the mood and sleep questionnaires (reported by the participant or their carer) in both groups. We compared the proportions of patients with neuropsychiatric adverse events (neurological, psychiatric, and total), time to first neuropsychiatric adverse event, and participant-reported responses to questionnaires capturing issues with mood, suicidal thoughts, and sleep problems. FINDINGS: Between Sept 20, 2016, and June 22, 2018, 707 participants were enrolled, of whom 345 (49%) were female and 362 (51%) were male, and 623 (88%) were Black-African. Of 707 participants, 350 (50%) were randomly assigned to dolutegravir-based antiretroviral therapy and 357 (50%) to non-dolutegravir-based standard-of-care. 311 (44%) of 707 participants started first-line antiretroviral therapy (ODYSSEY-A; 145 [92%] of 157 participants had efavirenz-based therapy in the standard-of-care group), and 396 (56%) of 707 started second-line therapy (ODYSSEY-B; 195 [98%] of 200 had protease inhibitor-based therapy in the standard-of-care group). During follow-up (median 142 weeks, IQR 124-159), 23 participants had 31 neuropsychiatric adverse events (15 in the dolutegravir group and eight in the standard-of-care group; difference in proportion of participants with ≥1 event p=0·13). 11 participants had one or more neurological events (six and five; p=0·74) and 14 participants had one or more psychiatric events (ten and four; p=0·097). Among 14 participants with psychiatric events, eight participants in the dolutegravir group and four in standard-of-care group had suicidal ideation or behaviour. More participants in the dolutegravir group than the standard-of-care group reported symptoms of self-harm (eight vs one; p=0·025), life not worth living (17 vs five; p=0·0091), or suicidal thoughts (13 vs none; p=0·0006) at one or more follow-up visits. Most reports were transient. There were no differences by treatment group in low mood or feeling sad, problems concentrating, feeling worried or feeling angry or aggressive, sleep problems, or sleep quality. INTERPRETATION: The numbers of neuropsychiatric adverse events and reported neuropsychiatric symptoms were low. However, numerically more participants had psychiatric events and reported suicidality ideation in the dolutegravir group than the standard-of-care group. These differences should be interpreted with caution in an open-label trial. Clinicians and policy makers should consider including suicidality screening of children or adolescents receiving dolutegravir. FUNDING: Penta Foundation, ViiV Healthcare, and UK Medical Research Council.

[Sleep disorders related to HIV treatment.] / Trastornos en la calidad del sueño asociados a los inhibidores de la integrasa en el tratamiento del VIH.

OBJECTIVE: HIV Clinical Guidelines have positioned integrase inhibitors recently as first-line treatment. However, two of these drugs have also been associated with adverse side effects on the central nervous system, especially with sleep disturbances. The objective was to analyse the influence of bictegravir and dolutegravir on the sleep quality in HIV patients. METHODS: An observational, cross-sectional study was carried out between December 2020 and January 2021 in HIV patients attended in a pharmacy care clinic. Demographic and adherence variables were collected. Sleep quality was measured using the Pittsburgh questionnaire or PSQI. We classified patients into two groups: patients with bictegravir or dolutegravir in their treatment (study group) and the rest (control group). The influence of the variables collected on the PSQI result was analysed using the Chi-Square test for categorical variables and the student t-test or Mann-Whitney U test for continuous variables. RESULTS: One hundred and nineteen patients were included. 64% in the study group and 67% in the control group suffered from sleep disorders according to the PSQI questionnaire (p=0.788). Neither were statistical differences found when the different components of sleep were analysed between the two groups. CONCLUSIONS: A high percentage of patients, regardless of whether their treatment includes bictegravir or dolutegravir, have problems with their sleep quality. We didn't find a correlation between sleep quality and treatment with bictegravir or dolutegravir compared to the other treatments.

OBJETIVO: Los inhibidores de la integrasa se han posicionado recientemente en todas las Guías Clínicas de VIH como tratamiento antirretroviral de primera línea para el VIH. Sin embargo, dos de estos fármacos se han asociado también a efectos adversos a nivel del sistema nervioso central, concretamente con alteraciones del sueño. El objetivo del trabajo fue analizar la influencia de bictegravir y dolutegravir en la calidad del sueño en personas que viven con VIH (PVIH). METODOS: Se realizó un estudio observacional y transversal entre los meses de diciembre de 2020 y enero de 2021 en las PVIH de las consultas de atención farmacéutica del hospital. Se recogieron variables demográficas y de adherencia. La calidad del sueño se midió mediante el Cuestionario de Pittsburgh o PSQI. Las PVIH se clasificaron en 2 grupos: el grupo estudio, constituido por participantes con bictegravir o dolutegravir en su tratamiento, y el grupo control, integrado por el resto de PVIH. Se analizó la influencia de las variables recogidas sobre el resultado del PSQI mediante la prueba de chi cuadrado/odds ratio para variables categóricas y el de t de Student o U de Mann Whitney para variables continuas. RESULTADOS: Se incluyeron 119 PVIH, de las cuales un 64% en el grupo estudio y un 67% en el grupo control sufrían trastornos del sueño según el PSQI (p=0,788). Tampoco hubo diferencias estadísticamente significativas cuando se compararon los diferentes componentes del sueño entre los dos grupos. CONCLUSIONES: Un elevado porcentaje de PVIH, independientemente de si el TAR incluye bictegravir o dolutegravir, tienen problemas relacionados con la calidad del sueño. No se encuentra correlación entre la calidad del sueño y el tratamiento con bictegravir o dolutegravir comparado con el resto de tratamientos.

Unraveling Dexamethasone-Induced Neurobehavioral and Sleep Problems in Children With ALL: Which Determinants Are Important?

PURPOSE: Dexamethasone, the preferred corticosteroid in most treatment protocols for pediatric acute lymphoblastic leukemia (ALL), can induce undesirable side effects. Neurobehavioral and sleep problems are frequently reported, but the interpatient variability is high. We therefore aimed to identify determinants for parent-reported dexamethasone-induced neurobehavioral and sleep problems in pediatric ALL. METHODS: Our prospective study included patients with medium-risk ALL and their parents during maintenance treatment. Patients were assessed before and after one 5-day dexamethasone course. Primary end points were parent-reported dexamethasone-induced neurobehavioral and sleep problems, measured with the Strengths and Difficulties Questionnaire and Sleep Disturbance Scale for Children, respectively. Analyzed determinants included patient and parent demographics, disease and treatment characteristics, parenting stress (Parenting Stress Index and Distress Thermometer for Parents), dexamethasone pharmacokinetics, and genetic variation (candidate single-nucleotide polymorphisms rs41423247 and rs4918). Statistically significant determinants identified in univariable logistic regression analyses were incorporated in a multivariable model. RESULTS: We included 105 patients: median age was 5.4 years (range, 3.0-18.8) and 61% were boys. Clinically relevant dexamethasone-induced neurobehavioral and sleep problems were reported by parents in 70 (67%) and 61 (59%) patients, respectively. In our multivariable regression models, we identified parenting stress as a significant determinant for parent-reported neurobehavioral (odds ratio [OR], 1.16; 95% CI, 1.07 to 1.26) and sleep problems (OR, 1.06; 95% CI, 1.02 to 1.10). Furthermore, parents who experienced more stress before start of a dexamethasone course reported more sleep problems in their child (OR, 1.16; 95% CI, 1.02 to 1.32). CONCLUSION: We identified parenting stress, and not dexamethasone pharmacokinetics, genetic variation, patient/parent demographics, or disease/treatment characteristics, as a significant determinant for parent-reported dexamethasone-induced neurobehavioral and sleep problems. Parenting stress may be a modifiable target to reduce these problems.

Hydrocortisone to reduce dexamethasone-induced neurobehavioral side-effects in children with acute lymphoblastic leukaemia-results of a double-blind, randomised controlled trial with cross-over design.

BACKGROUND: Dexamethasone is a cornerstone of paediatric acute lymphoblastic leukaemia (ALL) treatment, although it can induce serious side-effects. Our previous study suggests that children who suffer most from neurobehavioural side-effects might benefit from physiological hydrocortisone in addition to dexamethasone treatment. This study aimed to validate this finding. METHODS: Our phase three, double-blind, randomised controlled trial with cross-over design included ALL patients (3-18 years) during medium-risk maintenance therapy in a national tertiary hospital between 17th May 2018 and 5th August 2020. A baseline measurement before and after a 5-day dexamethasone course was performed, whereafter 52 patients with clinically relevant neurobehavioural problems were randomised to receive an intervention during four subsequent dexamethasone courses. The intervention consisted of two courses hydrocortisone (physiological dose 10 mg/m2/d in circadian rhythm), followed by two courses placebo, or vice versa. Neurobehavioural problems were assessed before and after each course using the parent-reported Strengths and Difficulties Questionnaire (SDQ) as primary end-point. Secondary end-points were sleep problems, health-related quality of life (HRQoL), hunger feeling, and parental stress, measured with questionnaires and actigraphy. A generalised mixed model was estimated to study the intervention effect. RESULTS: The median age was 5.5 years (range 3.0-18.8) and 61.5% were boys. The SDQ filled in by 51 primary caregivers showed no difference between hydrocortisone and placebo in reducing dexamethasone-induced neurobehavioral problems (estimated effect -2.05 (95% confidence interval (CI) -6.00-1.90). Also, no benefit from hydrocortisone compared to placebo was found for reducing sleep problems, hunger, parental stress or improving HRQoL. CONCLUSIONS: Hydrocortisone, when compared to placebo, had no additional effect in reducing clinically relevant dexamethasone-induced neurobehavioural problems. Therefore, hydrocortisone is not advised as standard of care for children with ALL who experience dexamethasone-induced neurobehavioural problems. TRIAL REGISTRATION: Netherlands Trial Register NTR6695/NL6507 (https://trialsearch.who.int/) and EudraCT 2017-002738-22 (https://eudract.ema.europa.eu/).

Occupational Exposure to Pesticides as a Risk Factor for Sleep Disorders.

Inadequate sleep has been linked to a variety of impairments in bodily functions, including endocrine, metabolic, higher cortical function, and neurological disorders. For this reason, the aim of this study was to analyze the link between occupational pesticide exposure and sleep health among farmers in Almeria. A cross-sectional study was conducted among a population living on the coast of Almeria (southeastern Spain), where about 33,321 hectares of land are used for intensive agriculture in plastic greenhouses. A total of 380 individuals participated in the study: 189 greenhouse workers and 191 control subjects. The participants were contacted during their annual scheduled occupational health survey. Data on sleep disturbances were collected using the Spanish version of the Oviedo Sleep Questionnaire. Agricultural workers were found to be at a significantly higher risk of insomnia, especially among those who did not wear protective gloves (OR = 3.12; 95% C.I. = 1.93-3.85; p = 0.04) or masks (OR = 2.43; 95% C.I. = 1.19-4.96; p = 0.01). The highest risk of insomnia related to pesticide applicators was observed in those who did not wear a mask (OR = 4.19; 95% C.I. = 1.30-13.50; p = 0.01) or goggles (OR = 4.61; 95% C.I. = 1.38-10.40; p = 0.01). This study supports previous findings indicating an increased risk of sleep disorder in agricultural workers exposed to pesticides at work.

Interactions between heavy metals and sleep duration among pre-and postmenopausal women: A current approach to molecular mechanisms involved.

The effects of heavy metals (cadmium, lead, and mercury) and their mixtures on sleep duration in pre-and postmenopausal women, particularly the molecular mechanisms, remain unknown. Here, we assessed the interaction between heavy metals and sleep duration among pre-and postmenopausal women (n = 1134). Furthermore, molecular mechanisms related to sleep disorders induced by studied heavy metals were further analyzed to support the previous findings. We found that serum lead levels were positively related to weekend and weekday sleep duration in premenopausal women. There were interactions between serum lead and mercury and menopausal status for sleep duration. Serum lead and mercury levels were shown to be inversely related to sleep duration in postmenopausal women. Despite the lack of statistically significant associations between mixed heavy metals and sleep duration, there were increasing trends in premenopausal women's sleeping patterns and decreasing trends in postmenopausal women's sleeping patterns. In silico analysis, IL1B, hsa-21-5p, hsa-887-3p, hsa-877-3p, and NR4A1 were identified as the most relevant genes, miRNAs, and transcription factors linked with sleep disorders induced by combined heavy metals (cadmium, lead, and mercury). Furthermore, "type 1 melanocortin receptor binding," "endocrine hormone secretion," "interleukin-1 receptor antagonist activity," "altered melanocortin system," and "sleep wake disorders" were identified as the predominant molecular mechanisms involved in the pathophysiology of sleep disorders induced by the studied heavy metals. Cut off point values and miRNA sponge templates for heavy metal exposure levels relevant to sleep disorders in pre- and postmenopausal women were reported. Future research is needed to verify our findings and provide insight into the molecular processes of long-term mixed heavy metal exposure in various populations, such as children and the elderly.

Psychosis in Parkinson's Disease: Looking Beyond Dopaminergic Treatments.

BACKGROUND: Parkinson's disease (PD) is the second most common neurodegenerative disorder worldwide. The symptoms of PD are characterized not only by motor alterations but also by a spectrum of nonmotor symptoms. Some of these are psychiatric manifestations such as sleep disorders; depression; cognitive difficulties that can evolve into dementia; and symptoms of psychosis, which include hallucinations, illusions, and delusions. Parkinson's disease psychosis (PDP) occurs in 18-50% of patients with PD. Treating PDP is challenging because antipsychotic drugs tend to be inefficient or may even worsen the disease's motor symptoms. OBJECTIVE: This review aims to summarize the current understanding of the molecular mechanisms involved in PDP and recent innovative alternatives for its treatment. METHODS: This is a narrative review in which an extensive literature search was performed on the Scopus, EMBASE, PubMed, ISI Web of Science, and Google Scholar databases from inception to August 2021. The terms "Parkinson's disease psychosis", "Parkinson psychosis," "neurodegenerative psychosis", and "dopamine psychosis" were among the keywords used in the search. RESULTS: Recently, views on the etiology of hallucinations and illusions have evolved remarkably. PDP has been cemented as a multifactorial entity dependent on extrinsic and novel intrinsic mechanisms, including genetic factors, neurostructural alterations, functional disruptions, visual processing disturbances, and sleep disorders. Consequently, innovative pharmacological and biological treatments have been proposed. Pimavanserin, a selective 5-HT2A inverse agonist, stands out after its approval to treat PDP-associated hallucinations and illusions. CONCLUSION: Future results from upcoming clinical trials should further characterize the role of this drug in the management of PDP as well as other treatment options with novel mechanisms of action, such as saracatinib, SEP-363856, cannabidiol, electroconvulsive therapy, and transcranial magnetic stimulation.

Sleep disturbances and restless legs syndrome in postmenopausal women with early breast cancer given adjuvant aromatase inhibitor therapy.

INTRODUCTION: Whether adjuvant therapy with aromatase inhibitors (AIs) causes sleep disturbances or not in postmenopausal women with early breast cancer (EBC) is still a controversial issue. METHODS: Between March 2014 and November 2017, validated questionnaires for assessing insomnia, anxiety, depression, quality of life (QoL) and restless legs syndrome (RLS) were administered to 160 EBC patients at baseline and after 3, 6, 12, and 24 months of AI therapy. RESULTS: AI therapy significantly decreased the patients' QoL, but did not influence insomnia, anxiety or depression. However, it significantly increased the frequency and severity of RLS. Patients with RLS at baseline (19%) or who developed RLS during AI therapy (26.3%) reported statistically lower quality of sleep, higher anxiety and depression, and worse QoL compared to patients who never reported RLS (54.7%). CONCLUSION: Although AI therapy does not affect sleep quality, it may increase RLS frequency. The presence of RLS could identify a group of EBC patients who may benefit from psychological support.

Chronic Opioid Use and Sleep Disorders.

Opioid medications are considered a significant component in the multidisciplinary management of chronic pain. In the past two decades, the use of opioid medications has dramatically risen in part because of an increased awareness by health care providers to treat chronic pain more effectively. In addition, patients are encouraged to seek treatment. The release of a sentinel joint statement in 1997 by the American Academy of Pain Medicine and the American Pain Society in a national effort to increase awareness and support the treatment of chronic pain has undoubtedly contributed to the opioid crisis.

Distinct sleep disturbance and cognitive dysfunction profiles in oncology outpatients receiving chemotherapy.

PURPOSE: Sleep disturbance and cancer-related cognitive impairment (CRCI) are two of the most common symptoms reported by patients undergoing chemotherapy. Less is known about how these symptoms co-occur and their associated risk factors. Study purposes were to identify subgroups of patients with distinct sleep disturbance and CRCI profiles and evaluate for differences among the subgroups in demographic and clinical characteristics, symptom severity scores, and QOL outcomes. METHODS: A total of 1,333 oncology outpatients receiving chemotherapy completed self-report questionnaires on sleep disturbance and cognitive dysfunction six times over two cycles of chemotherapy. Latent profile analysis was used to identify distinct sleep disturbance AND cognitive dysfunction profiles. Parametric and non-parametric tests were used to evaluate for differences among the classes. RESULTS: Two distinct profiles were identified (i.e., Low = low levels of both sleep disturbance and cognitive dysfunction (53.5%); High = high levels of both sleep disturbance and cognitive dysfunction (45.5%)). Patients in the High class were younger, more likely to be female, had a lower functional status and a higher level of comorbidity. In addition, these patients had a higher symptom burden and a lower quality of life. CONCLUSION: Almost half of the patients undergoing chemotherapy experienced clinically meaningful levels of both symptoms. Of note, sleep disturbance is frequently overlooked by both clinicians and patients. Clinicians need to recommend cognitive rehabilitation and physical activity programs to decrease patients' symptom burden.

Cannabis dosing and administration for sleep: a systematic review.

STUDY OBJECTIVES: As cannabis is increasingly used to treat sleep disorders, we performed a systematic review to examine the effects of cannabis on sleep and to guide cannabis prescribers in their recommendations to patients, specifically focusing on dosing. METHODS: We searched EMBASE, Medline, and Web of Science and identified 4550 studies for screening. Five hundred sixty-eight studies were selected for full-text review and 31 were included for analysis. Study results were considered positive based on improvements in sleep architecture or subjective sleep quality. Bias in randomized controlled trials was assessed using Cochrane Risk of Bias tool 2.0. RESULTS: Sleep improvements were seen in 7 out of 19 randomized studies and in 7 out of 12 uncontrolled trials. There were no significant differences between the effects of tetrahydrocannabinol and cannabidiol. Cannabis showed most promise at improving sleep in patients with pain-related disorders, as compared to those with neurologic, psychiatric, or sleep disorders, and showed no significant effects on healthy participants' sleep. While subjective improvements in sleep quality were often observed, diagnostic testing showed no improvements in sleep architecture. Adverse events included headaches, sedation, and dizziness, and occurred more frequently at higher doses, though no serious adverse events were observed. CONCLUSION: High-quality evidence to support cannabis use for sleep remains limited. Heterogeneity in cannabis types, doses, timing of administration, and sleep outcome measures limit the ability to make specific dosing recommendations.

Sleep disturbance exacerbates the cardiac conduction abnormalities induced by persistent heavy ambient fine particulate matter pollution: A multi-center cross-sectional study.

Fine particulate matter (PM2.5) exposure and sleep disturbance have been significantly associated with adverse cardiovascular outcomes, however, the combined effects of these two factors are still unclear. We conducted a multi-center cross-sectional study from November 2018 to May 2019 in the Beijing-Tianjin-Hebei region in China to investigate the potential modifying effects of sleep disturbance on associations between cardiac conduction abnormalities and PM2.5 exposure, as well as the combined effects of sleep disturbance and heavy pollution episodes, which were defined based on the PM2.5 mass concentration (≥75 µg/m3, falling in the 75th/90th percentile) and duration (1 day and ≥2 days). The sleep quality and sleep duration of all participants were evaluated using the Pittsburgh Sleep Quality Index. Standard 12-lead electrocardiogram (ECG) test was performed to measure the heart rate (HR), QRS duration (time taken for ventricular depolarization), HR corrected QT interval (time for ventricular depolarization and repolarization) and PR interval (time for atrioventricular conduction). Multivariable linear regression models were performed to evaluate the associations of PM2.5 and heavy pollution events on ECG parameters and the joint effects with sleep disturbance. We found PM2.5 exposure was independently associated with prolonged QRS and QTc intervals. Association between PM2.5 and the QTc interval was significantly stronger in participants with poor sleep quality. For each 10-µg/m3 increase in PM2.5 concentration, the QTc interval in the participants with poor sleep quality increased by 0.41 % (95 % confidence interval: 0.19, 0.64). In addition, heavy PM2.5 pollution episodes, especially extremely heavy pollution of long duration, were found to have synergistic effects with sleep disturbance on ECG parameters. Our findings provide evidence that PM2.5 exposure, especially heavy pollution episodes, may increase abnormal cardiac conduction and have a synergistic effect with sleep disturbance. Improving sleep hygiene is crucial to protect the heart health of the general population.

Safety and efficacy of melatonin, clonazepam, and trazodone in patients with Parkinson's disease and sleep disorders: a randomized, double-blind trial.

BACKGROUND: Sleep disturbances are common non-motor symptoms of Parkinson's disease (PD). We aimed to compare the safety and efficacy of trazodone with melatonin and clonazepam in patients with PD and sleep complaints. METHODS: This single-center, double-blind, randomized clinical trial was conducted on PD patients with subjective sleep complaints. Eligible patients were randomized 1:1:1 to receive melatonin 3 mg/day, clonazepam 1 mg/day, or trazodone 50 mg/day for 4 weeks. The primary outcome measure was the changes in Pittsburgh Sleep Quality Index (PSQI) scores. The mean change in Epworth Sleepiness Scale (ESS) and RBD screening questionnaire (RBDSQ) was considered as the secondary outcome measures. RESULTS: A total of 112 eligible patients were randomized and 93 participants, melatonin (n = 31), trazodone (n = 31), and clonazepam (n = 31), completed the study. There was a significant decrease in PSQI scores after 4 weeks of treatment in all groups. The mean changes of PSQI from baseline were similar among the treatment arms (P = 0.325). Mean changes of RBDSQ and ESS from baseline were significantly different between study arms (P < 0.05). Melatonin intake was associated with a higher decrease in RBDSQ score compared to trazodone (P = 0.011) and clonazepam (P = 0.004). Trazodone intake was associated with a higher decrease in ESS score compared to clonazepam (P = 0.010). Mild adverse events were reported in three patients in the clonazepam, two patients in the trazodone group, and none in the melatonin group. CONCLUSIONS: Trazodone 50 mg/day, clonazepam 1 mg/day, and melatonin 3 mg/day were all tolerable and effective in improving sleep quality in patients with PD. TRIAL REGISTRATION: Iranian Registry of Clinical Trials (registration number; IRCT20170821035819N2).

Cognitive Impairment, Sleep Disturbance, and Depression in Women with Silicone Breast Implants: Association with Autoantibodies against Autonomic Nervous System Receptors.

BACKGROUND: Silicone breast implants (SBIs) has been shown to be associated with an increased risk of autoimmune diseases. In the current study, we aimed to explore the potential association between circulating autoantibodies against the autonomic nervous system and cognitive impairment, memory deficit, and depressive symptoms reported by women with SBIs. METHODS: ELISA assays were used to quantify anti-adrenergic receptors (α1, α2, ß1, ß2), anti-muscarinic receptors (M1-M5), anti-endothelin receptor type A, and anti-angiotensin II type 1 receptor titers in the sera of 93 symptomatic female subjects with SBIs and 36 age-matched healthy female controls. RESULTS: A significant difference was detected in the level of autoantibodies against the autonomic nervous system receptors in women with SBIs who reported memory impairment, cognitive impairment, and sleep disturbance as compared with both women with SBIs who did not complain of these symptoms or with healthy individuals without SBIs. CONCLUSIONS: Clinical symptoms such as depression, cognitive impairment, and sleep disturbances were found to be associated with dysregulation of the levels of circulating autoantibodies targeting the autonomous nervous system receptors in women with SBIs. These autoantibodies may have diagnostic significance in diseases associated with breast implants.

A meta-analysis evaluating effects of the rotigotine in Parkinson's disease, focusing on sleep disturbances and activities of daily living.

BACKGROUND: Rotigotine transdermal patch (TP) is a useful dopaminergic medication for Parkinson's disease (PD). This meta-analysis attempted to evaluate the effects of rotigotine TP on motor performance, activities of daily living (ADL) limitations, and sleep disturbances in patients with PD. METHODS: Only randomized controlled clinical trials (RCTs) with placebo design were included in this study. The clinical outcomes, evaluated using the Unified Parkinson's Disease Rating Scale (UPDRS III), UPDRS-II, UPDRS Part II + III, Parkinson's Disease Sleep Scale (PDSS)-2, and adverse events (AEs) were evaluated. The Jadad scale was used to evaluate study quality. RESULTS: A total of 16 RCTs with 4682 patients with PD were enrolled in this study. We found that rotigotine TP significantly reduced the UPDRS-III, UPDRS-II, and UPDRS Part II + III scores, indicating that rotigotine TP led to a significant amelioration of movement symptoms and ADL limitations. Moreover, we found that rotigotine TP significantly reduced PDSS-2 scores, suggesting that rotigotine TP led to a remarkable improvement in sleep quality. Meanwhile, compared with the placebo group, patients taking rotigotine TP did not have added incidence of AEs. CONCLUSION: This study verified the efficacy and safety of rotigotine TP in treating PD. The findings of the present study provide compelling evidence concerning and insight into clinical usage of rotigotine TP. Future studies will focus on more non-motor symptoms affected by rotigotine TP.

Environmental exposure to per- and polyfluoroalkyl substances and sleep disturbance in pregnant women: A prospective cohort study.

Previous studies on the association between exposure to per- and polyfluoroalkyl substances (PFAS) and sleep patterns in pregnant women are limited. This cohort study aims to assess the associations between PFAS and sleep quality in pregnant women. Of the 4127 women who participated in the Shanghai Birth Cohort, 3174, 3070, and 2887 women in their first, second, and third trimesters of gestation, respectively, were included in our analysis. Sleep measures were taken using the Pittsburgh Sleep Quality Index questionnaire. Ten PFAS were measured in blood samples collected in early pregnancy. We first evaluate the associations between individual PFAS and sleep quality in the three trimesters. Weighted quantile sum (WQS) regression models were performed to test the overall effect of the PFAS mixture on sleep quality during the three trimesters. Longitudinal analyses throughout pregnancy were performed with generalized estimating equation models. Furthermore, the effect of the PFAS mixture on longitudinal sleep patterns was examined using longitudinal latent class analyses combined with WQS models. The single pollutant analysis suggested that most PFAS were associated with increased sleep disturbance risk, lower sleep efficiency, and shorter sleep duration in the three trimesters. Similarly, the WQS models revealed a significant association between the PFAS mixtures and elevated sleep disturbance risk in pregnant women, with perfluorobutane sulfonate acting as the predominant risk factor. Additionally, the longitudinal analysis confirmed the effects of PFAS exposure on increased sleep disturbance over time. The PFAS mixture was positively associated with higher risks of poor sleep quality and sleep medicine use [adjusted odds ratio (aOR) = 1.10; 95 % confidence interval (95%CI): 1.01, 1.20; and aOR = 1.25 (95%CI: 1.04, 1.50) respectively] throughout the three trimesters. Our study suggests that PFAS may increase the risk of sleep disturbance in pregnant women. Further studies are needed to confirm our results and elucidate potential mechanisms.

IL-4/13 Blockade and sleep-related adverse drug reactions in over 37,000 Dupilumab reports from the World Health Organization Individual Case Safety reporting pharmacovigilance database (VigiBase™): a big data and machine learning analysis.

OBJECTIVE: Atopic dermatitis displays a relevant sleep burden sustained by clinical (i.e., itch), psychological (i.e., inadequate coping strategies) and therapeutic (i.e., frequent loss of drug response) triggers. Dupilumab, the first biologic approved for atopic dermatitis, showed excellent effects on improving pruritus and sleep after only two weeks of treatment but, in some cases, may have paradoxical effects. The rate of sleep-related side-effects remains unknown. More specifically, adverse-drug reactions (ADRs) related to dupilumab have been investigated during the safety phase of randomized clinical trials or in small retrospective epidemiological surveys, but little is known about sleep-related ADRs in real-life settings. Therefore, we took advantage of a global large-scale pharmacovigilance database, carrying out a comprehensive data mining analysis to look at different sleep-related ADRs reported among patients under anti IL-4/13 therapy. MATERIALS AND METHODS: We analyzed individual case study reports (ICSRs) in VigiBaseTM, the World Health Organization (WHO) global pharmacovigilance database of ADRs collected by national drug authorities in > 140 countries (> 90% of the world population). We looked for patterns of potentially sleep-related ADRs and we applied a disproportionality analysis based on Bayesian Confidence Propagation Neural Network (BCPNN). A meta-analytical approach was used to synthesize the overall effect size of sleep-related ADRs potentially associated to Dupilumab administration. RESULTS: From inception up to March 9, 2021, 94,065 ADRs from 37,848 unique reports were included and analyzed in the present paper: 1,294 of them (1.4%) concerned sleep disturbances (n=27). Most of sleep-related complaints were generic sleep disorders (n=630), followed by insomnia (n=312), somnolence (n=81), lethargy (n=60), night sweats (n=30), middle insomnia (n=39), hypersomnia (n=25), poor-quality sleep (n=21), initial insomnia (n=17), sleep apnea syndrome (n=13), nightmares (n=11) and sleep deficit (n=11). Interestingly, restlessness and restless leg syndrome, nocturnal dyspnea, narcolepsy and bruxism were reported in 7, 6, 5, 4 and 3 cases, respectively. Only sleep deficit [OR 15.67 (95% CrI 8.61-28.51); IC 3.24 (95% CrI 2.26-3.97)], generic sleep disorder [OR 6.22 (95% CrI 5.74-6.73); IC 2.60 (95% CrI 2.48-2.71)], nocturnal dyspnea [OR 3.68 (95% CrI 1.53-8.87); IC 1.56 (95% CrI 0.03-2.56)] and middle insomnia [OR 1.87 (95% CrI 1.36-2.56); IC 0.88 (95% CrI 0.39-1.30)] achieved the statistical significance threshold. CONCLUSIONS: In this work, we identified over 37,000 unique case-reports of Dupilumab side-effects reported on the WHO pharmacovigilance database. We specifically categorized those related to sleep issues, which were 1,294. Our findings from large numbers of cases provide data supporting the clinical observations that Dupilumab is usually effective in improving sleep quality and sleep disturbances/impairments, given the lack of statistical significance of several sleep-related ADRs. Further work is needed to closely scrutinize the impact of Dupilumab on sleep, in terms of underlying mechanisms, and to better understand residual sleep disorders in patients with atopic dermatitis and other allergic diseases treated with Dupilumab. Thus, sleep monitoring may be helpful for dermatologists in managing atopic dermatitis patients treated with dupilumab. The limitations of spontaneous reporting systems including underreporting and reporting bias, heterogeneity of sources and impossibility to infer any causal relationship merit consideration and further research is needed.

Association of air pollution exposure with low arousal threshold obstructive sleep apnea: A cross-sectional study in Taipei, Taiwan.

Emerging evidence witnesses the association of air pollution exposure with sleep disorders or the risk of obstructive sleep apnea (OSA); however, the results are not consistent. OSA patients with or without a low arousal threshold (LAT) have different pathology and therapeutic schemes. No study has evaluated the potential diverse effects of air pollution on the phenotypes of OSA. The current study aimed to evaluate the associations of short-term and long-term exposure to air pollution with sleep-disordered measures and OSA phenotypes. This cross-sectional study consisted of 4634 participants from a sleep center in Taipei from January 2015 to April 2019. The personal exposure to ambient PM2.5 and NO2 was assessed by a spatial-temporal model. Overnight polysomnography was used to measure the sleep parameters. According to a developed clinical tool, we defined the low arousal threshold (LAT) and identified the OSA patients with or without LAT. We applied a generalized linear model and multinomial logistic regression model to estimate the change of sleep measures and risk of the OSA phenotypes, respectively, associated with an interquartile range (IQR) increment of personal pollution exposure after adjusting for the essential confounders. In the single-pollutant model, we observed the associations of NO2 with sleep-disordered measures by decreasing the total sleep time, sleep efficiency, extending the time of wake after sleep onset, and the association of NO2 with the increased risk of LAT OSA by around 15%. The two-pollutant model with both long-term and short-term exposures confirmed the most robust associations of long-term NO2 exposure with sleep measures. An IQR increment of NO2 averaged over the past year (6.0 ppb) decreased 3.32 min of total sleep time and 0.85% of sleep efficiency. Mitigating exposure to air pollution may improve sleep quality and reduce the risk of LAT OSA.