Presynaptic Dopaminergic Imaging Characterizes Patients with REM Sleep Behavior Disorder Due to Synucleinopathy.

OBJECTIVE: To apply a machine learning analysis to clinical and presynaptic dopaminergic imaging data of patients with rapid eye movement (REM) sleep behavior disorder (RBD) to predict the development of Parkinson disease (PD) and dementia with Lewy bodies (DLB). METHODS: In this multicenter study of the International RBD study group, 173 patients (mean age 70.5 ± 6.3 years, 70.5% males) with polysomnography-confirmed RBD who eventually phenoconverted to overt alpha-synucleinopathy (RBD due to synucleinopathy) were enrolled, and underwent baseline presynaptic dopaminergic imaging and clinical assessment, including motor, cognitive, olfaction, and constipation evaluation. For comparison, 232 RBD non-phenoconvertor patients (67.6 ± 7.1 years, 78.4% males) and 160 controls (68.2 ± 7.2 years, 53.1% males) were enrolled. Imaging and clinical features were analyzed by machine learning to determine predictors of phenoconversion. RESULTS: Machine learning analysis showed that clinical data alone poorly predicted phenoconversion. Presynaptic dopaminergic imaging significantly improved the prediction, especially in combination with clinical data, with 77% sensitivity and 85% specificity in differentiating RBD due to synucleinopathy from non phenoconverted RBD patients, and 85% sensitivity and 86% specificity in discriminating PD-converters from DLB-converters. Quantification of presynaptic dopaminergic imaging showed that an empirical z-score cutoff of -1.0 at the most affected hemisphere putamen characterized RBD due to synucleinopathy patients, while a cutoff of -1.0 at the most affected hemisphere putamen/caudate ratio characterized PD-converters. INTERPRETATION: Clinical data alone poorly predicted phenoconversion in RBD due to synucleinopathy patients. Conversely, presynaptic dopaminergic imaging allows a good prediction of forthcoming phenoconversion diagnosis. This finding may be used in designing future disease-modifying trials. ANN NEUROL 2024;95:1178-1192.

Parkinson's disease motor progression in relation to the timing of REM sleep behavior disorder presentation: an exploratory retrospective study.

REM sleep behavior disorder (RBD) is a frequent non-motor symptom of Parkinson's disease (PD), and the timing of its presentation might have a role in the underlying neurodegenerative process. Here, we aimed to define the potential impact of probable RBD (pRBD) on PD motor progression.We conducted a longitudinal retrospective study on 66 PD patients followed up at the University Hospital of Rome Tor Vergata. Patients were divided into three groups: with post-motor pRBD (pRBDpost, n = 25), without pRBD (pRBDwo, n = 20), and with pre-motor pRBD (pRBDpre, n = 21). Hoehn and Yahr (H&Y) scores, Unified PD Rating Scale (UPDRS) motor scores, and levodopa equivalent daily dose were collected at two follow-up visits conducted in a 5-year interval (T0 and T1). pRBDpost patients had a greater rate of motor progression in terms of the H&Y scale compared to pRBDpre and pRBDwo patients, without the influence of anti-parkinsonian treatment.These preliminary findings suggest that the post-motor occurrence of pRBD can be associated with an acceleration in PD motor progression.

Obstructive sleep apnea may induce sleep-wake cycle dysregulation: An actigraphic study.

Obstructive sleep apnea (OSA) causes sleep fragmentation and excessive daytime sleepiness (EDS). OSA has been hypothesised to impair the circadian sleep-wake rhythm, and this dysregulation may in turn exacerbate OSA-related diurnal symptoms. Hence, this study aimed to assess the sleep-wake rhythm through actigraphy, and its relationship with EDS in patients with untreated OSA. Patients with moderate-severe OSA (apnea-hypopnea index ≥15/h) and healthy controls (HC) underwent a 7-day actigraphic recording to evaluate the sleep-wake rhythm. Participants underwent a sleep medicine visit and completed the self-report questionnaires assessing EDS (Epworth sleepiness scale, ESS), sleep quality (Pittsburgh sleep quality index, PSQI), and chronotype (morningness-eveningness questionnaire, MEQ). This study included 48 OSA patients (72.9% males; mean age 56.48 ± 9.53 years), and 22 HC (45.5% males; mean age 53.73 ± 18.20 years). After controlling for MEQ scores, actigraphic recording showed that the OSA patients present a lower sleep time (p = 0.011) and sleep efficiency (p = 0.013), as well as a higher sleep latency (p = 0.047), and sleep fragmentation (p = 0.029) than the HC. Regarding the sleep-wake rhythm actigraphic parameters, the OSA patients showed a lower average activity during the most active 10-hour period (p = 0.036) and a lower day/night activity ratio (p = 0.007) than the HC. Patients with OSA also reported higher ESS (p = 0.005) and PSQI scores (p < 0.001), and a chronotype less of morning type (p = 0.027) than the HC. In conclusion, this study documented a reduced diurnal motor activity and lower day/night activity ratio in OSA patients than in controls. These findings suggest a dysregulation of the circadian sleep-wake rhythm in OSA, possibly related to both EDS and reduced daytime motor activity.

Progression of clinical markers in prodromal Parkinson's disease and dementia with Lewy bodies: a multicentre study.

The neurodegenerative synucleinopathies, including Parkinson's disease and dementia with Lewy bodies, are characterized by a typically lengthy prodromal period of progressive subclinical motor and non-motor manifestations. Among these, idiopathic REM sleep behaviour disorder is a powerful early predictor of eventual phenoconversion, and therefore represents a critical opportunity to intervene with neuroprotective therapy. To inform the design of randomized trials, it is essential to study the natural progression of clinical markers during the prodromal stages of disease in order to establish optimal clinical end points. In this study, we combined prospective follow-up data from 28 centres of the International REM Sleep Behavior Disorder Study Group representing 12 countries. Polysomnogram-confirmed REM sleep behaviour disorder subjects were assessed for prodromal Parkinson's disease using the Movement Disorder Society criteria and underwent periodic structured sleep, motor, cognitive, autonomic and olfactory testing. We used linear mixed-effect modelling to estimate annual rates of clinical marker progression stratified by disease subtype, including prodromal Parkinson's disease and prodromal dementia with Lewy bodies. In addition, we calculated sample size requirements to demonstrate slowing of progression under different anticipated treatment effects. Overall, 1160 subjects were followed over an average of 3.3 ± 2.2 years. Among clinical variables assessed continuously, motor variables tended to progress faster and required the lowest sample sizes, ranging from 151 to 560 per group (at 50% drug efficacy and 2-year follow-up). By contrast, cognitive, olfactory and autonomic variables showed modest progression with higher variability, resulting in high sample sizes. The most efficient design was a time-to-event analysis using combined milestones of motor and cognitive decline, estimating 117 per group at 50% drug efficacy and 2-year trial duration. Finally, while phenoconverters showed overall greater progression than non-converters in motor, olfactory, cognitive and certain autonomic markers, the only robust difference in progression between Parkinson's disease and dementia with Lewy bodies phenoconverters was in cognitive testing. This large multicentre study demonstrates the evolution of motor and non-motor manifestations in prodromal synucleinopathy. These findings provide optimized clinical end points and sample size estimates to inform future neuroprotective trials.

Daridorexant treatment for chronic insomnia: a real-world retrospective single-center study.

INTRODUCTION: Chronic insomnia disorder (CID) significantly impacts well-being and daily functioning. Daridorexant, a double orexin receptor blocker, has shown efficacy in randomized clinical trials and has been recently approved for the treatment of CID in adult patients. This retrospective observational study aimed to describe real-world data on daridorexant effectiveness and safety in adult patients with CID. METHODS: Consecutive patients initiating on-label daridorexant at the Sleep Medicine Centre, University Hospital of Rome Tor Vergata were enrolled. Baseline and 30-day follow-up (FU) evaluations included patients' and CID characteristics, comorbidities, and clinicians' and patients' subjective ratings of changes with the Clinical and Patient Global Impression-Improvement scores (CGI-Is and PGI-Is), as well as Insomnia Severity Index (ISI) scores in a subgroup of patients. RESULTS: Sixty-nine patients initiated 50-mg daily dosage. At FU, 58% of both patients and clinicians rated CID as improved on CGI-Is and PGI-Is, with no differences based on comorbidities, sex, or number of previous medications. No significant predictors of CGI-Is and PGI-Is improvement were identified. At FU, ISI scores (n = 24) significantly decreased from 18.25 ± 3.21 to 12.08 ± 6.12 (Z = 8.000; p < 0.001). Of these, eight patients (33.3%) had absence of insomnia symptoms, and no patients reported a worsening in ISI score categories. CONCLUSIONS: This study suggests daridorexant to be effective and safe in real-world CID treatment whether used as a first-ever treatment, switch, or add-on, as reflected by subjective and objective measures and the absence of serious treatment-related adverse events. Future research on larger cohorts should explore daridorexant potential across diverse patient characteristics.

Role of sleep in neurodegeneration: the consensus report of the 5th Think Tank World Sleep Forum.

Sleep abnormalities may represent an independent risk factor for neurodegeneration. An international expert group convened in 2021 to discuss the state-of-the-science in this domain. The present article summarizes the presentations and discussions concerning the importance of a strategy for studying sleep- and circadian-related interventions for early detection and prevention of neurodegenerative diseases. An international expert group considered the current state of knowledge based on the most relevant publications in the previous 5 years; discussed the current challenges in the field of relationships among sleep, sleep disorders, and neurodegeneration; and identified future priorities. Sleep efficiency and slow wave activity during non-rapid eye movement (NREM) sleep are decreased in cognitively normal middle-aged and older adults with Alzheimer's disease (AD) pathology. Sleep deprivation increases amyloid-ß (Aß) concentrations in the interstitial fluid of experimental animal models and in cerebrospinal fluid in humans, while increased sleep decreases Aß. Obstructive sleep apnea (OSA) is a risk factor for dementia. Studies indicate that positive airway pressure (PAP) treatment should be started in patients with mild cognitive impairment or AD and comorbid OSA. Identification of other measures of nocturnal hypoxia and sleep fragmentation could better clarify the role of OSA as a risk factor for neurodegeneration. Concerning REM sleep behavior disorder (RBD), it will be crucial to identify the subset of RBD patients who will convert to a specific neurodegenerative disorder. Circadian sleep-wake rhythm disorders (CSWRD) are strong predictors of caregiver stress and institutionalization, but the absence of recommendations or consensus statements must be considered. Future priorities include to develop and validate existing and novel comprehensive assessments of CSWRD in patients with/at risk for dementia. Strategies for studying sleep-circadian-related interventions for early detection/prevention of neurodegenerative diseases are required. CSWRD evaluation may help to identify additional biomarkers for phenotyping and personalizing treatment of neurodegeneration.

Children's satisfaction with nursing care during hospitalization: A cross-sectional study.

PURPOSE: To assess hospitalized children's satisfaction with nursing care. DESIGN AND METHODS: Cross-sectional study using the "Children Care Quality at Hospital" questionnaire. 61 children admitted to the Pediatrics Department of a hospital in the Northern Region of Portugal were enrolled. RESULTS: The ranged age of the participants was 6 to 15 (10,61 ± 2,66 years), and most were male (52.46%; n = 32). The mean score in the three domains was 128 (77.11%), reflecting children's high satisfaction with the nursing care provided during hospitalization. The domain most valued was Nurse Characteristics, while the least valued was Nursing Environment. CONCLUSION: Results provide essential input for the dimensions to be considered when planning nursing care for children, managing care, and the physical environment in the wards. IMPLICATIONS FOR PRACTICE: These results highlight the need to hear children's voices. This must encourage nurses to reflect on how children evaluate nursing care and, by doing so, to increase the quality of nursing care provided in Pediatrics settings.

The effect of lacosamide monotherapy on sleep architecture in patients with epilepsy: a preliminary evidence.

Lacosamide (LCM) is a third-generation antiseizure medication (ASM), and its effect on sleep architecture was supported by a few studies in patients with drug-resistant epilepsy in which LCM was used as an add-on treatment. To gather knowledge on ASMs effects on sleep, this study aimed at evaluating the effects of LCM monotherapy on sleep in patients with focal epilepsy. Ten patients diagnosed with epilepsy (mean age 58.00 ± 14.77, 60.0% female, mean monthly seizure frequency 1.20 ± 2.48) starting LCM as monotherapy were included. Sleep architecture was assessed through polysomnography at baseline and at the 6-month follow-up visit. A significant decrease was observed in seizure frequency (p = 0.004), being all patients seizure-free at follow-up. At baseline, eight patients had poor sleep efficiency (< 85%). Sleep efficiency increased at follow-up, with only three patients having an index < 85% (p = 0.022). From baseline to follow-up, a significant decrease was observed in sleep latency (p = 0.022) and wakefulness after sleep onset (p = 0.047). Moreover, a significant decrease was observed in the percentage of stage 1 (Md = 6.70 vs Md = 3.85, p = 0.005) and stage 3 (Md = 27.70 vs Md = 22.35, p = 0.01) of Non-REM sleep. This study suggests that LCM monotherapy may positively impact sleep architecture in patients with epilepsy. The sleep efficiency improvement and the decrease of sleep latency and wakefulness after sleep onset observed at follow-up highlight better sleep stability and continuity in patients treated with LCM. Notably, all patients were seizure-free at follow-up, and seizure freedom may also concur to sleep structure improvement.

Clinical and dopaminergic imaging characteristics of the FARPRESTO cohort of trial-ready idiopathic rapid eye movement sleep behavior patients.

INTRODUCTION: Idiopathic/isolated rapid eye movement (REM) sleep behavior disorder (iRBD) is considered the prodromal stage of alpha-synucleinopathies. Thus, iRBD patients are the ideal target for disease-modifying therapy. The risk FActoRs PREdictive of phenoconversion in iRBD Italian STudy (FARPRESTO) is an ongoing Italian database aimed at identifying risk factors of phenoconversion, and eventually to ease clinical trial enrollment of well-characterized subjects. METHODS: Polysomnography-confirmed iRBD patients were retrospectively and prospectively enrolled. Baseline harmonized clinical and nigrostriatal functioning data were collected at baseline. Nigrostriatal functioning was evaluated by dopamine transporter-single-photon emission computed tomography (DaT-SPECT) and categorized with visual semi-quantification. Longitudinal data were evaluated to assess phenoconversion. Cox regressions were applied to calculate hazard ratios. RESULTS: 365 patients were enrolled, and 289 patients with follow-up (age 67.7 ± 7.3 years, 237 males, mean follow-up 40 ± 37 months) were included in this study. At follow-up, 97 iRBD patients (33.6%) phenoconverted to an overt synucleinopathy. Older age, motor and cognitive impairment, constipation, urinary and sexual dysfunction, depression, and visual semi-quantification of nigrostriatal functioning predicted phenoconversion. The remaining 268 patients are in follow-up within the FARPRESTO project. CONCLUSIONS: Clinical data (older age, motor and cognitive impairment, constipation, urinary and sexual dysfunction, depression) predicted phenoconversion in this multicenter, longitudinal, observational study. A standardized visual approach for semi-quantification of DaT-SPECT is proposed as a practical risk factor for phenoconversion in iRBD patients. Of note, non-converted and newly diagnosed iRBD patients, who represent a trial-ready cohort for upcoming disease-modification trials, are currently being enrolled and followed in the FARPRESTO study. New data are expected to allow better risk characterization.

Sleep-wake cycle and daytime sleepiness in patients with epilepsy after initiating perampanel as adjunctive therapy.

BACKGROUND: Antiseizure medications (ASMs) may affect nocturnal sleep and daytime vigilance. Perampanel (PER), a third-generation ASM, showed to improve nocturnal sleep in patients with epilepsy (PWE). Although ASMs can have beneficial effects on nocturnal sleep and daytime sleepiness, no study investigated the effect of PER on both sleep-wake cycle and daytime sleepiness. Therefore, this study aimed to objectively evaluate the sleep-wake cycle and daytime sleepiness in PWE treated with PER as adjunctive therapy. METHODS: This prospective study included adult PWE who received PER as add-on treatment. Sleep-wake cycle was assessed through actigraphic monitoring and daytime sleepiness by the multiple sleep latency test (MSLT) performed at the end of the actigraphic recording. All patients performed both tests at baseline and at 6-month follow-up. RESULTS: Ten patients (mean age: 44.50 ± 22.71 years, 50.0% female) were included. The mean monthly seizure frequency was 3.20 ± 5.94. Six of ten patients started PER as a first add-on treatment. The final PER dose was 5.11 ± 2.02 mg/day, and nine of ten patients achieved seizure freedom at follow-up. There was a significant decrease in mean monthly seizure frequency from baseline to follow-up (p = 0.004). No significant changes were found in the sleep-wake cycle parameters. An increase in sleep latency mean was observed at MSLT at 6-month follow-up (p = 0.005). CONCLUSIONS: This study confirms that adjunctive PER is effective on seizures without pathologically change of the sleep-wake cycle in PWE and can even improve daytime sleepiness. This effect can be mediated by the achievement of seizure control. Therefore, PER may be promising in PWE with sleep disturbances and daytime sleepiness.

Brainstem impairment in obstructive sleep apnoea and the effect of CPAP treatment: an electrophysiological blink reflex study.

PURPOSE: This study aimed to evaluate the functionality of the brainstem structures through the blink reflex (BR) test in patients with obstructive sleep apnoea (OSA) and to assess the effects of continuous positive airway pressure (CPAP) treatment on BR responses. METHODS: Patients with moderate-severe OSA and controls underwent BR testing. Patients with OSA who were adherent to CPAP therapy repeated BR testing at 6 months follow-up. CPAP adherence was defined as CPAP use for ≥ 4 hour per night on > 5 nights per week with residual apnoea-hypopnea index less than 5 events per hour. RESULTS: A total of 22 patients with OSA (86% male, mean age 57.8 ± 10.6 years) and 20 controls (60% male, mean age 55.3 ± 9.3 years) were included. Patients with OSA showed longer right and left R1 latency, as well as delayed right ipsilateral and contralateral R2 latencies compared to controls. Patients with OSA who were compliant with CPAP treatment (n = 16; 88% men, mean age 58.8 ± 9.7 years) showed a significant decrease in latency of the right ipsilateral and contralateral R2 responses at 6 months. CONCLUSION: This study showed an abnormal pattern of BR responses in patients with OSA, consistent with a significant impairment of brainstem functionality in OSA. CPAP treatment partially improved the BR responses, suggesting the importance of treating OSA.

Hydrogels Based on Natural Polymers Loaded with Bentonite and/or Halloysite: Composition Impact on Spectroscopic, Thermal, and Swelling Properties.

Hydrogels are characterized by their property of absorbing and releasing a high content of water and water-based liquids; thus, they can be applied in agriculture as controlled-release water and fertilizer products. The focus of this research was efficient and low-cost natural polymer-based hydrogels obtained by crosslinking gellan gum (GGLA) and starch (ST) with acetic acid (CA) and loading them with either bentonite (BET) and/or halloysite (HAL). The hydrogels were obtained by mixing 100, 75, 50, 25, and 0 wt.% of GGLA with 0, 25, 50, 75, and 100 wt.% ST water solutions. To obtain the networks, they were crosslinked with 10, 5, and 2 wt.% of CA and loaded with 2, 5, and 10 wt.% of BET and/or HAL. The samples were analyzed by infrared spectroscopy (FTIR), differential scanning calorimetry (DSC), their swelling in water, and the state of bound water properties. The results of these analyses point to the formation of a polymeric network with a decomposition temperature of >250 °C, and tailorable swelling properties that vary between 3 and 77, depending on the hydrogel composition. In summary, GGLA-ST-BET/HAL hydrogels are a good option for eco-friendly agriculture materials.

Cognitive functioning, cerebrospinal fluid Alzheimer's disease biomarkers and cerebral glucose metabolism in late-onset epilepsy of unknown aetiology: A prospective study.

Epilepsy is increasing, being more common in older adults, with more than 20% of late-onset cases with unknown aetiology (LOEU). Although epilepsy was associated with cognitive impairment, few studies evaluated the trajectories of cognitive decline in patients with LOEU. The present study aimed at assessing biomarkers of Alzheimer's disease (AD) in patients with LOEU and evaluating their cognitive performance for 12 months. For this study, 55 patients diagnosed with LOEU and 21 controls were included. Participants underwent cognitive evaluation and cerebrospinal fluid (CSF) biomarker analysis (ß-amyloid42 , tau proteins) before starting anti-seizure medication and then repeated the cognitive evaluation at the 12-month follow-up. A subgroup of LOEU patients and controls also performed 18 F-fluoro-2-deoxy-D-glucose positron emission tomography (18 F-FDG PET) before starting anti-seizure medication. At baseline, LOEU patients showed lower Mini-Mental State Examination (MMSE) score, worse cognitive performance in several domains, lower ß-amyloid42 and higher tau proteins CSF levels than controls. Significantly reduced glucose consumption was observed in the right posterior cingulate cortex and left praecuneus areas in LOEU patients than controls, and this finding correlated with memory impairment. In the longitudinal analysis, a significant decrease in MMSE and an increase in verbal fluency scores were found in LOEU patients. These findings evidence that LOEU patients have a significant cognitive impairment, and alteration of cerebral glucose consumption and CSF AD biomarkers than controls. Moreover, they showed a progressive global cognitive decline at follow-up, although verbal fluency was preserved. Further studies are needed to better understand the pathophysiological aspects of LOEU and its association with AD.

Non-motor symptoms burden in motor-fluctuating patients with Parkinson's disease may be alleviated by safinamide: the VALE-SAFI study.

Parkinson's disease (PD) is characterized by motor symptoms often experienced in concomitance with non-motor symptoms (NMS), such as depression, apathy, pain, sleep disorders, and urinary dysfunction. The present study aimed to explore the effect of safinamide treatment on NMS and quality of life in motor-fluctuating PD patients. VALE-SAFI is an observational single-centre study performed in fluctuating PD patients starting safinamide treatment and followed for 6 months. The effects of safinamide on NMS, sleep, fatigue, depression and pain were assessed through validated sales. Changes in the scales from baseline to the 6-month follow-up visit were analysed. 60 PD patients (66.67% males) were enrolled at baseline, and 45 patients completed the 6-month follow-up. PD patients improved motor symptoms at follow-up, with the significant reduction of motor fluctuations. The global score of the NMS Scale significantly decreased between baseline and the follow-up. Regarding pain domains, patients reported a significant improvement in discolouration and oedema/swelling. Further, a significant improvement was observed from baseline to follow-up in sleep quality measured through the Pittsburgh Sleep Quality Index, while no changes were documented in daytime sleepiness. No differences were found in depression and fatigue between baseline and follow-up. Finally, the patient's perception of the impact of PD on functioning and well-being decreased from baseline to follow-up. The present findings confirmed the beneficial effect of safinamide on both motor and non-motor symptoms, also improving the quality of life of PD patients. Furthermore, these data support the positive effects of safinamide on pain and mood, as well as on sleep quality and continuity.

Determinants of the intention to donate umbilical cord blood in pregnant women.

BACKGROUND AND OBJECTIVES: Umbilical cord blood (UCB) donation is a behaviour promoted by many countries' health systems. However, UCB donation is not a widespread behaviour among expectant mothers, and little is known about the reasons that may lead to it. The aim of the present study was to analyse the contribution of Theory of Planned Behaviour (TPB) variables among both primiparous and multiparous women in predicting intention to donate UCB. MATERIALS AND METHODS: Three hundred seventy-six expectant mothers completed questionnaires that captured sociodemographic data, parity, previous donation, attitudes, subjective norms, perceived behavioural control (PBC) and intention to donate UCB. Multigroup analysis structural equation modelling was conducted using Mplus (version 8.02). RESULTS: Multigroup path analyses showed that intentions were strongly predicted by subjective norms and moderately predicted by positive attitudes and PBC in both primiparous and multiparous women. TPB constructs explained 71% of the variance in intentions for both groups. CONCLUSIONS: Future interventions to increase intention to donate among primiparous and multiparous women could primarily consider the influence of partner and significant others in determining positive intentions and secondarily target increasing positive attitudes and perceptions of control.

The type of SARS-CoV-2 vaccine influences serological response in kidney transplant recipients.

Vaccination is a promising strategy to control the ongoing pandemic; however, solid organ recipients tend to develop a weaker immune response to vaccination. Anti-spike SARS-CoV-2 antibodies titers were measured 2-4 weeks post-vaccination completion in 131 KT patients without previous infection. Demographic, clinical, and laboratorial parameters were analyzed to identify which factors contributed to seroconversion. Factors that influenced seroconversion, that occurred in 76 patients (58%), were longer time post-transplant, immunosuppression without an antiproliferative drug and vaccination with mRNA vaccines. Patients who received mRNA vaccines had significantly higher rates of seroconversion compared with adenovirus vector vaccines (67% vs 33%, P < .001) and higher anti-spike IgG titers. These findings reinforce the need to discuss the vaccination strategy in this population, including a third dose with a mRNA vaccine.

Effects of melatonin prolonged-release on both sleep and motor symptoms in Parkinson's disease: a preliminary evidence.

BACKGROUND: Sleep-related symptoms, especially insomnia, are frequently reported by patients with Parkinson's disease (PD) and can markedly affect motor symptoms and impair patients' quality of life. Melatonin has been shown to improve sleep in PD patients. This pilot study aimed at evaluating the effects of a 3-month treatment with 2 mg melatonin prolonged-release (PR) on sleep and motor disability in PD patients. MATERIALS AND METHODS: Twelve PD patients under stable antiparkinsonian treatment were enrolled in the study. Before treatment (T0), motor dysfunction was assessed with Unified Parkinson's Disease Rating Scale (UPDRS-III) and sleep architecture with polysomnography. Subjective sleep quality was also assessed through Pittsburgh Sleep Quality Index (PSQI) and daytime somnolence with Epworth Sleepiness Scale (ESS). Patients then started melatonin PR and all measures were repeated at the end of treatment after 3 months (T1). RESULTS: Sleep latency significantly decreased from T0 to T1, but no other significant differences were found in PSG parameters. Melatonin PR treatment significantly reduced the ESS scores from T0 to T1, while the PSQI scores presented a trend of improvement from T0 to T1. Motor dysfunction was not improved by melatonin PR, although there was a trend in decreasing UPDRS-III. Both clinical global improvement and patient clinical global impression documented an improvement in insomnia symptoms at T1. CONCLUSIONS: These findings suggest that melatonin may improve sleep symptoms in PD patients, although further evidence is needed in larger controlled studies to confirm these results and explore the possible direct and indirect influence of sleep improvement on motor dysfunction.

Depressive symptoms in patients with epilepsy and clinically associated features in a single tertiary center.

Although depressive symptoms are the most common psychiatric comorbidity in epilepsy, they remain underestimated and untreated in a large proportion of patients. The purpose of this study was to evaluate depression severity and related clinical features in people with epilepsy using a well-reliable self-report index of mood, the Beck Depression Inventory-II (BDI-II). One-hundred seventeen adult patients with epilepsy were recruited from a tertiary epilepsy center and completed the BDI-II. A single-item analysis of the 21 questions of the BDI-II was computed and differences between women and men in each depressive symptom were evaluated. Correlation and regression analyses were used to identify clinical features associated with the severity of depression. Results showed gender differences in some items, with women reporting overall higher depression severity than men. The most common symptoms regarded domains of sleeping patterns, tiredness, and loss of energy. Regression evidence suggested that being female, having an epilepsy duration < 10 years, as well as being treated with psychotropic drugs and reporting generalized seizure, were associated with higher depression severity. Despite its cross-sectional nature, this study reinforces the importance of investigating and possibly treating depressive symptoms in adult patients with epilepsy, since they negatively impact well-being, daytime activities, and sleep. Further studies identifying pharmacological and non-pharmacological treatments for depression in epilepsy need to be planned.

Changes in indications for outpatient percutaneous liver biopsy over 5 years: from hepatitis C to fatty liver disease.

INTRODUCTION: Although the use of non-invasive methods for assessment of liver fibrosis has reduced the need for biopsy, the diagnosis of liver damage still requires histological evaluation in many patients. We aim to describe the indications for percutaneous liver biopsy (PLB) and the rate of complications in an outpatient setting over 5 years. METHODS: This observational, single-center, and retrospective study included patients submitted to real-time ultrasound (US)-guided biopsies from 2015 to 2019. We collected age, gender, coagulation tests, comorbidities, and the number of needle passes. The association between the variables and complications was evaluated using the generalized estimating equations method. RESULTS: We analyzed 532 biopsies in 524 patients (55.3% male) with a median age of 49 years (range 13-74y). An average of 130.3 biopsies per year were performed in the first 3 years of the study versus 70.5 in the other 2y. The main indications were hepatitis C virus (HCV) infection (47.0%), autoimmune and cholestatic liver diseases (12.6%), and metabolic dysfunction-associated fatty liver disease (MAFLD) (12.1%). The number of HCV-related biopsies had a remarkable reduction, while MAFLD-related procedures have progressively raised over time. Around 54% of the patients reported pain, which was significantly associated with females (p=0.0143). Serious complications occurred in 11 patients (2.1%) and hospital admission was necessary in 10 cases (1.9%). No patient required surgical approach and there were no deaths. No significant association was found between the studied variables and biopsy-related complications. CONCLUSION: The indications for PLB in an outpatient setting have changed from HCV to MAFLD over the years. This procedure is safe and has a low rate of serious complications, but new strategies to prevent the pain are still needed, especially for females.

SARS-CoV-2/DENV co-infection: a series of cases from the Federal District, Midwestern Brazil.

BACKGROUND: Since the novel coronavirus disease outbreak, over 179.7 million people have been infected by SARS-CoV-2 worldwide, including the population living in dengue-endemic regions, particularly Latin America and Southeast Asia, raising concern about the impact of possible co-infections. METHODS: Thirteen SARS-CoV-2/DENV co-infection cases reported in Midwestern Brazil between April and September of 2020 are described. Information was gathered from hospital medical records regarding the most relevant clinical and laboratory findings, diagnostic process, therapeutic interventions, together with clinician-assessed outcomes and follow-up. RESULTS: Of the 13 cases, seven patients presented Acute Undifferentiated Febrile Syndrome and six had pre-existing co-morbidities, such as diabetes, hypertension and hypopituitarism. Two patients were pregnant. The most common symptoms and clinical signs reported at first evaluation were myalgia, fever and dyspnea. In six cases, the initial diagnosis was dengue fever, which delayed the diagnosis of concomitant infections. The most frequently applied therapeutic interventions were antibiotics and analgesics. In total, four patients were hospitalized. None of them were transferred to the intensive care unit or died. Clinical improvement was verified in all patients after a maximum of 21 days. CONCLUSIONS: The cases reported here highlight the challenges in differential diagnosis and the importance of considering concomitant infections, especially to improve clinical management and possible prevention measures. Failure to consider a SARS-CoV-2/DENV co-infection may impact both individual and community levels, especially in endemic areas.