Mind reading dysfunctions in patients with obstructive sleep apnoea: A neuropsychological approach.

Obstructive sleep apnoea syndrome (OSAS) is a prevalent sleep-related breathing disorder that has been extensively studied for its effects on cognitive functions. However, little attention has been given to investigating Mind Reading (MR) skills in patients with OSAS. In this study, we employed a neuropsychological approach to thoroughly assess various facets of MR skills in patients with OSAS. Forty-two patients with untreated moderate or severe OSAS (AHI ≥15; 30 men, 12 women) and 16 healthy controls (7 men and 9 women), matched by age, were enrolled. To assess MR skills, we used: (i) The Story-based Empathy Task (SET), which includes three experimental conditions: identifying intentions (SET-IA), emotional states (SET-EA), and a control condition for inferring causality reactions (SET-CI); (ii) the Ekman 60 Faces Test (Ek60), which measures emotion recognition from facial expressions. Our findings revealed that patients with OSAS exhibit deficits in emotion-related MR skills, while their ability to make inferences about the cognitive states of social partners remains largely preserved. This finding corroborates previous evidence indicating that social cognition, particularly MR skills, may be one of the cognitive domains affected by OSAS. It emphasizes the significance of investigating social cognition and the relationship between MR skills and social functioning as a new and intriguing area of research in patients with OSAS.

Practical recommendations for managing severe chronic rhinosinusitis with nasal polyps in the era of biologics.

Objective: We conducted a national survey to understand how rhinology practice has changed with the advent of biologics and how this affected patients with uncontrolled, severe chronic rhinosinusitis with nasal polyps (CRSwNP). We aimed to analyse the results of the survey and infer practical recommendations for clinical practice. Methods: A group of ear, nose, and throat specialists (ENTs) experienced in the management of CRSwNP developed a 74-question survey. ENTs from rhinology centres authorised to prescribe biologics in the context of the national health system were invited to answer it between 01/05/2022 and 31/07/2022. The responses underwent descriptive analyses, and the authors discussed the results and derived practical recommendations for clinical practice. Results: ENTs working in rhinology centres changed their practices coinciding with the advent of biologics. CRSwNP evaluations have become more complex because they involve diagnostic confirmation, determining the patients' immunologic profile, and other factors. We observed heterogenous behaviours in practice that may be conditioned by the novelty of the topic. The results of the survey were used to develop practical recommendations for ENTs and are summarised herein. Conclusions: Clinical practice in rhinology outpatient clinics has changed profoundly in the era of biologics. Our practical recommendations for clinicians working in rhinology centres are expected to help standardise practice and improve care.

Neuropsychological and socio-cognitive deficits in patients with obstructive sleep apnea.

Introduction: Patients with obstructive sleep apnea (OSA) suffer from several neurocognitive deficits. We investigated the cognitive and socio-cognitive profiles of patients with severe OSA, controlling for potentially relevant mediating variables (i.e. age, body-mass index, cognitive reserve and depression). Moreover, we studied the neuropsychological profile of a high-risk OSA phenotype characterized by severe OSA and severe nocturnal hypoxemia.Method: We assessed 29 previously untreated severe OSA patients with a mean age of 55.6 (± 9.9 years) and a mean apnea-hypopnea index (AHI) of 53.1 (± 17.4). A control group of 34 healthy participants was also enrolled. Participants completed an extensive neuropsychological battery that included social cognition, a relatively new investigation area among OSA patients.Data analysis: Data were analyzed with a Bayesian approach. Specifically, Bayesian ANCOVA was used to investigate whether the grouping variable could predict test performance. Age, body-mass index, cognitive reserve and state of depression were added as covariates to the null model to weight the effects of these potential confounding factors. Three groups were analyzed: healthy controls (H), OSA with severe apnea and severe nocturnal oxygen desaturation (D+), and OSA with severe apnea non-desaturators (D-). Performances on the various neuropsychological tests were treated as the dependent variables.Results: The results indicate that non-verbal reasoning, the theory of mind skills, and mental shifting ability were impaired in OSA patients. Patients with severe nocturnal hypoxemia underperformed compared to patients with the same severity of apnea but non-desaturators. Additionally, we observed a trend toward a worse performance among OSA desaturator patients in the following abilities: constructional ability, short term verbal memory, phonological fluency, and the ability to inhibit automatic and dominant responses.Conclusion: The data suggest a key role of hypoxemia in affecting cognitive functioning in OSA patients. Executive functions and the concomitant involvement of social cognition are particularly affected.

Association Between Severity of COVID-19 Respiratory Disease and Risk of Obstructive Sleep Apnea.

OBJECTIVES: The purpose of this observational retrospective study was to evaluate, in patients with a severe acute respiratory syndrome coronavirus 2 infection, the association between the severity of coronavirus disease 2019 (COVID-19) respiratory illness and the risk of infected patients to develop obstructive sleep apnea (OSA). METHODS: Ninety-six patients with confirmed COVID-19 infection were enrolled in the study. The STOP-BANG questionnaire to investigate the risk of the OSA syndrome was filled in by the patients at admission. The enrolled patients were divided into 2 groups according to the respiratory disease: group 1 (72 patients), hospitalized patients undergoing conventional oxygen therapy; group 2 (24 patients), patients requiring enhanced respiratory support. STOP-BANG results of these 2 groups were compared to observe whether patients with high OSA risk more frequently presented a severe form of COVID-19. RESULTS: 41.6% of the patients in group 2 had a STOP-BANG score between 5 and 8 (high risk of having apnea); in contrast, 20.8% of the patients in group 1 had a STOP-BANG score between 5 and 8, with a statistically significant difference between the 2 groups (P = .05). A complementary trend was observed regarding the proportion of patients in the range 0 to 2, which classifies patients at a low risk of OSA (48.6% vs 20.8% for groups 1 and 2, P = .01). CONCLUSIONS: According to our data, the chances of having a severe case of COVID-19 should be considered in patients at high risk of OSA. CURRENT KNOWLEDGE/STUDY RATIONALE: Emerging research suggests that OSA could represent a potentially important risk factor for the severe forms of COVID-19. The purpose of this observational retrospective study was to evaluate the potential association between OSA and the severity of COVID-19 disease. STUDY IMPACT: According to our data, the likelihood of contracting a severe form of COVID-19 disease should be considered in patients at high risk of OSA.

The Use of Middle Latency Auditory Evoked Potentials (MLAEP) as Methodology for Evaluating Sedation Level in Propofol-Drug Induced Sleep Endoscopy (DISE) Procedure.

To analyze the middle latency auditory evoked potential index (MLAEPi), compared to the standard bispectral index (BIS), as a method for evaluating the sedation level in drug-induced sleep endoscopy (DISE). In this controlled clinical study on a sample of 99 obstructive sleep apnea (OSA) or snoring patients, we compared the MLAEPi with the BIS after propofol infusion during the standard DISE technique in order to define the MLAEPi values within the observational window of the procedure. The DISE procedure was divided into eight steps, and we collected both MLAEPi and BIS data values from the same patient in every step. The MLAEPi showed a faster response than the BIS after propofol infusion during DISE. Therefore, the clinical use of the MLAEPi in evaluating the sedation level seems to be a good alternative to the current technological standards.

A New Technological Advancement of the Drug-Induced Sleep Endoscopy (DISE) Procedure: The "All in One Glance" Strategy.

To illustrate a new technological advance in the standard drug-induced sleep endoscopy (DISE) model, a new machine was used, the Experimental 5 Video Stream System (5VsEs), which is capable of simultaneously visualizing all the decisional parameters on a single monitor, and recording and storing them in a single uneditable video. The DISE procedure was performed on 48 obstructive sleep apnea (OSA) or snoring patients. The parameters simultaneously recorded on a single monitor are (1) the pharmacokinetics and pharmacodynamics of propofol (through the target controlled infusion (TCI) pump monitor), (2) the endoscopic upper airway view, (3) the polygraphic pattern, and (4) the level of sedation (through the bispectral index (BIS) value). In parallel to the BIS recording, the middle latency auditory evoked potential (MLAEP) was also recorded and provided. Recorded videos from the 5VsEs machine were re-evaluated six months later by the same clinician and a second clinician to evaluate the concordance of the therapeutic indications between the two. After the six-month period, the same operator confirmed all their clinical decisions for 45 out of 48 videos. Three videos were no longer evaluable for technical reasons, so were excluded from further analysis. The comparison between the two operators showed a complete adherence in 98% of cases. The 5VsEs machine provides a multiparametric evaluation setting, defined as an "all in one glance" strategy, which allows a faster and more effective interpretation of all the simultaneous parameters during the DISE procedure, improving the diagnostic accuracy, and providing a more accurate post-analysis, as well as legal and research advantages.

The Neuropsychological Profile of Attention Deficits of Patients with Obstructive Sleep Apnea: An Update on the Daytime Attentional Impairment.

INTRODUCTION: Patients with obstructive sleep apnea (OSA) suffer from several neurocognitive disturbances. One of the neuropsychological processes most investigated in OSA patients is attention, but the results have been controversial. Here, we update the attention profile of OSA patients with the final aim to improve attention assessment, with a possible impact on clinical and medical-legal practices, in terms of which attention subdomains and parameters need consideration and which one is a high-risk OSA phenotype for attention dysfunctions. METHOD: For this purpose, we assessed 32 previously untreated OSA patients (26 men and 6 women) under 65 years of age (mean age 53.2 ± 7.3; mean education level 10.4 ± 3.4 years) suffering from moderate to severe sleep apnea and hypopnea (mean apnea-hypopnea index (AHI) 45.3 ± 22.9, range 16.1-69.6). A control group of 34 healthy participants matched with OSA patients for age, education level, and general cognitive functioning were also enrolled. The OSA patients and healthy participants were tested through an extensive computerized battery (Test of Attentional Performance, TAP) that evaluated intensive (i.e., alertness and vigilance) and selective (i.e., divided and selective) dimensions of attention and returned different outcome parameters (i.e., reaction time, stability of performance, and various types of errors). Data analysis: The data were analyzed by ANCOVA which compared the speed and accuracy performance of the OSA and control participants (cognitive reserve was treated as a covariate). The possible mechanisms underlying attention deficits in OSA patients were examined through correlation analysis among AHI, oxygenation parameters, sleepiness scores, and TAP outcomes and by comparing the following three phenotypes of patients: severe OSA and severe nocturnal desaturators (AHI++D+), severe OSA nondesaturators (AHI++D-), and moderate OSA nondesaturators (AHI+D-). RESULTS: The results suggest that the OSA patients manifest deficits in both intensive and selective attention processes and that reaction time (RT) alone is ineffective for detecting and characterizing their problems, for which error analysis and stability of performance also have to be considered. Patients with severe OSA and severe hypoxemia underperformed on alertness and vigilance attention subtests. CONCLUSIONS: The data suggest the importance of evaluating attention deficits among OSA patients through several parameters (including performance instability). Moreover, the data suggest a multifaceted mechanism underlying attention dysfunction in OSA patients.

Obstructive Sleep Apnea Syndrome (OSAS): Occupational Health and other medical disciplines facing the problem. / La Sindrome delle Apnee Ostruttive nel Sonno (OSAS): la Medicina del Laboro (e non solo)di fronte al problema.

Obstructive Sleep Apnea Syndrome (OSAS) is one of the most common causes of excessive daytime sleepiness, therefore an important determinant of road and work accidents, as well as being associated with multiple chronic-degenerative diseases. The recent transposition of the European Commission Directive 2014/85/EU on driver licensing highlighted the need to tackle the problem appropriately, not only for its high prevalence in the general population, but also for its significant impact on occupational safety and health, and related social costs. The Occupational Health Physician is required to play a strategic role in this regard, not just for early diagnosis, but also for monitoring the therapeutic efficacy in maintaining or reintegrating workers into specific jobs. The effectiveness of his/her work will depend primarily on the level of interaction he/she will be able to establish with the different specialists who are in charge of the diagnostic and therapeutic process, in order to maintain a satisfactory work performance and to prevent possible deleterious effects on health in the medium and long-term period. The logic of this multidisciplinary approach has led nineteen scientific Societies and Associations to establish a Joint Technical Committee and to address the problem in the light of effectiveness and efficiency criteria in the interest of the individual and the community.

Obstructive sleep apnea (OSA): healthcare and social costs. / La Sindrome dell 'Apnea Ostruttiva nel sonno (OSAS): I costi sanitari e sociali.

Obstructive sleep apnea (OSA) syndrome is an underdiagnosed widespread chronic disease involving both sexes and all ages. Undiagnosed and untreated OSA is associated with workplace productivity losses and significant direct and indirect medical costs. A cost analysis of OSA was carried out in Italy ten years ago. Overall OSA medical costs, largely due to treatment of comorbidity, amounted to € 2,9 billion or 55% of total medical costs. Direct medical costs, due to diagnosis and treatment of OSA, were 6% of overall OSA costs, while medical costs due to the absence of diagnosis and of prevention of comorbidities represented 49% of the overall cost. Non-medical costs made up for the remaining 45%. € 1.5 billion could be saved by promoting screening campaigns aimed at detecting OSA that would otherwise remain undiagnosed and by improving adherence to treatment. Bearing in mind the increasing OSA prevalence and the recent quantification of avoidable OSA-related road accidents, the real cost of OSA is higher than estimated up to now.

Statins May Prevent Atherosclerotic Disease in OSA Patients without Co-Morbidities?

Obstructive sleep apnoea (OSA) is characterized by repetitive interruptions of breathing, causing Chronic Intermittent Hypoxia (CIH) that can be involved in the development and progression of cardiovascular diseases. There is evidence showing a close relationship between OSA and atherosclerosis, even in patients who do not show co-morbidities such as hypertension, diabetes, high levels of lowdensity lipoprotein cholesterol (LDL-C), cigarette smoking and obesity, which can activate the endothelium. This endothelium activation due to CIH and specific to OSA seems to be dependent on a different pathway. The current first line therapy for OSA is the application of the continuous positive airway pressure (CPAP), but it alone is not enough to reduce cardiometabolic risk in patients with OSA. In contrast, statins, via their pleiotropic property, might be able to change inflammation and early atherosclerosis, lipid profile and cardiovascular outcomes in OSA. The role of statins in OSA patients with or without any co-morbidities could potentially prevent coronary vascular risk and stroke and in the future, represent an additional treatment option along with CPAP therapy. Strengthening the prevention strategies against atherosclerosis in OSA should be one of the focal aims for healthcare programs of the future.

Obstructive sleep apnea syndrome: coagulation anomalies and treatment with continuous positive airway pressure.

INTRODUCTION: Obstructive sleep apnea syndrome (OSAS) is a highly prevalent sleep disorder associated with severe cardiovascular events, morbidity and mortality. Recent evidence has highlighted OSAS as an independent risk factor for an excessive platelet activation and arterial thrombosis, but the underlying mechanisms have not yet been determined. Studies in cell culture and animal models have significantly increased our understanding of the mechanisms of inflammation in OSAS. Hypoxia is a critical pathophysiological element that leads to an intense sympathetic activity, in association with systemic inflammation, oxidative stress and procoagulant activity. While platelet dysfunction and/or hypercoagulability play an important role in the pathogenesis of vascular disease, there are limited studies on the potential role of blood viscosity in the development of vascular disease in OSAS. CONCLUSION: Further studies are required to determine the precise role of hypercoagulability in the cardiovascular pathogenesis of OSAS, particularly its interaction with oxidative stress, thrombotic tendency and endothelial dysfunction. Nasal continuous positive airway pressure (nCPAP), the gold standard treatment for OSAS, not only significantly reduced apnea-hypopnoea indices but also markers of hypercoagulability, thus representing a potential mechanisms by which CPAP reduces the rate of cardiovascular morbidity and mortality in OSAS patients.

Diagnostic Accuracy of Obstructive Airway Adult Test for Diagnosis of Obstructive Sleep Apnea.

RATIONALE: The gold standard for the diagnosis of Obstructive Sleep Apnea (OSA) is polysomnography, whose access is however reduced by costs and limited availability, so that additional diagnostic tests are needed. OBJECTIVES: To analyze the diagnostic accuracy of the Obstructive Airway Adult Test (OAAT) compared to polysomnography for the diagnosis of OSA in adult patients. METHODS: Ninety patients affected by OSA verified with polysomnography (AHI ≥ 5) and ten healthy patients, randomly selected, were included and all were interviewed by one blind examiner with OAAT questions. MEASUREMENTS AND MAIN RESULTS: The Spearman rho, evaluated to measure the correlation between OAAT and polysomnography, was 0.72 (p < 0.01). The area under the ROC curve (95% CI) was the parameter to evaluate the accuracy of the OAAT: it was 0.91 (0.81-1.00) for the diagnosis of OSA (AHI ≥ 5), 0.90 (0.82-0.98) for moderate OSA (AHI ≥ 15), and 0.84 (0.76-0.92) for severe OSA (AHI ≥ 30). CONCLUSIONS: The OAAT has shown a high correlation with polysomnography and also a high diagnostic accuracy for the diagnosis of OSA. It has also been shown to be able to discriminate among the different degrees of severity of OSA. Additional large studies aiming to validate this questionnaire as a screening or diagnostic test are needed.

Analysis of cystic fibrosis gene mutations in children with cystic fibrosis and in 964 infertile couples within the region of Basilicata, Italy: a research study.

INTRODUCTION: Cystic fibrosis is the most common autosomal recessive genetic disease in the Caucasian population. Extending knowledge about the molecular pathology on the one hand allows better delineation of the mutations in the CFTR gene and the other to dramatically increase the predictive power of molecular testing. METHODS: This study reports the results of a molecular screening of cystic fibrosis using DNA samples of patients enrolled from January 2009 to December 2013. Patients were referred to our laboratory for cystic fibrosis screening for infertile couples. In addition, we identified the gene mutations present in 76 patients affected by cystic fibrosis in the pediatric population of Basilicata. RESULTS: In the 964 infertile couples examined, 132 subjects (69 women and 63 men) resulted heterozygous for one of the CFTR mutations, with a recurrence of carriers of 6.85%. The recurrence of carriers in infertile couples is significantly higher from the hypothetical value of the general population (4%). CONCLUSIONS: This study shows that in the Basilicata region of Italy the CFTR phenotype is caused by a small number of mutations. Our aim is to develop a kit able to detect not less than 96% of CTFR gene mutations so that the relative risk for screened couples is superimposable with respect to the general population.

Obstructive sleep apnea syndrome: blood viscosity, blood coagulation abnormalities, and early atherosclerosis.

Obstructive sleep apnea syndrome (OSAS) is an independent risk factor for atherosclerosis and arterial thrombosis, which are associated with high cardiovascular (CV) morbidity and mortality. In studies performed in clinical populations with elevated CV event risk profiles, the occurrence of moderate to severe OSAS was very often accompanied by a worsened vascular function and increased prevalence of structural abnormalities. Recent investigations of atherosclerosis in OSAS have focused on thrombotic tendency and blood viscosity, providing new insight into mechanisms of the disease. Despite that knowledge about the mechanisms of development of CV disease in patients with OSAS is still incomplete, observations confirm a relationship between sleep-disordered breathing and the rheological properties (flow properties) of blood. While platelet dysfunction and hypercoagulability (PDMPs, PaI-1, and SF) play important roles in the pathogenesis of vascular disease, there are limited studies on the potential role of blood viscosity in the development of vascular disease in OSAS.

Penetration of prulifloxacin into sinus mucosa of patients undergoing paranasal sinus elective endoscopic surgery.

The aim of this study was to assess the concentration of ulifloxacin, the active metabolite of prulifloxacin, in sinuses mucosa and plasma of patients with chronic rhinosinusitis, requiring sinus elective endoscopic surgery. Thirty-nine patients (30 males, 9 females; age range 22-77 years) with chronic sinusitis were enrolled, 35 were treated with the investigational medication. Samples from four untreated patients were used to validate the analytical method, while four treated patients dropped out before surgery. One 600 mg prulifloxacin tablet once daily was administered for 5 days before surgery. The last dosing was scheduled from 2 to 12 hours from tissue and plasma sampling. In each patient, two samples of paranasal sinus mucosa (from ethmoid and turbinate, respectively) and one blood sample were collected. Concentrations of ulifloxacin in plasma and sinuses mucosa were measured using validated bioanalytical LC/MS/MS methods. Individual and mean ulifloxacin concentrations in tissues were always higher than the relevant plasma levels. The highest concentrations were observed between 2.5 and 4.5 hours after the last dosing in all districts. The mean tissue/plasma ratios were 2.5 and 3.0 for ethmoid and turbinate, respectively. Data expressed as Area Under the Curves (AUC±SD) showed that ulifloxacin concentrations in the ethmoid were slightly higher (18.68±6.48 µg/g*h) than in turbinate (15.00±2.89 µg/g*h), and definitely higher than in plasma (6.32±1.14 µg/ml*h). The AUC ratios between tissues and plasma were 3.0 for ethmoides and 2.4 for turbinates. One patient reported two treatment-related episodes of diarrhea, which spontaneously resolved after the drug suspension. Results from this study seem to suggest that prulifloxacin showed good distribution in sinus tissues, where it reaches concentrations significantly higher than in plasma. These findings strongly call for confirmatory clinical trials in patients with bacterial rhinosinusitis.

Study of a family in the province of Matera presenting with glucose-6-phosphate dehydrogenase deficiency and Gilbert's syndrome.

Glucose-6-phosphate dehydrogenase (G6PD) deficiency, a recessive X-linked trait, is the most common enzyme deficiency in the world. The most devastating clinical consequence of this deficit is severe neonatal jaundice, which results in sensorineural deficit, and severe haemolytic anemia. However, patients may be asymptomatic. The most common clinical sign is hyperbilirubinemia (h↑), that is also related to Gilbert's syndrome, a condition associated with the promoter polymorphism of the UDP-glucuronosyltransferase 1 (UGT1A1) gene. The aim of this study was to underline (as is usually done by DNA molecular analysis) to detect and to clarify the genetic deficiency that is the reason of the disorder in question. In this study, different techniques were applied to analyse a family of four individuals presenting with hyperbilirubinemia: bilirubinic dosage, electrophoresis and enzymatic activity dosage of G6PD; molecular analysis of the UGT1A promoter to detect a thymine-adenine (TA) insertion, that causes the [A(TA)7TAA] mutation. The results showed that in certain cases, the presence of hyperbilirubinemia is not only associated with G6PD deficiency, but may be caused by the co-presence of a mutation in the UGTA1 promoter related to Gilbert's syndrome. As being affected by these two conditions predisposes to adverse effects towards certain drug treatments, it is advisable to study the UGTA1 gene before prescribing drugs for specific antineoplastic or retroviral treatment. We emphasize that investigating both the UGT1A gene and G6PD activity is the most reliable way to make a correct differential diagnosis.