Predictive tools for nocturnal respiratory failure in patients with moderate and severe OSAS.

PURPOSE: The impact of obstructive sleep apnea syndrome (OSAS) in terms of mortality, morbidity, and quality of life has been well established. Phenotyping OSAS is essential in order to make the best therapeutic choice. A particular subset of patients with OSAS shows nocturnal respiratory failure, defined by a nighttime oxygen saturation <90% in more than 30% of the total sleep time (TST90). The aim of this study was to identify possible predictive factors for nighttime respiratory failure (NRF) in patients with OSAS. METHODS: In this retrospective study, patients with suspected OSAS who underwent a sleep study were enrolled. Of 116 patients with moderate/severe OSAS who met the inclusion criteria, 67 also had nocturnal respiratory failure. We compared clinical, anthropometric, and laboratory data in patients with OSAS vs. OSAS and nocturnal respiratory failure. RESULTS: Patients with OSAS and nocturnal respiratory failure were more frequently female, had a higher BMI, lower daytime oxygen partial pressure (PaO2) in arterial blood, higher Apnea Hypopnea Index (AHI), and a lower number of sleep hours per night. Chronic obstructive pulmonary disease (COPD) was more diagnosed in the group of patients with nocturnal respiratory failure. A lower number of total sleep hours, lower daytime PaO2, lower AHI, increased oxygen desaturation index (ODI), and the presence of a diagnosed COPD were all found to increase the risk of having nocturnal respiratory failure. CONCLUSION: COPD, AHI, ODI, daytime PaO2, and total sleep hours are the main predictors for NRF in patients with moderate and severe OSAS.

Economic impact of implementing prescription of single-inhaler triple therapies versus current multiple-inhaler triple therapies for COPD in the Apulia Region.

BACKGROUND: The most impacting direct costs associated to COPD for the National Health Systems (NHS) are those related to accesses to the emergency room and hospital admissions, due to the onset of one or more COPD exacerbations. At the same time, severe COPD treatment, that often require a combination of medicaments, represents a substantial economic burden for the National Health Systems (NHS). This study aimed to evaluate the potential saving deriving from the implementation in the prescription of the two currently available single-inhaler triple therapies (SITTs) versus the currently used multiple-inhaler triple therapies (MITTs) in an eligible COPD population residing in the Apulia Region. METHODS: A budget impact model was developed hypothesizing the progressive replacement of the different MITTs on the reference market (Scenario A) with the pre-established SITTs, assuming a degree of penetration of 30%, 50% and 100% (Scenario B). Drug costs were based on prices published on the Official Gazette and therapy durations were based on prescribing information over the year 2019 (IQVIA™ prescription dataset). RESULTS: Our analysis showed that the extemporaneous MITT with the highest prevalence on the reference market was the inhaled corticosteroids/long-acting ß2-agonists (ICS/LABA) combination plus a long-acting muscarinic antagonists (LAMA). This association of medicaments was paradoxically also the one associated to the highest expense value. The expanded use of a pre-established ICS/LAMA/LABA SITT was associated to a significant economic saving, ranging from a minimum of -€ 1,108,814 (SITT use: 30%) to a maximum of -€ 3,658,950 (SITT use: 100%). The cheapest pre-established SITT contained the fluticasone furoate/umeclidinium/vilanterol (FF/UMEC/VI) combination. CONCLUSION: A pre-fixed ICS/LAMA/LABA SITT is cost-saving, compared to the different currently used extemporaneous MITTs. Clinicians should consider the potential benefits of finding less expensive regimens while maintaining adequate efficacy in the prescriptive decision making process of COPD patients.

The association between dysphagia and OSA.

OBJECTIVE: The aim of our study was to investigate the presence of dysphagia in patients with Obstructive Sleep Apnoea (OSA) and to correlate swallowing impairment with hypnologic and anatomic parameters. METHODS: The study population includes 36 patients suffering from OSA. Patients were divided into two groups using the presence of dysphagia as a distinctive parameter. Group 1 included 27 OSA patients without signs of dysphagia and Group 2 included 9 OSA patients with signs of dysphagia. RESULTS: The age of patients in Group 2 was higher compared with the age of patients in Group 1. Analysis of Continuous Positive Airway Pressure (CPAP), obtained in the titration phase, showed that OSA patients with signs of dysphagia required a higher level of CPAP pressure than those who were not affected by swallowing abnormalities (12.6 ± 1 vs 10.5 ± 1.9 p = 0.003). No other differences in anthropometric, hypnologic, or arterial blood gas values were found between the two groups. CONCLUSIONS: In clinical practice, all OSA patients should undergo a complete ENT exam, including assessment of swallowing, before CPAP therapy is started. This may predict the need for higher CPAP pressure settings to resolve apnoea episodes in the presence of dysphagia as well as guide the choice of CPAP interfaces (orofacial vs. nasal) in these patients.

The Intermittent Abdominal Pressure Ventilator as an Alternative Modality of Noninvasive Ventilatory Support: A Narrative Review.

ABSTRACT: Noninvasive ventilation has become the initial treatment for symptomatic ventilatory pump failure but, when used at ventilatory support settings, can be an alternative to tracheostomy mechanical ventilation. The intermittent abdominal pressure ventilator, a corset with an internal air sack inflated by a ventilator, allows to increase tidal volumes through the raising of the diaphragm and its consequent passive descent. It has been used for daytime support for more than 70 yrs, but its knowledge among clinicians is scarce. A narrative review was performed by searching PubMed, Medline, and the Cochrane Database of Systematic Reviews using the terms "IAPV" or "pneumobelt." One hundred forty patients were cited using the intermittent abdominal pressure ventilator from 1946 until it went off the market in the 1970s, although many continued to use it. There was only one publication on its use from 2003 to 2017, but three publications from 2017 through 2021. It has been used for full diurnal ventilatory support by some patients for more than 50 yrs and has even been used throughout the labor of a mother with no ventilator-free breathing ability. The intermittent abdominal pressure ventilator is a ventilatory support alternative for patients with ventilatory pump failure. It can be effective and well tolerated and maintain quality of life without facial interfaces. More widespread application is warranted.

Prolonged Active Prone Positioning in Spontaneously Breathing Non-intubated Patients With COVID-19-Associated Hypoxemic Acute Respiratory Failure With PaO2/FiO2 >150.

Background: The COVID-19 pandemic has led to new approaches to manage patients outside the ICU, including prone positioning in non-intubated patients. Objectives: To report the use of prolonged active prone positioning in spontaneously breathing patients with COVID-19-associated acute respiratory failure. Spontaneously breathing vs non-invasive respiratory support for COVID19 associated acute respiratory failure. Methods: Patients with PaO2/FiO2 > 150, with lung posterior consolidations as assessed by means of lung ultrasound, and chest x-ray were studied. Under continuous pulse oximetry (SpO2) monitoring, patients maintained active prone position. A PaO2/FiO2 < 150 was considered as treatment failure and patients had to be switched to non-invasive respiratory support. Retrospectively, data of 16 patients undergoing who refused proning and underwent non-invasive respiratory support were used as controls. The primary outcome was the proportion of patients maintaining prolonged prone position and discharged home. Secondary outcomes included improvement in oxygenation, hospital length of stay, and 6-month survival. Results: Three out of 16 (18.7%) patients did not tolerate the procedure. Three more patients showed a worsening in PaO2/FiO2 to <150 and required non-invasive support, two of whom finally needing endotracheal intubation. After 72 h, 10 out of 16 (62.5%) patients improved oxygenation [PaO2/FiO2: from 194.6 (42.1) to 304.7 (79.3.2) (p < 0.001)] and were discharged home. In the control group, three out of 16 failed, required invasive ventilatory support, and died within 1 month in ICU. Thirteen were successful and discharged home. Conclusion: In non-intubated spontaneously breathing COVID-19 patients with PaO2/FiO2 >150, active prolonged prone positioning was feasible and tolerated with significant improvement in oxygenation.

Risk factors for transfer from Respiratory Intermediate Care Unit to Intensive Care Unit in COVID-19.

BACKGROUND: Patients hospitalized for COVID-19-related pneumonia often need several degrees of ventilatory support, which are performed between Respiratory Intermediate Care Units (RICUs) and Intensive Care Units (ICUs), and which depend on the severity of acute respiratory distress syndrome. There is no firm consensus on transfer predictors from the RICU to the ICU. METHODS: In this retrospective observational single center study, we evaluated 96 COVID-19 patients referred to the RICU for acute respiratory failure (ARF) according to their transferal to the ICU or their stay at the RICU. We compared demographic data, baseline laboratory profile, and final clinical outcomes to identify early risk factors for transfer. RESULTS: The best predictors for transfer to the ICU were elevated C-reactive protein and lymphopenia. The mortality rate was lower in the RICU than in the ICU, where transferred patients who died were mostly younger men and with less comorbidities than those in the RICU. CONCLUSIONS: Few inflammatory markers can predict the need for transfer from the RICU to the ICU. Due to the ongoing COVID-19 pandemic, we urge better clinical stratification by early and meaningful profiles in patients admitted to the RICU who are at risk of transferal to the ICU.

Galectin-3 and neutrophil-to-lymphocyte ratio are indicative of heart remodelling and disease severity in patients with obstructive sleep apnoea.

BACKGROUND: Galectin-3, considered as a new inflammatory marker; it is increased in cardiovascular disease. We investigated Galectin-3 in relation to heart damage in patients with OSA and its role in inflammation, based on the Neutrophil-to-Lymphocyte Ratio (NLR). METHODS: Sixty-three consecutive patients (45 males, 18 females, 58.60 ± 12.28 years old) were studied. According to the Apnoea-Hypopnoea Index (AHI) patients were divided into Group 1 - non-severe (AHI <30) (17 males and 10 females, 59.89 ± 10.62 years old) and Group 2 - severe (AHI ≥30) (29 males and 6 females, aged 57.53 ± 13.30 years old) OSA. All patients underwent morning blood gas analysis, laboratory tests, nocturnal polygraphy, and echocardiography. RESULTS: Galectin-3 was significantly increased in Group 2 (p = 0.027) patients. Moreover, it was directly related to left ventricle (LV) mass, left ventricle hypertrophy and LV posterior wall diameter. Tissue Doppler septal velocity (e'), that measures wall motion, was inversely correlated to Galectin-3. Furthermore, a direct association to diastolic dysfunction, evaluated as E/e' ratio, was observed. In line with these data, a direct correlation between Galectin-3 and left atrium volume was also found. Galectin-3 and percentage of total registration time with nocturnal oxygen saturation <90% (TST90) were directly correlated (p = 0.0003), while Galectin-3 and mean nocturnal SpO2 were negatively correlated (p = 0.0045). We found a direct correlation between Galectin-3 and NLR (p = 0.011). Finally, Galectin-3 was able to predict 3-yr mortality with a specificity of 83.33% and a sensitivity of 91.84%. CONCLUSION: Galectin-3 showed a direct association to nocturnal respiratory indices and to cardiac remodelling in patients with OSA. OSA-induced inflammation may play an important role in the pathogenesis of heart damage.

Bilevel and continuous positive airway pressure and factors linked to all-cause mortality in COVID-19 patients in an intermediate respiratory intensive care unit in Italy.

Objectives: In the present single-centered, retrospective, observational study, we reported findings from 78 consecutive laboratory-confirmed COVID-19 patients with moderate-to-severe acute respiratory distress syndrome (ARDS) hospitalized in an intermediate Respiratory Intensive Care Unit, subdividing the patients into two groups according to their clinical outcome, dead patients and discharged patients.Methods: We further subdivided patients depending on the noninvasive respiratory support used during hospitalization.Results: In those patients who died, we found significant older age and higher multimorbidity and higher values of serum lactate dehydrogenase, C-reactive protein, and D-dimer. Among patients who were submitted to bilevel positive airway pressure (BPAP), those who died had a significant shorter number of days in overall length of stay and lower values of arterial oxygen partial pressure to fractional inspired oxygen ratio (PaO2/FiO2 ratio) compared to those who survived. No difference in all-cause mortality was observed between the two different noninvasive respiratory support groups [48% for continuous positive airway pressure (CPAP) and 52% for BPAP].Conclusion: In COVID-19 patients with moderate-to-severe ARDS using BPAP in an intermediate level of hospital care had more factors associated to all-cause mortality (shorter length of stay and lower baseline PaO2/FiO2 ratio) compared to those who underwent CPAP.

Baseline characteristics and outcomes of COVID-19 patients admitted to a Respiratory Intensive Care Unit (RICU) in Southern Italy.

The recent Coronavirus disease 19 (COVID-19) pandemic, first in China and then also in Italy, brought to the attention the problem of the saturation of Intensive Care Units (ICUs). Almost all previous reports showed that in ICU less than half of patients were treated with invasive mechanical ventilation (IMV) and the rest of them with non-invasive respiratory support. This highlighted the role of respiratory intensive care units (RICUs), where patients with moderate to severe respiratory failure can be treated with non-invasive respiratory support, avoiding ICU admission. In this report, we describe baseline characteristics and clinical outcomes of 97 patients with moderate to severe respiratory failure due to COVID-19 admitted to the RICU of the Policlinico of Bari from March 11th to May 31st 2020. In our population, most of the subjects were male (72%), non-smokers (76%), with a mean age of 69.65±14 years. Ninety-one percent of patients presented at least one comorbidity and 60% had more than two comorbidities. At admission, 40% of patients showed PaO2/FiO2 ratio between 100 and 200 and 17% showed Pa02/FiO2 ratio <100. Mean Pa02/FiO2 ratio at admission was 186.4±80. These patients were treated with non-invasive respiratory support 40% with CPAP, 38% with BPAP, 3% with HFNC, 11% with standard oxygen therapy or with IMV through tracheostomy (patients in step down from ICU, 8%). Patients discharged to general ward (GW) were 51%, 30% were transferred to ICU and 19% died. To the best of our knowledge, this is one of the few described experiences of patients with respiratory failure due to COVID-19 treated outside the ICU, in a RICU. Outcomes of our patients, characterized by several risk factors for disease progression, were satisfactory compared with other experiences regarding patients treated with non-invasive respiratory support in ICU. The strategical allocation of our RICU, between ED and ICU, might have positively influenced clinical outcomes of our patients.

Gender differences in safety issues during Fingolimod therapy: Evidence from a real-life Relapsing Multiple Sclerosis cohort.

OBJECTIVE: Benefits and risks of new therapies in Multiple Sclerosis (MS) must be balanced carefully and tailored to patients. We aimed to describe our experience with Fingolimod (FTY), correlating demographics, clinical and hematological features of the Relapsing MS (RMS) cohort with the occurring Adverse Events (AEs). MATERIAL AND METHODS: Pretreatment screening tests, cardiological observation, and safety follow-up data were analyzed in 225 RMS patients. Changes in continuous data were analyzed post hoc with Wilcoxon ranks test; categorical variables were examined using McNemar test. Two-way repeated-measures analysis of variance (ANOVA) was used to analyze differences between baseline characteristic of the cohorts and Liver Function Tests (LFT) alterations. Binary logistic regression models were used to identify which of the baseline factors influenced LFT alterations and the occurrence of infections. RESULTS: During 2 years of follow-up 24 patients (10%) interrupted FTY. Discontinuation most often was due to AEs (n = 14) or breakthrough disease (n = 5). The most frequently AEs were infections (10.6%). After the first year patients showing an infectious episode were mostly female (p = .04). The infections did not correlate with the decrease in white blood cells or to lymphocyte count. AST and ALT alterations ​​were observed mostly in males (p = .002 and p = .01, respectively), and increase in GGT ​​was reported in subjects older at FTY beginning (p < .05). CONCLUSIONS: For a patient-centered safety monitoring of FTY, we may apply gender-specific warnings, for the detection of transaminases abnormalities and infectious episodes.

The Cost of Relapsing-Remitting Multiple Sclerosis Patients Who Develop Neutralizing Antibodies during Interferon Beta Therapy.

BACKGROUND: Relapsing Remitting Multiple Sclerosis (RRMS) patients treated with interferon beta (IFN beta) can develop neutralizing antibodies (NAbs) that reduce treatment efficacy. Several clinical studies explored the association of NAb+ status with increased disease activity. OBJECTIVE: The aim of this study was to estimate the cost of RRMS patients who develop NAbs while treated with IFN beta by the Italian National Healthcare Service (NHS) and the Italian Society perspectives. METHODS: The clinical data derived from a published observational study on 567 RRMS Italian patients treated with IFN beta. The management cost data derived from the published literature. Cost data were inflated to Euro 2014. RESULTS: The annual direct cost to treat a patient was estimated in €15,428 in the NAb+ cohort and €14,317 in the NAb- cohort. The annual societal cost was estimated in €33,890 and €30,790 in NAb+ and NAb- patients, respectively. The cost increase related to the NAb+ status was €3,100 in the Italian societal perspective and €1,111 in the Italian NHS perspective. CONCLUSION: The results of this economic evaluation suggest the presence of an association between NAb+ status and increased costs for the management of RRMS in Italy. Further pharmacoeconomic research will be needed to confirm this first result.

Exploratory analysis of predictors of patient adherence to subcutaneous interferon beta-1a in multiple sclerosis: TRACER study.

OBJECTIVE: The TRACER multicenter retrospective study aimed to collect data on treatment adherence in a real-life setting, in order to identify predictors of adherence at baseline. METHODS: We recruited 384 relapsing-remitting (RR) multiple sclerosis patients with at least 12 months of use of RebiSmart®. This electronic device records the performed injections and assesses adherence as the percentage of 'not missing doses', through the connection to the iMed database. Subjects with at least 80% of completed doses at the 12 month of therapy were defined 'treatment adherents'. RESULTS: After 12 months, 89.3% of patients were adherent; 93.2% of patients aged 26-40 years at baseline were adherent (vs 79% of the ≤25 and 87.5% of the ≥41 year olds; p = 0.006). Furthermore, 90.5% of patients with a baseline Expanded Disability Status Scale (EDSS) score <4 showed ≥80% adherence (vs 71.4% in those with EDSS score ≥4; p = 0.016). Fifty-four percent of the patients who were not adherent after 3 months were also not adherent after 12 months (OR 16.8; CI 95%:7.1-39.8). CONCLUSIONS: Patients aged 26-40 years and with an EDSS score <4 at baseline were the most adherent. The status of 'treatment adherent' in the first 3 months was predictive of higher adherence in the long term.

Long-Term Data of Efficacy, Safety, and Tolerability in a Real-Life Setting of THC/CBD Oromucosal Spray-Treated Multiple Sclerosis Patients.

Delta-9-tetrahydrocannabinol (THC)/cannabidiol (CBD) oromucosal spray was approved as add-on therapy for spasticity in patients with multiple sclerosis (MS). We show our 40-week postmarketing experience regarding efficacy and safety of THC/CBD spray in an Italian cohort of 102 MS patients. Patients were evaluated using the Expanded Disability Status Scale (EDSS) score, the Numerical Rating Scale (NRS) for spasticity, the Ambulation Index (AI), and Timed 25-Foot Walk (T25-FW) at the beginning of treatment and then every 3 months. After 4 weeks, if a clinically significant improvement in spasticity (at least 20% of baseline NRS score) was not seen, administration of the drug was stopped. In our cohort, patients received an average of 6.5 ± 1.6 sprays each day. The mean reduction to the NRS spasticity score was 2.5 ± 1.2 points (P < .0001). Thirty-seven patients (36.2%) discontinued the treatment. The incidence of adverse events (AEs) was 40.2%. Fifty-eight patients (56.9%) were also assessed using the NRS for pain, and 46 patients (45.1%) with bladder dysfunction were assessed for the IPSS (International Prostatic Symptoms Score) score, showing a significant improvement in these scales (P = .011 and P = .001, respectively). In conclusion, treatment with THC/CBD spray appears to be a valid answer to some of the unmet needs in MS patients, such as spasticity and other refractory-to-treatment symptoms.

Tryptase-positive mast cells correlate with angiogenesis in early breast cancer patients.

Literature data indicate that mast cells (MCs) are involved in tumor angiogenesis due to the release of several pro-angiogenetic factors among which tryptase, a serine protease stored in MCs granules, is one of the most active. However, no data are available concerning the role of MCs in angiogenesis in primary human breast cancer. In this study, we have evaluated the correlations between the number of MCs positive to tryptase (MCDPT), the area occupied by MCs positive to tryptase (MCAPT) and microvascular density (MVD) and endothelial area (EA) in a series of 88 primary T1-3, N0-2 M0 female breast cancer, by means of immunohistochemistry and image analysis methods. Data demonstrated a significant (r = from 0.78 to 0.89; p-value from 0.001 to 0.002 by Pearson's analysis respectively) correlation between MCDPT, MCAPT, MVD, EA to each other. No correlation concerning MCDPT, MCAPT, MVD, EA and the main clinicopathological features was found. Our results suggest that tryptase-positive MCs play a role in breast cancer angiogenesis. In this context several tryptase inhibitors such as gabexate mesilate and nafamostat mesilate might be evaluated in clinical trials as a new anti-angiogenetic approach.