Epidemiology of SLE in Italy: an observational study using a primary care database.

OBJECTIVES: To estimate the incidence and prevalence of SLE in Italy, and to describe the demographic and clinical characteristics of patients with newly diagnosed SLE. METHODS: A retrospective cohort study was conducted using The Health Improvement Network general practice database in Italy, encompassing data from 634 753 people. SLE cases were identified over the period 2017-2022, employing three alternative definitions to provide a more detailed understanding of SLE characteristics. Incidence rates were expressed as cases per 100 000 person-years and prevalence as cases per 100 000 people. Demographic and clinical characteristics of incident SLE cases were also studied. RESULTS: From 2017 to 2022, a total of 191 incident and 1385 prevalent cases were identified under our first definition. In 2022, the incidence rate was 6.51 cases (95% CI 6.29 to 6.74) per 100 000 person-years, and the prevalence 60.57 (95% CI 59.89 to 61.25) per 100 000 people, being the prevalence five times higher in women compared with men. Both estimates have trended upwards since 2017. A geographical variation across the country was also seen. The demographic and clinical characteristics of incident SLE cases were described, while the potential associations of SLE incidence with some pre-existing conditions were observed, such as chronic kidney disease, chronic hepatic disease, rheumatoid arthritis and Sjogren's syndrome. CONCLUSIONS: The results of this nationwide study, the first conducted in Italy, showed that the incidence of SLE has increased in Italy in recent years. Age, sex, and area of residence strongly correlate with the epidemiology of this condition.

Corrigendum: Time-Trends in Air Pollution Impact on Health in Italy, 1990-2019: An Analysis from the Global Burden of Disease Study 2019.

[This corrects the article DOI: 10.3389/ijph.2023.1605959.].

The value-based healthcare approach to haemophilia: Development of outcome measures for the evaluation of care of people with haemophilia.

INTRODUCTION: Considering the advances in haemophilia management and treatment observed in the last decades, a new set of value-based outcome indicators is needed to assess the quality of care and the impact of these medical innovations. AIM: The Value-Based Healthcare in Haemophilia project aimed to define a set of clinical outcome indicators (COIs) and patient-reported outcome indicators (PROIs) to assess quality of care in haemophilia in high-income countries with a value-based approach to inform and guide the decision-making process. METHODS: A Value-based healthcare approach based on the available literature, current guidelines and the involvement of a multidisciplinary group of experts was applied to generate a set of indicators to assess the quality of care of haemophilia. RESULTS: A final list of three COIs and five PROIs was created and validated. The identified COIs focus on two domains: musculoskeletal health and function, and safety. The identified PROIs cover five domains: bleeding frequency, pain, mobility and physical activities, Health-Related Quality of Life and satisfaction. Finally, two composite outcomes, one based on COIs, and one based on PROIs, were proposed as synthetic outcome indicators of quality of care. CONCLUSION: The presented standard set of health outcome indicators provides the basis for harmonised longitudinal and cross-sectional monitoring and comparison. The implementation of this value-based approach would enable a more robust assessment of quality of care in haemophilia, within a framework of continuous treatment improvements with potential added value for patients. Moreover, proposed COIs and PROIs should be reviewed and updated routinely.

Transthoracic impedance variability to assess quality of chest compression in out-of-hospital cardiac arrest.

BACKGROUND: Chest compression is a lifesaving intervention in out-of-hospital cardiac arrest (OHCA), but the optimal metrics to assess its quality have yet to be identified. The objective of this study was to investigate whether a new parameter, that is, the variability of the chest compression-generated transthoracic impedance (TTI), namely ImpCC , which measures the consistency of the chest compression maneuver, relates to resuscitation outcome. METHODS: This multicenter observational, retrospective study included OHCAs with shockable rhythm. ImpCC variability was evaluated with the power spectral density analysis of the TTI. Multivariate regression model was used to examine the impact of ImpCC variability on defibrillation success. Secondary outcome measures were return of spontaneous circulation and survival. RESULTS: Among 835 treated OHCAs, 680 met inclusion criteria and 565 matched long-term outcomes. ImpCC was significantly higher in patients with unsuccessful defibrillation compared to those with successful defibrillation (p = .0002). Lower ImpCC variability was associated with successful defibrillation with an odds ratio (OR) of 0.993 (95% confidence interval [95% CI], 0.989-0.998, p = .003), while the standard chest compression fraction (CCF) was not associated (OR 1.008 [95 % CI, 0.992-1.026, p = .33]). Neither ImpCC nor CCF was associated with long-term outcomes. CONCLUSIONS: In this population, consistency of chest compression maneuver, measured by variability in TTI, was an independent predictor of defibrillation outcome. ImpCC may be a useful novel metrics for improving quality of care in OHCA.

Treatment patterns in essential tremor: Real-world evidence from a United Kingdom and France primary care database.

BACKGROUND AND PURPOSE: Essential tremor (ET) is one of the most common neurological disorders, but information on treatment pattern is still scant. The aim of this study was to describe the demographic and clinical characteristics, treatment patterns, and determinants of drug use in patients with newly diagnosed ET in France and the United Kingdom. METHODS: Incident cases of ET diagnosed between January 1, 2015 and December 31, 2018 with 2 years of follow-up were identified by using The Health Improvement Network (THIN®) general practice database. During the follow-up, we assessed the daily prevalence of use and potential switches from first-line to second-line treatment or other lines of treatment. Logistic regression models were conducted to assess the effect of demographic and clinical characteristics on the likelihood of receiving ET treatment. RESULTS: A total of 2957 and 3249 patients were selected in the United Kingdom and France, respectively. Among ET patients, drug use increased from 12 months to 1 month prior the date of index diagnosis (ID). After ID, nearly 40% of patients received at least one ET treatment, but during follow-up drug use decreased and at the end of the follow-up approximately 20% of patients were still on treatment. Among treated patients, ≤10% maintained the same treatment throughout the entire follow-up, nearly 20% switched, and 40%-75% interrupted any treatment. Results from the multivariate analysis revealed that, both in France and the United Kingdom, patients receiving multiple concomitant therapies and affected by psychiatric conditions were more likely to receive an ET medication. CONCLUSION: This study shows that ET is an undertreated disease with a lower-than-expected number of patients receiving and maintaining pharmacological treatment. Misclassification of ET diagnosis should be acknowledged; thus, results require cautious interpretation.

Time-Trends in Air Pollution Impact on Health in Italy, 1990-2019: An Analysis From the Global Burden of Disease Study 2019.

Objectives: We explored temporal variations in disease burden of ambient particulate matter 2.5 µm or less in diameter (PM2.5) and ozone in Italy using estimates from the Global Burden of Disease Study 2019. Methods: We compared temporal changes and percent variations (95% Uncertainty Intervals [95% UI]) in rates of disability adjusted life years (DALYs), years of life lost, years lived with disability and mortality from 1990 to 2019, and variations in pollutant-attributable burden with those in the overall burden of each PM2.5- and ozone-related disease. Results: In 2019, 467,000 DALYs (95% UI: 371,000, 570,000) were attributable to PM2.5 and 39,600 (95% UI: 18,300, 61,500) to ozone. The crude DALY rate attributable to PM2.5 decreased by 47.9% (95% UI: 10.3, 65.4) from 1990 to 2019. For ozone, it declined by 37.0% (95% UI: 28.9, 44.5) during 1990-2010, but it increased by 44.8% (95% UI: 35.5, 56.3) during 2010-2019. Age-standardized rates declined more than crude ones. Conclusion: In Italy, the burden of ambient PM2.5 (but not of ozone) significantly decreased, even in concurrence with population ageing. Results suggest a positive impact of air quality regulations, fostering further regulatory efforts.

Clinical risk factors for increased respiratory drive in intubated hypoxemic patients.

BACKGROUND: There is very limited evidence identifying factors that increase respiratory drive in hypoxemic intubated patients. Most physiological determinants of respiratory drive cannot be directly assessed at the bedside (e.g., neural inputs from chemo- or mechano-receptors), but clinical risk factors commonly measured in intubated patients could be correlated with increased drive. We aimed to identify clinical risk factors independently associated with increased respiratory drive in intubated hypoxemic patients. METHODS: We analyzed the physiological dataset from a multicenter trial on intubated hypoxemic patients on pressure support (PS). Patients with simultaneous assessment of the inspiratory drop in airway pressure at 0.1-s during an occlusion (P0.1) and risk factors for increased respiratory drive on day 1 were included. We evaluated the independent correlation of the following clinical risk factors for increased drive with P0.1: severity of lung injury (unilateral vs. bilateral pulmonary infiltrates, PaO2/FiO2, ventilatory ratio); arterial blood gases (PaO2, PaCO2 and pHa); sedation (RASS score and drug type); SOFA score; arterial lactate; ventilation settings (PEEP, level of PS, addition of sigh breaths). RESULTS: Two-hundred seventeen patients were included. Clinical risk factors independently correlated with higher P0.1 were bilateral infiltrates (increase ratio [IR] 1.233, 95%CI 1.047-1.451, p = 0.012); lower PaO2/FiO2 (IR 0.998, 95%CI 0.997-0.999, p = 0.004); higher ventilatory ratio (IR 1.538, 95%CI 1.267-1.867, p < 0.001); lower pHa (IR 0.104, 95%CI 0.024-0.464, p = 0.003). Higher PEEP was correlated with lower P0.1 (IR 0.951, 95%CI 0.921-0.982, p = 0.002), while sedation depth and drugs were not associated with P0.1. CONCLUSIONS: Independent clinical risk factors for higher respiratory drive in intubated hypoxemic patients include the extent of lung edema and of ventilation-perfusion mismatch, lower pHa, and lower PEEP, while sedation strategy does not affect drive. These data underline the multifactorial nature of increased respiratory drive.

A Cross-Indication Budget Impact Model of Secukinumab for the Treatment of Psoriasis, Psoriatic Arthritis, Ankylosing Spondylitis and Non-radiographic Axial Spondyloarthritis in Italy.

BACKGROUND: Recent developments improved outcomes in patients with autoimmune diseases. Biologics were approved as first-line treatment in selected naïve patients with plaque psoriasis (PsO), psoriatic arthritis (PsA), ankylosing spondylitis (AS) and non-radiographic axial spondyloarthritis (nr-axSpA). Among them, secukinumab was most recently approved for treatment of active nr-axSpA in adults. In this work, we assessed the budget impact of new secukinumab treatment options in the Italian market. METHODS: A cross-indication budget impact model was designed to estimate the effects of adding secukinumab in the Italian market from the National Health System perspective over a 3-year period. The model included all adults with PsO, PsA, AS and nr-axSpA, treated with biologics or biosimilars. It compared costs between two scenarios, secukinumab availability or absence, for the four diseases combined and taken individually. A sensitivity analyses was conducted. RESULTS: There were 68,121 adult patients treated with biologics in 2021 and 68,341 in 2023. The budget impact analysis (BIA) on all indications showed a cost reduction of €33.7 million (- 1.5%) over 3 years with the introduction of secukinumab. PsA patients had the highest saving (- €34.9 million), followed by PsO patients (- €7.8 million). Cost saving in PsO patients was balanced by increased budget reported in AS patients (+ €8.0 million). In nr-axSpA patients, secukinumab reported no significant budget increase (+ 1.0%). CONCLUSION: This BIA accounted for the new indication of secukinumab in nr-axSpA patients, reporting no significant changes in the required budget and adding an effective treatment option. Considering all indications, secukinumab is a sustainable treatment option.

Statins Use in Patients with Cardiovascular Diseases and COVID-19 Outcomes: An Italian Population-Based Cohort Study.

BACKGROUND: The role of statins among patients with established cardiovascular diseases (CVDs) who are hospitalized with COVID-19 is still debated. This study aimed at assessing whether the prior use of statins was associated with a less severe COVID-19 prognosis. METHODS: Subjects with CVDs infected with SARS-CoV-2 and hospitalized between 20 February 2020 and 31 December 2020 were selected. These were classified into two mutually exclusive groups: statins-users and non-users of lipid-lowering therapies (non-LLT users). The relationship between statins exposure and the risk of Mechanical Ventilation (MV), Intensive Care Unit (ICU) access and death were evaluated by using logistic and Cox regressions models. RESULTS: Of 1127 selected patients, 571 were statins-users whereas 556 were non-LLT users. The previous use of statins was not associated with a variation in the risk of need of MV (Odds Ratio [OR]: 1.00; 95% Confidence Intervals [CI]: 0.38-2.67), ICU access (OR: 0.54; 95% CI: 0.22-1.32) and mortality at 14 days (Hazard Ratio [HR]: 0.42; 95% CI: 0.16-1.10). However, a decreased risk of mortality at 30 days (HR: 0.39; 95% CI: 0.18-0.85) was observed in statins-users compared with non-LLT users. CONCLUSIONS: These findings support the clinical advice for patients CVDs to continue their treatment with statins during SARS-CoV-2 infection.

Time trends in the incidence of essential tremor: Evidences from UK and France primary care data.

Introduction: Although essential tremor (ET) is considered a common adult movement disorder, evidence on its incidence is still scant. This study aims at estimating ET incidence in two European countries, namely, the UK and France. Methods: Incident cases of ET were identified within the Health Improvement Network (THIN®) database between 1st January 2014 and 31 December 2019. Yearly crude and standardized incidence rates (IR) were estimated across the study period for both countries. Poisson regression models were built to assess temporal trends in IRs and differences between sexes and age classes. Results: In total, 4,970 and 4,905 incident cases of ET were identified in the UK and France, respectively. The yearly average crude IR (per 100,000 person-years) was 18.20 (95%CI: 15.09-21.32) in UK and 21.42 (17.83-25.00) in France, whereas standardized ones were 19.51 (18.97-20.01) and 19.50 (18.97-20.05). Regression analyses showed slightly increasing trends in both countries, higher incidence among males, and a significant increase with age. Yearly average IR increased from 3.96 (0.95-6.97) and 5.28 (1.12-9.44) in subjects aged <20 years to 49.27 (26.29-72.24) and 51.52 (30.19-72.86) in those aged >80 year in UK and France. Conclusions: Standardized ET incidence was comparable in the UK and France, showing a slight increase in both countries, reporting a higher value among people aged 60 years and older. This study outlines the need to conduct future studies to estimate the burden of ET in terms of disease control and healthcare resource utilization.

Azithromycin use and outcomes in patients with COVID-19: an observational real-world study.

OBJECTIVES: Previous studies ruled out the benefits of azithromycin for treatment of patients with COVID-19 who are hospitalized. However, the effects of azithromycin for treatment of patients with positive SARS-CoV-2 test results in the community remains a matter of debate. This study aimed to assess whether azithromycin, when used in subjects with positive test results for SARS-CoV-2, is associated with a reduced risk of hospitalization, in-hospital COVID-19 outcomes, and death. METHODS: Two study cohorts were selected. Cohort A included subjects with positive test results for SARS-CoV-2 between February 20, 2020 and December 10, 2020; cohort B included subjects infected with SARS-CoV-2 and hospitalized between February 20, 2020 and December 31, 2020. We compared the risk of hospitalization, intensive care unit access, need for mechanical ventilation, and death in azithromycin users versus nonusers. A clustered Fine-Gray analysis was employed to assess the risk of hospitalization; logistic and Cox regressions were performed to assess the risk of intensive care unit access, mechanical ventilation, and death. RESULTS: In cohort A, among 4861 azithromycin users and 4861 propensity-matched nonusers, azithromycin use was associated with higher risk of hospitalization (hazard ratio [HR] 1.59, 95% confidence interval [CI] 1.45-1.75) compared with nonuse. In cohort B, among 997 subjects selected in both groups, azithromycin use was not significantly associated with intensive care unit access (odds ratio [OR] 1.22, 95% CI 0.93-1.56), mechanical ventilation (OR 1.30, 95% CI 0.99-1.70), 14-day mortality (HR0.88, 95% CI 0.74-1.05), or 30-day mortality (HR 0.89, 95% CI 0.77-1.03). CONCLUSION: Our findings confirm the lack of benefits of azithromycin treatment among community patients infected with SARS-CoV-2, raising concern on potential risks associated with its inappropriate use.

Multiple Sclerosis Progressive Courses: A Clinical Cohort Long-Term Disability Progression Study.

OBJECTIVES: Improving the understanding of multiple sclerosis (MS) mechanism and disability progression over time is essential to assess the value of healthcare interventions. Poor or no data on disability progression are available for progressive courses. This study aims to fill this gap. METHODS: An observational cohort study of patients with primary MS (PPMS) and secondary progressive MS (SPMS) was conducted on 2 Italian MS centers disease registries over an observational time of 34 years. Annual transition probabilities among Expanded Disability Status Scale (EDSS) states were estimated using continuous Markov models. A sensitivity analysis was performed in relation to clinical characteristic associated to disability progression. RESULTS: The study cohort included 758 patients (274 PPMS and 434 SPMS) with a median follow-up of 8.2 years. Annual transition probability matrices of SPMS and PPMS reported different annual probabilities to move within EDSS levels. Excluding EDSS associated to relapse events or patient with relapses, the annual probability of staying stable in an EDSS level increased in both disease courses even not significantly. CONCLUSIONS: This study provides estimates of annual disability progression as EDSS changes for PPMS and SPMS. These estimates could be a useful tool for healthcare decision makers and clinicians to properly assess impact of clinical interventions.

Antidepressants Drug Use during COVID-19 Waves in the Tuscan General Population: An Interrupted Time-Series Analysis.

In Italy, during the COVID-19 waves two lockdowns were implemented to prevent virus diffusion in the general population. Data on antidepressant (AD) use in these periods are still scarce. This study aimed at exploring the impact of COVID-19 lockdowns on prevalence and incidence of antidepressant drug use in the general population. A population-based study using the healthcare administrative database of Tuscany was performed. We selected a dynamic cohort of subjects with at least one ADs dispensing from 1 January 2018 to 27 December 2020. The weekly prevalence and incidence of drug use were estimated across different segments: pre-lockdown (1 January 2018-8 March 2020), first lockdown (9 March 2020-15 June 2020), post-first lockdown (16 June 2020-15 November 2020) and second lockdown (16 November 2020-27 December 2020). An interrupted time-series analysis was used to assess the effect of lockdowns on the observed outcomes. Compared to the pre-lockdown we observed an abrupt reduction of ADs incidence (Incidence-Ratio: 0.82; 95% Confidence-Intervals: 0.74-0.91) and a slight weekly decrease of prevalence (Prevalence-Ratio: 0.997; 0.996-0.999). During the post-first lockdown AD use increased, with higher incidence- and similar prevalence values compared with those expected in the absence of the outbreak. This pandemic has impacted AD drug use in the general population with potential rebound effects during the period between waves. This calls for future studies aimed at exploring the mid-long term effects of this phenomenon.

Impact of COVID-19 Lockdown, during the Two Waves, on Drug Use and Emergency Department Access in People with Epilepsy: An Interrupted Time-Series Analysis.

BACKGROUND: In 2020, during the COVID-19 pandemic, Italy implemented two national lockdowns aimed at reducing virus transmission. We assessed whether these lockdowns affected anti-seizure medication (ASM) use and epilepsy-related access to emergency departments (ED) in the general population. METHODS: We performed a population-based study using the healthcare administrative database of Tuscany. We defined the weekly time series of prevalence and incidence of ASM, along with the incidence of epilepsy-related ED access from 1 January 2018 to 27 December 2020 in the general population. An interrupted time-series analysis was used to assess the effect of lockdowns on the observed outcomes. RESULTS: Compared to pre-lockdown, we observed a relevant reduction of ASM incidence (0.65; 95% Confidence Intervals: 0.59-0.72) and ED access (0.72; 0.64-0.82), and a slight decrease of ASM prevalence (0.95; 0.94-0.96). During the post-lockdown the ASM incidence reported higher values compared to pre-lockdown, whereas ASM prevalence and ED access remained lower. Results also indicate a lower impact of the second lockdown for both ASM prevalence (0.97; 0.96-0.98) and incidence (0.89; 0.80-0.99). CONCLUSION: The lockdowns implemented during the COVID-19 outbreaks significantly affected ASM use and epilepsy-related ED access. The potential consequences of these phenomenon are still unknown, although an increased incidence of epilepsy-related symptoms after the first lockdown has been observed. These findings emphasize the need of ensuring continuous care of epileptic patients in stressful conditions such as the COVID-19 pandemic.

Trends in cardiovascular diseases burden and vascular risk factors in Italy: The Global Burden of Disease study 1990-2017.

AIMS: An exhaustive and updated estimation of cardiovascular disease burden and vascular risk factors is still lacking in European countries. This study aims to fill this gap assessing the global Italian cardiovascular disease burden and its changes from 1990 to 2017 and comparing the Italian situation with European countries. METHODS: All accessible data sources from the 2017 Global Burden of Disease study were used to estimate the cardiovascular disease prevalence, mortality and disability-adjusted life years and cardiovascular disease attributable risk factors burden in Italy from 1990 to 2017. Furthermore, we compared the cardiovascular disease burden within the 28 European Union countries. RESULTS: Since 1990, we observed a significant decrease of cardiovascular disease burden, particularly in the age-standardised prevalence (-12.7%), mortality rate (-53.8%), and disability-adjusted life years rate (-55.5%). Similar improvements were observed in the majority of European countries. However, we found an increase in all-ages prevalence of cardiovascular diseases from 5.75 m to 7.49 m Italian residents. Cardiovascular diseases still remain the first cause of death (34.8% of total mortality). More than 80% of the cardiovascular disease burden could be attributed to known modifiable risk factors such as high systolic blood pressure, dietary risks, high low density lipoprotein cholesterol, and impaired kidney function. CONCLUSIONS: Our study shows a decline in cardiovascular mortality and disability-adjusted life years, which reflects the success in reducing disability, premature death and early incidence of cardiovascular diseases. However, the burden of cardiovascular diseases is still high. An approach that includes the cooperation and coordination of all stakeholders of the Italian National Health System is required to further reduce this burden.

Management of pregnancy blood pressure increase in the emergency room: role of PlGF-based biochemical markers and relative economic impact.

INTRODUCTION: To evaluate the clinical and economic impact of healthcare management of pregnant women with blood pressure increase (BPI) accessing emergency room (ER) and the utility of the introduction of a PlGF-based test in clinical practice. MATERIALS AND METHODS: This retrospective cohort study included women with single pregnancies who performed at least 1 ER access for BPI after the 20th gestational week in 2016. BPI was subsequently classified as significant if associated with preeclampsia (PE) or Fetal Growth Restriction (FGR) and not significant otherwise. Two experts evaluated potential changes in patients' management with the introduction of a PlGF-based test. The direct healthcare cost was estimated. RESULTS: We enrolled 107 patients, of which 30% showed significant BPI (17 PE cases, 13 FGR, and 2 both pathologies). Anamnestic, clinical, and laboratory evaluations were not effective in differentiating between significant and not significant BPI (p-values: .8320, .2856, and .2297, respectively). The introduction of a PlGF-based test would have reduced overtreatment and undertreatment. The test would have avoided 18% of all hospitalizations, 35% of hospitalizations for BPI, 43% of outpatient referrals, and 13% of ER accesses. The number of avoidable accesses was higher in women with not significant BPI. Overall, the mean total cost (from first ER access until delivery) was €2634 per woman and €401 would have been avoidable. CONCLUSION: The clinical integration of PlGF-based tests is advantageous in diagnostic, prognostic and economic terms, as an objective marker of placental dysfunction.

Sigh in Patients With Acute Hypoxemic Respiratory Failure and ARDS: The PROTECTION Pilot Randomized Clinical Trial.

BACKGROUND: Sigh is a cyclic brief recruitment maneuver: previous physiologic studies showed that its use could be an interesting addition to pressure support ventilation to improve lung elastance, decrease regional heterogeneity, and increase release of surfactant. RESEARCH QUESTION: Is the clinical application of sigh during pressure support ventilation (PSV) feasible? STUDY DESIGN AND METHODS: We conducted a multicenter noninferiority randomized clinical trial on adult intubated patients with acute hypoxemic respiratory failure or ARDS undergoing PSV. Patients were randomized to the no-sigh group and treated by PSV alone, or to the sigh group, treated by PSV plus sigh (increase in airway pressure to 30 cm H2O for 3 s once per minute) until day 28 or death or successful spontaneous breathing trial. The primary end point of the study was feasibility, assessed as noninferiority (5% tolerance) in the proportion of patients failing assisted ventilation. Secondary outcomes included safety, physiologic parameters in the first week from randomization, 28-day mortality, and ventilator-free days. RESULTS: Two-hundred and fifty-eight patients (31% women; median age, 65 [54-75] years) were enrolled. In the sigh group, 23% of patients failed to remain on assisted ventilation vs 30% in the no-sigh group (absolute difference, -7%; 95% CI, -18% to 4%; P = .015 for noninferiority). Adverse events occurred in 12% vs 13% in the sigh vs no-sigh group (P = .852). Oxygenation was improved whereas tidal volume, respiratory rate, and corrected minute ventilation were lower over the first 7 days from randomization in the sigh vs no-sigh group. There was no significant difference in terms of mortality (16% vs 21%; P = .337) and ventilator-free days (22 [7-26] vs 22 [3-25] days; P = .300) for the sigh vs no-sigh group. INTERPRETATION: Among hypoxemic intubated ICU patients, application of sigh was feasible and without increased risk. TRIAL REGISTRY: ClinicalTrials.gov; No.: NCT03201263; URL: www.clinicaltrials.gov.

Magnitude and time-course of excess mortality during COVID-19 outbreak: population-based empirical evidence from highly impacted provinces in northern Italy.

BACKGROUND: The real impact of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) on overall mortality remains uncertain as surveillance reports have attributed a limited number of deaths to novel coronavirus disease 2019 (COVID-19) during the outbreak. The aim of this study was to assess the excess mortality during the COVID-19 outbreak in highly impacted areas of northern Italy. METHODS: We analysed data on deaths that occurred in the first 4 months of 2020 provided by the health protection agencies (HPAs) of Bergamo and Brescia (Lombardy), building a time-series of daily number of deaths and predicting the daily standardised mortality ratio (SMR) and cumulative number of excess deaths through a Poisson generalised additive model of the observed counts in 2020, using 2019 data as a reference. RESULTS: We estimated that there were 5740 (95% credible set (CS) 5552-5936) excess deaths in the HPA of Bergamo and 3703 (95% CS 3535-3877) in Brescia, corresponding to a 2.55-fold (95% CS 2.50-2.61) and 1.93 (95% CS 1.89-1.98) increase in the number of deaths. The excess death wave started a few days later in Brescia, but the daily estimated SMR peaked at the end of March in both HPAs, roughly 2 weeks after the introduction of lockdown measures, with significantly higher estimates in Bergamo (9.4, 95% CI 9.1-9.7). CONCLUSION: Excess mortality was significantly higher than that officially attributed to COVID-19, disclosing its hidden burden likely due to indirect effects on the health system. Time-series analyses highlighted the impact of lockdown restrictions, with a lower excess mortality in the HPA where there was a smaller delay between the epidemic outbreak and their enforcement.

Estimates of the initial impact of the COVID-19 epidemic on overall mortality: evidence from Italy.

This study provides evidence of the enormous death toll attributable to COVID-19 https://bit.ly/2X4C6a8.