Application of machine learning approach in emergency department to support clinical decision making for SARS-CoV-2 infected patients.

To support physicians in clinical decision process on patients affected by Coronavirus Disease 2019 (COVID-19) in areas with a low vaccination rate, we devised and evaluated the performances of several machine learning (ML) classifiers fed with readily available clinical and laboratory data. Our observational retrospective study collected data from a cohort of 779 COVID-19 patients presenting to three hospitals of the Lazio-Abruzzo area (Italy). Based on a different selection of clinical and respiratory (ROX index and PaO2/FiO2 ratio) variables, we devised an AI-driven tool to predict safe discharge from ED, disease severity and mortality during hospitalization. To predict safe discharge our best classifier is an RF integrated with ROX index that reached AUC of 0.96. To predict disease severity the best classifier was an RF integrated with ROX index that reached an AUC of 0.91. For mortality prediction the best classifier was an RF integrated with ROX index, that reached an AUC of 0.91. The results obtained thanks to our algorithms are consistent with the scientific literature an accomplish significant performances to forecast safe discharge from ED and severe clinical course of COVID-19.

The stress response of intensive care unit medical doctors facing repeated severe emergencies

Objectives This study assesses the psychopathological distress experienced by doctors working in an Intensive care unit (ICU) during the COVID-19 pandemic. These doctors were the same who faced the consequences of a previous natural disaster, a severe 6.3 magnitude earthquake. A second objective is to evaluate their current mental attitude, professional performances and coping strategies adopted in the pandemic in relation to the conditioning effect of that first emergency, the earthquake. Methods Thirty-seven ICU medical doctors were recruited and assessed using Rapid Stress Assessment (RSA) rating scale, Symptom Checklist-90 Revised (SCL-90-R), Zung Self-Rating Anxiety Scale, Beck Depression Inventory, Beck Hopelessness Scale, Millon Clinical Multiaxial Inventory III. Comparison between exposure to the earthquake and COVID pandemic has been made in terms of professional role and psychological burden. Results Comparison between 2009 earthquake catastrophe and COVID pandemic conditions evidenced relevant changes in professional role, team, environment, shifts, and work organization. Conclusion The doctors, who already experienced the 2009 earthquake reported a feeling of greater insecurity facing this latter catastrophe, the COVID pandemic, as well as perception of greater concern for their family and the global situation. However, having participated in the medical management of another emergency (the 2009 earthquake) appears to have contributed to limiting demoralization and psychological distress. The feeling of having greater decision-making possibilities and participation in the organization of work, strengthen coping skills in the face of the emergency.

Hypopharynx, oropharynx morphology and histology in severe Coronavirus 2 patients treated by noninvasive ventilation: comparison between full-face mask and helmet strategies.

BACKGROUND: Non-invasive ventilation may alter the morphology and histology of the upper airway mucosa. This study aimed to investigate the alterations of hypopharynx and oropharynx mucosa, identified during oro-tracheal intubation procedure via video-assisted laryngoscopy, in severe acute respiratory syndrome Coronavirus 2 related, treated by non-invasive ventilation via full-face mask or helmet. METHODS: Data of patients affected by Coronavirus 2 admitted to COVID Hospital of L'Aquila (Italy), presenting hypopharynx and oropharynx morphology alterations, requiring oro-tracheal intubation for invasive ventilation and initially treated with non-invasive ventilation were included in the study. The study aimed to investigate the upper airway mucosa alterations using oropharyngeal and hypopharyngeal images and biopsies taken during video-assisted-laryngoscopy. Data from the hypopharynx and oropharynx morphology and histology alterations between non-invasive ventilation via a full-face mask or helmet used during hospitalization were compared. RESULTS: From 220 data recorded, 60 patients were included in the study and classified into non-invasive ventilation full-face mask group (30/60) and via helmet group. Comparing data between groups, significant differences were found with respect to hyperemia (77% vs. 20%), laryngeal bleeding ulcerations (87% vs. 13%), and vocal cord edema with >50% narrowing of the tracheal lumen (73% vs. 7%), respectively. The histology examination revealed fibrin-necrotic exudate with extensive necrotic degenerative changes in the sample tissue of the groups. There were not any differences in the duration time of non-invasive ventilation, time from hospitalization and the start of ventilation between groups. CONCLUSIONS: The data from this research suggested that there were differences in airway mucosa damages among patients treated with a full-face mask or helmet. Further studies should be planned to understand which non-invasive ventilation support may mitigate upper airway mucosa damages when oro-tracheal intubation is requested for invasive respiratory support.

Pain in critically ill COVID-19 patients: An Italian retrospective study.

We retrospectively analyzed the data from patients admitted to the intensive care unit (ICU) of the Hospital of L'Aquila during the first and second waves of pandemic to identify pain related to COVID-19. Pain was evaluated by using the Numerical Rating Scale, and the assessment for neuropathic disturbances of pain was performed with von Frey's hair and Lindblom tests. Pain increased significantly during hospitalization (from 48% at hospital admission to 94.3% at ICU discharge). Female patients were affected by somatic pain in 32.8% of the cases and by somatic pain and pain with neuropathic features (NFs) in 23.5% of the cases, during the ICU stay. Somatic pain and pain with NFs affected more frequently patients with cardiological and respiratory comorbidities. Patients treated with continuous positive airway pressure via helmet had a higher frequency of somatic pain and pain with neuropathic disturbances (84 and 74%, respectively). The frequency of somatic pain and pain with neuropathic disturbances was lower in patients sedated with propofol combined with ketamine. Females have been associated with a higher risk of somatic pain and pain with NFs. Patients with cardiological and respiratory comorbidities undergoing noninvasive ventilation had higher levels of pain. As conclusion, ketamine may reduce the promotion or the worsening of pain in COVID-19 patients.

Analysis on Burnout, Job Conditions, Alexithymia, and Other Psychological Symptoms in a Sample of Italian Anesthesiologists and Intensivists, Assessed Just before the COVID-19 Pandemic: An AAROI-EMAC Study.

Background. It was previously reported that health care professionals working in the fields of anesthesiology and emergency are at higher risk of burnout. However, the correlations between burnout, alexithymia, and other psychological symptoms are poorly investigated. Furthermore, there is a lack of evidence on which risk factors, specific to the work of anesthetists and intensivists, can increase the risk of burnout, and which are useful for developing remedial health policies. Methods. This cross-sectional study was conducted in 2020 on a sample of 300 professionals recruited from AAROI-EMAC subscribers in Italy. Data collection instruments were a questionnaire on demographic, education, job characteristics and well-being, the Maslach Burnout Inventory Tool, the Toronto Alexithymia Scale, the Symptom Checklist-90-R, and the Rosenberg Self-Esteem Scale administered during refresher courses in anesthesiology. Correlations between burnout and physical and psychological symptoms were searched. Results. With respect to burnout, 29% of individuals scored at high risk on emotional exhaustion, followed by 36% at moderate-high risk. Depersonalization high and moderate-high risk were scored by 18.7% and 34.3% of individuals, respectively. Burnout personal accomplishment was scored by 34.7% of respondents. The highest mean scores of burnout dimensions were related to dissatisfaction with one's career, conflicting relationships with surgeons, and, finally, difficulty in explaining one's work to patients. Conclusions. Burnout rates in Italian anesthesiologists and intensivists have been worrying since before the COVID-19 pandemic. Anesthesiologists with higher levels of alexithymia are more at risk for burnout. It is therefore necessary to take urgent health policy measures..

A phase 2 randomized, double-blinded, placebo-controlled, multicenter trial evaluating the efficacy and safety of raloxifene for patients with mild to moderate COVID-19.

Background: Current available therapeutic options for Coronavirus Disease-2019 (COVID-19) are primarily focused on treating hospitalized patients, and there is a lack of oral therapeutic options to treat mild to moderate outpatient COVID-19 and prevent clinical progression. Raloxifene was found as a promising molecule to treat COVID-19 due to its activity to modulate the replication of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) and act as an immunomodulator to decrease proinflammatory cytokines. Methods: This was a phase 2 multicenter, randomized, placebo-controlled trial to evaluate the efficacy and safety of raloxifene in adult patients with mild to moderate COVID-19 between October 2020 to June 2021 in five centers located in Italy. This was a planned 2/3 adaptive study, but due to operational difficulties, the study was discontinued during the phase 2 study segment. Participants were randomized 1:1:1 to receive oral placebo, raloxifene 60 mg, or raloxifene 120 mg by self-administration for a maximum of two weeks. The primary outcomes were the proportion of patients with undetectable SARS-CoV-2 via nasopharyngeal swabs at day 7 and the proportion of patients who did not require supplemental oxygen therapy or mechanical ventilation on day 14. Safety was assessed. The trial is registered (EudraCT 2021-002,476-39, and ClinicalTrials.gov: NCT05172050). Findings: A total of 68 participants were enrolled and randomized to placebo (n = 21), raloxifene 60 mg (n = 24), and raloxifene 120 mg (n = 23). The proportion of participants with undetectable SARS-CoV-2 after seven days of treatment with raloxifene 60 mg [36.8%, 7/19 vs. 0.0%, 0/14] and 120 mg [22.2%, 4/18 vs. 0.0%, 0/14] was better compared to placebo, [risk difference (RD) = 0·37 (95% C.I.:0·09-0·59)] and [RD = 0·22 (95% C.I.: -0·03-0·45)], respectively. There was no evidence of effect for requirement of supplemental oxygen and/or mechanical ventilation with effects for raloxifene 60 mg and raloxifene 120 mg over placebo, [RD = 0·09 (95% C.I.: -0·22-0·37)], and [RD = 0·03 (95% C.I.: -0·28-0·33)], respectively. Raloxifene was well tolerated at both doses, and there was no evidence of any difference in the occurrence of serious adverse events. Interpretation: Raloxifene showed evidence of effect in the primary virologic endpoint in the treatment of early mild to moderate COVID-19 patients shortening the time of viral shedding. The safety profile was consistent with that reported for other indications. Raloxifene may represent a promising pharmacological option to prevent or mitigate COVID-19 disease progression. Funding: The study was funded by Dompé Farmaceutici SpA and supported by the funds from the European Commission - Health and Consumers Directorate General, for the Action under the Emergency Support Instrument- Grant to support clinical testing of repurposed medicines to treat SARS-COV-2 patients (PPPA-ESI-CTRM-2020-SI2.837140), and by the COVID-2020-12,371,675 Ricerca finalizzata and line 1 Ricerca Corrente COVID both funded by Italian Ministry of Health.

Strengths and Weaknesses of Cancer Pain Management in Italy: Findings from a Nationwide SIAARTI Survey.

OBJECTIVES: Despite guidelines, a large percentage of cancer patients continue to suffer from ineffectively treated pain. The authors undertook this survey to assess the strengths and weaknesses of cancer pain management in Italy. DESIGN: This was a prospectively administered survey. PARTICIPANTS: The participants were anesthesiologists of the Italian Society of Anesthesia, Analgesia, Resuscitation and Intensive Care (SIAARTI). INTERVENTION: A 58-item questionnaire covered the demographics and features of cancer pain management in the Italian context. RESULTS: The authors received responses from 611 pain therapists of 279 centers. Only 22% of physicians are exclusively pain therapists. Seventy-five percent are specialists in anesthesiology, intensive care, and pain medicine. Most pain centers are hospital or university facilities (78%). The strengths of cancer pain management in Italy are the careful opioid prescriptions, the use of strategies for the treatment of neuropathic pain, patient/healthcare provider partnerships, and breakthrough cancer pain management. Weaknesses to be addressed include poor adherence to guidelines, inadequate attention toward the patient's quality of life, insufficient use of minimally invasive techniques, lack of teamwork approaches, inappropriate timing of pain specialist engagement, and poor telemedicine use. CONCLUSIONS: Despite several strengths, further efforts are needed to improve the care of patients suffering from cancer pain in Italy.

A Delphi Consensus Approach for the Management of Chronic Pain during and after the COVID-19 Era.

Due to a lack of published evidence on the topic, a modified Delphi approach was used to develop recommendations useful for chronic pain management during and after the COVID-19 pandemic. Focusing on the available literature and personal clinical expertise, an Italian board of nine professionals from different disciplines identified four main topics: prevention of chronic pain, treatment of chronic pain, consequences of inadequate treatment, and perspectives. They elaborated a semi-structured questionnaire. A multidisciplinary panel of experts in the field of pain management was requested to comment on the statements. Based on the answers provided, a structured questionnaire was prepared (Round 1). It included 21 statements divided into three categories (organizational issues; diagnosis and therapies; telemedicine and future perspectives). A five-point Likert scale was adopted. The threshold for consensus was set at a minimum of 70% of the number of respondents (level of agreement ≥ 4, Agree or Strongly Agree). A final questionnaire with rephrasing of the statements that did not reach the consensus threshold was elaborated (Round 2). A total of 29 clinicians were included in the panel. Twenty clinicians (69%) responded in both the first and second round. After two rounds, consensus (≥70%) was achieved in 20 out of 21 statements. The lack of consensus was recorded for the statement regarding the management of post-COVID pain (55%; Median 4; IQR 2.3). Another statement on telemedicine reached the threshold in the first round (70%), but the value was not confirmed in Round 2 (65%; Median 4; IQR 2). Most of the proposed items reached consensus, suggesting the need to make organizational changes, the structuring of careful diagnostic and therapeutic pathways, and the application of new technologies in pain medicine. Long-COVID-19 care is an issue that needs further research. Remote assistance for chronic pain must be regulated.

Open Issues and Practical Suggestions for Telemedicine in Chronic Pain.

Telemedicine represents a major opportunity to facilitate continued assistance for patients with chronic pain and improve their access to care. Preliminary data show that an improvement can be expected of the monitoring, treatment adherence, assessment of treatment effect including the emotional distress associated with pain. Moreover, this approach seems to be convenient and cost-effective, and particularly suitable for personalized treatment. Nevertheless, several open issues must be highlighted such as identification of assessment tools, implementation of monitoring instruments, and ability to evaluate personal needs and expectations. Open questions exist, such as how to evaluate the need for medical intervention and interventional procedures, and how to define when a clinical examination is required for certain conditions. In this context, it is necessary to establish dynamic protocols that provide the right balance between face-to-face visits and telemedicine. Useful tips are provided to start an efficient experience. More data are needed to develop precise operating procedures. In the meantime, the first experiences from such settings can pave the way to initiate effective care pathways in chronic pain.

Anti-AT1R autoantibodies and prediction of the severity of Covid-19.

The stimulation of AT1R (Angiotensin II Receptor Type 1) by Angiotensin II has, in addition to the effects on the renin-angiotensin system, also pro-inflammatory effects through stimulation of ADAM17 and subsequent production of INF-gamma and Interleukin-6. This pro-inflammatory action stimulate the cytokine storm that characterizes the most severe forms of SARS-CoV-2 infection. We studied the effect of AT1Rab on the AT1R on 74 subjects with SARS-CoV-2 infection with respiratory symptoms requiring hospitalization. We divided the patients into 2 groups: 34 with moderate and 40 with severe symptoms that required ICU admission. Hospitalized subjects showed a 50% reduction in the frequency of AT1Rab compared to healthy reference population. Of the ICU patients, 33/40 (82.5%) were AT1Rab negative and 16/33 of them (48.5%) died. All 7 patients positive for AT1Rab survived. These preliminary data seem to indicate a protective role played by AT1R autoantibodies on inflammatory activation in SARS-CoV-2 infection pathology.

Chronic pain and COVID-19: pathophysiological, clinical and organizational issues.

During the lockdown phase of the COVID-19 pandemic, a call not to neglect the continuum of care of patients who present with chronic diseases, including pain, was made. In the field of pain, COVID-19 had an impact both from a clinical (i.e., the influence of SARS-CoV-2 infection on pain) and organizational (i.e., how patients with chronic pain should be managed in the post-COVID-19 era) perspective. Furthermore, patients with chronic pain are also frequently frail subjects, affected from multiple comorbidities and hence are at increased risk of infection. On these bases, how the necessity to continue pain therapy will be pursued in the post-COVID-19 era? In this paper, we comment on the above-mentioned topics, on the basis of available data and our experience as pain therapists.

How to communicate with families living in complete isolation.

IMPORTANCE: During the SARS-CoV-2 pandemic, a complete physical isolation has been worldwide introduced. The impossibility of visiting their loved ones during the hospital stay causes additional distress for families: in addition to the worries about clinical recovery, they may feel exclusion and powerlessness, anxiety, depression, mistrust in the care team and post-traumatic stress disorder. The impossibility of conducting the daily meetings with families poses a challenge for healthcare professionals. OBJECTIVE: This paper aims to delineate and share consensus statements in order to enable healthcare team to provide by telephone or video calls an optimal level of communication with patient's relatives under circumstances of complete isolation. EVIDENCE REVIEW: PubMed, Cochrane Database of Systematic Reviews, Database of Abstracts and Reviews of Effectiveness and the AHCPR Clinical Guidelines and Evidence Reports were explored from 1999 to 2019. Exclusion criteria were: poor or absent relevance regarding the aim of the consensus statements, studies prior to 1999, non-English language. Since the present pandemic context is completely new, unexpected and unexplored, there are not randomised controlled trials regarding clinical communication in a setting of complete isolation. Thus, a multiprofessional taskforce of physicians, nurses, psychologists and legal experts, together with some family members and former intensive care unit patients was established by four Italian national scientific societies. Using an e-Delphi methodology, general and specific questions were posed, relevant topics were argumented, until arriving to delineate position statements and practical checklist, which were set and evaluated through an evidence-based consensus procedure. FINDINGS: Ten statements and two practical checklists for phone or video calls were drafted and evaluated; they are related to who, when, why and how family members must be given clinical information under circumstances of complete isolation. CONCLUSIONS AND RELEVANCE: The statements and the checklists offer a structured methodology in order to ensure a good-quality communication between healthcare team and family members even in isolation, confirming that time dedicated to communication has to be intended as a time of care.