A Business Process Reengineering of the Surgical Path through Lean Technique: The Real Case Study of a Midsize Italian Hospital

This period of pandemic has had important consequences on the flow and the entire organization of any hospital. In particular, the number of accesses to the emergency room has increased, with the consequent urgent need to reorgani ze it quickly. The model proposed in this paper allows to respond to these needs by freeing not only shifts of nursing staff but also surgical staff. This workforce can then be relocated in the emergency room or of the intensive care unit who are in fact at the forefront of emergency management. The aim of this study conducted by the authors is to analyze, inside the context of a midsize Italian hospital, the actual organization model, and then to approach it by Business Process Reengineering (BPR) methodology with the goal to propose a KPI management system that evaluates the efficiency of the whole surgical path. The second objective of the study is to verify if the Operating Rooms (ORs) are properly sized to cover the surgical workload or if it would be necessary to build new ORs (answer to this question is the project mandate by Surgical Wards Chiefs). The last objective is to implement a flexible to cope with emergency situations such as a pandemic. The main result is the approximate maintenance of surgical annual activity (8169 vs 7889). The fewer resources required can be reallocated to deal with emergencies such as the current COVID-19 pandemic. In fact, the surgical shifts decreased during the test case from 464 versus 365 (-15,32%). The rooms’ utilization coefficient rose from 41% to over 52%, whereas the surgeons’ utilization coefficient rose to 61% (with values over 68% for parallel shifts). The results achieved demonstrate that improving efficiency of surgical processes is feasible and a systematic approach allows to respond to new global health challenges. © 2022, AIDI - Italian Association of Industrial Operations Professors. All rights reserved.

Engineering Solutions 4.0 in the fight against the spread of Covid 19 A new Methodology including processes, procedures and devices

Thanks to the principles and technologies made available by Industry 4.0, the authors conceptualized and modeled a new strategy, capable of making an effective contribution to the problem of limiting contagion from Covid19 today, and tomorrow from any possible other type virus, bacteria or pathogen agent introduced by subjects who, although unaware of being vectors, develop the infection only after their access to the places of stay (Hotel, office, Infrastructure, etc.) where they go to reside. The key point of the strategy is a 4.0 thermoscanner, created by the authors, which is positioned in appropriately chosen locations of the settlement and an innovative method of disinfection of the same implemented by means of UV-C rays and Ozone in the gaseous state, produced by a machine, also conceptualized and developed by the authors, capable of reproducing the Chapman Cycle with the associated advantages. Therefore, it is operated an absolute disinfection based on a reversible cycle Oxygen-Ozone-Oxygen, with a prompt re-habitability of the treated rooms, with minimal treatment costs and without the use of expensive and unhealthy chemicals or wet water vapor (incompatible with paper and electronics). This technology was described in the paper “Sanitizing of Confined Spaces Using Gaseous Ozone Produced by 4.0 Machines” presented by the authors to the WCE 2021 IAENG Congress and awarded with the “Best Paper Award of the 2021 International Conference of Systems Biology and Bioengineering”. In the presence of a Person with a fever, the thermoscanner automatically launches an alert to the site Safety officers, who confine him to an isolated place and make the Health Institutions intervene and take it over. © 2022, AIDI - Italian Association of Industrial Operations Professors. All rights reserved.

SkinTracker: A novel smartphone app enabling remote clinical research in dermatology

A highly visual practice, dermatology as a field has significant potential to use emerging technology such as mobile applications for research and patient-centered mapping of the disease process. The UCSF team is working to create SkinTracker, a mobile application for patients with skin disease to remotely participate in clinical trials and research studies. The initial iteration of the application focuses on atopic dermatitis. The application includes an enrollment and consent module, validated surveys including the Patient Oriented Eczema Measure (POEM), Dermatology Life Quality Index (DLQI), Numerical Rating Scale (NRS) for itch, link to a wearable device that collects biometric data, a voice diary, and a patient-directed photography module to facilitate physician evaluation of disease. Also included is the ability to report medication use, adverse events, and the ability to chat with the study team. The patient information is available to the research team on a secure online website, where researchers can assess patient photographs to perform Eczema Area and Severity Index (EASI) scoring, note important patient observations from the voice diary, and view quantitative data from both patient surveys and health measures like physical activity, sleep, and environmental factors. We believe this application and website will facilitate patient interest and participation in research, continue research despite in-person restrictions placed during the COVID-19 pandemic, and allow enrollment of more diverse patients for clinical studies who would otherwise be less likely to participate in research due to time or financial constraints.

POST-TRAUMATIC STRESS DISORDER and SYMPTOMS in PATIENTS with RHEUMATIC and MUSCULOSKELETAL DISEASES during the COVID-19 PANDEMIC: PRELIMINARY RESULTS from the PERMAS STUDY

Background: The COVID-19 pandemic, with its uncertainties, fears of contagion, mass lockdowns and containment measures, has dramatically impacted on people's everyday lives leading to an increased risk of mental disorders, particularly Post-Traumatic Stress Disorder (PTSD). Despite evidence in general population and healthcare workers1,2, scant data emerged on vulnerable populations, such as of patients with chronic illness, particularly rheumatic and musculoskeletal diseases (RMDs)3,4, who also underwent difficulties in the management and treatment of their disorders. Objectives: To assess PTSD and post-traumatic stress symptoms in a sample of patients with RMDs, during the COVID-19 pandemic in Italy. Methods: PERMAS is a monocentric prospective observational study led by the Rheumatology Unit, the Psychiatric Clinic and the Institute of Management of the School of Advanced Studies. Patients with a RMD diagnosis, were consecutively enrolled from May 2021 to January 2022. During the visit, sociodemographic characteristics and psychopathological data were collected through online survey, whereas clinical data were collected by physician. The survey included the Trauma and Loss Spectrum-Self Report (TALS-SR) and the Impact of Event Scale-Revised (IES-R), aimed to assess symptomato-logical PTSD and post-traumatic stress symptoms related to the impact of the COVID-19 pandemic. Results: A total of 194 eligible patients, with a mean age of 50.3±12.17 years, was included: 142 (73.19%) were females;112 (57.74%) patients reported connective tissue diseases (CTD), 63 (32.47%) arthritis and 19 (9.8%) vasculitis. A total of 33 (17%) subjects reported a symptomatological PTSD by means of the TALS-SR. The prevalence of Partial PTSD (defned by at least 2 out of the 4 criteria for DSM-5 diagnosis of the disorder) was 56.7%, with signifcant higher rates among females (90, 81.8%) with respect to males (20, 18.2%) (p=.013). Accordingly, a IES-R mean total score of 21.90 ±15.98 was found in the total sample and a gender difference emerged, with higher mean scores among females rather than males (23.42 ±16.26 vs 21.90 ±15.98, p=.031). Conclusion: The present fndings point out high prevalence rates of symptoma-tological PTSD among patients suffering from RMDs, highlighting the potentially traumatic burden of the COVID-19 pandemic in this particular population, especially among females, suggesting the need of further investigations to address tailored prevention and intervention strategies.

COVID-19 MRNA VACCINE BOOSTER in PATIENTS with SYSTEMIC AUTOIMMUNE DISEASES

Background: Patients with systemic autoimmune diseases (SADs) are often treated with drugs that interfere with the immune system and previous data showed a reduced seroconversion rate after anti-SARS-CoV2 vaccine in these subjects compared to healthy controls1. Administration of a booster dose of the vaccine could be particularly important in these patients, but data available to date are still scarce. Objectives: To evaluate the antibody response to the booster dose of mRNA SARS-CoV2 vaccine in patients with SADs and to compare it to the response after completion of the frst vaccination course. Secondly, to fnd possible correlations between a low antibody titre and patients' clinical features, with special regard to ongoing immunosuppressive therapies. Methods: Consecutive patients with an established diagnosis of SADs undergoing SARS-CoV2 vaccine were prospectively enrolled from January 2021;among them, we selected the patients who received the third vaccination dose between September and December 2021. Demographic and clinical data were collected at enrolment (sex, age, diagnosis, disease duration, ongoing therapies, previous SARS-CoV2 infection, presence of hypogammaglobulinemia);the last three elements were reassessed at each follow-up visit. Blood samples were collected 4 weeks both after the second (W4a) and the third (W4b) dose of the vaccine;a minority of patients was also tested 12 weeks after the second dose (W12). IgG antibodies to SARS-CoV2 receptor-binding domain (RBD) and neutralizing antibodies inhibiting the interaction between RBD and angiotensin converting enzyme 2 were evaluated. IgG anti-RBD were detected by solid phase assay on plates coated with recombinant RBD, while neutralising antibodies by using the kit SPIA (Spike Protein Inhibition Assay). Cut-off values were defned as the 97.5th percentile of a pre-vaccine healthy population. Statistical analysis was performed using IBM SPSS Statistics 20 and GraphPad Prism statistical packages. P values <0.05 were considered signifcant. Results: Forty-five patients (95.6% female;mean age ±SD 55.6±14.1 years;mean disease duration 12.9±10.6 years) were enrolled. Diagnosis was in most cases connective tissue disease (31/45, 68.9%), followed by infammatory arthritis (11/45, 24.4%) and systemic vasculitis (3/45, 6.7%). Two patients (4.4%) had a previous SARS-CoV2 infection and three had hypogammaglobulinemia (6.7%). At the time of the second dose, 18/45 patients were treated with glucocorticoids (GCs) [mean daily 6-methylprednisolone (6MP) dose 3.9 mg (min. 2, max. 14)], 17/45 with conventional synthetic disease-modifying anti-rheumatic drugs (csDMARDs) and 12/45 with biologic DMARDs (bDMARDs). At the third dose administration, 19/45 patients were treated with GCs [mean daily 6MP dose 4.1 mg (min. 1.5, max. 10)], 18/45 with csDMARDs and 13/45 with bDMARDs. Anti-RBD IgG were positive in 42/45 patients (93.3%) at W4a, in 16/18 (88.9%) at W12 and in 42/45 (93.3%) at W4b. Neutralizing antibodies were present in 38/45 patients (84.4%) at W4a, in 14/18 (77.8%) at W12 and in 42/45 (93.3%) at W4b. Both anti-RBD IgG titers and neutralizing antibody titers signifcantly increased after the third dose if compared to W4a (p<0.0001 both) (Figure 1). Interestingly, of the 7 patients who had not developed an adequate neutralizing antibody response after the frst vaccination course, 5 mounted an adequate titer after the booster. Two non-responder patients were both on combination therapy (one with low dose of GCs plus mycophenolate mofetil, the other with methotrexate and infiximab). Conclusion: Our data suggest that in patients with SADs there is a decline in the antibody titers developed after COVID-19 vaccination, however the booster dose is effective in restoring an adequate antibody titre. These data consolidate the importance of a booster dose of COVID-19 vaccination in patients with SADs to aid in the generation of an immune response.

IMPACT of COVID-19 PANDEMIC on HEALTHCARE RESOURCE USE and CLINICAL OUTCOMES in A COHORT of PATIENTS with SYSTEMIC AUTOIMMUNE DISEASES-AN INTERIM ANALYSIS from the PERMAS PROJECT

Background: Management of the health emergency caused by COVID-19 pandemic majorly disrupted the delivery of healthcare services to patients with chronic conditions like Systemic Autoimmune Diseases (SAD), both because resources were mainly channeled towards the care of infected patients, but also because patients tended to avoid seeking medical care for fear of becoming infected. PER-MAS is a 2-year project aimed at assessing the clinical, psychopathological, and socio-economic impact of COVID-19 in a cohort of patients with SAD. Objectives: To assess the impact of COVID-19 pandemic on drug withdrawal, disease fares and hospitalizations for disease exacerbation in a cohort of patients with SAD through an interim analysis of data from the PER-MAS project. Methods: A sample of 214 consecutive patients was recruited in a reference center for rare and complex autoimmune diseases from April 2021 to January 2022. Inclusion criteria were definite diagnosis of SAD (Connective Tissue Disease (CTD), Inflammatory Arthritis (IA) or Vasculitis), regular follow-up and at least 2 years of disease. Patients were asked to fill out an extensive self-administered questionnaire on disease activity and healthcare resource use during the pandemic (March 2020-moment of assessment). Pre-pandemic (March 2019-February 2020) and early pandemic (March 2020-February 2021) clinical data were recorded through retrospective chart review and patient interview. Results: At enrolment, 119 patients were affected by CTDs (55.6%), 71 by IA (33.18%), 24 by vasculitis (11.21%), with mean age 50.44± 12.97, and mean disease duration 11.17 ± 8.94. 30.37% took steroids, 39.7% hydroxy-chloroquine, 61.68% DMARDs, and 9.3% vasoactive drugs. Overall, disease course was similar in pre-pandemic and early pandemic phase: in the first period, rheumatologic condition was stable in 57.35% of patients, persistently active in 27.3% and 35.61% had ≥ 1 episode of disease exacerbation (mean 0.665±1.15, range 0-6);in the second period, 60.56% of patients was stable, 24.88% persistently active, and 39.44% had ≥1 exacerbation (mean 0.49 ±0.77, range 0-4). Mean number of visits (2.56±2.57 and 2.61±2.79), hos-pitalizations (0.168±0.698 and 0.14±0.473, p=0.6), number of patients with outpatient visits=0 (7.47 vs 7%), and number of patients with ≥ 1 hospital admission (10.28 vs 11.6%) were also similar, while the number of patients with hospital admissions for disease exacerbation was significantly higher in the second period (6.1 vs 11.21%, p=0.001). 170 patients completed the survey: from March 2020 to enrolment, 18.2% suspended ≥1 anti-rheumatic drug (6.25% of them for fear of contracting COVID-19 disease, 15.6% for difficulty in obtaining medications), 20% self-managed ≥ 1 disease exacerbation, and 40% had ≥ 1 telemedicine consult. From March to July 2020, 41.76% had their visit rescheduled (35.23% for hospital access restrictions, 5.3% for travel restrictions, 1.17% for fear). Conversely, only 14.7% of patients had their visit rescheduled (8.23% for hospital access restrictions, 4.7% for other reasons) from July 2020 to enrolment. Conclusion: In the early pandemic phase, overall disease course was similar to the pre-pandemic phase, but we observed an increase in the number of patients with ≥ 1 hospitalization for disease. Moreover, despite our efforts, patients reported a non-negligible rate of drug discontinuation for non-medical indication and difficulty to get access to rheumatologic consultation, highlighting the need of alternative organizational models in case of future pandemics.

BARICITINIB and PULSE STEROIDS COMBINED TREATMENT in SEVERE COVID-19 PNEUMONIA: PRELIMINARY DATA from A RHEUMATOLOGIC EXPERIENCE in INTENSIVE CARE UNIT

Background: Growing evidence from in vitro and clinical studies have highlighted important similarities between severe COVID-19 and rapidly progressive interstitial lung diseases (ILD) occurring in systemic autoimmune disorders. These data supported the use of anti-rheumatic drugs, baricitinib and glucocor-ticoids, for the treatment of COVID-19 pneumonia. Objectives: To compare mortality rate and infammatory response in critically ill COVID-19 patients treated with either a 'rheumatologic approach' based on baricitinib plus pulse steroids (BPS) or with a 'conventional approach' (Standard of Care, SoC). Methods: In this retrospective study, we enrolled patients admitted to the Intensive Care Unit (ICU) with CT-proven SARS-CoV2 pneumonia, from September 2020 to April 2021. Demographic, laboratory, and clinical data were collected at the admission to ICU and after one week of treatment. SoC included dexameth-asone 6 to 8 mg daily plus remdesivir (+/-antibiotics and hydroxychloroquine);BPS approach was based on baricitinib 4 mg daily for 10-14 days plus 6-methyl-prednisolone pulses (250-500 mg) for three consecutive days followed by rapid tapering. The primary endpoint was the intra-ICU mortality rate;the secondary endpoint was the change in infammatory biomarkers at week 1 after treatment. Results: We enrolled a total of 210 consecutive patients with SARS-CoV2 pneumonia (male 61.4%, mean age 66.6 ± 10.9 years);137/210 (male 59.8%, mean age 66.3 ± 11.9 years) were treated with SoC and 73/210 (male 64.3%, mean age 67.3 ± 8.8 years) with BPS. At admission in ICU, all patients presented lag time from the frst symptom of SARS-CoV2 infection ≤ 10 days, laboratory biomarkers' alterations suggestive of hyper-infammatory response (CRP 10.8 ± 11.9 mg/dL, ferritin 1238 ± 1005 μ g/L, fbrinogen 575 ± 173 mg/dL, LDH 385 ± 152 U/L) and severe respiratory failure, requiring non-invasive or invasive ventilatory support. Lung-CT pattern showed multiple and diffuse areas of ground glass opacities, septal thickening, and/or consolidation. No statistically signifcant differences were found between SoC and BPS groups in terms of demographic, laboratory, and clinical features at enrolment. 59/210 (28.1%) patients died during ICU hospitalization (mean ICU length of stay 14.6 ± 9.6 days). Mortality rate in the BPS group (13/73, 17.8%) resulted signifcantly lower compared to that in the SoC group (46/137, 33.6%) (p= 0.016). Furthermore, patients in the BPS group had signifcantly lower levels of CRP (BPS=1.9 ± 2.8 vs SoC 6.1 ± 7.3, p<0.001) and fbrinogen (BPS=335 ± 108 vs SoC 453 ± 172, p<0.001) at one week after the start of treatment. Conclusion: Our real-life experience, in an ICU setting, showed that baricitinib and pulse steroids combination was associated with a lower mortality rate paralleled by a prompt reduction of infammatory biomarkers. These results shed new light on the possible usefulness of baricitinib for the treatment of rapidly progressive ILD in patients with systemic autoimmunity and hyper-infammation.

LONG-TERM OUTCOMES of COVID-19 VACCINATION in PATIENTS with RARE and COMPLEX CONNECTIVE TISSUE DISEASES: AN AD-INTERIM ANALYSIS of ERN-RECONNET VACCINATE STUDY

Background: Since the COVID-19 vaccination campaign was launched all over Europe, there has been general agreement on how benefts of SARS-CoV2 vaccines outweigh the risks in patients with rare connective tissue diseases (rCTDs). Yet, there is still limited evidence regarding safety and efficacy of such vaccines in these patients, especially in the long-term. For this reason, in the framework of ERN-ReCONNET, an observational long-term study (VACCINATE) was designed in order to explore the long-term outcome of COVID-19 vaccination in rCTDs patients. The consent form was developed thanks to the involvement of the ERN ReCONNET ePAG Advocates (European Patients Advocacy Group). Objectives: To evaluate the safety profile of COVID-19 vaccination in rCTDs patients and the potential impact on disease activity. Primary endpoints were the prevalence of adverse events (AEs) and of disease exacerbations post-vaccination. Secondary endpoints were the proportion of serious adverse events (SAEs) and adverse events of special interest for COVID-19 (adapted from https://bright-oncollaboration.us/wp-content/uploads/2021/01/SO2-D2.1.2-V1.2-COVID-19- AESI-update-23Dec2020-review-fnal.pdf) Methods: The frst ad-interim analysis of the VACCINATE study involved 9 ERN-ReCONNET Network centres. Patients over 18 years of age with a known rCTD and who received vaccine against COVID-19 were eligible for recruitment. Demographic data and diagnoses were collected at the time of enrolment, while the appearance of AEs and potential disease exacerbations were monitored after one week from each vaccination dose, and then after 4, 12 and 24 weeks from the second dose. A disease exacerbation was defned as at least one of the following: new manifestations attributable to disease activity, hospital-ization, increase in PGA from previous evaluation, addition of corticosteroids or immunosuppressants. Results: A cohort of 300 patients (261 females, mean age 52, range 18-85) was recruited. Systemic lupus erythematosus (44%) and systemic sclerosis (16%) were the most frequent diagnoses, followed by Sjogren's syndrome (SS,12%), idiopathic infammatory myositis (IMM,10%), undifferentiated connective tissue disease (UCTD,8%), mixed connective tissue disease (MCTD,4%), Ehlers-Dan-los's syndrome (EDS,4%), antiphospholipid syndrome (APS,2%). AEs appearing 7 days after the frst and second doses were reported in 93 (31%) and 96 (32%) patients respectively, mainly represented by fatigue, injection site reaction, headache, fever and myalgia. Otitis, urticaria, Herpes Simplex-related rash, stomatitis, migraine with aura, vertigo, tinnitus and sleepiness were reported with very low frequency. Less than 2% of patients experienced AEs within 24 weeks from the second dose. No SAEs or AEs of special interest were observed in the study period. There were 25 disease exacerbations (8%), 7 of which severe. The highest number of exacerbations was observed after 4 weeks from the second dose (12 within week 4, 6 within week 12 and 7 within week 24). Disease exacerbation was most frequent in patients with EDS (33%) and MCTD (25%). Conclusion: This preliminary analysis shows that COVID-19 vaccination is safe in rCTDs patients. AEs appear most often early after vaccination and are usually mild. Disease exacerbations are not frequent, but can be potentially severe and tend to occur most frequently within the frst month after vaccination. Exacerbations can also occur 3-6 months after vaccination, although a causal relationship with the vaccination remains to be established. Our present data underline the importance of long-term observational studies.

A PHYSICAL EXERCISE PROGRAM for the MANAGEMENT of FATIGUE in SYSTEMIC LUPUS ERYTHEMATOSUS (SLE) at the TIME of PANDEMIC: A PILOT STUDY

Background: Fatigue in SLE has a multifactorial origin and disease activity seems to contribute only minimally to its genesis. Therefore, non-pharmacological therapeutic strategies should also be considered in the management of fatigue. There is some evidence on the effectiveness of aerobic exercise programs in improving fatigue, without a negative impact on disease manifestations. Objectives: the aim of this study was to analyze fatigue and Health Related Quality of Life (HRQoL) in a monocentric cohort of patients with SLE, in a condition of stable remission or low disease activity, before and after a program of physical exercise, through the administration of validated Patient Reported Outcomes (PROs). Methods: this is a cross-sectional interventional study which included patients with SLE, aged between 18 and 55 years, in a condition of stable (≥12 months) remission (DORIS)1 or low disease activity (LLDAS)2. Patients enrolled had a FACIT score ≤40 in the previous 6 months. Patients with other possible causes of fatigue (e.g.: anemia, hypothyroidism, severe vitamin D defciency), active arthritis or physical disabilities were excluded. For each patient, demographics, comorbidities, treatment, clinical and laboratory data were collected. Disease activity was evaluated with the SELENA-SLEDAI and organ damage with the SLICC/DI. Each patient completed the following PROs before and after the interventional program: SF-36, FACIT-Fatigue, LIT, HADS. Due to the limitations related to the COVID-19 pandemic, the physical exercise sessions were carried out using the Google Meet digital platform. Patients were asked to participate to at least 70% of the lessons. The physical exercise program included moderate intensity aerobic exercises (muscle strengthening, joint mobility, breathing, static and dynamic stretching, balance and neuro-dynamics);workouts were performed 3 times a week, consisting of 60 minutes each. The program lasted for 12 weeks. Results: we enrolled 12 female patients, regularly followed at the Rheumatology Unit of Pisa;only 9 of them completed the study (mean age 38.56 ± 9.1 years;median disease duration 7 years (IQR 5,25-9,75)). 8/9 were in stable remission, while 1/9 was in LLDAS for the presence of leukopenia. 2/9 patients presented organ damage, one for cataract and one for renal insufficiency, while none presented damage in the musculoskeletal system. 33.3% of patients had fbromyalgia. 88.8% was on treatment with Hydroxy-chloroquine, 55.5% was on low dose steroids (2±1.9 mg/daily), 33.3% was on Mycophenolate Mofetil;only 1 patient was on Belimumab. All PROs showed a trend to improvement at the end of the 12-week program of physical activity (Table 1). We demonstrated a statistically signifcant improvement of: FACIT, LIT, depression score of the HADS and MCS of the SF-36. The items of role physical (RP), vitality (VT) and mental health (MH) of the SF-36 also showed a signifcant improvement. Conclusion: In a small cohort of SLE patients in remission but with severe fatigue, in the difficult context of COVID-19 pandemic, we demonstrated that an online program of physical exercise may determine a signifcant improvement of fatigue, perception of disease burden and mental health. In the context of a multidisciplinary management, fnding effective intervention programs to improve fatigue and HRQoL in SLE patients appears of utmost importance, with the fnal aim of improving patients' health status.

THE IMPACT of LOCKDOWN in PATIENTS with RHEUMATOID ARTHRITIS

Background: The COVID-19 pandemic has impacted on face to face assessments of patients with rheumatic diseases, including rheumatoid arthritis (RA) and telemedicine has offered a valid opportunity to follow these patients. DEDI-CARE is a Patient Support Program (PSP) which has been active at our center since 2016, which allows the telemonitoring of PROs (Patient Reported Outcomes) for patients being treated with abatacept. Since 2016, 98 RA patients followed at out Unit entered the DEDICARE program. During COVID19 pandemic these patients continued their monitoring using this PSP. Objectives: To evaluate the impact of the frst COVID wave on PROs and CROs (Clinical Reported Outcomes) in patients with RA included in the DEDICARE programme Methods: Data collected in the dedicated platform three months before (from December 2019 to February 2020, pre-lockdown), during (from March 2020 to May 2020, lockdown) and after (from June 2020 to August 2020, post-lockdown) the frst lockdown period in Italy were compared. In detail DAS28 (CRP, ESR), CDAI and SDAI were evaluated before and after the lockdown period;while VAS-pain, Global Health (GH);Patient Global Assessment of Disease Activity (PGA);Health Assessment Questionnaire (HAQ);Functional Assessment Chronic Illness Therapy (FACIT) were evaluated pre, during e post lockdown with the DEDICARE platform. Results: 36 RA patients, all females, were included in the study;mean age was 62.4 (32-85) years;mean disease duration 15.5 (5-38) years;18 were ACPA and RF+. All patients were treated with abatacept, 13 as monotherapy and 23 in association with csDMARDs. No patients had COVID19 disease during the evaluated period. A signifcant worsening of global health and patient global assessment of disease activity was observed;while no differences were observed regarding the CROs and other PROs (Figure 1) Conclusion: In the present study we were able to compare PROs in patients with RA before and after the frst COVID wave in Italy. While no signifcant changes in disease activity were observed, patients experienced an increased perception of disease activity and a decline in their overall health status which began during the lockdown and continued over the following 3 months. This may highlight a discordance between the patient and the physician perception of the disease, which may partly due to the psychological impact of pandemic on the general perception of health particular in patients with chronic diseases. Since this discrepancy may have consequences on disease management, and particularly on treatment adherence, there is a need to promote studies to better understand the reasons for these discrepancies and to improve the patient perception of their disease particularly in difficult situations such as COVID 19 pandemic.

The added value of a European Reference Network on rare and complex connective tissue and musculoskeletal diseases: insights after the first 5 years of the ERN ReCONNET

In order to address the main challenges related to the rare diseases (RDs) the European Commission launched the European Reference Networks (ERNs), virtual networks involving healthcare providers (HCPs) across Europe. The mission of the ERNs is to tackle low prevalence and RDs that require highly specialised treatment and a concentration of knowledge and resources. In fact, ERNs offer the potential to give patients and healthcare professionals across the EU access to the best expertise and timely exchange of lifesaving knowledge, trying to make the knowledge travelling more than patients. For this reason, ERNs were established as concrete European infrastructures, and this is particularly crucial in the framework of rare and complex diseases in which no country alone has the whole knowledge and capacity to treat all types of patients. It has been five years since their kick-off launch in Vilnius in 2017. The 24 ERNs have been intensively working on different transversal areas, including patient management, education, clinical practice guidelines, patients' care pathways and many other fundamental topics. The present work is therefore aimed not only at reporting a summary of the main activities and milestones reached so far, but also at celebrating the first 5 years of the ERN on Rare and Complex Connective Tissue and Musculo-skeletal Diseases (ReCONNET), in which the members of the network built together one of the 24 infrastructures that are hopefully going to change the scenario of rare diseases across the EU.

Sanitizing of Confined Spaces Using Gaseous Ozone Produced by 4.0 Machines

A fundamental aspect of the fight against the Coronavirus and against any other virus, is represented by the sanitization of the sites and objects contained therein. This operation is normally carried out using mixtures of ozone and steam and it is certainly effective but also limited due the damages that the vapor can cause to rooms and objects. The following paper introduce machines able to overcome this issue thanks to innovative systems based on the principles of Engineering 4.0. Those systems reproduce the Chapman cycle in the to-be sanitized environments which allows producing ozone in a gaseous state, in the proper quantity and for the time necessary for sanitization. At the end of the operation, the ozone will be converted back into oxygen, leaving the environment re-habitable by humans and pets in a short time. The operation has low costs and times and guarantees positive results. This is therefore a real revolution to be considered today against the COVID-19. © 2021 Newswood Limited. All rights reserved.

Tolérance de la vaccination contre le SRAS-CoV-2 chez les patients atteints de maladies rhumatologiques inflammatoires/auto-immunes : résultats du registre EULAR-COVAX chez 5121 patients

Introduction Les patients atteints de maladies musculosquelettiques inflammatoires/auto-immunes (I-RMD) n’ont pas été inclus dans les études de tolérance des vaccins contre le SARS-CoV-2 et sont souvent inquiets quant à la tolérance de la vaccination. Notre objectif est d’étudier la tolérance des vaccins contre le SARS-CoV-2 chez les patients atteints de maladies musculosquelettiques inflammatoires/auto-immunes (I-RMD). Patients et méthodes Pour cela, nous avons créé avec l’EULAR un registre international de cas rapportés par les médecins rhumatologues et internistes de patients atteints d’I-RMD et de RMD non inflammatoire (NI-RMD) vaccinés contre le SARS-CoV-2. Du 5 février 2021 au 27 juillet 2021, nous avons recueilli des données sur la démographie, la vaccination, le diagnostic de RMD, l’activité de la maladie, les traitements immunomodulateurs/immunosuppresseurs, les poussées, les événements indésirables (EI) et les infections COVID-19 chez les patients vaccinés. Les données ont été analysées de manière descriptive. Résultats L’étude a inclus 5121 participants de 30 pays, la majorité de France (40 %), Italie (16 %) et Portugal (14 %), 90 % avec des I-RMD (n=4604, 68 % de femmes, âge moyen 60,5 ans) et 10 % avec des NI-RMD (n=517), 77 % de femmes, âge moyen 71,4 ans. La polyarthrite rhumatoïde (33 %), les connectivites (18 %), les spondyloarthrites (11 %), le rhumatisme psoriaqique (10 %) et les vascularites (12 %) étaient les diagnostics les plus fréquents ;54 % des patients ont reçu des traitements de fond synthétiques conventionnels (csDMARD), 42 % des DMARD biologiques ou ciblés et 35 % des immunosuppresseurs. La plupart des patients ont reçu le vaccin Pfizer/BioNTech (70 %), 17 % AstraZeneca/Oxford et 8 % Moderna. Une infection COVID post-vaccination a été signalée dans 0,7 à 1,1 % des cas, selon le statut vaccinal (entièrement/partiellement vacciné) et le groupe RMD. Des poussées d’I-RMD ont été signalées dans 4,4 % des cas (0,6 % de poussées sévères), dont 1,5 % ont entraîné des changements de médicaments. Des EI ont été signalés dans 37 % des cas (37 % I-RMD, 40 % NI-RMD), des EI sévères dans 0,4 % des cas, très divers et avec une fréquence comparable et même inférieure à celle observée chez les patients atteints de NI-RMD (1,1 %). Discussion La tolérance au vaccin n’était pas différente entre les groupes I-RMD et NI-RMD. Dans les essais cliniques de vaccins à ARN contre le SRAS-CoV-2 dans la population générale, les taux d’EI graves étaient très semblables à ceux de notre étude, allant de 0,4 % à 0,6 % dans le groupe vacciné et de 0,5 % à 0,6 % dans le groupe témoin, ce qui suggère que ces EI graves ne sont pas nécessairement liés au vaccin. Conclusion Il s’agit de la plus grande étude de la tolérance des vaccins anti-SRAS-CoV-2 chez près de 5000 patients atteints de maladies inflammatoires/auto-immunes rhumatologiques. Le profil de sécurité des vaccins contre le SRAS-CoV-2 chez les patients atteints d’I-RMD était rassurant, et comparable à celui des patients atteints de NI-RMD. La majorité des patients ont bien toléré leur vaccination, avec de rares poussée d’I-RMD et de très rares EI sévères probablement non liés à la vaccination. Ces résultats devraient rassurer les rhumatologues et les personnes vaccinées, et favoriser la confiance dans la sécurité du vaccin COVID-19 chez les patients atteints de I-RMD.

COVID-19 vaccine safety in patients with rheumatic and musculoskeletal disease

Background: The consequences of the COVID-19 outbreak are unprecedented and have been felt by everyone around the world, including people with rheumatic and musculoskeletal diseases (RMDs). With the development of vaccines, the future is becoming brighter. Vaccines are a key pillar of public health and have been proven to prevent many serious diseases. However, vaccination also raises questions, especially for patients with inflammatory RMDs and/or treated with drugs that influence their immune system. Objectives: Our aim was to collect safety data among RMD patients receiving COVID-19 vaccines. Methods: The EULAR COVID-19 Vaccination (COVAX) Registry is an observational registry launched on 5 February 2021. Data are entered voluntarily by clinicians or associated healthcare staff;patients are eligible for inclusion if they have an RMD and have been vaccinated against SARS-CoV-2. Descriptive statistics are presented. Results: As of 27 April 2021, 1519 patients were reported to the registry. The majority were female (68%) and above the age of 60 (57%). Mean age was 63 years (SD 16), ranging from 15 to 97 years. A total of 28 countries contributed to the registry, with France (60%) and Italy (13%) as the highest contributors. The majority (91%) had inflammatory RMDs. Inflammatory joint diseases accounted for 51% of cases, connective tissue diseases 19%, vasculitis 16%, other immune mediated inflammatory diseases 4%, and non-inflammatory/mechanical RMDs 9%. The most frequent individual diagnoses were rheumatoid arthritis (30%), axial spondyloarthritis (8%), psoriatic arthritis (8%), systemic lupus erythematosus (SLE, 7%) and polymyalgia rheumatica (6%). At the time of vaccination, 45% were taking conventional synthetic DMARDs, 36% biological DMARDs, 31% systemic glucocorticoids, 6% other immunosuppressants (azathioprine;mycophenolate;cyclosporine;cyclophosphamide;tacrolimus), and 3% targeted synthetic DMARDs. The most frequent individual DMARDs were methotrexate (29%), TNF-inhibitors (18%), antimalarials (10%) and rituximab (6%). The vaccines administered were: 78% Pfizer, 16% AstraZeneca, 5% Moderna and 1% other/unknown;66% of cases received two doses and 34% one dose. Mean time from 1st and 2nd dose to case report was 41 days (SD 26) and 26 days (SD 23), respectively. COVID-19 diagnosis after vaccination was reported in 1% (18/1519) of cases. Mean time from first vaccination until COVID-19 diagnosis was 24 days (SD 17). Disease flares were reported by 5% (73/1375) of patients with inflammatory RMDs, with 1.2% (17/1375) classified as severe flares. Mean time from closest vaccination date to inflammatory RMD flare was 5 days (SD 5). The most common flare types were arthritis (35/1375=2.5%), arthralgia (29/1375=2.1%), cutaneous flare (11/1375=0.8%) and increase in fatigue (11/1375=0.8%). Potential vaccine side effects were reported by 31% of patients (467/1519). The majority were typical early adverse events within 7 days of vaccination, namely pain at the site of injection (281/1519=19%), fatigue (171/1519=11%) and headache (103/1519=7%). Organ/system adverse events were reported by 2% (33/1519) but only 0.1% (2/1519) reported severe adverse events, namely a case of hemiparesis in a patient with systemic sclerosis/ SLE overlap syndrome (ongoing at the time of reporting), and a case of giant cell arteritis in a patient with osteoarthritis (recovered/resolved without sequelae). Conclusion: The safety profiles for COVID-19 vaccines in RMD patients was reassuring. Most adverse events were the same as in the general population, they were non-serious and involved short term local and systemic symptoms. The overwhelming majority of patients tolerated their vaccination well with rare reports of inflammatory RMD flare (5%;1.2% severe) and very rare reports of severe adverse events (0.1%). These initial findings should provide reassurance to rheumatologists and vaccine recipients, and promote confidence in COVID-19 vaccine safety in RMD patients, namely those with inflammatory RMDs and/or taking treatments that influence their immune system.

COVID-19 emergency and psychosocial well-being of healthcare professionals: A systematic literature review

The emergency from COVID-19 places health organizations in front of a challenge and involves unprecedented work overload for healthcare workers. Doctors and nurses were bearing significantly increased workload in a consequent reorganization of the work with the shortage of protective equipment, isolation, and directly contacting with COVID-19 patients. This has a negative impact on performance and psychological well-being. This paper aimed at reviewing findings from the literature concerning the well-being and malaise of healthcare workers during the initial stage of the COVID- 19 malaise. Three main themes emerged from the analysis: (1) work-related stress and psychophysical malaise;(2) differences in the role and socio-demographic characteristics of healthcare workers;(3) training, support, and organizational learning. The studies focused on health workers' stress and burnout without ever considering, in a positive psychology perspective, the analysis of mental well-being levels. Differences emerged between roles, age, and role. This systematic review highlights the need to develop practices to support healthcare workers involved in the COVID-19 emergency, also considering the differences in gender, role, and professional setting. Individual interventions to manage stress, group support, and an engaged organizational culture could help prevent psychosocial risks during the pandemic. Among the limitations, mainly cross-sectional studies and the inclusion of very different geographic realities and health organizations. © 2021 Franco Angeli Edizioni. All rights reserved.