Analyzing Health System Resilience From the Perspective of Rare Diseases

Objectives: Health systems resilience (HSR) is generally understood as the capacity to absorb, adapt or transform in order to maintain essential functions when faced shocks. Following the COVID-19 pandemic, the concept of HSR has gained popularity, and there is now greater recognition of the importance of HSR among healthcare professionals and policymakers. A deep understanding of factors affecting HSR and practical strategies to achieve it, is still a matter of debate. Therefore, the present study aims at exploring HSR in the field of rare diseases, a vulnerable group exhibiting unique demands and particular requirements for ongoing care. Method(s): By a scoping review of the literature, we identified 53 characteristics relevant toHSR. by classifying characteristics according to the WHO building blocks, we developed a survey directed to healthcare professionals dealing with rare diseases. The survey aims to understand to which extent each characteristic matters for achieving HSR in this context. After the preliminary development of the survey, comprehensiveness and clarity were assessed, sharing the survey with a restricted group of experts working and not with rare diseases. Based on their feedback, the survey was revised and. Result(s): Feedback from the restricted groups was generally positive, and minimal changes were introduced to improve the clarity of the survey and to include specific questions in addition to characteristics found in the literature review (i.e., the importance of being part of a large network dealing with a rare disease). The survey was implemented online and then shared using social media and directly mailing the link to an expert in the treatment of rare diseases. Conclusion(s): We expect to figure out a comprehensive set of characteristics that are appropriate to define resilience in the context of rare diseases. Our framework will help to suggest strategies to deal with shocks within such a context effectively. Copyright © 2022

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.

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.

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.

Evaluation of ECLIA antigen detection tests as screening methods for COVID-19 in comparison with molecular analysis

In the ongoing COVID-19 pandemic, rapid diagnostic testing for SARS-CoV-2 is necessary to limit virus spread. Different diagnostic rapid tests have been developed as rapid and helpful tools for diagnosis of COVID-19, based on virus proteins detection in respiratory samples.This study aims to evaluate the performances of the Elecsys SARS-CoV-2 Antigen test, in comparison to rRT-PCR, the gold standard.Molecular analysis was carried on 110 swabs from Lifebrain laboratory. According to rRT-PCR, 76 samples were positive, 34 were negative. Initially, the sensitivity and specificity were 85% and 100%, respectively. However, since most of the discordant cases had cycle threshold (Ct) values > 28, it was assumed a new measure to evaluate sensitivity and specificity. At this point, samples with Ct values <28 were selected and a sensitivity of 94% was achieved. The level of agreement between the two tests was 89,1% with η value of 0,77 for total data and 95,9% with η value of 0,95 for samples with <28 Ct.The Antigen test is a well performed tool, timely and effortless, in presence of high viral loads. The comparison data validated the method as a proper approach for rapid screening of patients with high SARSCoV-2 viral load. Also, a double test for confirmatory analysis on the same swab could increase the overall lab-workflow, but the rate of sensitivity is still highly Ctdependent.

Late chronotypes, late mealtimes. Chrononutrition and sleep habits during the COVID-19 lockdown in Italy.

The emerging field of chrononutrition provides useful information on how we manage food intake across the day. The COVID-19 emergency, and the corresponding restrictive measures, produced an unprecedented change in individual daily rhythms, possibly including the distribution of mealtimes. Designed as a cross-sectional study based on an online survey, this study aims to assess the chrononutrition profiles (Chrononutrition Profile Questionnaire, CP-Q) in a sample of 1298 Italian participants, during the first COVID-19 lockdown, and to explore the relationship with chronotype (reduced Morningness-Eveningness Questionnaire, rMEQ), sleep quality (Pittsburgh Sleep Quality Index, PSQI) and socio-demographics. Our findings confirm a change in eating habits for 58% of participants, in terms of mealtimes or content of meals. Being an evening chronotype and experiencing poor sleep imply a higher likelihood of changing eating habits, including a delay in the timing of meals. Also, under these unprecedented circumstances, we report that the timing of breakfast is a valuable proxy capable of estimating the chronotype. From a public health perspective, the adoption of this straightforward and low-cost proxy of chronotype might help in the early detection of vulnerable subgroups in the general population, eventually useful during prolonged stressful conditions, as the one caused by COVID-19 pandemic.

Poor sleep quality and unhealthy lifestyle during the lockdown: an Italian study.

BACKGROUND: The lockdown measure implemented to face the 2019 Coronavirus Disease (COVID-19) first wave deeply modified the lifestyle of the Italian population. Despite its efficacy in limiting the number of infections, forced home confinement was paralleled by sleep/wake cycle disruptions, psychological distress and maladaptive coping strategies (i.e., unhealthy behaviours, such as tobacco and alcohol consumption). Under these unprecedented stress conditions, we explored a possible association between poor sleep quality and increased likelihood of engaging in an unhealthy lifestyle. METHODS: A cross-sectional study was conducted by disseminating an online survey via social networks and e-mail. We collected information on demographics, COVID-19-related data, sleep quality, chronotype, circadian misalignment, and lifestyle before and during the lockdown (i.e., consumption of cigarettes, alcoholic beverages, coffee, hypnotics, comfort food and fresh food; practice of physical activity). A global healthiness score was computed to assess participants' modifications in lifestyle since the beginning of the lockdown. RESULTS: 1297 respondents were included in the study: 414 (31.9%) from Northern Italy, 723 (55.8%) from Central Italy, 160 (12.3%) from Southern Italy. The following variables were found to be significant predictors of the adoption of an unhealthy lifestyle since the beginning of the lockdown: poor sleep quality, high BMI and considering the measures adopted by the government to fight the pandemic as excessive. Living in Northern Italy, instead, was associated with healthier habits compared to living in Central Italy. CONCLUSIONS: Poor sleepers may represent the share of the general population who paid the highest price for social isolation. Further investigations are required to explore the role of sleep quality assessment in the identification of individuals vulnerable to unhealthy behaviours under stressful conditions.

Sleep quality mediates the effect of chronotype on resilience in the time of COVID-19.

This study aimed to explore the relationship between chronotype and resilience, sleep quality, and post-traumatic stress reactions during the first COVID-19 lockdown in Italy. An online survey was distributed through social networks during forced home confinement, collecting data from1298 participants of 19 different Italian regions. Chronotype was evaluated using the reduced version of the Morningness/Eveningness Questionnaire (rMEQ); sleep quality was assessed by the Pittsburgh Sleep Quality Index (PSQI); resilience levels were measured by the 10-item version of the Connor-Davidson Resilience Scale (CD-RISC10); post-traumatic stress reactions were assessed by the 6-item version of the Impact of Event Scale (IES6). Resilience and sleep quality were significantly lower in the evening compared to non-evening types, as well as in females as compared to males. Moreover, resilience was negatively correlated with post-traumatic stress reactions and positively correlated with sleep quality. A negative correlation was also reported between sleep quality and post-traumatic stress reactions. Sleep quality was identified as a possible mediator between chronotype and resilience, and between resilience and post-traumatic stress reactions, after controlling for age and sex. These findings provide new insights into the role of chronotype in adapting to continuous stressful situations. Sleep quality seems to mediate the causal path between the antecedents of resilience and the development of trauma. Further research is needed to explore the suitability of primary interventions based on chronobiology and sleep hygiene to mitigate the impact of pandemic-related home confinement measures on mental health among the general population.

SARS-CoV-2 infection serology validation of different methods: Usefulness of IgA in the early phase of infection

In the late December 2019, an outbreak of pneumonia of unknown origin was reported in Wuhan, Hubei province, China. A novel coronavirus was isolated from the respiratory samples of patients with pneumonia as showed by the sequence analysis of the virus genomes obtained;The novel coronavirus was named SARSCoV-2. Reverse-transcriptase real-time PCR (rRT-PCR) is the method of choice for detecting SARS-CoV-2 infection. Despite the high sensitive of the real-time PCR tests, sometimes samples from the upper respiratory tract may result negative even in the presence of radiological findings of pneumonia probably due to the viral load in the upper respiratory tract is low compared to the lower respiratory tract;low quality of the collected sample or technical reasons linked to the assay used. The use of serological assays may help in making diagnosis. The antibody response to SARS-CoV-2 is not well understood yet, but the availability of sensitive and specific serological assays will be crucial for the early diagnosis of infection, for epidemiological studies, for defining the presence of neutralizing antibodies in response to a possible vaccine. In this work, we tested and compared the performances of one chemiluminescent immunoassay, two ELISA assays and an ECLIA assay. Among the platforms assessed in this study, the ECLIA serological assay performed best, and may be a valid screening method for SARS-COV-2 infection. The IgA detected by the ELISA assay might be a more reliable and stable early serological marker than IgM. Instead, IgGs, as expected, showed stable level after 10 days from symptoms onset. Taken together, if a reflex test could be set in the laboratory, the ECLIA method could be used as screening test, considering both the excellent performance and the cost per single test;while ELISA assay for IgG and IgA, which are present at a higher level than IgM and last longer, might be used as confirmatory test.