The district operation centres in one of the largest local health authorities in Italy to manage COVID-19 surveillance and homecare. First implementation and results of a survey addressed to general practitioners

Background: COVID-19 pandemic represented a shock for healthcare systems. Italy was one of the first country to deal with a huge number of patients to be diagnosed, isolated, and treated with scarce evidence-based guidelines and resources. Several organizational and structural changes were needed to face the pandemic at local level. The article aims at studying the perceived impact of the newly implemented District Operation Centres (DOCs) of Local Health Authority (LHA) Roma 1 in managing active surveillance and home care of COVID-19 patients and their close contacts in cooperation with general practitioners (GPs). Methods: A questionnaire, developed according to Delphi methodology, was validated by 7 experts and administered to a randomized sample of GPs and family paediatricians (FPs). All medical doctors selected received a phone interview between December 2020 and January 2021. The questionnaire investigated general characteristics of the sample, relations with DOC and its usefulness, and potential developments. A descriptive analysis was performed and inferential statistical tests were used to assess differences. Results: In April 2020 the LHA Roma 1 implemented one DOCs in each local health district. 215 medical doctors were interviewed, reaching the sample target for health districts (80% CL and 10% MOE) and the whole LHA (90% CL and 5% MOE). Several aspects in the management of COVID-19 cases and close contacts of COVID-19 cases, and of the support of DOCs to GPs/FPs were investigated. More than 55% of the GPs and FPs interviewed found the DOCs useful and more than 78% would recommend a service DOC-like to other LHAs. The medical professionals interviewed would use DOCs in the future as support in treating vulnerable patients, utilizing digital health tools, enlisting specialist doctors, establishing networks, and facilitating professional counselling by nurses. Conclusions: This study is an attempt to evaluate an organizational change happened during COVID-19 pandemic. DOCs were created to support GPs and FPs as a link between primary healthcare and public health. Although several difficulties were disclosed, DOCs' experience can help to overcome the fragmentation of the systems and the duality between primary care and public health and make the system more resilient

The “Lazio advice” telemedicine platform. First results of general practitioners’ usage, facilitators and barriers in the local health authority Roma 1

Background: Telemedical approaches represent a valuable tool for the management of coronavirus disease 2019 patients, allowing daily clinical assessment, monitoring of vital parameters, remote visits, and prescription of treatment or hospital ization in case of clinical worsening. This cross-sectional study aims to evaluate the use, barriers and facilitators of the “Lazio ADVICE” telemedical platform, a regional system for remote assistance for coronavirus disease 2019 patients at home, according to General Practitioners and Family Pediatricians of the Local Health Authority Roma 1, during the coronavirus disease 2019 pandemic. Methods: An interview-based survey was performed between December 2020 and January 2021. The survey investigated the demographic information of General Practitioner and Family Pediatricians, the knowledge of the platform, frequency of util ization, usefulness, strengths and weaknesses, and hypothesis of future implementation proposed. Results: We interviewed 214 physicians and 89 (41.6%) were classified as users and 125 (58.4%) as non-users. Older age and working in District 1, 14 and 15 (vs. District 13) significantly reduced the probability of using the platform physician. Among the 89 users, 19 (21.3%) used the platform every day or even several times a day, 40 (44.9%) several times a week but less than one access per day, 30 (33.7%) used the platform several times a month up to one entry per week. Most of them (92.3%) consider the platform useful. Barriers were poor integration with software and work routine (76.4%), and usability issues (53.9%). Among the 125 non-users, 14 (11.2%) didn’t know the existence of the platform, 60 (48.0%) never tried it and 51 (40.8%) tried to use it. Reported reasons for the interruption of use were not very user friendly (45.1%), perceived useless (37.3%), non-optimal functioning (23.5%), and lack of time (19.6%). Conclusion: The pandemic accelerated the implementation of telemedicine services around Lazio Region, starting a positive and continuous exchange of experiences, activities and best practices among physicians

Outcomes of TB Treatment by HIV Status in National Recording Systems in Brazil, 2003–2008

BACKGROUND: Although the Brazilian national reporting system for tuberculosis cases (SINAN) has enormous potential to generate data for policy makers, formal assessments of treatment outcomes and other aspects of TB morbidity and mortality are not produced with enough depth and rigor. In particular, the effect of HIV status on these outcomes has not been fully explored, partly due to incomplete recording in the national database. METHODOLOGY/PRINCIPAL FINDINGS: In a retrospective cohort study, we assessed TB treatment outcomes, including rates of cure, default, mortality, transfer and multidrug resistant TB (MDR-TB) among a purposively chosen sample of 161,481 new cases reported in SINAN between 2003 and 2008. The study population included all new cases reported in the six States with the highest level of completeness of the HIV status field in the system. These cases were mostly male (67%), white (62%), had pulmonary TB (79%) and a suspect chest X ray (83%). Treatment outcomes were best for those HIV negative cases and worst for those known HIV positive patients (cure rate of 85.7% and 55.7% respectively). In multivariate modeling, the risk of having an unfavorable outcome (all outcomes except cure) was 3.09 times higher for those HIV positive compared with those HIV negative (95% CI 3.02-3.16). The risk of death and default also increased with HIV positivity. The group without a known HIV status showed intermediate outcomes between the groups above, suggesting that this group includes some with HIV infection. CONCLUSIONS: HIV status played an important role in TB treatment outcomes in the study period. The outcomes observed in those with known HIV were poor and need to be improved. Those in the group with unknown HIV status indicate the need for wider HIV testing among new TB cases

Colorectal Cancer Stage at Diagnosis Before vs During the COVID-19 Pandemic in Italy

IMPORTANCE Delays in screening programs and the reluctance of patients to seek medical attention because of the outbreak of SARS-CoV-2 could be associated with the risk of more advanced colorectal cancers at diagnosis. OBJECTIVE To evaluate whether the SARS-CoV-2 pandemic was associated with more advanced oncologic stage and change in clinical presentation for patients with colorectal cancer. DESIGN, SETTING, AND PARTICIPANTS This retrospective, multicenter cohort study included all 17 938 adult patients who underwent surgery for colorectal cancer from March 1, 2020, to December 31, 2021 (pandemic period), and from January 1, 2018, to February 29, 2020 (prepandemic period), in 81 participating centers in Italy, including tertiary centers and community hospitals. Follow-up was 30 days from surgery. EXPOSURES Any type of surgical procedure for colorectal cancer, including explorative surgery, palliative procedures, and atypical or segmental resections. MAIN OUTCOMES AND MEASURES The primary outcome was advanced stage of colorectal cancer at diagnosis. Secondary outcomes were distant metastasis, T4 stage, aggressive biology (defined as cancer with at least 1 of the following characteristics: signet ring cells, mucinous tumor, budding, lymphovascular invasion, perineural invasion, and lymphangitis), stenotic lesion, emergency surgery, and palliative surgery. The independent association between the pandemic period and the outcomes was assessed using multivariate random-effects logistic regression, with hospital as the cluster variable. RESULTS A total of 17 938 patients (10 007 men [55.8%]; mean [SD] age, 70.6 [12.2] years) underwent surgery for colorectal cancer: 7796 (43.5%) during the pandemic period and 10 142 (56.5%) during the prepandemic period. Logistic regression indicated that the pandemic period was significantly associated with an increased rate of advanced-stage colorectal cancer (odds ratio [OR], 1.07; 95%CI, 1.01-1.13; P = .03), aggressive biology (OR, 1.32; 95%CI, 1.15-1.53; P < .001), and stenotic lesions (OR, 1.15; 95%CI, 1.01-1.31; P = .03). CONCLUSIONS AND RELEVANCE This cohort study suggests a significant association between the SARS-CoV-2 pandemic and the risk of a more advanced oncologic stage at diagnosis among patients undergoing surgery for colorectal cancer and might indicate a potential reduction of survival for these patients

Ensuring Equitable Access to the COVID-19 Vaccine: The Experience of A Local Health Unit in Rome, Italy

Growing evidence is emerging on the higher risk of infection and adverse outcomes for the most disadvantaged groups of the population, and COVID-19 vaccination campaigns worldwide are struggling to ensure equitable access to immunization for all. From 21 June 2021 to 15 October 2021, the Local Health Unit ASL Roma 1 adopted a tailored immunization strategy to reach socially vulnerable groups of the population with the primary vaccination course. This strategy was developed with a step-by-step, participatory approach. Through engagement with internal and external stakeholders, target groups were identified, potential barriers analyzed, solutions discussed, and tailored interventions designed. Over nine thousand individuals from among irregular migrants, homeless people and hard-to-reach communities were contacted and vaccinated

COA – Centrale Operativa Aziendale dell’ASL Roma 1

No abstract availabl

The ubiquitin ligase TRIM32 promotes the autophagic response to Mycobacterium tuberculosis infection in macrophages

Abstract Mycobacterium tuberculosis (Mtb) is known to evade host immune responses and persist in macrophages for long periods. A mechanism that the host uses to combat Mtb is xenophagy, a selective form of autophagy that targets intracellular pathogens for degradation. Ubiquitination of Mtb or Mtb-containing compartments is a key event to recruit the autophagy machinery and mediate the bacterial delivery to the lysosome. This event relies on the coordinated and complementary activity of different ubiquitin ligases, including PARKIN, SMURF1, and TRIM16. Because each of these factors is responsible for the ubiquitination of a subset of the Mtb population, it is likely that additional ubiquitin ligases are employed by macrophages to trigger a full xenophagic response during Mtb infection. In this study, we investigated the role TRIM proteins whose expression is modulated in response to Mtb or BCG infection of primary macrophages. These TRIMs were ectopically expressed in THP1 macrophage cell line to assess their impact on Mtb replication. This screening identified TRIM32 as a novel player involved in the intracellular response to Mtb infection, which promotes autophagy-mediated Mtb degradation. The role of TRIM32 in xenophagy was further confirmed by silencing TRIM32 expression in THP1 cells, which causes increased intracellular growth of Mtb associated to impaired Mtb ubiquitination, reduced recruitment of the autophagy proteins NDP52/CALCOCO2 and BECLIN 1/BECN1 to Mtb and autophagosome formation. Overall, these findings suggest that TRIM32 plays an important role in the host response to Mtb infection through the induction of autophagy, representing a promising target for host-directed tuberculosis therapies

Cysteamine with In Vitro Antiviral Activity and Immunomodulatory Effects Has the Potential to Be a Repurposing Drug Candidate for COVID-19 Therapy

The ongoing pandemic of coronavirus disease-2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), needs better treatment options both at antiviral and anti-inflammatory levels. It has been demonstrated that the aminothiol cysteamine, an already human applied drug, and its disulfide product of oxidation, cystamine, have anti-infective properties targeting viruses, bacteria, and parasites. To determine whether these compounds exert antiviral effects against SARS-CoV-2, we used different in vitro viral infected cell-based assays. Moreover, since cysteamine has also immune-modulatory activity, we investigated its ability to modulate SARS-CoV-2-specific immune response in vitro in blood samples from COVID-19 patients. We found that cysteamine and cystamine decreased SARS-CoV-2-induced cytopathic effects (CPE) in Vero E6 cells. Interestingly, the antiviral action was independent of the treatment time respect to SARS-CoV-2 infection. Moreover, cysteamine and cystamine significantly decreased viral production in Vero E6 and Calu-3 cells. Finally, cysteamine and cystamine have an anti-inflammatory effect, as they significantly decrease the SARS-CoV-2 specific IFN-γ production in vitro in blood samples from COVID-19 patients. Overall, our findings suggest that cysteamine and cystamine exert direct antiviral actions against SARS-CoV-2 and have in vitro immunomodulatory effects, thus providing a rational to test these compounds as a novel therapy for COVID-19

Cysteamine/Cystamine Exert Anti-<i>Mycobacterium abscessus</i> Activity Alone or in Combination with Amikacin

Host-directed therapies are emerging as a promising tool in the curing of difficult-to-treat infections, such as those caused by drug-resistant bacteria. In this study, we aim to test the potential activity of the FDA- and EMA-approved drugs cysteamine and cystamine against Mycobacterium abscessus. In human macrophages (differentiated THP-1 cells), these drugs restricted M. abscessus growth similar to that achieved by amikacin. Here, we use the human ex vivo granuloma-like structures (GLS) model of infection with the M. abscessus rough (MAB-R) and smooth (MAB-S) variants to study the activity of new therapies against M. abscessus. We demonstrate that cysteamine and cystamine show a decrease in the number of total GLSs per well in the MAB-S and MAB-R infected human peripheral blood mononuclear cells (PBMCs). Furthermore, combined administration of cysteamine or cystamine with amikacin resulted in enhanced activity against the two M. abscessus morpho variants compared to treatment with amikacin only. Treatment with cysteamine and cystamine was more effective in reducing GLS size and bacterial load during MAB-S infection compared with MAB-R infection. Moreover, treatment with these two drugs drastically quenched the exuberant proinflammatory response triggered by the MAB-R variant. These findings showing the activity of cysteamine and cystamine against the R and S M. abscessus morphotypes support the use of these drugs as novel host-directed therapies against M. abscessus infections