Over-the-scope clip as first-line treatment of peptic ulcer bleeding: a multicenter randomized controlled trial (TOP Study).

BACKGROUND: First-line over-the-scope (OTS) clip treatment has shown higher efficacy than standard endoscopic therapy in acute nonvariceal upper gastrointestinal bleeding (NVUGIB) from different causes. We compared OTS clips with through-the-scope (TTS) clips as first-line mechanical treatment in the specific setting of peptic ulcer bleeding. METHODS: We conducted an international, multicenter randomized controlled trial on consecutive patients with suspected NVUGIB. Patients with Forrest Ia-IIb gastroduodenal peptic ulcer were randomized 1:1 to OTS clip or TTS clip treatment. The primary outcome was the rate of 30-day rebleeding after successful initial hemostasis. Secondary outcomes included the rates of successful initial hemostasis and overall clinical success, defined as the composite of successful initial hemostasis and no evidence of 30-day rebleeding. RESULTS: 251 patients were screened and 112 patients were randomized to OTS (n = 61) or TTS (n = 51) clip treatment. The 30-day rebleeding rates were 1.6% (1/61) and 3.9% (2/51) in patients treated with OTS clips and TTS clips, respectively (Kaplan-Meier log-rank, P = 0.46). Successful initial hemostasis rates were 98.4% (60/61) in the OTS clip group and 78.4% (40/51) in the TTS clip group (P = 0.001). Overall clinical success rates were 96.7% (59/61) with OTS clips and 74.5% (38/51) with TTS clips (P = 0.001). CONCLUSIONS: Low rates of 30-day rebleeding were observed after first-line endoscopic treatment of acute peptic ulcer bleeding with either OTS or TTS clips. However, OTS clips showed higher efficacy than TTS clips in achieving successful initial hemostasis and overall clinical success.

Occurrence of complications in patients restored with implants.

OBJECTIVES: To determine the occurrence and clustering of complications in subjects restored with fixed implant-supported prostheses. METHODS: In the present retrospective case series, 241 subjects treated at one clinical centre and provided with 729 implants were included. A clinical and radiographic examination was performed after a mean follow-up period of 4.8 ± 2.0 years. Additional information on occurrence of technical (chipping, loss of retention, fracture of components) and biological complications (marginal bone loss, implant loss) during follow-up was extracted from patient records. For each type of complication and complications overall, regression analyses were performed to identify potential risk factors. Cox regression analyses were used to evaluate time to event for implant loss and technical complications. RESULTS: In all, 30% of the 241 patients presented with at least one complication of technical and/or biological character during the follow-up period. Technical complications affected 19.5% of subjects, while 14.1% presented with marginal bone loss >2 mm. Implant loss occurred in 4.6% of subjects. While technical complications were noted already early during the maintenance period (<1200 days), implant loss typically occurred during a later phase. A small subgroup of subjects (7.9%) experienced more than one type of complication. CONCLUSIONS: Complications occurred frequently and the most common type of complication was of technical character. Technical and biological complications occurred independently of each other.

Bone loss at implants and teeth in the same inter-proximal unit: A radiographic study.

OBJECTIVE: This study was performed to determine whether the distance between an implant and a tooth present in an inter-proximal unit influenced the amount of marginal bone loss that occurred at the two facing (adjacent) surfaces. MATERIALS AND METHODS: One hundred and eighty patients with a total of 278 inter-proximal units were included. Radiographs of implants that also included adjacent (facing) natural tooth/teeth were digitalized, and various linear measurements were performed using a software program. The marginal bone level and the bone level change that had occurred during a mean of 5.8 years were assessed as well as distance between the implant and the adjacent tooth/teeth. RESULTS: The mean amount of additional marginal bone loss that took place during the observation period was about 0.4 mm at both implants and adjacent tooth surfaces. The horizontal distance between an implant and the facing tooth did not influence the amount of marginal bone loss that had occurred. In most inter-proximal units, more advanced bone loss (>1 mm, >2 mm) had ensued either at the implant or at the facing tooth surface. Advanced additional bone loss occurred at both the implant and the tooth in only about 3% of the examined subjects. CONCLUSION: Bone loss at implants and teeth appears to be a site-specific phenomenon and not dependent on the inter-proximal distance.

Diagnosis and treatment of rheumatoid arthritis in the Emilia Romagna region: a prospective population-based study.

OBJECTIVES: To perform a population-based study in rheumatoid arthritis (RA) patients, in order to evaluate the efficacy and safety of pharmacologic treatments. METHODS: 1087 patients with RA were enrolled; inclusion criteria were: newly diagnosed RA, already diagnosed RA with high disease activity (HDA) (DAS28≥4.2) starting biologic DMARDs (bDMARDs), already diagnosed RA with HDA continuing with conventional DMARDs (cDMARDs). The following data were collected: demographics, clinical and laboratory features, imaging and prescribed drugs. All parameters except immunology and imaging (performed yearly) were repeated at each follow-up evaluations (after 3, 6 and 12 months, and thereafter every 12 months). In order to evaluate clinical response, the EULAR response criteria were used as the gold standard. RESULTS: 414 (38.1%) newly diagnosed patients with RA, 477 (43.9%) RA patients who started bDMARDs and 196 (18.0%) RA patients who continued with cDMARDs were enrolled from April 2012 to March 2015 at 12 Rheumatology Centres in the Emilia Romagna Region. Statistical analyses showed a relative risk ratio (RRR) for moderate response of 1.65 in RA patients who started bDMARDs (p=0.16) and 2.49 for newly diagnosed RA (p=0.01). Sex, age and Health Assessment Questionnaire were not statistically significant. A RRR of 2.00 has been confirmed for RA patients who started bDMARDs (p<0.0005) for a good response as well as 2.20 for newly diagnosed RA (p<0.0005). An increase in adverse events among bDMARDs was found, but when looking at infections or neoplasia, no differences were highlighted between RA which started bDMARDs and RA who continued with cDMARDs. CONCLUSIONS: Our results are in line with already published papers from British and Swedish Registries: a greater likelihood to have a good response is demonstrated for not longstanding RA starting cDMARDs or RA with HDA when a bDMARD is started. Also a good safety profile is demonstrated.

Comparison of 4 different strategies of DAPT after PCI in ACS real world population from a Northern Italy registry.

Aim of the study was to compare four different strategies of dual antiplatelet therapy (DAPT) in patients with acute coronary syndromes (ACS) treated with PCI. DAPT with Clopidogrel, Ticagrelor and Prasugrel has proved to be effective in patients with ACS treated with percutaneous coronary intervention (PCI) by reducing major adverse cardiovascular outcomes (MACE). However, the effect of the different strategies in a real-world population deserves further verification. A retrospective analysis of 2404 discharged ACS patients treated with PCI was performed, with a median follow-up of 1 year. The study population was stratified in four drug treatment cohorts: ASA + Clopidogrel (A-C), ASA + Plavix (A-PLx), ASA + Ticagrelor (A-T), ASA + Prasugrel (A-P). We assessed the incidence of net adverse cardiovascular events (NACE): all-cause death, myocardial infarction (MI), target vessel revascularization (TVR), stroke and bleeding during follow-up. At 1-year, the use of A-C and A-PLx was associated with the highest cumulative incidence of NACE in comparison with A-T and A-P therapies (respectively 14.8 and 29.6% vs. 9.2 and 6%). This difference was mainly driven by the mortality and TVR outcomes. Considering selection bias and differences in the patients baseline characteristics, the association of A-T and A-P seems to be superior in comparison with a DAPT strategy of A-C and A-PLx in low risk ACS-PCI patients from real world. In our Region the prescription is consistent with guidelines recommendations and Clopidogrel and Plavix are still predominantly used in older patients with more comorbidities, and this could partially explain the inferiority of this association.

Bone loss at implants and teeth in the same segment of the dentition in partially dentate subjects.

BACKGROUND: Some studies have indicated that marginal bone loss at implants and at teeth are similar, while results from other studies showed that implants lost more bone than teeth in the same dentition. AIM: To determine the amount of progressive marginal bone loss that had occurred at implants and teeth in the same segment of the dentition following implant placement in partially dentate subjects. MATERIAL AND METHODS: A total of 217 patients with a total of 573 implants and 318 teeth present in the same segments of the dentition were included. Radiographs were available from 1 year (baseline) and ≥3 years after loading. RESULTS: The mean bone loss that occurred between the two examinations was at implants 0.42 ± 0.68 mm and at teeth 0.44 ± 0.52 mm. Thirty-eight subjects (18%) had ≥1 implant exhibiting >1 mm bone loss. Bone loss at the 148 implants in this category of patients was 1.30 ± 1.04 mm with a corresponding loss at the 69 teeth of 0.53 ± 0.62 mm. Eighteen subjects (8%) had ≥1 tooth that exhibited >1 mm bone loss. The mean amount of bone loss in this sample was 1.37 ± 0.87 mm (38 teeth) and 0.29 ± 0.31 mm (56 implants). CONCLUSIONS: This study showed that marginal bone loss at implants and teeth in many partially dentate subjects might be independent phenomena.

A population based study on the night-time effect in trauma care.

BACKGROUND: The so-called off hour effect-that is, increased mortality for patients admitted outside normal working hours-has never been demonstrated in trauma care. However, most of the studies excluded transferred cases. Because these patients are a special challenge for trauma systems, we hypothesised that their processes of care could be more sensitive to the off hour effect. METHODS: The study design was retrospective, cohort and population based. We compared the mortality of all patients by daytime and night-time admittance to hospitals in an Italian region, with 4.5 million inhabitants, following a major injury in 2011. Logistic regression was used, adjusted for demographics and severity of injury (TMPM-ICD9), and stratified by transfer status. RESULTS: 1940 major trauma cases were included; 105 were acutely transferred. Night-time admission had a significant pejorative effect on mortality in the adjusted analysis (OR=1.49; 95% CI 1.05 to 2.11). This effect was most evident in transferred cases (OR=3.71; 95% CI 1.11 to 12.43). CONCLUSIONS: The night-time effect in trauma care was demonstrated for the first time and was maximal in transferred cases. This may explain why it was not found in previous studies where these patients were mostly excluded. Also, the use of population based data-whereby patients not accessing trauma centre care and presumably receiving poorer care were included-may have contributed to the findings.

Recent temporal trends for first-time hospitalization for acute myocardial infarction. Treatment patterns and clinical outcome in a large cohort study.

BACKGROUND: The objective was to report recent trends in the incidence, adoption of evidence-based treatment, and clinical outcomes for first-time hospitalization for acute myocardial infarction. METHODS: This is a large retrospective population-based cohort study using medical administrative data (International Classification of Diseases, Ninth Revision, Clinical Modification, codes) performed in the Emilia-Romagna Region of Italy (approximately 4.5 million inhabitants). We identified 60,673 patients with a first hospitalization for acute myocardial infarction from 2002 through 2009. RESULTS: The standardized incidence rate per 100,000 person-years of acute myocardial infarction increased from 173 cases in 2002 to a peak of 197 cases in 2004 and then decreased each year thereafter to 167 cases in 2009. The proportion of patients who underwent coronary angiography and angioplasty in the acute phase increased over time, respectively, from 45.4% and 27.1% to 72.3% and 57.2% (P < .001). Medication use within 12 months of discharge increased for aspirin, ß-blockers, and statins. A reduction in crude and adjusted in-hospital all-cause (16.1% in 2002 vs 12.8% in 2009, P < .001) and cardiovascular mortality (13.6% in 2002 vs 9.5% in 2009, P < .001) was observed over time. At 1 year after hospital discharge, no significant variations occurred in adjusted risk for all-cause mortality or cardiovascular mortality. Notably, crude and adjusted risk for in-hospital and postdischarge bleeding showed a significant increment. CONCLUSIONS: The utilization of evidence-based treatments in patients with myocardial infarction increased between 2002 and 2009. These changes in practice over time favored a reduction in early case fatality at the cost of a significant increase in bleeding.

Patterns of utilisation of specialist care after SARS-Cov-2 infection: a retrospective cohort study.

OBJECTIVE: To explore the pattern of health services utilisation of people who had had a documented SARS-Cov-2 infection. DESIGN: Retrospective cohort study. SETTING: The Italian province of Reggio Emilia. PARTICIPANTS: 36 036 subjects who recovered from SARS-CoV-2 infection during the period September 2020-May 2021. These were matched for age, sex and Charlson Index with an equal number of subjects never found positive at the SARS-Cov-2 swab test over the study period. MAIN OUTCOME MEASURES: Hospital admissions for all medical conditions and for respiratory or cardiovascular conditions only; access to emergency room (for any cause); outpatient specialist visits (pneumology, cardiology, neurology, endocrinology, gastroenterology, rheumatology, dermatology, mental health) and overall cost of care. RESULTS: Within a median follow-up time of 152 days (range 1-180), previous exposure to SARS-Cov-2 infection was always associated with higher probability of needing access to hospital or ambulatory care, except for dermatology, mental health and gastroenterology specialist visits. Post-COVID subjects with Charlson Index≥1 were hospitalised more frequently for heart disease and for non-surgical reasons than subjects with Charlson index=0, whereas the opposite occurred for hospitalisations for respiratory diseases and pneumology visits. A previous SARS-CoV-2 infection was associated with 27% higher cost of care compared with people never infected. The difference in cost was more evident among those with Charlson Index>1. Subjects who had anti-SARS-CoV-2 vaccination had lower probability of falling in the highest cost quartile. CONCLUSIONS: Our findings reflect the burden of post-COVID sequelae, providing some specific insight on their impact on the extra-use of health services according to patients' characteristics and vaccination status. Vaccination is associated with lower cost of care following SARS-CoV-2 infection, highlighting the favourable impact of vaccines on the use of health services even when they do not prevent infection.

Analysis on a database of ship accidents in port areas.

In the last 15 years, the number of vessels in the world fleet has grown by around 53% and their gross tonnage has increased by 47%, with a consequent significant increment of marine accidents worldwide. Accident database are the basic resource for risk assessment methods to help decision-makers to enact strategies and undergo hazard and vulnerability mitigation measures. Understanding ship accidents distribution in terms of involved GT, typical age of the affected vessels, category of the ships, as well as distribution of underlying causes and consequences is the first necessary step to improve accident mitigation actions to be implemented for future assessments. In the present work, the results of an analysis on a database of vessel accidents in Mediterranean and worldwide port areas developed within the framework of the project ISY PORT (Integrated SYstem for navigation risk mitigation in PORTs) is herein presented. The distribution of accidents was analyzed in terms of relevant vessel characteristics i.e. Grosse Tonnage (GT), age at the time of the accident, ship's category, causality event, weather conditions and number of fatalities/injuries/lost at sea. The database can be used as a basis for maritime risk assessment methods and for calibration of real-time ship collision avoidance scenarios.

End-of-life care in cancer patients: how much drug therapy and how much palliative care? Record linkage study in Northern Italy.

OBJECTIVES: Investigating end-of-life use of anticancer drugs and of palliative care services. DESIGN: Population based cohort linked to mortality registry and administrative databases. SETTING: Emilia-Romagna Region (Northern Italy). PARTICIPANTS: 55 625 residents who died of cancer between 2017 and 2020. PRIMARY AND SECONDARY OUTCOME MEASURES: Multivariate analyses were carried out to assess the relationship between cancer drug therapy and palliative care services, and their association with factors related to tumour severity. RESULTS: In the last month of life, 15.3% of study population received anticancer drugs (from 12.5% to 16.9% across the eight Local Health Authorities-LHA) and 40.2% received palliative care services (from 36.2% to 43.7%). Drug therapy was inversely associated with receiving palliative care services within the last 30 days (OR 0.92, 95% CI 0.87 to 0.97), surgery within the last 6 months (OR 0.59, 95% CI 0.52 to 0.67), aggressive tumours (OR 0.88, 95% CI 0.84 to 0.93) and increasing age (OR 0.95, 95% CI 0.95 to 0.95). Drug therapy was more likely among those with haematologic tumours (OR 2.15, 95% CI 2.00 to 2.30) and in case of hospital admissions within the last 6 months (OR 1.63, 95% CI 1.55 to 1.72). Palliative care was less likely among those with haematologic compared with other tumours (OR 0.52, 95% CI 0.49 to 0.56), in case of surgery (OR 0.44, 95% CI 0.39 to 0.49) or hospital admissions (OR 0.70, 95% CI 0.67 to 0.72) within the last 6 months, if receiving anticancer drugs during the last 30 days (OR 0.90, 95% CI 0.85 to 0.94) and for each year of increasing age (OR 0.99, 95% CI 0.99 to 0.99). Palliative care was more likely in the presence of aggressive tumours (OR 1.12, 95% CI 1.08 to 1.16). CONCLUSION: Use of anticancer drugs and palliative care in the last month of life were inversely associated, showing variability across different LHAs. While administrative data have limits, our findings are in line with conclusions of other studies.

Prompt Resumption of Screening Programme Reduced the Impact of COVID-19 on New Breast Cancer Diagnoses in Northern Italy.

The aim of this study is to evaluate the real impact of COVID-19 during the entire 2020 period, compared with 2019. The data comes from a Cancer Registry in Northern Italy and we compared clinical and treatment characteristics of breast cancer by age, stage, treatment, and status screening. In 2020 there was no decrease in invasive tumours nor in in situ (513 vs. 493 and 76 vs. 73, respectively), while there was a significant decrease in surgery and increase in neoadjuvant chemotherapy (p = 0.016). In the screening range (aged 45-74), no change in stage and grading was observed. In the four periods examined there was an increase in new diagnoses during pre-lockdown, a decrease in tumours especially at age 75+ [IRR 0.45; 95%CI 0.25-0.79] during lockdown, a recovery of new diagnoses in women 45+ in the low incidence period while in the last period there was a significant increase only for ages 45-74 [IRR 1.48; 95% CI 1.11-1.98]. Screening activities were suspended from March to May, but over the summer and autumn the backlog was addressed. This suggests that a prompt resumption of programmed screening may have limited the impact of the pandemic on the delay of breast cancer diagnoses.

Beta-blocker initiation and adherence after hospitalization for acute myocardial infarction.

AIMS: We sought to: (1) estimate the proportion of patients who initiated beta-blocker therapy after acute myocardial infarction (AMI) in Regione Emilia-Romagna (RER); (2) examine predictors of post-AMI beta-blocker initiation; and (3) assess adherence to such therapy. METHODS AND RESULTS: Using healthcare claims data covering all of RER, we identified a cohort of 24,367 patients with a hospitalization for AMI between 2004 and 2007, who were discharged from the hospital alive and without contraindications to beta-blocker therapy. We estimated the proportion of eligible patients with at least one prescription for a beta-blocker following discharge and performed a multivariable logistic regression analysis to identify independent predictors of post-AMI beta-blocker initiation. We computed the proportion of days covered (PCD) as a measure of medication adherence at 6 and 12 months post-discharge. Following discharge, 16,383 (67%) cohort members initiated beta-blocker therapy. Independent predictors of beta-blocker initiation included age and receipt of invasive procedures during hospitalization, such as coronary artery bypass graft surgery (odds ratio [OR], 2.37; 95% confidence interval [CI], 2.00-2.81), percutaneous transluminal coronary angioplasty (OR, 1.42; 95% CI, 1.31-1.54), and cardiac catheterization (OR, 1.21; 95% CI, 1.11-1.32). Among initiators, adherence to beta-blocker treatment at 6 and 12 months was low and decreased in each study year. CONCLUSION: Overall, use of and adherence to post-AMI beta-blocker therapy was suboptimal in RER between 2004 and 2007. Older patients and those with indicators of frailty were less likely to initiate therapy. The proportion of patients adherent at 6 and 12 months decreased over time.

The effects of centralizing cancer surgery on postoperative mortality: A systematic review and meta-analysis.

OBJECTIVES: To review the evidence of the effects of centralization of cancer surgery on postoperative mortality. METHODS: We searched Medline, Embase, Cinahl, Cochrane and Scopus (up to November 2019) for studies that (i) assessed the effects of centralization of cancer surgery policies on in-hospital or 30-day mortality, or (ii) described changes in both postoperative mortality for a surgical intervention and degree of centralization using reduction in the number of hospitals or increases in the proportion of patients undergoing cancer surgery at high volume hospitals as proxy. PRISMA guidelines were followed. We estimated pooled odds ratios (OR) and conducted meta-regression to assess the relationship between degree of centralization and mortality. RESULTS: A total of 41 studies met our inclusion criteria of which 15 evaluated the effect of centralization policies on postoperative mortality after cancer surgery and 26 described concurrent changes in the degree of centralization and postoperative mortality. Policy evaluation studies mainly used before-after designs (n = 13) or interrupted time series analysis (n = 2), mainly focusing on pancreatic, oesophageal and gastric cancer. All but one showed some degree of reduction in postoperative mortality, with statistically significant effects demonstrated by six studies. The pooled odds ratio for centralization policy effect was 0.68 (95% Confidence interval: 0.54-0.85; I2 = 80%). Meta-regression analysis of the 26 descriptive studies found that an increase of the proportion of patients treated at high volume hospitals was associated with greater reduction in postoperative mortality. CONCLUSIONS: Centralization of cancer surgery is associated with reduced postoperative mortality. However, existing evidence tends to be of low quality and estimates of the effect size are likely inflated. There is a need for prospective studies using more robust approaches, and for centralization efforts to be accompanied by well-designed evaluations of their effectiveness.

Implantable electrical devices for prevention of sudden cardiac death: data on implant rates from a 'real world' regional registry.

AIMS: International and national consensus guidelines define appropriate indications for implantable cardioverter-defibrillators (ICDs), but the variability in implant rates in 'real world' clinical practice is still unknown. METHODS AND RESULTS: In Emilia-Romagna, an Italian region with around 4.3 million inhabitants, a web-based registry was instituted to collect data for all ICDs implanted. Between January 2006 and December 2008, data from all consecutive patients resident in this region who underwent first implant of an ICD or a biventricular ICD were collected and standardized, considering each regional area (i.e. each of the nine provinces). The overall number of implanted ICDs had an increase in years 2007 and 2008, with a relative increase in comparison to 2006, by 14 and 48% respectively, reaching an average value of 16.2 per 10,000 inhabitants in 2008. Most of the increase was due to a rise in ICDs for primary prevention. The ratio between the implant rates of the provinces with the highest and the lowest implant rates, respectively, was around 2 in 2008. CONCLUSION: Implant rates for ICDs, considering both primary and secondary prevention of sudden death, show up to two-fold variations even in a geographical region where the general level of health care is advanced and well appreciated by the population. The lack of a common strategy for sudden death prevention, approved by both physicians and institutional regional authorities, together with some degree of variability in translating guidelines into clinical practice, were identified as the main factors explaining the heterogeneity in ICD implant rates.

Characteristics and outcomes of a cohort of COVID-19 patients in the Province of Reggio Emilia, Italy.

This is a population-based prospective cohort study on archive data describing the age- and sex-specific prevalence of COVID-19 and its prognostic factors. All 2653 symptomatic patients tested positive for SARS-CoV-2 from February 27 to April 2, 2020 in the Reggio Emilia province, Italy, were included. COVID-19 cumulative incidence, hospitalization and death rates, and adjusted hazard ratios (HR) with 95% confidence interval (95% CI) were calculated according to sociodemographic and clinical characteristics. Females had higher prevalence of infection than males below age 50 (2.61 vs. 1.84 ‰), but lower in older ages (16.49 vs. 20.86 ‰ over age 80). Case fatality rate reached 20.7% in cases with more than 4 weeks follow up. After adjusting for age and comorbidities, men had a higher risk of hospitalization (HR 1.4 95% CI 1.2 to 1.6) and of death (HR 1.6, 95% CI 1.2 to 2.1). Patients over age 80 compared to age < 50 had HR 7.1 (95% CI 5.4 to 9.3) and HR 27.8 (95% CI 12.5 to 61.7) for hospitalization and death, respectively. Immigrants had a higher risk of hospitalization (HR 1.3, 95% CI 0.99 to 1.81) than Italians and a similar risk of death. Risk of hospitalization and of death were higher in patients with heart failure, arrhythmia, dementia, coronary heart disease, diabetes, and hypertension, while COPD increased the risk of hospitalization (HR 1.9, 95% CI 1.4 to 2.5) but not of death (HR 1.1, 95% CI 0.7 to 1.7). Previous use of ACE inhibitors had no effect on risk of death (HR 0.97, 95% CI 0.69 to 1.34). Identified susceptible populations and fragile patients should be considered when setting priorities in public health planning and clinical decision making.

Association between Exposure to Influenza Vaccination and COVID-19 Diagnosis and Outcomes.

We explored whether influenza vaccination (IV) affects susceptibility to SARS-CoV-2 infection and clinical outcomes in COVID-19 patients in 17,608 residents of the Italian province of Reggio Emilia undergoing a SARS-CoV-2 test. Exposure to IV was ascertained and the strength of the association with SARS-CoV-2 positivity expressed with odds ratios (OR). Rates of hospitalisations and death in those found positive were assessed and hazard ratios (HR) were estimated. The prevalence of IV was 34.3% in the 4885 SARS-CoV-2 positive and 29.5% in the 12,723 negative subjects, but the adjusted OR indicated that vaccinated individuals had a lower probability of testing positive (OR = 0.89; 95% CI 0.80-0.99). Among the 4885 positive individuals, 1676 had received IV. After adjusting for confounding factors, there was no association between IV and hospitalisation (1.00; 95% CI 0.84-1.29) or death (HR = 1.14; 95% CI 0.95-1.37). However, for patients age ≥65 vaccinated close to the SARS-CoV-2 outbreak, HRs were 0.66 (95% CI: 0.44-0.98) and 0.70 (95% CI 0.50-1.00), for hospitalisation and death, respectively. In this study, IV was associated with a lower probability of COVID-19 diagnosis. In COVID-19 patients, overall, IV did not affect outcomes, although a protective effect was observed for the elderly receiving IV almost in parallel with the SARS-CoV-2 outbreak. These findings provide reassurance in planning IV campaigns and underscore the need for exploring further their impact on COVID-19.

Renin-Angiotensin-Aldosterone System Inhibitors and Risk of Death in Patients Hospitalised with COVID-19: A Retrospective Italian Cohort Study of 43,000 Patients.

INTRODUCTION: The epidemic due to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has been spreading globally, raising increasing concerns. There are several controversial hypotheses on the potentially harmful or beneficial effects of antihypertensive drugs acting on the renin-angiotensin-aldosterone system (RAAS) in coronavirus disease 2019 (COVID-19). Furthermore, there is accumulating evidence, based on several observational studies, that angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) do not increase the risk of contracting SARS-CoV-2 infection. On the other hand, conflicting findings regarding the role of ACEIs/ARBs as prognosis modifiers in COVID-19 hospitalised patients have been reported. OBJECTIVE: The aim of this large-scale, retrospective cohort study was to investigate whether prior exposure to ACEIs and/or ARBs was associated with all-cause mortality among over 40,000 hospitalised COVID-19 patients compared with calcium channel blockers (CCBs), a potential therapeutic alternative. METHODS: This study was conducted using COVID-19 registries linked to claims databases from Lombardy, Veneto and Reggio Emilia (overall, 25% of Italian population). Overall, 42,926 patients hospitalised between 21 February and 21 April 2020 with a diagnosis of COVID-19 confirmed by real-time polymerase chain reaction tests were included in this study. All-cause mortality occurring in or out of hospital, as reported in the COVID-19 registry, was estimated. Using Cox models, adjusted hazard ratios (HRs) of all-cause mortality (along with 95% confidence intervals [CIs]) were estimated separately for ACEIs/ARBs and other antihypertensives versus CCBs and non-use. RESULTS: Overall, 11,205 in- and out-of-hospital deaths occurred over a median of 24 days of follow-up after hospital admission due to COVID-19. Compared with CCBs, adjusted analyses showed no difference in the risk of death among ACEI (HR 0.97, 95% CI 0.89-1.06) or ARB (HR 0.98, 95% CI 0.89-1.06) users. When non-use of antihypertensives was considered as a comparator, a modest statistically significant increase in mortality risk was observed for any antihypertensive use. However, when restricting to drugs with antihypertensive indications only, these marginal increases disappeared. Sensitivity and subgroup analyses confirmed our main findings. CONCLUSIONS: ACEI/ARB use is not associated with either an increased or decreased risk of all-cause mortality, compared with CCB use, in the largest cohort of hospitalised COVID-19 patients exposed to these drugs studied to date. The use of these drugs therefore does not affect the prognosis of COVID-19. This finding strengthens recommendations of international regulatory agencies about not withdrawing/switching ACEI/ARB treatments to modify COVID-19 prognosis.

Survival of Hospitalized COVID-19 Patients in Northern Italy: A Population-Based Cohort Study by the ITA-COVID-19 Network.

INTRODUCTION: COVID-19 case fatality rate in hospitalized patients varies across countries and studies. Reliable estimates, specific for age, sex, and comorbidities, are needed to monitor the epidemic, to compare the outcome in different settings, and to correctly design trials for COVID-19 interventions. The aim of this study was to provide population-based survival curves of hospitalized COVID-19 patients. MATERIALS AND METHODS: A cohort study was conducted in three areas of Northern Italy, heavily affected by SARS-CoV-2 infection (Lombardy and Veneto Regions, and Reggio Emilia province), using a loco-regional COVID-19 surveillance system, linked to hospital discharge databases. We included all patients testing positive for SARS-CoV-2 RNA by RT-PCR on nasopharyngeal/throat swab samples who were hospitalized from 21 February to 21 April 2020. Kaplan-Meier survival estimates were calculated at 14 and 30 days for death in any setting, stratifying by age, sex, and the Charlson Index. RESULTS: Overall, 42,926 hospitalized COVID-19 patients were identified. Patients' median age was 69 years (IQR: 57-79), 62.6% were males, and 6.0% had a Charlson Index ≥3. Survival curves showed that 22.0% (95% CI 21.6-22.4) of patients died within 14 days and 27.6% (95% CI 27.2-28.1) within 30 days from hospitalization. Survival was higher in younger patients and in females. The negative impact of comorbidities on survival was more pronounced in younger age groups. CONCLUSION: The high fatality rate observed in the study (28% at 30 days) suggests that studies should focus on death as primary endpoint during a follow-up of at least one month.