Effectiveness and Safety of Remdesivir in Treating Hospitalised Patients with COVID-19: A Propensity Score Analysis of Real-Life Data from a Monocentric Observational Study in Times of Health Emergency.

BACKGROUND AND OBJECTIVES: Remdesivir is an antiviral agent, which was shown to be safe and effective in treating early COVID-19, but its favourable impact in hospitalised patients with non-critical disease is still under investigation. The present study aimed to assess the effectiveness and safety of remdesivir as a treatment for hospitalised patients with COVID-19 by a propensity score analysis of observational data. METHODS: In this monocentric retrospective cohort study, the effectiveness and safety of a 5-day course of remdesivir (200 mg intravenously at Day 1, then 100 mg from Days 2-5) in association with the standard of care were assessed in comparison with the standard of care only. The primary endpoint was the proportion of recovery on Day 14. RESULTS: Of 3662 eligible inpatients who tested positive for the severe acute respiratory syndrome coronavirus 2 genome by nasopharyngeal swab at admission, 861 (24%) non-critical patients were included in a propensity score analysis and 281 (33%) were exposed to remdesivir. In total, 242/281 (86.1%) and 435/580 (75.0%) patients recovered in exposed and non-exposed, respectively, with a relative improvement of 11.1% (95% CI + 5.8 to 16.5%; unadjusted odds ratio: 2.07, 95% CI 1.40-3.05, p = 0.0001; after adjustment by propensity score weighting, odds ratio: 1.92, 95% CI 1.30-2.83, p = 0.001). In treated patients, 1 (0.03%) anaphylactic reaction and 1 (0.03%) acute reaction during drug injection were reported, and 24 (8.5%) patients stopped the treatment due to adverse reactions. No significant differences were found with respect to the secondary efficacy endpoints (in-hospital all-cause death, need for intensive care treatments, clinical improvement score at Day 28) and safety endpoints (any and serious adverse reactions). CONCLUSION: A 5-day course of remdesivir in association with the standard of care effectively promoted recovery from COVID-19 among non-critical in-hospital patients and had an acceptable safety profile.

Antibody Response to COVID-19 Booster Vaccination in Healthcare Workers.

Objective: To evaluate the mean increase of anti-S IgG antibody titer between the basal, pre-booster level to the titer assessed 14 days after the booster dose of BNT162b2. Patients and Methods: The RENAISSANCE study is an observational, longitudinal, prospective, population-based study, conducted on healthcare workers of Niguarda Hospital in Milan, Italy who received a BNT162b2 booster dose at least 180 days after their second dose or after positivity for SARS-CoV-2 and accepted to take part in the study. The RENAISSANCE study was conducted from January 1, 2021 through December 28, 2021. Findings: 1,738 subjects were enrolled among healthcare workers registered for the booster administration at our hospital. Overall, 0.4% of subjects were seronegative at the pre-booster evaluation, and 1 subject had a titer equal to 50 AU/ml: none of the evaluated subjects was seronegative after the booster dose. Thus, the efficacy of the booster in our population was universal. Mean increase of pre- to post-booster titer was more significant in subjects who never had SARS-CoV-2 (44 times CI 95% 42-46) compared to those who had it, before (33 times, CI 95% 13-70) or after the first vaccination cycle (12 times, CI 95% 11-14). Differently from sex, age and pre-booster titers affected the post-booster antibody response. Nevertheless, the post-booster titer was very similar in all subgroups, and independent of a prior exposure to SARS-CoV-2, pre-booster titer, sex or age. Conclusion: Our study shows a potent universal antibody response of the booster dose of BNT162b2, regardless of pre-booster vaccine seronegativity.

Trends in all-cause mortality of hospitalized patients due to SARS-CoV-2 infection from a monocentric cohort in Milan (Lombardy, Italy).

Background: Robust data on case fatality rate (CFR) among inpatients with COVID-19 are still lacking, and the role of patient characteristics in in-hospital deaths remains under-investigated. This study quantified the overall CFR and described its trend in a cohort of hospitalized patients with SARS-CoV-2 in Italy. Admission to ICU, death, or discharge were the secondary outcomes. Methods: This retrospective study is based on administrative health data and electronic case records of inpatients consecutively admitted to Niguarda Hospital between 21 February and 8 November 2020. Results: An overall CFR of 18% was observed. CFR was significantly reduced during the second wave of contagion (1 June to 30 September, 16%) compared with the first wave (21 February to 31 May, 21% p = 0.015). Such reduction was mainly observed among male inpatients between 40 and 80 years with limited comorbidities. Admission to ICU was associated with a high risk of mortality in both waves. The incidence of severe disease and the need for ICU admission were lower in the second wave. Conclusion: CFR in SARS-CoV-2 inpatients was demonstrated to decrease over time. This reduction may partly reflect the changes in hospital strategy and clinical practice. The reasons for this improvement should be further investigated to plan an exit strategy in case of future outbreaks. Key messages: What is already known on this topic Before the advent of anti-COVID-19 vaccines, a multi-wave pattern of contagion was observed, and this trend conditioned the inpatient case fatality rate (CFR), which varied over time accordingly to the waves of contagion.Only preliminary results on the in-hospital mortality trend are available, along with a partial analysis of its determinants. Consequently, robust data on CFR among inpatients with SARS-CoV-2 infection are still lacking, and the role of patient characteristics in in-hospital deaths remains under-investigated. What this study adds This study shows that the in-hospital mortality in patients with SARS-CoV-2 infection decreases over time.Such reduction was mainly observed among male inpatients between 40 and 80 years with limited comorbidities. Admission to ICU was invariably associated with a high risk of mortality during the whole study period (21 February to 8 November 2020), but the incidence of severe disease and the need for ICU admission were lower in the second wave of contagions (1 October to 8 November 2020). This reduction may partly reflect the impact of changes in hospital strategy and clinical practice. The reasons for this improvement should be further investigated to inform the response to future outbreaks and to plan exit strategy by prioritizing high-risk populations. Supplementary Information: The online version contains supplementary material available at 10.1007/s10389-021-01675-y.

Payment for performance (P4P): any future in Italy?

BACKGROUND: Pay for Performance (P4P) programs, based on provision of financial incentives for service quality, have been widely adopted to enhance quality of care and to promote a more efficient use of health care resources whilst improving patient outcomes. In Italy, as in other countries, the growing concern over the quality of health services provided and the scarcity of resources would make P4P programs a useful means of improving their performance. The aim of this paper is to evaluate whether it is possible to implement P4P programs in the Lombardy Region, in Italy, based on the existing data set. METHODS: Thirteen quality measures were identified regarding four clinical conditions (acute myocardial infarction (AMI), heart failure (HF), ischemic stroke and hip and knee replacement) on the basis of an international literature review. Data was collected using the database of three institutions, which included hospital discharge records (Scheda di Dimissione ospedaliera-SDO-) and letters of discharge. The study population was identified using both the Principal ICD-9-CM diagnosis codes and the discharge date. A Statistical Analysis System (SAS) program was used for the text analysis. RESULTS: It was possible to calculate almost all the parameters pertaining to the three hospitals as all the data required was available with the exception of inpatient mortality in two hospitals and smoking cessation advice/counseling in one hospital. CONCLUSIONS: On the ground of this analysis, we believe that it is possible to implement a P4P program in the Lombardy Region. However, for this program to be initiated, all necessary data must be available in electronic format and uniformly collected. Moreover, several other factors must be assessed: which clinical conditions should be included, the threshold for each quality parameter, the amount of financial incentives offered and how they will be provided.

The role of chromogranin A in the management of patients with phaeochromocytoma.

OBJECTIVE: Chromogranin A (CgA) is the most accurate general marker of neuroendocrine tumours. Supranormal CgA concentrations have been recorded in patients with tumours of neuroectodermal origin such as phaeochromocytoma and paraganglioma. DESIGN: The present study was performed to assess the role of CgA determination in the management of patients with phaeochromocytoma, in comparison with urinary catecholamines and their metabolites. PATIENTS: The patients studied included 22 cases with phaeochromocytoma at initial presentation or at relapse some years after surgical cure or during follow-up of a malignant phaeochromocytoma. Seventeen patients were evaluated before and after surgical removal of phaeochromocytoma. To assess the specificity of the hormonal parameters, 20 subjects were enrolled as controls; they were from a group of patients referred to our observation for possible phaeochromocytoma and who were subsequently proven not to have the disease. RESULTS: Urinary epinephrine and norepinephrine were supranormal in 82% and 77% of patients, respectively. Urinary metanephrines and normetanephrines were supranormal in 84% and 89% of patients, respectively. The combination of urinary metanephrine and normetanephrine had a sensitivity of 100% in identifying a phaeochromocytoma. CgA was supranormal in 91% of patients. Combining the results of CgA and urinary catecholamines (epinephrine and norepinephrine), the sensitivity for diagnosis of phaeochromocytoma was 100%. Urinary catecholamines, metabolites (metanephrine and normetanephrine) and CgA levels in patients with malignant phaeochromocytoma did not differ significantly from those of patients with benign lesions. In most cases, CgA normalized after surgery. CONCLUSIONS: Our results indicate that CgA is a good marker of phaeochromocytoma; measurement of CgA could have a role in the follow-up of patients operated on for phaeochromocytoma.

Hormone replacement therapy and risk of nonfatal acute myocardial infarction in Italy.

BACKGROUND: Observational studies, but not clinical trials, found lower risk of coronary heart disease (CHD) in hormone replacement therapy (HRT) users. We analyzed the relation between HRT use and the risk of nonfatal acute myocardial infarction (AMI) in Italy. METHODS: We used a combined dataset from three hospital-based case-control studies including a total of 479 women aged > or =45 years with a first episode of nonfatal AMI and 822 hospital controls. RESULTS: Compared to never-HRT users, the multivariate odds ratio in ever users was 1.4 (95% confidence interval, 0.9-2.2); no consistent pattern of risk was observed according to duration or time since last use. CONCLUSIONS: HRT use was not associated with nonfatal AMI in Italian women according to the findings of clinical trials.

Risk factors for non-fatal acute myocardial infarction in Italian women.

BACKGROUND: We analyzed the relation between selected lifestyles and diseases and the risk of non-fatal acute myocardial infarction (AMI) in women in Northern Italy. METHODS: We used a combined data set from three case-control studies, including 558 cases and 1,044 hospital controls. RESULTS: The strongest risk factor for AMI was smoking, the odds ratio (OR) being 4.0 in current smokers (11.6 for > or = 5 cigarettes/day). Other risk factors were diabetes (OR 4.4), hypertension (OR 3.3), hyperlipidemia (OR 1.6), and family history of AMI (OR 2.1). Moderate alcohol drinking was protective (OR 0.8 for < 2 drinks/day) compared to non-drinkers, and heavy coffee drinking non-significantly increased the risk (OR 1.4 for >3 cups/day). Inverse association was found with fish (OR 0.7 for >1 portion/week), vegetables (0.7 for > or = 10 portions/week), and fruit (OR 0.6 for > or = 14 portions/week), while meat, whole-grain, and diary products were unrelated. Smoking effect was stronger in combination with diabetes (OR 27.7), hypertension (OR 15.7), hyperlipidemia (OR 6.3), family history of AMI (OR 8.7), and heavy coffee drinking (OR 5.7). CONCLUSIONS: The strongest risk factor for AMI was smoking, responsible of about 37% of cases, followed by diabetes, hypertension, hyperlipidemia, family history of AMI. Avoidance of smoking and increasing fish, vegetables, and fruit would reduce AMI risk of about 50%.

Coffee and tea intake and risk of oral, pharyngeal and esophageal cancer.

The relation between coffee, decaffeinated coffee, tea and oral/pharyngeal, and esophageal cancer risk is inadequately quantified. Data were derived from hospital-based case-control studies conducted in Italy and Switzerland. The study on oral/pharyngeal cancer included 749 cases and 1772 controls, and that of esophageal cancer 395 cases and 1066 controls. Multivariate odds ratios (OR) and 95% confidence intervals (CI) were computed. The OR for >3 cups/day of coffee compared with

Family history of ischemic heart disease and risk of acute myocardial infarction.

BACKGROUND: Several aspects of the relation between family history of ischemic heart disease (IHD) and risk of acute myocardial infarction (AMI) need further quantification. METHODS: A case-control study was conducted in Italy in 1995-1999 on 378 men and 129 women with a first nonfatal AMI, and 297 male and 181 female controls in a hospital for selected acute conditions. Odds ratios (OR) of AMI according to family history of IHD were estimated using unconditional logistic regression, adjusting for other AMI risk factors and family size. RESULTS: The overall OR for those having > or =1 first-degree relatives with IHD was 2.1, and 3.8 for > or =2 relatives. The OR for those with an affected parent or sibling were similar. The OR were also similar across strata of sex, age at diagnosis of the proband or the relative, and selected AMI risk factors, which were risk factors also in those with a positive family history. CONCLUSIONS: Family history of IHD is an independent risk factor for AMI, and intervention on modifiable risk factors may be beneficial also in those with a family history of the disease.

Diabetes mellitus as a contributor to the risk of acute myocardial infarction.

The risk of nonfatal acute myocardial infarction (AMI) has been studied in relation to diabetes and other risk factors, combining data from three Italian case-control studies including 1,737 cases with nonfatal AMI and 2,317 controls in hospital for acute diseases unrelated to AMI risk factors. The multivariate odds ratio (OR) of AMI for diabetes was 2.3 (95% confidence interval, 1.8-2.9); the association with AMI risk was apparently stronger in patients diagnosed with diabetes when aged <40 years (OR 2.9), and in women (OR 4.4). When the combined effect of diabetes and other known risk factors on the risk of AMI was considered, compared to nondiabetic subjects with each factor at the lowest risk level, the OR for diabetic subjects was 4.7 in smokers, 2.8 in heavy coffee drinkers, 2.7 in those with higher body mass index, 3.4 in patients with high cholesterol levels, 3.3, 4.3, and 2.7 for diabetic subjects with history of hyperlipidemia, hypertension, and obesity, respectively, and 4.3 for those with a family history of AMI in first degree relatives. The association of each risk factor was much stronger in diabetic women. Preventive measures to reduce the prevalence of each additional risk factors in diabetic subjects could led to a substantial reduction of risk of AMI.