Estimating COVID-19 recovery time in a cohort of Italian healthcare workers who underwent surveillance swab testing.

OBJECTIVES: The COVID-19 pandemic is putting a huge strain on the provision and continuity of care. The length of sickness absence of the healthcare workers as a result of SARS-CoV-2 infection plays a pivotal role in hospital staff management. Therefore, the aim of this study was to explore the timing of COVID-19 recovery and viral clearance, and its predictive factors, in a large sample of healthcare workers. STUDY DESIGN: This is a retrospective cohort study. METHODS: The analysis was conducted on data collected during the hospital health surveillance programme for healthcare staff at the University Hospital of Verona; healthcare workers were tested for SARS-CoV-2 through RT-PCR with oronasopharyngeal swab samples. The health surveillance programme targeted healthcare workers who either had close contact with SARS-CoV-2-infected patients or were tested as part of the screening-based strategy implemented according to national and regional requirements. Recovery time was estimated from the first positive swab to two consecutive negative swabs, collected 24 h apart, using survival analysis for both right-censored and interval-censored data. Cox proportional hazard was used for multivariate analysis. RESULTS: During the health surveillance programme, 6455 healthcare workers were tested for SARS-CoV-2 and 248 (3.8%, 95% confidence interval [CI]: 3.4-4.3) reported positive results; among those who tested positive, 49% were asymptomatic, with a median age of 39.8 years, which is significantly younger than symptomatic healthcare workers (48.2 years, P < 0.001). Screening tests as part of the health surveillance programme identified 31 (12.5%) of the positive cases. Median recovery time was 24 days (95% CI: 23-26) and 21.5 days (95% CI: 15.5-30.5) in right- and interval-censoring analysis, respectively, with no association with age, sex or presence of symptoms. Overall, 63% of participants required >20 days to test negative on two consecutive swabs. Hospitalised healthcare workers (4.8%) were older and had a significantly longer recovery time compared with non-hospitalised healthcare workers in both analyses (33.5 vs 24 days, P = 0.005). CONCLUSIONS: Recovery from COVID-19 and viral clearance may take a long time, especially in individuals who are hospitalised. To detect asymptomatic cases, screening programmes for healthcare workers is recommended.

Biologics and global burden of asthma: A worldwide portrait and a call for action.

Biologics for severe asthma can significantly impact on the burden of disease and also have the potential to reduce asthma mortality. By reviewing the literature and contacting the pharmaceutical companies, the present paper aims at providing a worldwide snapshot of biologic drugs availability, related with the trend of asthma mortality rate, as a marker of the burden of the disease. A decline in the global rate of annual asthma mortality was observed until the 1980s, but overall no further reduction occurred, and the current mortality estimation is 0.19 deaths per 100.000 people. A higher mortality rate has been registered in low and middle-income countries (LMICs), where poor socioeconomic conditions and lack of access to the medical resources are more relevant. The availability of monoclonal antibodies is mainly limited to the developed and high-income countries. Furthermore the overall "asthma management system" in LMICs suffers from a number of restrictions that hamper the widespread availability of biologics besides their costs. The availability of generic drugs in the field of biologics for severe asthma could contribute to facilitate their widespread accessibility. But before that, awareness and expertise regarding severe asthma, and proper tools to assess and manage it, deserve to be shared worldwide. Collaboration projects involving physicians from all the countries through the scientific Academies network and with the support of the Companies active in the field may provide an initial concrete opportunity.

The potential role of local pharmacies to assess asthma control: an Italian cross-sectional study.

BACKGROUND: Asthma control and monitoring still represents a challenge worldwide. Although the international guidelines suggest the interplay between secondary and primary care services as an effective strategy to control the disease, community pharmacies' are seldom involved in asthma control assessment. The present cross-sectional study aimed at providing a picture of the relationship between asthma severity and control in community pharmacies within the health district of the city of Verona (Veneto Region, North-Eastern Italy). METHODS: A call for participation was launched through the Pharmacists' Association of Verona. Patients referring to the participating pharmacies with an anti-asthmatic drug medical prescription and an asthma exemption code were asked to complete the Asthma Control Test (ACT) and a brief questionnaire collecting information on their age, sex, smoking status, aerobic physical exercise and usual asthma therapy, which also defined asthma severity. A multinomial logistic regression model was fitted to investigate the risk of uncontrolled as well as poorly controlled vs. controlled asthma (base). Results were expressed as relative risk ratios (RRR) with 95% confidence interval (95%CI). RESULTS: Fifty-seven community pharmacies accepted to participate and 584 asthmatic patients (54% females; mean-age: 51 ± 19 years) were consecutively recruited from 1st January to 30th June 2018 (6 months). Based upon ACT score 50.5% patients had a controlled asthma, 22.3% a poorly controlled and 27.2% uncontrolled. A variable proportion of patients with uncontrolled asthma were observed for every level of severity, although more frequently with mild persistent form of asthma. Most patients (92%) self-reported regular compliance with therapy. At multinomial regression analysis, patients under regular asthma treatment course (RRR = 0.33; 95%CI: 0.15; 0.77) were less likely to have an ACT< 16 compared to those not taking medications regularly. CONCLUSIONS: Overall, our findings highlighted an unsatisfactory asthma control in the general population, independently of the severity level of the disease. Community pharmacies could be a useful frontline interface between patients and the health care services, supporting an effective asthma management plan, from disease assessment and monitoring treatment compliance to referral of patients to specialist medical consultancies.

Association between increased plasma ceramides and chronic kidney disease in patients with and without ischemic heart disease.

AIM: Plasma levels of certain ceramides are increased in patients with ischemic heart disease (IHD). Many risk factors for IHD are also risk factors for chronic kidney disease (CKD), but it is currently uncertain whether plasma ceramide levels are increased in patients with CKD. METHODS: We measured six previously identified high-risk plasma ceramide concentrations [Cer(d18:1/16:0), Cer(d18:1/18:0), Cer(d18:1/20:0), Cer(d18:1/22:0), Cer(d18:1/24:0) and Cer(d18:1/24:1)] in 415 middle-aged individuals who attended our clinical Cardiology and Diabetes services over a period of 9 months. RESULTS: A total of 97 patients had CKD (defined as e-GFRCKD-EPI<60ml/min/1.73m2 and/or urinary albumin-to-creatinine ratio≥30mg/g), 117 had established IHD and 242 had type 2 diabetes. Patients with CKD had significantly (P=0.005 or less) higher levels of plasma Cer(d18:1/16:0), Cer(d18:1/18:0), Cer(d18:1/20:0), Cer(d18:1/22:0), Cer(d18:1/24:0), and Cer(d18:1/24:1) compared to those without CKD. The presence of CKD remained significantly associated with higher levels of plasma ceramides (standardized beta coefficients ranging from 0.124 to 0.227, P<0.001) even after adjustment for body mass index, smoking, hypertension, diabetes, prior IHD, plasma LDL-cholesterol, hs-C-reactive protein levels and use of any lipid-lowering medications. Notably, more advanced stages of CKD and abnormal albuminuria were both associated (independently of each other) with increased levels of plasma ceramides. These results were consistent in all subgroups considered, including patients with and without established IHD or those with and without diabetes. CONCLUSION: Increased levels of plasma ceramides are associated with CKD independently of pre-existing IHD, diabetes and other established cardiovascular risk factors.

Association between lower plasma adiponectin levels and higher plasma thrombin generation parameters in men with type 2 diabetes: role of plasma triglycerides.

OBJECTIVE: Previous studies showed a significant association between lower plasma adiponectin levels and higher risk of adverse cardiovascular outcomes in patients with and without type 2 diabetes mellitus (T2DM). Presently, it is uncertain whether lower plasma adiponectin levels are associated with greater plasma thrombin generation in patients with T2DM. PATIENTS AND METHODS: We studied 82 middle-aged men with non-insulin-treated T2DM [mean age ± SD: 64.1 ± 8 years; median duration of diabetes: 12.5 (inter-quartile range 6-19) years; mean hemoglobin A1c 7.0 ± 0.7%], consecutively attending our diabetes outpatient service over a 6-month period. Using the newly developed fully automated thrombin generation analyzer ST Genesia®, we measured the plasma parameters lag time (LT), time to peak (TP), peak height (PH) and endogenous thrombin potential (ETP) in all participants. RESULTS: In univariable linear regression analyses, lower plasma adiponectin levels were significantly associated with higher plasma thrombin generation parameters, as reflected by higher values of PH (Pearson's r coefficient = - 0.228, p = 0.039) and EPT (r = - 0.293, p = 0.007). Plasma adiponectin levels were not significantly associated with other thrombin generation parameters (LT and TP). Notably, the significant associations of plasma adiponectin levels with thrombin PH and EPT values persisted after adjustment for age and adiposity measures, but they were lost after additional adjustment for plasma triglycerides. CONCLUSION: Our findings show for the first time the existence of a significant association between lower levels of plasma adiponectin and greater plasma thrombin generation (as assessed by the ST Genesia® analyzer) in men with non-insulin-treated T2DM, which appears to be largely mediated by plasma triglycerides.

Psychological impact of COVID-19 pandemic on healthcare workers in a highly burdened area of north-east Italy.

AIMS: Healthcare workers exposed to coronavirus 2019 (COVID-19) patients could be psychologically distressed. This study aims to assess the magnitude of psychological distress and associated factors among hospital staff during the COVID-19 pandemic in a large tertiary hospital located in north-east Italy. METHODS: All healthcare and administrative staff working in the Verona University Hospital (Veneto, Italy) during the COVID-19 pandemic were asked to complete a web-based survey from 21 April to 6 May 2020. Symptoms of post-traumatic distress, anxiety and depression were assessed, respectively, using the Impact of Event Scale (IES-R), the Self-rating Anxiety Scale (SAS) and the Patient Health Questionnaire (PHQ-9). Personal socio-demographic information and job characteristics were also collected, including gender, age, living condition, having pre-existing psychological problems, occupation, length of working experience, hospital unit (ICUs and sub-intensive COVID-19 units vs. non-COVID-19 units). A multivariable logistic regression analysis was performed to identify factors associated with each of the three mental health outcomes. RESULTS: A total of 2195 healthcare workers (36.9% of the overall hospital staff) participated in the study. Of the participants, 35.7% were nurses, 24.3% other healthcare staff, 16.4% residents, 13.9% physicians and 9.7% administrative staff. Nine per cent of healthcare staff worked in ICUs, 8% in sub-intensive COVID-19 units and 7.6% in other front-line services, while the remaining staff worked in hospital units not directly engaged with COVID-19 patients. Overall, 63.2% of participants reported COVID-related traumatic experiences at work and 53.8% (95% CI 51.0%-56.6%) showed symptoms of post-traumatic distress; moreover, 50.1% (95% CI 47.9%-52.3%) showed symptoms of clinically relevant anxiety and 26.6% (95% CI 24.7%-28.5%) symptoms of at least moderate depression. Multivariable logistic regressions showed that women, nurses, healthcare workers directly engaged with COVID-19 patients and those with pre-existing psychological problems were at increased risk of psychopathological consequences of the pandemic. CONCLUSIONS: The psychological impact of the COVID-19 pandemic on healthcare staff working in a highly burdened geographical of north-east Italy is relevant and to some extent greater than that reported in China. The study provides solid grounds to elaborate and implement interventions pertaining to psychology and occupational health.

Emotional, cognitive and social factors of antimicrobial prescribing: can antimicrobial stewardship intervention be effective without addressing psycho-social factors?

There is increasing evidence that psycho-social factors can influence antimicrobial prescribing practice in hospitals and the community, and represent potential barriers to antimicrobial stewardship interventions. Clinicians are conditioned both by emotional and cognitive factors based on fear, uncertainty, a set of beliefs, risk perception and cognitive bias, and by interpersonal factors established through social norms and peer and doctor-patient communication. However, a gap is emerging between research and practice, and no stewardship recommendation addresses the most appropriate human resource allocation or modalities to account for psycho-social determinants of prescribing. There is a need for translation of the evidence available from human behaviour studies to the design and implementation of stewardship interventions and policies at hospital and community levels. The integration of behaviour experts into multidisciplinary stewardship teams seems essential to positively impact on prescribers' communication and decision-making competencies, and reduce inappropriate antibiotic prescribing.

Enhanced recovery protocol in esophagectomy, is it really worth it? A cost analysis related to team experience and protocol compliance.

Application of enhanced recovery protocols (ERP) in esophageal surgery seems to lead an advantage in terms of length of hospital staying and outcomes, but only few data exist on its cost effectiveness. Previous literature analyzed pre- and post-ERP groups, finding a cost reduction with the introduction of the pathway. We aimed to study the influence on costs of accumulating experience and compliance in an ERP group. Seventy-one patients have been treated at our institution from January 2014 to June 2017 with our ERP for Ivor-Lewis esophagectomy. Direct costs were divided into subcategories and were analyzed as a function of calendar year and compliance. Factor affecting costs were searched. Univariable analysis highlighted a significant reduction in costs over time. Increase in compliance led to a progressive cost reduction for each ERP item completed (€14 852-€11 045). While age was not found to significantly influence the cost (p = 0.341), complications seemed to nullify the effect of experience: the median was €11 507 in uncomplicated patients, and increased to €13 791 in Clavien-Dindo 3-4 (CD3-4) patients. Compliance and CD3-4 remained significant also in multivariable analysis, accomplished by quantile regression, while year of surgery lost its significance. Our results evidence how accumulating experience in ERP led to a cost reduction over time, which was mainly mediated by an increase in compliance. Indeed, compliance was the main factor in reducing ERP cost while CD3-4 complications were the most important factor in cost increasing, nullifying the benefit of compliance.

Evaluation of asthma control in the pharmacy: an Italian cross-sectional study.

SUMMARY: Background. In Western countries a large proportion of asthmatic patients remain uncontrolled, despite the availability of effective drugs. An involvement of pharmacies / pharmacists in asthma management has been suggested in guidelines, since this could provide a relevant support. Objective. The present cross-sectional study aimed at assessing the level of asthma control, by using ACT questionnaire, in the community pharmacies in the County of Verona, North East of Italy. Methods. A call for participation was sent by Verona Pharmacists' Association to all the pharmacies located in the Verona municipality. Patients with a medical prescription and an asthma exemption code were recruited in pharmacies. They were asked to fill the ACT questionnaire and to answer some additional questions on asthma treatment, smoke habits and comorbidities. Results. Thirty-seven community pharmacies recruited 239 patients. According to the ACT score, more than 50% of patients had a controlled asthma but 20% of them were totally uncontrolled and 12% were using oral steroid. Only 2.9% of patients had received an asthma action plan. Asthma was intermittent in 17.6% of patients, mild persistent in 13.8%, moderate persistent in 63.1% and severe in 5.4%. Discordance was observed between the self-perceived asthma control and objective parameters, when available. Of note, in the severe asthma group, most patients had an ACT > 20. Conclusion. This is the first Italian pharmacy-based study on asthma control. A better asthma control was recorded in this study in comparison with other trials, but about 50% of patients were insufficiently controlled. The community pharmacies can play a relevant role in the preliminary assessment of asthma control by using easy and not time consuming tools, such as ACT.

Epidemiological trends and direct costs of diabetes in a Northern Italy area: 2012 health administrative records analysis LHT n. 20 Verona.

OBJECTIVE: This analysis estimates type 1 and type 2 diabetes direct costs in 2012, in terms of hospital care, outpatient visits, diagnostics and medications, in a local healthcare trust in Northern Italy (ULSS n.20 Verona). METHODS: The Johns Hopkins Adjusted Clinical Group (ACG®) System was used to analyze data, including hospital discharges, emergency room admissions, medical encounter records, disease registries, copayment exemptions, home care services, psychiatric services, rehabilitation services, and medications. Data from general practitioners and nursing homes were not directly available. Patients obtained from the first analysis were subsequently divided in two groups (type 1 and type 2 diabetes) according to ATC drug classification system and age. Costs were estimated from inpatient and outpatients fees and drugs costs. RESULTS: ULSS n. 20 takes care of about 480.000 people. We identified 974 people affected by type 1 diabetes (prevalence 0,2%) and 24.087 people affected by type 2 diabetes (prevalence 5,0%) among the residents in 2012. Hospitalization mean annual cost was 4.753,50€ (SD 9.330,19€) for type 1 diabetes and 1.718,08€ (SD 5.087,34€) for type 2 diabetes. Outpatient care mean annual cost was 1.401,76€ (SD 4.394,88€) for type 1 diabetes and 669,15€ (SD 2.121,24€) for type 2 diabetes. Medications mean annual cost was 1,369,35€ (SD1.781,18€) for type 1 diabetes and 874,07€ (SD 2.832,2€) for type 2 diabetes. CONCLUSIONS: ACG® diabetes data analysis agrees with data obtained by more expensive methods and seems to be a comprehensive and applicable tool to analyze chronic diseases dynamics in the Italian setting in order to prioritize future research and analyze the effects of interventions aimed to ensure the sustainability of public health services. Because of the combination between prevalence data and epidemiological trends, we could be at the eve of a dramatic increase of diabetes costs with major concerns for the Italian NHS ability to withstand.

Allergic rhinitis: pharmacotherapy in pregnancy and old age.

INTRODUCTION: Allergic rhinitis (AR) affects 20-30% of women in reproductive age and may worsen during pregnancy. About 10% of the elderly suffer from AR, and it could be under-diagnosed in these patients. Many drugs are currently available, however AR treatment during pregnancy and old age represents a challenging issue. AREAS COVERED: A review of the literature on the topic has been performed. Expert commentary: In pregnancy, drug avoidance should be carefully balanced with the need for AR optimal control. Topical drugs are suggested as a first approach. The safety and tolerability profile of second-generation antihistamines is well supported. If allergen immunotherapy (AIT) is ongoing and well tolerated, there is no reason for stopping it. AIT initiation in pregnancy is not recommended. For elderly patients, no specific concerns have been highlighted regarding topical treatments, except from nasal decongestionants. Second generation antihistamines are generally well tolerated. Old age should not preclude AIT.

[Increasing immunization coverage by intervening on determinants of refusal]. / Aumentare le coperture vaccinali intervenendo sui determinanti del rifiuto.

With the regional decree 3664/2008, the Veneto Region adopted measures for improvements in the immunization program, among which the "Investigation into determinants for vaccine refusal in the Veneto Region", entrusted by the Department of Prevention Local Health Unit 20 (Ulss 20) of Verona. The objective of the study was to understand which type of parent that accessed immunization services (total adherent, partial adherent or complete refusals) and what factors lead to their choice regarding immmunizations in order to better plan strategies to maintain vaccination coverage.

Chronic obstructive pulmonary disease: the Disability Adjusted Life Years in northern Italy.

AIM: The DALY measure represents a new tool for improving the capacity of local health unit to assess population health needs and priorities. Our study aimed to increase the validity of the Disability Adjusted Life Years (DALY), by incorporating local estimates of the disease incidence and applying population-specific disability weights. METHODS: This is a prospective cohort study enrolling subjects aged 45+ years, first-time admitted to the hospital with principal diagnosis of 490-492, 496 ICD IX-CM codes and followed for one year to evaluate the vital status. A subset was administered the Saint George Respiratory Questionnaire to estimate the distribution of the chronic obstructive pulmonary disease (COPD)-related disability. RESULTS: Estimates of total DALY (per 1000) for COPD varied between 2.1 to 3.4 years among men and between 1.0 to 2.3 years among women; percentages of years of life lost due to a premature mortality were between 60 and 70%. CONCLUSION: The DALY represents a new tool for improving the capacity to assess population health needs and priorities. Policy makers owning such a further element of evaluation may be better oriented in allocating resources for COPD among the different health care chapters: prevention, emergency, chronicity and rehabilitation.

On the role of arbitration of discordant double readings of screening mammography: experience from two Italian programmes.

PURPOSE: The authors sought to assess the role of arbitration by a third reader of discordant double readings to reduce the rate of recalls to diagnostic assessment. MATERIALS AND METHODS: A consecutive series of 7,660 double readings of screening examinations were considered. Discordant recalls were arbitrated by an expert reader (negative/positive). Diagnostic assessment was performed irrespective of arbitration results, and its outcome was used as reference standard for the study purpose. Assuming that negative arbitration would deny recall, its impact was assessed in terms of reduced recall rate and reduced cancer detection rate. Cost analysis of introducing arbitration was performed according to these results. RESULTS: Recalls at double reading were 528 (6.8%), of which 230 (43.5%) were concordant and 298 (56.5%) were discordant. The latter underwent arbitration, which was negative in 216 (72.4%) and positive in 82 (27.6%) cases, respectively. Overall, 49 cancers were detected (6.39 ‰ screened, 9.2% recalled): 43 cancers were detected among concordant (5.6 ‰ screened, 18.6% concordant) and six among discordant recalls (0.7 ‰ screened, 2.0% discordant). Six cancers were observed among arbitrated cases: five (6%) in positive and one (4.6 ‰) in negative arbitrations. Negative arbitration would have spared 216 assessment procedures (2.8% absolute, 40.9% relative reduction of recall rate) while missing one cancer case (0.13 ‰ absolute, 2.0% relative reduction of cancer detection rate). Arbitration cost was 74 euro, whereas 216 spared assessment procedures would have cost 14,558.4-23,346 euro. CONCLUSIONS: Arbitration is a cost-effective procedure that could be employed as a first measure to counterbalance excess recall rate observed in a double-reading scenario.

NADPH oxidase activity and chemotaxis by neutrophils in two patients with glycogen storage disease type Ib treated with recombinant human granulocyte-monocyte colony-stimulating factor.

Polymorphonuclear neutrophils play an important role against pathogens through the production of toxic oxygen metabolites by the NADPH oxidase enzyme, which reduces oxygen to superoxide anion in the respiratory burst. Neutropenia, infectious complications and impaired neutrophil function are often reported in glycogen storage disease type Ib (GSDIb), a metabolic disorder characterized by increased glycogen and decreased glucose-6-phosphatase (G-6-P) activity in the liver. Two children with GSDIb and associated neutropenia with recurrent bacterial infections were treated daily with different doses of rHu-GM-CSF. NADPH oxidase activity and chemotaxis in patients were assessed before and during therapy in stimulated and unstimulated neutrophils. During rHu-GM-CSF treatment, any increase found in the NADPH oxidase activity of patients was not significant with respect to that in controls. In one patient chemotaxis was greater than of controls. This finding suggests that in patients with GSDIb both neutropenia and PMN abnormalities may be responsible for infections, and PMN dysfunction probably depends on the degree of inherited functional G-6-P deficit.

Quantitative cytochemistry of human leukocyte elastase compared with plasma elastase and acute phase proteins in inflammatory diseases.

Plasma levels of human leukocyte elastase, a serine proteinase stored in the azurophilic granules of polymorphonuclear granulocytes, increase in the early stages of several inflammatory diseases. We studied the intracellular enzyme activity by cytochemical quantitative image analysis and the amount of elastase released in plasma by an automatic immunoactivation immunoassay method in 66 patients with inflammatory diseases and in a control group. The patients were divided into two groups with infective disease (severe and moderate) and one group with non-infective inflammation. Intracellular activity and plasmatic levels of elastase were also compared with other inflammatory markers, i.e. erythrocyte sedimentation rate, C-reactive protein, alpha 1-antitrypsin, haptoglobin, alpha 1-acid glycoprotein and fibrinogen. Our studies suggest that plasma and leukocyte elastase are correlated both with etiology and with the severity of the inflammation.

A quantitative method to measure alkaline phosphatase activities in individual leukocytes by image analysis.

Leucocyte alkaline phosphatase (L-ALP) is well known as leukemia marker, but recent results suggest its usefulness for the diagnosis of several diseases. The aim of this study was to develop a quantitative method to measure alkaline phosphatase activities in individual leukocytes by image analysis. We studied the reaction rate of L-ALP in human polymorphonuclear leucocytes by a microscope attached to a TV camera and a computerized image analyzer. The optical density (OD) measured was standardized by grey filters with known absorbance. We measured IOD for individual cells after a set incubation time by end-point measurements. Studies of kinetic parameters of L-ALP were performed by single-point measurements in the linear phase of the reaction and at increasing substrate concentrations. Cellular IOD increased proportionally with incubation time up to 10 min. The mean KM(mM) and Vmax(delta IOD/min) values were 0.70 +/- 0.11 and 1.76 +/- 0.2 (mean +/- SE, n = 5) respectively. Our findings are comparable to previous results using a polyvynil alcohol method in microphotometry analysis. The image analysis of cellular L-ALP activity appears a valuable tool for quantitative studies.