Cost-effectiveness and diagnostic accuracy of focused cardiac ultrasound in the pre-participation screening of athletes: the SPORT-FoCUS study.

AIMS: The role of pre-participation screening (PPS) modalities in preventing sudden cardiac death (SCD) in athletes is debated due to a high false-positive rate. Focused cardiac ultrasound (FoCUS) has shown higher sensitivity and specificity, but its cost-effectiveness remains uncertain. This study aimed to determine the diagnostic performance and cost-effectiveness of FoCUS use in PPS. METHODS AND RESULTS: A total of 2111 athletes (77.4% male, mean age 24.9 ± 15.2years) underwent standardized family and medical history collection, physical examination, resting electrocardiography (ECG), FoCUS (10 min/5 views protocol), comprehensive echocardiography and exercise stress test. We prospectively evaluated three PPS incremental models: Model A, standardized medical history and physical examination Model B, Model A plus resting and stress ECG and Model C, Model B plus FoCUS (10 min/5 views protocol). We determined their incremental diagnostic accuracy and cost-effectiveness ratio. A total of 30 athletes were diagnosed with a cardiac condition associated with SCD: 3 were identified by Model A, 14 by Model B, and 13 athletes by Model C. The introduction of FoCUS markedly increased the sensitivity of PPS, compared with Model A and Model B (sensitivity 94% vs. 19% vs. 58% specificity 93% vs. 93% vs. 92%). The total screening costs were as follows: Model A 35.64 euros, Model B 87.68 euros, and Model C 120.89 euros. Considering the sole conditions at risk of SCD, the incremental cost-effectiveness ratio was 135.62 euros for Model B and 114.31 for Model C. CONCLUSIONS: The implementation of FoCUS into the PPS allows to identify a significantly greater number of athletes at risk of SCD and markedly lowers the false negative rate. Furthermore, the incorporation of FoCUS into the screening process has shown to be cost-effective.

A significant electrocardiography false-positive rate makes pre-participation screening (PPS) for sudden cardiac death (SCD) in athletes controversial. Focused cardiac ultrasound (FoCUS) may increase sensitivity and specificity however, its cost-effectiveness is unknown. This study evaluates the diagnostic performance and cost-effectiveness of FoCUS in PPS. Incorporating a simplified echocardiographic exam called FoCUS into PPS resulted in higher diagnostic reliability, with a lower rate of false negatives and a higher number of athletes at risk for SCD identified.The integration of FoCUS into the screening process resulted to be cost-effective in our athletes' cohort.

Metabolic syndrome and risk of COVID-19-related hospitalization: a large, population-based cohort study carried out during the first European outbreak of SARS-CoV-2 infection in the Metropolitan area of Milan (Lombardy Region, Northern Italy).

BACKGROUND: since the beginning of the COVID-19 pandemic, specific characteristics of the infected subjects appeared to be associated with a severe disease, leading to hospitalization or death. OBJECTIVES: to evaluate the association between three components of the metabolic syndrome (diabetes mellitus, dyslipidaemia, and hypertension), alone and in combination, and risk of hospitalization in subjects with nasopharyngeal swab-confirmed COVID-19. DESIGN: cohort study. SETTING AND PARTICIPANTS: the study subjects were all COVID-19 cases diagnosed in the area of the Agency for Health Protection of the Metropolitan Area of Milan (Lombardy Region, Northern Italy) between 10.02.2020 and 25.04.2020, whose data were gathered with an ad hoc information system developed at the beginning of the pandemic. MAIN OUTCOME MEASURES: the association between metabolic syndrome components (alone and in combination) and hospitalization (both in any ward and in intensive care unit) was measured by means of cause-specific Cox models with gender, age, and comorbidities as potential confounders. RESULTS: the cohort included 15,162 subjects followed from diagnosis up to 20.07.2020. Adjusted hazard ratios (HRs) of hospitalization in any ward estimated by the Cox model were 1.26 for uncomplicated diabetes mellitus (95%CI 1.18-1.34); 1.21 for complicated diabetes mellitus (95%CI 1.05-1.39); 1.07 for dyslipidaemia (95%CI 1.00-1.14); and 1.11 for hypertension (95%CI 1.05-1.17). When all components coexisted in the same subject, the HR was 1.46 (95%CI 1.31-1.62). A significant increase in risk of hospitalization in intensive care unit was found for uncomplicated diabetes mellitus (HR 1.38; 95%CI 1.15-1.66). CONCLUSIONS: this population-based study confirms that metabolic syndrome components increase the risk of hospitalization for COVID-19. The HR increases in an additive manner when the three components are simultaneously present.

Development of a multivariable model predicting mortality risk from comorbidities in an Italian cohort of 18,286 confirmed COVID-19 cases aged 40 years or older.

OBJECTIVES: to develop a risk prediction model for 30-day mortality from COVID­19 in an Italian cohort aged 40 years or older. DESIGN: a population-based retrospective cohort study on prospectively collected data was conducted. SETTING AND PARTICIPANTS: the cohort included all swab positive cases aged 40 years older (No. 18,286) among residents in the territory of the Milan's Agency for Health Protection (ATS-MI) up to 27.04.2020. Data on comorbidities were obtained from the ATS administrative database of chronic conditions. MAIN OUTCOME MEASURES: to predict 30-day mortality risk, a multivariable logistic regression model, including age, gender, and the selected conditions, was developed following the TRIPOD guidelines. Discrimination and calibration of the model were assessed. RESULTS: after age and gender, the most important predictors of 30-day mortality were diabetes, tumour in first-line treatment, chronic heart failure, and complicated diabetes. The bootstrap-validated c-index was 0.78, which suggests that this model is useful in predicting death after COVID-19 infection in swab positive cases. The model had good discrimination (Brier score 0.13) and was well calibrated (Index of prediction accuracy of 14.8%). CONCLUSIONS: a risk prediction model for 30-day mortality in a large COVID-19 cohort aged 40 years or older was developed. In a new epidemic wave, it would help to define groups at different risk and to identify high-risk subjects to target for specific prevention and therapeutic strategies.

Assessing the Impact of Individual Characteristics and Neighborhood Socioeconomic Status During the COVID-19 Pandemic in the Provinces of Milan and Lodi.

Social inequalities in health are known to be influenced by the socioeconomic status of the territory in which people live. In the context of the ongoing coronavirus disease 2019 (COVID-19) pandemic, this study is aimed at assessing the role of 5 area-level indicators in shaping the risk of contagion in the provinces of Milan and Lodi (Lombardy, Italy), namely: educational disadvantage, unemployment, housing crowding, mobility, and population density. The study area includes the municipalities at the origin of the first Italian epidemic outbreak. Data on COVID-19 patients from the Integrated Datawarehouse for COVID Analysis in Milan were used and matched with aggregate-level data from the National Institute of Statistics Italy (Istat). Multilevel logistic regression models were used to estimate the association between the census block-level predictors and COVID-19 infection, independently of age, sex, country of birth, and preexisting health conditions. All the variables were significantly associated with the outcome, with different effects before and after the lockdown and according to the province of residence. This suggests a pattern of socioeconomic inequalities in the outbreak, which should be taken into account in the eventuality of future epidemics to contain their spread and its related disparities.

Association between autoimmune diseases and COVID-19 as assessed in both a test-negative case-control and population case-control design.

BACKGROUND: COVID-19 epidemic has paralleled with the so called infodemic, where countless pieces of information have been disseminated on putative risk factors for COVID-19. Among those, emerged the notion that people suffering from autoimmune diseases (AIDs) have a higher risk of SARS-CoV-2 infection. METHODS: The cohort included all COVID-19 cases residents in the Agency for Health Protection (AHP) of Milan that, from the beginning of the outbreak, developed a web-based platform that traced positive and negative cases as well as related contacts. AIDs subjects were defined ad having one the following autoimmune disease: rheumatoid arthritis, systemic lupus erythematosus, systemic sclerosis, Sjogren disease, ankylosing spondylitis, myasthenia gravis, Hashimoto's disease, acquired autoimmune hemolytic anemia, and psoriatic arthritis. To investigate whether AID subjects are at increased risk of SARS-CoV-2 infection, and whether they have worse prognosis than AIDs-free subjects once infected, we performed a combined analysis of a test-negative design case-control study, a case-control with test-positive as cases, and one with test-negative as cases (CC-NEG). RESULTS: During the outbreak, the Milan AHP endured, up to April 27th 2020, 20,364 test-positive and 34,697 test-negative subjects. We found no association between AIDs and being positive to COVID-19, but a statistically significant association between AIDs and being negative to COVID-19 in the CC-NEG. If, as likely, test-negative subjects underwent testing because of respiratory infection symptoms, these results imply that autoimmune diseases may be a risk factor for respiratory infections in general (including COVID-19), but they are not a specific risk factor for COVID-19. Furthermore, when infected by SARS-CoV-2, AIDs subjects did not have a worse prognosis compared to non-AIDs subjects. Results highlighted a potential unbalance in the testing campaign, which may be correlated to the characteristics of the tested person, leading specific frail population to be particularly tested. CONCLUSIONS: Lack of availability of sound scientific knowledge inevitably lead unreliable news to spread over the population, preventing people to disentangle them form reliable information. Even if additional studies are needed to replicate and strengthen our results, these findings represent initial evidence to derive recommendations based on actual data for subjects with autoimmune diseases.

Describing the epidemic trends of COVID-19 in the area covered by Agency for Health Protection of the Metropolitan Area of Milan.

OBJECTIVES: to describe the epidemic trends of COVID-19 over time and by area in the territory covered by Milan's Agency for Health Protection (ATS-MI) from February to May 2020. DESIGN: descriptive study of COVID-19 cases. SETTING AND PARTICIPANTS: a new information system was developed to record COVID-19 cases with positive nasopharyngeal swab. Patients resident in the area covered by ATS-MI with symptom onset between February and May 2020 were selected. Different epidemic periods were considered based on the timeline of the various regional and national containment measures. MAIN OUTCOME MEASURES: case fatality ratios, incidence rates, and reproduction number by epidemic period and sub-area of ATS-MI. RESULTS: a total of 27,017 swab-positive COVID-19 cases were included. Mean age was 65 years and males were 45%. Incidence in the ATS-MI area was 776 per 100,000 population. The number of deaths was 4,660, the crude case fatality ratio was 17.3%, higher in males (21.2%) than in females (14.0%). The estimated reproduction number registered its peak (3.0) in the early stages of the epidemic and subsequently decreased. Territorial differences were observed in the epidemic spread, with a higher incidence in the Lodi area. CONCLUSIONS: estimated incidence and case fatality ratios were higher than national estimates for Italy. Each ATS-MI area had different epidemic spread patterns.

Assessment of the Overall Mortality during the COVID-19 Outbreak in the Provinces of Milan and Lodi (Lombardy Region, Northern Italy).

OBJECTIVES: to describe the overall mortality increase in the provinces of Milan and Lodi - area covered by the Agency for Health Protection of Milan - during the COVID-19 epidemic in the first four months of 2020, compare it with the same time period in the years 2016-2019, and evaluate to what extent the mortality can be directly attributed to the outbreak. DESIGN: cohort study. SETTING AND PARTICIPANTS: using a new information system developed during the pandemic, we gathered data on the number of daily deaths in the population residing in the provinces of Milan and Lodi by Local Health Unit (ASST) and age groups. To describe the case fatality of COVID-19, we performed a record linkage with a database specially constructed during the epidemic to identify deaths that occurred in confirmed cases. MAIN OUTCOME MEASURES: mortality and excess mortality were analysed by comparing the number of observed deaths in the first 4 months of 2020 with the average deaths of the years 2016-2019 in the same calendar period and with expected deaths, estimated using a Poisson model. Furthermore, a measure of relative risk was calculated as observed/expected ratio with a 95% confidence interval. RESULTS: the increase in mortality for all causes occurring in the study population in the first 4 months of 2020 was 48.8%, 30.8% for ages between 60 and 69, 43.9% for ages between 70 and 79, and 56.7% for subjects above 80 years of age. Focusing on the epidemic period, from 1 March to 30 April, the excess is quantifiable as more than 2-fold and mainly concerns the population over 60 years of age. The excess mortality was observed in all local health units (ASSTs). The highest increments were in the province of Lodi and the North-East of Milan (ASST Nord). In the ASSTs of Lodi and Melegnano-Martesana the mortality excess was detectable from March 15th, while for the other ASSTs the increase began in the first week of April. CONCLUSIONS: evaluation of overall mortality in the provinces of Milan and Lodi during the first wave of the Covid-19 epidemic showed a significant excess compared to the first 4 months of the years 2016-2019, mainly in the population over 60 years of age. However, this excess cannot be completely attributed directly to COVID-19 itself. This phenomenon was more intense in the Lodi ASST, with daily deaths up to 5 times higher than expected.

Preoperative immunonutrition in frail patients with colorectal cancer: an intervention to improve postoperative outcomes.

PURPOSE: The aim of this study is to evaluate whether preoperative immunonutrition can shorten length of stay and improve postoperative outcomes in frail patients who are candidates for major oncologic colorectal surgery. METHODS: A single center retrospective analysis of a prospectively collected database of frail patients, who underwent surgery with curative intent for colorectal cancer between January 2014 and December 2017, was performed. From March 2016, frail oncological patients undergoing major surgery were recommended to receive preoperative immunonutrition; their postoperative outcomes were compared to those of patients not treated with any preoperative nutritional support. Propensity score matching in a 1:1 ratio was used to balance patient characteristics. RESULTS: Overall, 175 patients were included in the study. Of 74 patients receiving immunonutrition, 65 were matched with the group not treated with immunonutrition (n = 101). Baseline characteristics were comparable after matching. Although differences in postoperative length of stay were nonsignificant (p = 0.38), patients who received immunonutrition showed a shorter gastrointestinal (GI) recovery time (3.00 [2.00-4.00] versus 4.00 [2.00-5.00], p = 0.04), a lower rate of situs site infections complications (0.31 [0.10, 0.94], p = 0.04) and less need of antibiotic treatment (0.19 [0.06, 0.64], p = 0.01). CONCLUSION: Preoperative immunonutrition was found to reduce both postoperative situs site infections and need of antibiotic treatment during the postoperative course. This study encourages the use of preoperative immune-enhancing nutrition as a part of multimodal prehabilitation programs in the management of frail colorectal cancer patients.

Residential distance from high-voltage overhead power lines and risk of Alzheimer's dementia and Parkinson's disease: a population-based case-control study in a metropolitan area of Northern Italy.

BACKGROUND: The association between the extremely low-frequency magnetic field generated by overhead power lines and neurodegenerative disease is still a matter of debate. METHODS: A population-based case-control study was carried out on the residents in the Milan metropolitan area between 2011 and 2016 to evaluate the possible association between exposure to extremely low-frequency magnetic fields generated by high-voltage overhead power lines and Alzheimer's dementia and Parkinson's disease. A statistical analysis was performed on cases and controls matched by sex, year of birth and municipality of residence (with a case to controls ratio of 1 : 4) using conditional logistic regression models adjusted for socio-economic deprivation and distance from the major road network as potential confounders. RESULTS: Odds ratios for residents <50 m from the source of exposure compared with residents at ≥600 m turned out to be 1.11 (95% confidence interval: 0.95-1.30) for Alzheimer's dementia and 1.09 (95% confidence interval: 0.92-1.30) for Parkinson's disease. CONCLUSIONS: The finding of a weak association between exposure to the extremely low-frequency magnetic field and neurodegenerative diseases suggests the continuation of research on this topic. Moreover, the low consistency between the results of the already existing studies emphasises the importance of increasingly refined study designs.

Substitution of sedentary time with light physical activity is related to increased bone density in U.S. women over 50 years old. An iso-temporal substitution analysis based on the National health and Nutrition Examination Survey.

U.S. women are ageing. This is causing rises in osteoporosis prevalence and risk of fracture with related increases in health care costs. Replacing sedentary time with light physical activity may represent a cost effective public health solution to osteoporosis in elderly women. The National Health and Nutrition Examination Survey conducted over the period 2003-2006 provided cross-sectional data on bone mineral density and objectively assessed physical activity among 1,052 women aged 50-85 years old. Substitution analysis was applied to estimate increased bone mineral density and reduced osteoporosis for those women replacing 30 min of sedentary time with an equivalent amount of light physical activity. Substitution of 30 min of sedentary time with an equal amount of light physical activity was associated with increased bone mineral density of about 3 mg/cm2 and a 12% reduced risk of osteoporosis in the spine. When considering overweight women and women over 65 years of age, this association was reinforced and it extended to the pelvis, legs and trunk, resulting in a consistent bone mineral density increase of about 3-6 mg/cm2. The substitution of 30 min of sedentary time with an equal amount of light physical activity appears a possible primary prevention method to reduce osteoporosis and related increases in risk of fracture, mortality, and health care costs in women over 50 years old.

Incidence, risk factors, and outcome of BK polyomavirus infection after kidney transplantation.

BACKGROUND: Polyomavirus-associated nephropathy is a leading cause of kidney allograft failure. Therapeutic options are limited and prompt reduction of the net state of immunosuppression represents the mainstay of treatment. More recent application of aggressive screening and management protocols for BK-virus infection after renal transplantation has shown encouraging results. Nevertheless, long-term outcome for patients with BK-viremia and nephropathy remains obscure. Risk factors for BK-virus infection are also unclear. AIM: To investigate incidence, risk factors, and outcome of BK-virus infection after kidney transplantation. METHODS: This single-centre observational study with a median follow up of 57 (31-80) mo comprises 629 consecutive adult patients who underwent kidney transplantation between 2007 and 2013. Data were prospectively recorded and annually reviewed until 2016. Recipients were periodically screened for BK-virus by plasma quantitative polymerized chain reaction. Patients with BK viral load ≥ 1000 copies/mL were diagnosed BK-viremia and underwent histological assessment to rule out nephropathy. In case of BK-viremia, immunosuppression was minimized according to a prespecified protocol. The following outcomes were evaluated: patient survival, overall graft survival, graft failure considering death as a competing risk, 30-d-event-censored graft failure, response to treatment, rejection, renal function, urologic complications, opportunistic infections, new-onset diabetes after transplantation, and malignancies. We used a multivariable model to analyse risk factors for BK-viremia and nephropathy. RESULTS: BK-viremia was detected in 9.5% recipients. Initial viral load was high (≥ 10000 copies/mL) in 66.7% and low (< 10000 copies/mL) in 33.3% of these patients. Polyomavirus-associated nephropathy was diagnosed in 6.5% of the study population. Patients with high initial viral load were more likely to experience sustained viremia (95% vs 25%, P < 0.00001), nephropathy (92.5% vs 15%, P < 0.00001), and polyomavirus-related graft loss (27.5% vs 0%, P = 0.0108) than recipients with low initial viral load. Comparison between recipients with or without BK-viremia showed that the proportion of patients with Afro-Caribbean ethnicity (33.3% vs 16.5%, P = 0.0024), panel-reactive antibody ≥ 50% (30% vs 14.6%, P = 0.0047), human leukocyte antigen (HLA) mismatching > 4 (26.7% vs 13.4%, P = 0.0110), and rejection within thirty days of transplant (21.7% vs 9.5%; P = 0.0073) was higher in the viremic group. Five-year patient and overall graft survival rates for patients with or without BK-viremia were similar. However, viremic recipients showed higher 5-year crude cumulative (22.5% vs 12.2%, P = 0.0270) and 30-d-event-censored (22.5% vs 7.1%, P = 0.001) incidences of graft failure than control. In the viremic group we also observed higher proportions of recipients with 5-year estimated glomerular filtration rate < 30 mL/min than the group without viremia: 45% vs 27% (P = 0.0064). Urologic complications were comparable between the two groups. Response to treatment was complete in 55%, partial in 26.7%, and absent in 18.3% patients. The nephropathy group showed higher 5-year crude cumulative and 30-d-event-censored incidences of graft failure than control: 29.1% vs 12.1% (P = 0.008) and 29.1% vs 7.2% (P < 0.001), respectively. Our multivariable model demonstrated that Afro-Caribbean ethnicity, panel-reactive antibody > 50%, HLA mismatching > 4, and rejection were independent risk factors for BK-virus viremia whereas cytomegalovirus prophylaxis was protective. CONCLUSION: Current treatment of BK-virus infection offers sub-optimal results. Initial viremia is a valuable parameter to detect patients at increased risk of nephropathy. Panel-reactive antibody > 50% and Afro-Caribbean ethnicity are independent predictors of BK-virus infection whereas cytomegalovirus prophylaxis has a protective effect.

Physical activity volume in relation to risk of atrial fibrillation. A non-linear meta-regression analysis.

Background Light physical activity is known to reduce atrial fibrillation risk, whereas moderate to vigorous physical activity may result in an increased risk. However, the question of what volume of physical activity can be considered beneficial remains poorly understood. The scope of the present work was to examine the relation between physical activity volume and atrial fibrillation risk. Design A comprehensive systematic review was performed following the PRISMA guidelines. Methods A non-linear meta-regression considering the amount of energy spent in physical activity was carried out. The first derivative of the non-linear relation between physical activity and atrial fibrillation risk was evaluated to determine the volume of physical activity that carried the minimum atrial fibrillation risk. Results The dose-response analysis of the relation between physical activity and atrial fibrillation risk showed that physical activity at volumes of 5-20 metabolic equivalents per week (MET-h/week) was associated with significant reduction in atrial fibrillation risk (relative risk for 19 MET-h/week = 0.92 (0.87, 0.98). By comparison, physical activity volumes exceeding 20 MET-h/week were unrelated to atrial fibrillation risk (relative risk for 21 MET-h/week = 0.95 (0.88, 1.02). Conclusion These data show a J-shaped relation between physical activity volume and atrial fibrillation risk. Physical activity at volumes of up to 20 MET-h/week is associated with reduced atrial fibrillation risk, whereas volumes exceeding 20 MET-h/week show no relation with risk.

Exercise might improve cardiovascular autonomic regulation in adolescents with type 1 diabetes.

Considering that changes in exercise routines might have relevance in treatment of adolescents with type 1 diabetes mellitus, we sought to assess whether spontaneous modifications to weekly exercise habits might occur in these patients and whether such variations would be accompanied by alterations in autonomic profile. In this observational study, we examined 77 patients (age 15.0 ± 0.6 years.) who in addition to a tailored optimal insulin treatment were invited to perform at least 1 h a day of moderate, aerobic exercise, as suggested by recent guidelines. Patients were studied at baseline (T0) and after 15.8 ± 0.7 months (T1). They were divided into three subgroups according to increased, unchanged and diminished total estimated weekly METs between T0 and T1. Autonomic profile was evaluated by assessing spontaneous baroreflex gain and low-frequency oscillation in arterial pressure, using spectral analysis of RR and systolic arterial pressure time series. Insulin therapy and biochemical data were similar among the 3 groups at T0 and T1, while body mass index standard deviation score was slightly reduced (p < 0.04) and markers of autonomic performance were improved (alpha index, from 17 ± 1 to 20 ± 2 ms/mmHg, p < 0.002) in the group who increased the amount of exercise (from 1627 ± 250 to 3582 ± 448 METs min wt(-1), p < 0.001). Furthermore, the change in total weekly METs significantly correlates with changes of key indices of autonomic regulation. The favourable autonomic effects of moderate increase in spontaneous exercise load suggest testing more formally this intervention in adolescents with type 1 diabetes.