Metabolic-associated fatty liver disease and liver fibrosis scores as COVID-19 outcome predictors: a machine-learning application.

Patients with COVID-19 and metabolic-dysfunction associated fatty liver disease (MAFLD) appear to be at higher risk for severe manifestations, especially in the youngest decades. Our aim was to examine whether patients with MAFLD and/or with increased liver fibrosis scores (FIB-4) are at risk for severe COVID-19 illness, using a machine learning (ML) model. Six hundred and seventy two patients were enrolled for SARS-CoV-2 pneumonia between February 2020 and May 2021. Steatosis was detected by ultrasound or computed tomography (CT). ML model valuated the risks of both in-hospital death and prolonged hospitalizations (> 28 days), considering MAFLD, blood hepatic profile (HP), and FIB-4 score. 49.6% had MAFLD. The accuracy in predicting in-hospital death was 0.709 for the HP alone and 0.721 for HP + FIB-4; in the 55-75 age subgroup, 0.842/0.855; in the MAFLD subgroup, 0.739/ 0.772; in the MAFLD 55-75 years, 0.825/0.833. Similar results were obtained when considering the accuracy in predicting prolonged hospitalization. In our cohort of COVID-19 patients, the presence of a worse HP and a higher FIB-4 correlated with a higher risk of death and prolonged hospitalization, regardless of the presence of MAFLD. These findings could improve the clinical risk stratification of patients diagnosed with SARS-CoV-2 pneumonia.

Common and specific gait patterns in people with varying anatomical levels of lower limb amputation and different prosthetic components.

The present study's aim was to identify the kinematic and kinetic gait patterns and to measure the energy consumption in people with amputation according to both the anatomical level of amputation and the type of prosthetic components in comparison with a control group matched for the gait speed. Fifteen subjects with unilateral transtibial amputation (TTA), forty with unilateral transfemoral amputation (TFA) (9 with mechanical, 17 with CLeg and 14 with Genium prosthesis) and forty healthy subjects were recruited. We computed the time-distance gait parameters; the range of angular motion (RoM) at hip, knee and ankle joints, and at the trunk and pelvis; the values of the 2 peaks of vertical force curve; the full width at half maximum (FWHM) and center of activity (CoA) of vertical force; the mechanical behavior in terms of energy recovery (R-step) and energy consumption. The main results were: i) both TTA and TFA show a common gait pattern characterized by a symmetric increase of step length, step width, double support duration, pelvic obliquity, trunk lateral bending and trunk rotation RoMs compared to control groups. They show also an asymmetric increase of stance duration and of Peak1 in non-amputated side and a decrease of ankle RoM in amputated side; ii) only TFA show a specific gait pattern, depending on the level of amputation, characterized by a symmetric reduction of R-step and an asymmetric decrease of stance duration, CoA and FWHM and an increase of Peak1 in the amputated side and of hip and knee RoM, CoA and FWHM in the non-amputated side; iii) people with amputation with Genium prosthesis show a longer step length and increased hip and knee RoMs compared to people with amputation with mechanical prosthesis who conversely show an increased pelvic obliquity: these are specific gait patterns depending of the type of prosthesis. In conclusion, we identified both common and specific gait patterns in people with amputation, either regardless of, or according to their level of amputation and the type of prosthetic component.

Use of adjuvanted trivalent influenza vaccine in older-age adults: a systematic review of economic evidence.

Seasonal influenza is a very common disease. Yearly vaccination of at-risk population groups is a well-recognized cost-effective/cost-saving preventive measure. It is, however, unclear which available alternative has the most favorable economic profile. Some available options are: trivalent (TIV) and quadrivalent (QIV) inactivated vaccines, adjuvanted TIV (aTIV). Because of immunosenescence, aTIV has been specifically developed for elderly. The present study aimed at assessing the available evidence of aTIV use in elderly from the economic perspective. A systematic literature review targeting aTIV economic evaluations in adults aged ≥65 years was performed using Medline via Ovid, Embase, DARE and NHS/EED. Of a total of 3,654 papers screened, 18 studies (13 full papers, 5 conference abstracts) were included. It emerged that compared with both non-vaccination or non-adjuvanted vaccines, aTIV was cost-effective or cost-saving. The vaccinations strategies incorporating aTIV based on age and/or risk profile are associated with the most favorable economic outcomes.

Non-destructive vacuum decay method for pre-filled syringe closure integrity testing compared with dye ingress testing and high-voltage leak detection.

UNLABELLED: In reaction to the limitations of the traditional sterility test methods, in 2008, the U.S. Food and Drug Administration issued the guidance "Container and Closure System Integrity Testing in Lieu of Sterility Testing as a Component of the Stability Protocol for Sterile Products" encouraging sterile drug manufacturers to use properly validated physical methods, apart from conventional microbial challenge testing, to confirm container closure integrity as part of the stability protocol. The case study presented in this article investigated the capability of four container closure integrity testing methods to detect simulated defects of different sizes and types on glass syringes, prefilled both with drug product intended for parenteral administration and sterile water. The drug product was a flu vaccine (Agrippal, Novartis Vaccines, Siena, Italy). Vacuum decay, pharmacopoeial dye ingress test, Novartis specific dye ingress test, and high-voltage leak detection were, in succession, the methods involved in the comparative studies. The case study execution was preceded by the preparation of two independent sets of reference prefilled syringes, classified, respectively, as examples of conforming to closure integrity requirements (negative controls) and as defective (positive controls). Positive controls were, in turn, split in six groups, three of with holes laser-drilled through the prefilled syringe glass barrel, while the other three with capillary tubes embedded in the prefilled syringe plunger. These reference populations were then investigated by means of validated equipment used for container closure integrity testing of prefilled syringe commercial production; data were collected and analyzed to determine the detection rate and the percentage of false results. Results showed that the vacuum decay method had the highest performance in terms of detection sensitivity and also ensured the best reliability and repeatability of measurements. An innovative technical solution, preventing possible prefilled syringe plunger movement during container closure integrity testing execution, is presented as well. LAY ABSTRACT: The growing need to meet sterile drug products' regulatory, quality, and safety expectations has progressively driven new developments and improvements both in container closure integrity testing methods and in the respective equipment, over the last years. Indeed, container closure integrity testing establishes the container closure system capability to provide required protection to the drug product and to demonstrate maintenance of product sterility over its shelf life. This article describes the development of four container closure integrity testing approaches for the evaluation of glass prefilled syringe closure integrity, including two destructive (pharmacopoeial and Novartis specific dye ingress test) and two non-destructive (vacuum decay and high-voltage leak detection) methods. The important finding from the validation of comparative studies was that the vacuum decay method resulted in the most effective, reliable and repeatable detection of defective samples, whether the defect was exposed to sterile water, to drug product, or to air. Complete sets of known defects were created for this purpose (5 µm, 10 µm, 20 µm certified leakages by laser drilled holes and capillary tubes). All investigations and studies were conducted at Bonfiglioli Engineering S.r.l. (Vigarano Pieve, Ferrara, Italy) and at Novartis Vaccines (Sovicille, Siena, Italy).

Priority persistent contaminants in people dwelling in critical areas of Campania Region, Italy (SEBIOREC biomonitoring study).

To investigate if protracted living in degraded environments of the Caserta and Naples provinces (Campania Region, Italy) had an impact on exposure of local people, highly toxic persistent contaminants were measured in blood, blood serum, and human milk of a large number of healthy donors. Sampling was carried out from 2008 to 2009. Blood was collected from over 850 20-64-year old donors; by pooling, 84 blood and 84 serum samples were obtained. Milk was donated by 52 mothers: specimens were pooled into six samples. Polychlorodibenzodioxins (PCDDs), polychlorodibenzofurans (PCDFs), and polychlorobiphenyls (PCBs, dioxin-like (DL) and non-dioxin-like (Σ6PCBs)), arsenic (As), cadmium (Cd), mercury (Hg), and lead (Pb) were measured in serum (organic biomarkers) and blood (metals); these chemicals and polybromobiphenyl ethers (Σ9PBDEs) were analyzed in milk. PCDD+PCDF, DL-PCB, TEQTOT, and Σ6PCB concentration ranges (medians) in serum were 6.26-23.1 (12.4), 3.42-31.7 (11.5), 10.0-52.8 (23.9) pgTEQ97/g fat, and 55.5-647 (219) ng/g fat, respectively, while in milk concentration ranges were 5.99-8.77, 4.02-6.15, 10.0-14.2 pgTEQ97/g fat, and 48.7-74.2 ng/g fat. Likewise, As, Cd, Hg, and Pb findings in blood spanned 2.34-13.4 (5.83), 0.180-0.930 (0.475), 1.09-7.60 (2.60), 10.2-55.9 (28.8) µg/L, respectively; only Pb could be measured in milk (2.78-5.99 µg/L). Σ9PBDE levels in milk samples were 0.965-6.05 ng/g fat. Biomarkers' concentrations were found to be compatible with their current values in European countries and in Italy, and consistent with an exposure primarily determined by consumption of commercial food from the large distribution system. Based on relatively higher biomarker values within the hematic biomonitoring database, the following municipalities were flagged as possibly deserving attention for health-oriented interventions: Brusciano and Caivano (As), Giugliano (Hg), Pianura (PCDDs+PCDFs), and Qualiano-Villaricca (As, Hg). The analysis of samples' qualitative variability indicated that biomarker composition was sensitive at municipality level, a feature that can potentially drive interventions for future local risk assessment and/or management measures.

Improving adherence rates to a cocooning program: a pilot experience in Italy.

Cocoon is defined as a strategy to reduce the risk for transmission of pertussis to newborn infants by vaccinating household members including parents and siblings. Programmatic challenges make implementation of cocooning program complex. At the local health care unit "ASL Napoli 1 Centro," a one-year pilot project to evaluate the newborn contacts adherence to a cocoon strategy was started on May, 1st 2011. Healthcare providers (HCPs) offered for free a dTpa booster dose to newborns parents (mothers were immunized after delivery) and household contacts. Until June 30th, overall only 7 dTpa booster doses out of 261 newborns (2.6%) were administered for cocooning. Then, an improvement in communication strategy to the families was introduced by preparing specific information leaflets, increasing the HCPs devoted to the cocoon, and focusing the interaction with families during the visiting time at the maternity ward. Overall, 601 out of 762 (78,8%) contacted new mothers received dTpa booster. Cocoon high acceptance rates could be reached providing that proper communication tools and enough skilled HCPs were engaged in the interaction with the families. This report is, to our knowledge, the first to document successful implementation of pertussis cocooning in an Italian setting.

Mortality study in an asbestos cement factory in Naples, Italy.

The objective of this paper is to investigate mortality among 1247 male asbestos-cement workers employed in an asbestos-cement plant located in Naples. The cohort included 1247 men hired between 1950 and 1986. The follow-up began on January 1st 1965. The vital status and causes of death were ascertained up to December 31 2005. Cause-specific mortality rates of the Campania Region population were used as reference. Relative risks were estimated using Standardized Mortality Ratios (SMRs), and the confidence intervals were calculated at a 95% level (95% CI). A significant increase in mortality was observed for respiratory disease (81 deaths; SMR = 187; 95% CI = 149- 233), particularly for pneumoconiosis (42 deaths; SMR = 13 313; 95% CI = 9595-17 996) of which 41 deaths for asbestosis (SMR = 43 385; 95% CI = 31 134-58 857), for pleural cancer (24 deaths; SMR = 2617; 95% CI = 1677-3893), for lung cancer (84 deaths; SMR=153; 95% CI = 122-189) and for peritoneal cancer (9 deaths; SMR = 1985; 95% CI = 908-3769). Non-significant increases were also observed for rectum cancer (6 deaths; SMR = 157; 95% CI = 58-342). In conclusion, consistently with other mortality studies on asbestos-cement workers performed in different countries, an increased mortality from asbestosis, lung cancer, pleural and peritoneal mesothelioma was detected in the present cohort.

[Epidemiology of breast cancer in a local health organisation of Naples (Italy), 1995-2003]. / L'Epidemiologia del ca mammario nel distretto 46 dell'ASL NA1: anni 1995-2003.

A database was created by the authors to collect data on breast cancer epidemiology in a local health organisation of Naples. Data on women residing in the territory of the local health organisation and who had received a diagnosis of breast cancer, based on clinical, radiological, and pathology criteria, between 1 January 1995 and 31 December 2003, was collected through linkage of various data sources. Overall, 475 new cases were identified in women aged over 34 years at diagnosis. Though yearly raw incidence rates show an increasing trend, this was not confirmed by subsequent analysis of standardized rates. The age-specific incidence curve depicts a sharp increase from ages 30 to 50-54 years and a slower rise after the menopause, analogously to what has been shown for Europe. Standardised morbidity rates in the examined period (1996-2003) are lower than those detected by the pool of Italian tumour registries (Italian Association of Tumor Registries - AIRT) but similar to those observed by the two Campania regional tumour registries. Standardised mortality rates were found to be similar to those observed by the AIRT Pool and by the two regional registries. Age-specific mortality rates indicate three levels of risk: low-risk below 39 years of age, intermediate risk between 40-59 years of age and high risk = 60 years.

[Carcinoid tumours of the bile ducts]. / Carcinoide delle vie biliari.

Carcinoid tumors of the extrahepatic bile ducts are extremely rare and account for only 0.2-2% of all gastrointestinal endocrine neoplasms. They are particularly difficult to diagnose preoperatively and distinguish from cholangiocarcinoma. We report the case of a 52-year-old patient with a carcinoid tumour of the common bile duct presenting with obstructive jaundice. Laboratory and imaging studies (US, CT, MRI) showed an obstructive lesion measuring 2 cm in diameter in the common bile duct. A biliary stent was inserted initially to decompress the bile ducts. Brushing was negative for malignant cells. With a suspicion of malignancy (confirmed intraoperatively), the patient underwent radical resection of the extrahepatic duct, portal lymphadenectomy and a Roux-en-Y hepaticojejunostomy. The pathology examination revealed a well-differentiated neuroendocrine tumour of the common hepatic duct. The tumour cells were immunopositive for chromogranin A and synoptophysin. There was no evidence of metastases in the nodes removed and negative surgical margins were achieved. The patient is disease-free after a follow up of 3 months, and levels of chromogranin A and neuron-specific enolase are normal. Local and systemic aggressiveness of these tumours is rare. Radical surgery offers the only chance of a cure and has to be considered whenever possible.

[Data quality of a breast cancer database in Naples, Italy. Do the necessary conditions exist for implementing a disease registry?]. / Qualità dell'informazione della banca dati del ca mammario.

Data quality is one of the fundamental aspects of health information systems and is influenced both by the type and accuracy of the data sources used. The aim of this study was to assess the quality of data in a breast cancer database held by a local health authority in Naples (Italy) and to evaluate the possibility of implementing a disease registry. The database collects information from different sources and was evaluated in terms of completeness, accuracy and comparability. Data linkage of all district data sources was performed; these included medical charts of the Integrated Territorial Oncology Service (SOTI), hospital discharge abstract forms, disability registry, list of subjects affected by specific disorders and therefore entitled to exemption from healthcare costs related to their disease, and the Nominal Registry of Causes of Death (ReNCaM). From 1 January 1995 to 31 December 2003, 475 incident cases of breast cancer were identified; 313 (65.9%) of which through the Integrated Territorial Oncology Service, and 71 (14,9%) through discharge abstract records, while only 3.6%, 4.0% and 11.6%, respectively, through the disability registry, lists of subjects with healthcare costs exemptions, and the ReNCaM. Medical charts of the Oncology Service were found to be the most complete data source for demographic information, hospital name, staging and treatments given, histologic diagnosis, and for most risk factors. By linking 178 patients registered both in the discharge abstract forms and in the Oncology medical charts, discordant demographic data, name of hospital, and date of diagnosis were found respectively in 7.3%, 16.3%, and 42.1% of cases. Overall the quality of data was found to be good and comparable to other registries. However the database cannot yet be considered as a disease registry in view of the small geographical area involved and the lack of continuous and systematic data flow; the latter can be provided only by facilities with sufficient economic resources and personnel specifically assigned to the task.

Deprivation, immigration and tuberculosis incidence in Naples, 1996-2000.

Most of the tuberculosis cases in Campania occur in Naples, the biggest city in the South of Italy with the highest unemployment and immigration rates. However, the occurrence of tuberculosis differs between the different neighbourhoods and it is not known whether these differences are associated with poverty or with immigration. We describe tuberculosis incidence and its association with socio-economic status and immigration in the city of Naples during the period 1996-2000. The basic design was an ecological study, correlating the incidence of tuberculosis which was calculated on the basis of notified tuberculosis cases to census data on immigration and socio-economic deprivation per neighbourhood. Immigrants had a high risk for tuberculosis (RR=34 for Africans) but the incidence of TB varied largely by districts and seemed independent of immigration. All socioeconomic factors increased the incidence of TB significantly. In a multivariate Poisson regression analysis only the rate of unemployment (p=0.02) and the population density (p=0.002) remained independently associated with tuberculosis incidence. In this study we showed that deprivation explained differences in tuberculosis incidence in Naples to a greater extent than immigration.

Factors affecting the compliance of the antenatal hepatitis B screening programme in Italy.

The effectiveness in the prevention of perinatally transmitted HBV infection was assessed in 11858 pregnant women consecutively recruited in public and private hospitals in six Italian regions during a 2 months period in 2001. Of them 10881 (91.8%) attended HBsAg antenatal screening. The overall HBsAg prevalence was 1.7% (CI 95%: 1.4-1.9); it was 1.4% (CI 95%: 1.2-1.7) in pregnant women born in Italy but 5.9% (CI 95%: 4.1-8.1) in those born in Asia, Africa, central and south America, and eastern Europe. Results of multiple logistic regression analysis indicate that birth in foreign countries (OR 2.0; CI 95%: 1.3-3.0), family size with more than 4 members in the household (OR 3.5; CI 95%:2.7-4.6), and birth in a private hospital (OR 1.9; CI 95%: 1.3-2.8) were all independent predictors of lack of adherence to HBsAg screening. Out of the 182 new-borns of HBsAg positive mothers 172 (95.0%) were given active plus passive immunisation; this figure was 100% in new-borns of foreign mothers. These findings evidence a good effectiveness in the prevention of perinatally transmitted HBV in Italy. More efforts should be addressed to improve the effectiveness of the programme among foreign pregnant women who have high rate of HBsAg and more likely escape HBsAg screening than Italian pregnant women.

Evaluation of immunization practices in Naples-Italy.

This paper reports the results of a survey on vaccination coverage among children born in January 1995 and residing at the beginning of the study (March 1998) in the city of Naples, Italy. The percentages vaccinated, at various times from birth, with oral polio vaccine (OPV), have been compared with those found in a similar survey conducted at the end of 1985 regarding the cohort of children born in June 1983. By the fourth month of life 67% of the 1995 cohort were vaccinated with the first doses of OPV, an increase of about 26% on that found in the 1983 cohort. Similar results were found with the second doses. Among the 1995 cohort 49% were vaccinated with the third dose of OPV within the thirteenth month of life; the corresponding value for the 1983 cohort was 33%. Within the twenty-fourth month of life, in the 1995 cohort, 86% completed the primary cycle of vaccination with OPV; the corresponding figure for the 1983 cohort was 65%. At the end of the third year of life 80% of the 1995 cohort received the fourth dose of OPV. A significant association has been found between socioeconomic status and coverage level.