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In this study, we investigated associations among subclinical intra-mammary infection (IMI) and quarter-level milk composition, udder health indicators, and cheesemaking traits. The dataset included records from 450 Holstein cows belonging to three dairy herds. After an initial screening (T0) to identify animals infected by Streptococcus agalactiae , Streptococcus uberis , Staphylococcus aureus , and Prototheca spp., 613 quarter milk samples for 2 different sampling times (T1 and T2, 1 mo after T1) were used for analysis. Milk traits were analyzed using a hierarchical linear mixed model including the effects of days in milk, parity and herd, and bacteriological and inflammatory category [culture negative with somatic cell count (SCC) <200,000 cells/mL; culture negative with SCC ≥200,000 cells/mL; or culture positive]. All udder health indicators were associated with increased SCC and IMI at both sampling times. The largest effects were detected at T2 for milk lactose (−7% and −5%) and milk conductivity (+9% and +8%). In contrast, the increase in differential SCC (DSCC) in samples with elevated SCC was larger at T1 (+17%). Culture-negative samples with SCC ≥200,000 cells/mL had the highest SCC and greatest numbers of polymorphonuclear-neutrophils-lymphocytes and macrophages at both T1 and T2. Regarding milk cheesemaking ability, samples with elevated SCC showed the worst pattern of curd firmness at T1 and T2. At T2, increased SCC and IMI induced large decreases in recoveries of nutrients into the curd, in particular recovered protein (−14% and −16%) and recovered fat (−12% and −14%). Different behaviors were observed between Strep. agalactiae and Prototheca spp., especially at T2. In particular, samples that were positive for Strep. agalactiae had higher proportions of DSCC (+19%) compared with negative samples with low SCC, whereas samples that were positive for Prototheca spp. had lower DSCC (−11%). Intramammary infection with Prototheca spp. increased milk pH compared with culture-negative samples (+3%) and negative samples that had increased SCC (+2%). The greatest impairment in curd firmness at 30 min from rennet addition was observed for samples that were positive for Prototheca spp. (−99% compared with negative samples, and −98% compared with negative samples with high SCC). These results suggest that IMI caused by Prototheca spp. have detrimental effects on milk technological traits that deserve further investigation of the mechanisms underlying animals' responses to infection. [ABSTRACT FROM AUTHOR]

RATIONALE: Acute effects of ozone on mortality have been extensively documented in clinical and epidemiological research. However, only a few studies have focused on subgroups of the population especially vulnerable to these effects. OBJECTIVES: To estimate the association between exposure to ozone and cause-specific mortality, and to evaluate whether individual sociodemographic characteristics or chronic conditions confer greater susceptibility to the adverse effects of ozone. METHODS: A case-crossover analysis was conducted in 10 Italian cities. Data on mortality were collected for the period 2001 to 2005 (April-September) for 127,860 deceased subjects. Information was retrieved on cause of death, sociodemographic characteristics, chronic conditions from previous hospital admissions, and location of death. Daily ozone concentrations were collected from background fixed monitors. MEASUREMENTS AND MAIN RESULTS: We estimated a 1.5% (95% confidence interval [CI], 0.9-2.1) increase in total mortality for a 10 microg/m(3) increase in ozone (8-h, lag 0-5). The effect lasted several days for total, cardiac and respiratory mortality (lag 0-5), and it was delayed for cerebrovascular deaths (lag 3-5). In the subgroup analysis, the effect was more pronounced in people older than 85 years of age (3.5%; 95% CI, 2.4-4.6) than in 35- to 64-year-old subjects (0.8%; 95% CI, -0.8 to 2.5), in women (2.2%; 95% CI, 1.4-3.1) than in men (0.8%; 95% CI, -0.1 to 1.8), and for out-of-hospital deaths (2.1%; 95% CI, 1.0-3.2), especially among patients with diabetes (5.5%; 95% CI, 1.4-9.8). CONCLUSIONS: A greater vulnerability of elderly people and women was indicated; subjects who died at home and had diabetes emerged as especially affected. [ABSTRACT FROM AUTHOR]

Ultrasound (US) imaging has been proposed as a noninvasive tool for monitoring liver dysfunction in dairy cows. This study, carried out on 306 clinically healthy Holstein cows in the first 120 d of lactation kept in 2 herds in northern Italy, aimed at investigating the association between US imaging-derived traits, namely predicted liver triacylglycerol content (pTAG, mg/g), liver depth (LD, mm), portal vein depth (PVD, mm) and area (PVA, mm2), and body size measurements, body condition score (BCS), and milk productivity indicators. Transcutaneous US examination, milk sampling, body size measurements (withers height and heart girth), and BCS were collected once from all cows in 10 sampling batches. The body weights (BW) of a subsample of 73 cows were recorded and used together with an existing data set of BW and measures of Holstein Friesian cows (n = 399) to develop a regression equation to predict BW, which was then used to compute productivity indicators by scaling the milk production traits to predicted BW. Body size measures, BCS, milk traits, and productivity indicators were classified (low, medium, and high) in 0.75 units of standard deviation of the residuals generated from a linear model that included the effects of parity, days in milk, and sampling batch. Liver pTAG, PVA, PVD, and LD were analyzed with a sequence of linear mixed models that included the fixed effects of days in milk and parity and the random effect of sampling batch as common terms, whereas the classes of body and milk traits and the productivity indicators were included one by one. The US-related traits were found to be associated with body size measurements and BCS. Specifically, pTAG was inversely related to BCS, whereas PVD and LD increased with increasing heart girth, BCS, and predicted BW. Generally, no relevant associations were observed between the US parameters and milk production traits, including when expressed in terms of productivity. In conclusion, this study suggests that US measures of liver dimensions of clinically healthy cows are related to their size, whereas pTAG concentrations reflect body condition status, with no particular implications for milk production and productivity. Moreover, healthy cows seemed able to counteract the metabolic stress of the first 120 d of the lactation period without straining liver functionality. Finally, US imaging proved to be a promising technique to assess liver metabolic conditions. However, further studies are needed to confirm its potential as a noninvasive tool for monitoring liver conditions in healthy cows. [ABSTRACT FROM AUTHOR]

The aim of this study was to investigate the associations between differential somatic cell count (DSCC) and milk quality and udder health traits, and for the first time, between DSCC and milk coagulation properties and cheesemaking traits in a population of 1,264 Holstein cows reared in northern Italy. Differential somatic cell count represents the combined proportions of polymorphonuclear neutrophils plus lymphocytes (PMN-LYM) in the total somatic cell count (SCC), with macrophages (MAC) making up the remaining proportion. The milk traits investigated in this study were milk yield (MY), 8 traits related to milk composition and quality (fat, protein, casein, casein index, lactose, urea, pH, and milk conductivity), 9 milk coagulation traits [3 milk coagulation properties (MCP) and 6 curd firming (CF) traits], 7 cheesemaking traits, 3 cheese yield (CY) traits, and 4 milk nutrient recovery in the curd (REC) traits. A linear mixed model was fitted to explore the associations between SCS combined with DSCC and the aforementioned milk traits. An additional model was run, which included DSCC expressed as the PMN-LYM and MAC counts, obtained by multiplying the percentage of PMN-LYM and MAC by SCC in the milk for each cow in the data set. The unfavorable association between SCS and milk quality and technological traits was confirmed. Increased DSCC was instead associated with a linear increase in MY, casein index, and lactose proportion and a linear decrease in milk fat and milk conductivity. Accordingly, DSCC was favorably associated with all MCP and CF traits (with the exception of the time needed to achieve maximum, CF), particularly with rennet coagulation time, and it always displayed linear relationships. Differential somatic cell count was also positively associated with the recovery of milk nutrients in the curd (protein, fat, and energy), which increased linearly with increasing DSCC. The PMN-LYM count was rarely associated with milk traits, even though the pattern observed confirmed the results obtained when both SCS and DSCC were included in the model. The MAC count, however, showed the opposite pattern: MY, casein index, and lactose percentage decreased and milk conductivity increased with an increasing MAC count. No significant association was found between PMN-LYM count and MCP, CF, CY, and REC traits, whereas MAC count was unfavorably associated with MCP, CF traits, some CY traits, and all REC traits. Our results showed that the combined information derived from SCS and DSCC might be useful to monitor milk quality and cheesemaking-related traits. [ABSTRACT FROM AUTHOR]

Musculoskeletal allografts represent an important practice in orthopedic surgeries and the demand for them has been growing. For this reason, in order to reduce clinical risk and to more efficiently manage the increase of allograft usage and also to optimize timing of the surgeries, the thawing and washing processes with aseptic technique were centralized in the department of Hospital Pharmacy. This study describe the design and execution of an adapted Media Fill Test (MFT) to demonstrate aseptic thawing and washing of allografts. For this specific and innovative setting, to better simulate the actual processing steps, a surrogate system was developed to simulate the tendon allograft. The aseptic technique of four operators was assessed and an initial performance validation and the first revalidation were described. All MFT were completed successfully, with no observation of turbidity. The readapted MFT shown in this study can provide insight into this innovative and growing field to other health professionals who want to implement this service., (© 2023. The Author(s), under exclusive licence to Springer Nature B.V.)

Objectives: On 21 December 2020 the European Commission granted conditional marketing authorisation in the European Union for the anti-COVID-19 mRNA vaccine Bnt162b2 (Comirnaty, Pfizer/BioNTech). The main endpoint of this epidemiological, observational, prospective and monocentric study was to identify the number, types, and severity of adverse events following immunisation that occurred in subjects who had been previously infected with COVID-19, and in those who had not, after vaccination with Comirnaty, and to compare the two groups of subjects looking at events that occurred within a month after the first and the second dose., Methods: Data were gathered by a questionnaire. The results included the responses of all healthcare workers (2030) of the IRCCS Sacro Cuore Don Calabria Hospital (Italy) vaccinated between 1st January and 28th February 2021. Adverse effects of the vaccine were reported after the first and the second doses., Results: There was a statistically significant increase (p<0.001, χ 2 =35.60) in participants who experienced some side-effects after receiving the first dose of the vaccine and who had previously been infected with the coronavirus, compared with participants who had not previously been infected. 46.76% (136) of the participants who had previously been infected experienced some side-effects after the first dose of vaccine, and 63.23% (184) experienced some side-effects after the second dose, compared with 29.15% (507) after the first dose and 70.79% (1231) after the second dose in those who had not been previously infected. The number of participants who experienced side-effects after the second dose and had previously been infected was significantly lower compared with participants who had not previously been infected (p=0.0094, χ 2 =6.743)., Conclusions: Most of the side-effects identified in this trial were also reported by the manufacturer and the US Food and Drug Administration. Active surveillance should always continue to constantly check the vaccine's risk/benefit ratio over time., Competing Interests: Competing interests: None declared., (© European Association of Hospital Pharmacists 2023. No commercial re-use. See rights and permissions. Published by BMJ.)

Objectives: The transplantation of human tissues is a greatly expanding field of medicine with unquestionable benefits that raise questions about safety, quality and ethics. Since 1 October 2019, the Fondazione Banca dei Tessuti del Veneto (FBTV) stopped sending thawed and ready to be transplanted cadaveric human tissues to hospitals. A retrospective analysis of the period 2016-2019 found a significant number of unused tissues. For this reason, the hospital pharmacy has developed a new centralised service characterised by thawing and washing human tissues for orthopaedic allografts. This study aims to analyse the hospital cost and benefit derived from this new service., Methods: Aggregate data relating to tissue flows were obtained retrospectively for the period 2016-2022 through the hospital data warehouse. All tissues arriving from FBTV for each year were analysed, dividing them according to the outcome (if used or wasted). The percentage of wasted tissues as well as the economic loss due to wasted allografts were analysed per year and trimester., Results: We identified 2484 allografts requested for the period 2016-2022. In the last 3 years of the analysis, characterised by the new tissue management of the pharmacy department, we found a statistically significant reduction in wasted tissues (p<0.0001) from 16.33% (216/1323) with a cost to the hospital of 176 866€ during the period 2016-2019 to 6.72% (78/1161) with a cost to the hospital of 79 423€ during the period 2020-2022., Conclusion: This study shows how the centralised processing of human tissues in the hospital pharmacy makes the procedure safer and more efficient, demonstrating how the synergy between different hospital departments, high professional skills and ethics can lead to a clinical advantage for patients and a better economic impact for the hospital., Competing Interests: Competing interests: None declared., (© European Association of Hospital Pharmacists 2023. No commercial re-use. See rights and permissions. Published by BMJ.)

Ethical networks are an emerging form of social alliance based on collaboration between organizations that share a common ethical commitment. Grounded in a theoretical framework of virtue-based business ethics and focusing on nonprofit alliances, this study investigates the virtuousness of ethical networks; that is, how they trigger virtuous practices in their member nonprofit organizations. Adopting a qualitative grounded theory approach, the study focuses on one of the largest Italian ethical networks of nonprofit organizations operating in the social care sector. The findings show that shared ethical values and religious beliefs are positively associated with ethical network building. Based on these findings, a circular model of virtuousness is proposed in which ethical networks foster virtuous practices among their members at four levels: (1) the strategic orientation level, (2) the institutional level, (3) the organizational level, and (4) the relational level. At each of these levels, ethical networks foster a habituation to virtues and the propagation of virtuous behaviors among their members. Theoretical, practical, and social implications of the research findings are discussed., Competing Interests: Conflict of interestThe authors declare that they have no conflict of interest., (© The Author(s) 2023.)

Bovine respiratory disease (BRD) is a global infectious disease, causing decreased well-being and economic losses in livestock, frequently during the restocking period. The aim of this study was to evaluate the feasibility of thoracic ultrasonography (TUS) to assess BRD in restocked animals, and the effectiveness of tulathromycin and ketoprofen treatment in sick animals. A total of 60 Limousin fattening bulls were enrolled. On the day of restocking (T0), the animals were divided into two groups based on TUS assessment of six lung areas: group C (ultrasonography score (US score) < 3) and group D (US score ≥ 3). Group D received a single administration of tulathromycin and ketoprofen at T0: this group was revaluated after 1.5, 3, 7, and 14 days. Both groups were revaluated after 21 days. The two groups showed a significant difference both in US score and clinical symptoms (respiratory score, nasal and ocular discharges, and rectal temperature) at T0. In group D, the treatment was effective in improving the clinical symptoms and US score, particularly reducing the severity of lung lesions. TUS represents a non-invasive and cost-effective tool for BRD early diagnosis and for monitoring treatment efficacy in restocked livestock.

Recently, the atrial fibrillation treatment guidelines have been updated to now recommend Non-vitamin K antagonist oral anticoagulants (NOACs) as the preferred alternative to warfarin for systemic embolism and stroke prevention in patients with non-valvular atrial fibrillation. NOACs have major pharmacologic advantages over warfarin, although the most common complications are gastrointestinal bleeding and NOAC-induced nephropathy within 6 weeks after starting therapy, as several recent case-reports stated. We are reporting for the first time a chronic delayed adverse reaction (regularly reported to Authorities) observed in an 82-year-old woman 27 months after starting dabigatran (110 mg twice a day), characterized by concomitant gastrointestinal bleeding and nephropathy. Idarucizumab administration immediately improved both bleeding and renal parameters. Moreover, we are going to highlight the importance of the compliance, the adherence to the therapeutic plan and the supervision of the Hospital Pharmacy on drug prescriptions. In fact in our case, dabigatran was firstly prescribed by the neurologist and delivered by the hospital pharmacy, but the patient continued the treatment for 27 months, prescribed by general practitioner without any laboratory control. This lack of supervision certainly contributed to the onset of the adverse reaction reported., Competing Interests: Declaration of Conflicting Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2021.)

High concentrations of ivermectin demonstrated antiviral activity against SARS-CoV-2 in vitro. The aim of this study was to assess the safety and efficacy of high-dose ivermectin in reducing viral load in individuals with early SARS-CoV-2 infection. This was a randomised, double-blind, multicentre, phase II, dose-finding, proof-of-concept clinical trial. Participants were adults recently diagnosed with asymptomatic/oligosymptomatic SARS-CoV-2 infection. Exclusion criteria were: pregnant or lactating women; CNS disease; dialysis; severe medical condition with prognosis <6 months; warfarin treatment; and antiviral/chloroquine phosphate/hydroxychloroquine treatment. Participants were assigned (ratio 1:1:1) according to a randomised permuted block procedure to one of the following arms: placebo (arm A); single-dose ivermectin 600 μg/kg plus placebo for 5 days (arm B); and single-dose ivermectin 1200 μg/kg for 5 days (arm C). Primary outcomes were serious adverse drug reactions (SADRs) and change in viral load at Day 7. From 31 July 2020 to 26 May 2021, 32 participants were randomised to arm A, 29 to arm B and 32 to arm C. Recruitment was stopped on 10 June because of a dramatic drop in cases. The safety analysis included 89 participants and the change in viral load was calculated in 87 participants. No SADRs were registered. Mean (S.D.) log 10 viral load reduction was 2.9 (1.6) in arm C, 2.5 (2.2) in arm B and 2.0 (2.1) in arm A, with no significant differences (P = 0.099 and 0.122 for C vs. A and B vs. A, respectively). High-dose ivermectin was safe but did not show efficacy to reduce viral load., (Copyright © 2022 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Lameness represents one of the main causes of decreased productive performance and impaired animal welfare in the bovine industry. Young beef bulls are predisposed to develop diseases of the growing skeleton, especially growth plate lesions. Early diagnosis is indispensable for ensuring correct treatment, fast recovery and reduction losses. However, when dealing with beef cattle, this is not always possible. Fast and reliable diagnostic imaging techniques are necessary to improve dealing with lameness in beef animals. The aim of the present study was to examine the potential of thermographic imaging as a non-invasive tool for rapidly screening beef bulls for the presence of growth plate lesions. Here, 20 Charolais and Limousine beef bulls affected by growth plate lesions in one of the rear limbs were selected. IRT was performed on both hind limbs using a digital infrared camera (ThermaCam T420 Model, Flir Systems, Boston, MA, USA), prior to radiographic imaging and clinical examination. The temperature of healthy and affected limbs was measured in two regions: the area correspondent to the growth plate (AR01) and the whole area of the metatarsus (AR02). Growth plate lesions were found to increase the maximum, mean, and minimum temperatures in AR01; and the mean and maximum temperatures in AR02, therefore, indicating the potential of IRT as a reliable, practical tool for screening growth plate lesions in beef bulls.

Metabolic disorders, including hepatic lipidosis and ketosis, severely affect animal health status and welfare with a large economic burden in dairy herds. The gold standard for diagnosing hepatic lipidosis is the liver biopsy, which is impractical and invasive for the screening at farm level. Ultrasound (US) imaging is a promising technique for identifying liver dysfunction, but standardized specifications in physiological conditions are needed. Herein, we described the features of four US measurements, namely the liver predicted triacylglycerol (pTAG) content, liver depth (LD), and portal vein area (PVA) and depth (PVD) and we investigated their associations with a set of hematochemical (HC) indicators in 342 clinically healthy Holstein Friesian dairy cows. Liver pTAG content was negatively associated with hematocrit and positively with globulin, whereas PVA was negatively associated with thiol group levels, and LD positively with ceruloplasmin. We found significant interactions between some HC parameters and parity: in particular, creatinine, thiol groups and globulin for PVA, and aspartate aminotransferase, paraoxonase and ceruloplasmin for PVD. This study offers new insights on variations in liver function occurring after calving and pave the way for the potential use of minimally invasive techniques for prompt detection of metabolic disorders in dairy herds., (© 2021. The Author(s).)

Competing Interests: Conflict of interest statement The authors declare no conflict of interest.

Ketosis is a metabolic disease of pregnant and lactating ewes linked to a negative energy balance which can cause different economic losses. The aims of this study were to understand the metabolic status of the early-lactating ewes and to identify biomarkers for early diagnosis of subclinical ketosis. Forty-six Sarda ewes were selected in the immediate post-partum for the collection of the biological samples. A blood sample from the jugular vein was used to determine β-Hydroxybutyrate (BHB) concentrations. Animals were divided into two groups: BHB 0 or healthy group ( n = 28) with BHB concentration < 0.86 mmol/L; and BHB 1 or subclinical ketosis ( n = 18) with a BHB concentration ≥ 0.86 mmol/L. Ten mL of pool milk were collected at the morning milking for the analyses. The concentration of 34 milk fatty acids was evaluated using gas chromatography. Two biochemical parameters and 11 milk fatty acids of the total lipid fraction presented a p -value ≤ 0.05. The study revealed different relationships with tricarboxylic acid cycle, blood flows, immune and nervous systems, cell functions, inflammatory response, and oxidative stress status. Eight parameters were significant for the receiver operating characteristic (ROC) analysis with an area under the curve greater than 0.70.

The transition period is a central moment in dairy cows breeding because metabolic disorders may occur in relation to a dramatic increase in energy demand. This research aimed to identify new biomarkers for the diagnosis of hyperketonemia in bovine in early lactation phase with different value of plasmatic non-esterified fatty acid (NEFA). The profile of plasma fatty acids (FAs) divided into four lipid classes was evaluated using thin layer chromatography and gas chromatographic techniques (TLC-GC). A group of 60 multiparous Holstein-Friesian dairy cows were recruited in the present study. Blood samples were collected from the coccygeal vein and NEFA and the β-hydroxybutyrate (BHB) were evaluated. All animals were divided in 2 groups based on NEFA, NEFA0 group had as mean value 0.24 ± 0.12 mEq/L and NEFA1 group had as mean value 0.87 ± 0.23 mEq/L. Plasma FA concentrations were analyzed separately in free fatty acids, cholesterol esters, phospholipids and triglycerides. Six FAs demonstrated a predictive value in the hyperketonemic dairy cows. In the free fatty acid class, the predictive FAs were C14:0 (AUC = 0.77), C18:1 ω 9 (AUC = 0.72), C18:1 ω 7 (AUC = 0.70) and C18:3 ω 3 (AUC = 0.68). In the phospholipids class the predictive parameters were C12:0 (AUC = 0.78) and C8:0 (AUC = 0.73). In cholesterol, esters and triglycerides lipidic classes no FA had a predictive function.

Excessive mobilization of adipose tissue in high milk producing dairy cows predisposes to metabolic diseases. The aim of this research was to identify the plasma fatty acids in four lipid classes as biomarkers for the diagnosis of hyperketonemia in bovines using thin layer chromatography and gas chromatographic techniques (TLC-GC). Sixty multiparous Holstein-Friesian dairy cows were enrolled in the study. Blood samples from the coccygeal vein were collected and β-hydroxybutyrate (BHB) was evaluated. All animals were divided into three groups on the basis of ketonemia: BHB < 0.50 mmol/L, 0.50 < BHB < 1.0 mmol/L, and BHB > 1.0 mmol/L. Plasma fatty acid concentrations were evaluated in four lipid classes: Free Fatty Acids (FFA), Triglycerides (TG), Cholesterol Esters (CE) And Phospholipids (PL). The concentration of fatty acids was analyzed using TLC-GC. The results showed the following significance in the lipid classes: 19 fatty acids were significant ( p < 0.053) in FFA, nine fatty acids were significant ( p < 0.050) in TG, eight fatty acids were significant ( p < 0.050) in CE and three fatty acids were significant ( p < 0.049) in PL. Eleven parameters were considered as predictive fatty acids related to animals in hyperketonemia. The FFA increased simultaneously with blood BHB levels, although the identified predictive fatty acids related to the TG and CE lipid classes decreased, meanwhile the BHB values increased. In the PL lipid class, no fatty acids were predictive.

The activation of the B cell receptor (BCR) is nowadays known to play a primary role in the etiopathogenesis of a multitude of B cell malignancies, being one of the main factors responsible for the enhanced proliferation and survival of transformed cells. Thanks to the characterization and continuous discovery of the pathways driving B cell proliferation in consequence to BCR activation, it has been possible to develop a small molecule inhibitor specifically antagonizing the Bruton's tyrosine kinase (BTK), an enzyme located in an early strategic position within the whole pathway. Ibrutinib, formerly PCI-32765, is a first in class, potent, specific, irreversible and relatively safe BTK inhibitor, demonstrating so far an impressive efficacy in the treatment of chronic lymphocytic leukemia, diffuse large B cell lymphoma, follicular lymphoma, mantle cell lymphoma (MCL), Waldenström macroglobulinemia and multiple myeloma. This review will summarize the most important pharmacological evidences available as of today and will take in consideration the latest findings regarding the mechanism of action of ibrutinib.

Background: Epidemiological studies have shown positive associations between particulate matter (PM) air pollution and short-term mortality and morbidity for asthma. The hypothesis that lung inflammation is responsible for these effects has been tested in panel and controlled exposure studies in asthmatic adults, with inconsistent results., Objectives: We investigated whether personal exposure to PM10 and PM2.5 were related to changes in the clinical course of asthma and to lung inflammatory responses in adult asthmatics., Methods: A cohort of 32 asthmatic patients was followed for 2 years. Asthma control test (ACT) and St George's Respiratory Questionnaire (SGRQ) scores, forced expired volume in the first second (FEV1), exhaled nitric oxide (Fe(NO)), and pH of exhaled breath condensate (EBC) were determined on 6 occasions during different seasons. Personal exposure to PM was measured for 24 hours prior to clinical assessments., Results: A 10 microg/m3 increase in PM10 personal exposure was associated with an increase in SGRQ scores (regression coefficient beta = 0.22; 95% confidence interval [CI], -0.005 to 4.451; P =.055) and with a decrease in ACT scores (beta = -0.022; 95% CI, -0.045 to 0.001; P = .060), whereas no associations were found between PM10 and FEV1, Fe(NO), or EBC pH. A positive association was detected between Fe(NO) and outdoor O3 (P = .042) and SO2 (P = .042) concentrations in the subgroup of nonsmoking asthmatics., Conclusions: We concluded that increments in personal exposure to PM10 are associated with a decrease in asthma control and health-related quality of life. However, this study does not provide evidence that 24-hour exposures to PM are associated with short-term changes in lung function or inflammatory responses of the lung.

Objectives: We evaluated the association between PM(10) concentration and out-of-hospital coronary deaths in eight Italian cities during 1997-2004., Methods: 16 989 subjects aged >35 years who died out-of-hospital from coronary causes were studied and hospital admissions in the previous 2 years identified. We studied the effect of the mean of current and previous day PM(10) values (lag 0-1). A city-specific case-crossover analysis was applied using a time-stratified approach considering as confounders weather, holidays, influenza epidemics, and summer decrease in population. The pooled percentage increase (95% CI) in mortality per 10 microg/m(3) increase in PM(10) was estimated., Results: A statistically significant increase in out-of-hospital coronary deaths was related to a 10 microg/m(3) increase in PM(10): 1.46% (95% CI 0.50 to 2.43). Although no statistically significant effect modification by age was found, the effect was stronger among subjects aged >65 years (1.60%, 0.59 to 2.63), particularly those aged 65-74 (3.01%, 0.74 to 5.34). People in the lowest socio-economic category (3.34%, 1.28 to 5.45) had a stronger effect than those in the highest category. No clear effect modification was seen for gender, season or any specific comorbidity. An indication of negative effect modification was seen for previous admission for cardiac dysrhythmias. Subjects without hospital admissions in the previous 2 years were slightly more affected by PM(10) effects (1.91%, 0.28 to 3.47) than those with at least one previous hospital admission (1.44%, 0.09 to 2.82)., Conclusions: Our results show that short term exposure to PM(10) is associated with coronary mortality especially among the elderly and socio-economically disadvantaged. No clear effect modification by previous hospitalisations was detected except for cardiac dysrhythmias, possibly due to protective treatment.

The aim of the present study was to test the effects of exposure to air pollutants on lung function. A panel of 19 adult asthmatics living in Padua (Italy) was followed for five 30-day periods during 2 yrs consecutively (1,492 morning and 1,434 evening measures analysed). Peak expiratory flow (PEF) and forced expiratory volume in 1 s (FEV(1)) were measured using a pocket electronic meter. Daily levels of air pollutants and meteorological variables were collected at outdoor city monitoring sites. Significant inverse associations were observed between morning and evening PEF and carbon monoxide level (p = 0.01-0.03), without clear differences between lags (0-3 days). An increment of 1 mg.m(-3) CO was associated with a PEF variation ranging -2.6- -2.8%. All effect estimates on PEF for CO remained significant and even increased after controlling for particles with a 50% cut-off aerodynamic diameter of 10 microm (PM(10)), nitrogen dioxide and sulphur dioxide in single and multi-pollutant models. A similar trend was observed for FEV(1), but the associations were nonsignificant. A nonsignificant inverse relationship between evening PEF and SO(2) was also detected. PEF and FEV(1) were not related to PM(10) and NO(2) concentrations. The present results indicate that, in this panel of adult asthmatics, the worsening of lung function is associated with exposure to gaseous pollutants and occurs at levels of CO and SO(2) lower than current European standards.

The aim of the present study was to evaluate the possible association between occurrence of soft tissue sarcomas in Verona (Italy) and residence near a steel foundry, whose emissions of dioxin-like compounds may be relevant. Exposure to total suspended particulate (TSP) emitted from the plant as estimated by ADMS-urban dispersion model was used as an indirect index of exposure to dioxin-like compounds. Verona municipality was divided in six subareas according to the decreasing levels of estimated TSP exposure, and soft tissue sarcomas cases were mapped according to residence at time of diagnosis. Standardized incidence ratios were computed. No statistically significant departures between observed and expected cases were detected as illustrated by trend-test results.

Introduction: the relationship between air pollution and hospital admissions has been well studied. In this study, the results of the Italian EpiAir Project are reported on the effect of air pollution on hospital admissions in 9 Italian cities during 2001-2005. The association between particulate matter (PM10) and gases (NO2 and O3) and hospital admissions for cardiac, cerebrovascular, respiratory conditions, pulmonary embolism and diabetes has been evaluated., Material and Methods: The study population consists of 701,902 hospital admissions of subjects residents in nine Italian cities and hospitalized in the city in the period 2001- 2005. We used a case-crossover approach and the statistical analysis considered the relevant temporal and meteorological factors for confounding adjustment. The results for ozone refer to the warm semester. The analysis of the association between air pollution and admissions was conducted for each city, and the city-specific estimates were meta-analyzed to obtain pooled results., Results: we found an immediate effect of PM10 and NO2 (lag 0) for cardiac diseases as a group and for specific conditions (coronary syndrome and heart failure). No effect of ozone was observed. For cerebrovascular diseases we did not observe a positive effect of the three pollutants. An effect of NO2 on pulmonary embolism was detected. The association between air pollutants and hospitalization for respiratory diseases (respiratory infections, COPD and asthma) showed different lags for the three pollutants: the effect of PM10 was immediate at lag 0-1 while the effects of NO2 and ozone were prolonged at lag 0-5. The strongest association was between NO2 and asthma admissions, especially in children. No effects on diabetes were found., Conclusions: the main results of the present study confirm the deleterious short term impact of air pollution on cardiovascular and respiratory morbidity in Italian cities.

Objective: the relationship between air pollution and mortality has been well established in national and international scientific literature. This study reports the results of the EpiAir Project relative to the effect of air pollution on mortality in 10 Italian cities during 2001-2005. The association between particulate matter (PM10) and gases (nitrogen dioxide, NO2, and ozone, O3), and all natural mortality, as well as cardiac, cerebrovascular and respiratory mortality, is presented. Specific issues have been investigated, such as the latency of the air pollution-mortality effects and the identification of individual demographic characteristics and clinical conditions that result in greater susceptibility to the effects of particulate matter., Methods: the study population consisted of 276,205 subjects aged 35+ years old, resident in one of the 10 Italian cities studied, which died in the city between 2001-2005. For each subject, information was collected on cause of death, location of death, demographical variables and hospital discharge diagnoses in the previous 2-year period. The statistical analysis was adjusted for the relevant temporal and meteorological factors using the case-crossover approach. The results for ozone are limited to the warm semester (April through September). An analysis of the association between air pollution and mortality was conducted for each city, and the city-specific estimates were meta-analyzed on a second level to obtain a pooled result, and reported inter-city heterogeneity., Results: a short-term effect of PM10 on mortality has been detected for all the groups of causes considered, with latencies ranging from lag 0 for cerebrovascular mortality to lag 0-3 for respiratory mortality. The association between NO2 and mortality displays strong and similar effects for all death causes, with prolonged effects (lag 0-5) for all groups of causes. The results for O3 are similar to those found for NO2, with prolonged latency (lag 0-5) for all causes of death with the exception of cerebrovascular mortality, for which a delayed effect (lag 3-5) was identified. Individual susceptibility factors of the PM10-natural mortality association include age, as elderly subjects are especially vulnerable to the effects of particles., Conclusions: the main results of the study suggest that the air pollution originated by vehicular traffic is the most relevant environmental problem in Italian cities from a public health viewpoint.

Introduction: the EpiAir (Air pollution and health: epidemiological surveillance and prevention) Project has been conducted in 10 Italian cities. In this paper we describe the health data used to detect adverse health effects associated with air pollution exposure (mortality and hospital discharge databases) and to identify comorbidities (based on hospital discharge databases) as susceptibility factors to the effects of air pollution., Material and Methods: for each city, we performed descriptive analyses of mortality data included in the study.We considered subjects aged 35+ years old, resident and deceased within the cities in the study period (2001-2005) for non-accidental causes. For each deceased subject, information were collected on hospital discharge diagnoses in the previous 2-year period. Urgent hospital admissions of subjects resident in nine cities and hospitalized within the city for specific diseases (including cardiac, cerebrovascular and respiratory conditions) were also included as endpoints. Annual mean raw death and hospitalization rates were calculated for each city., Results: 276,205 deaths and 701,902 urgent hospital admissions have been included in the study. Annual mean crude death rates for non accidental causes in the population aged +35 yrs resident and deceased in the municipalities ranged from 12.1 and 15.7 per 1,000 residents.The percentage of deceased subjects with at least one of the selected comorbidities ranged from 32 to 48%. Annual mean crude urgent hospitalization rates in the resident population ranged from 5.5 to 11.7 per 1,000 residents for cardiac diseases; 1.7 to 3.7 per 1,000 residents for cerebrovascular diseases and 3.3 to 10.7 per 1,000 residents for respiratory diseases. Several factors can explain the between-cities differences observed, especially in the hospitalization rates, including availability and variability in the health care services utilization., Conclusion: an epidemiological surveillance system based on health databases has to take into account the observed differences.

Objective: to produce environmental indicators suitable for an epidemiological surveillance in 10 Italian cities part of the EpiAir Project (2001-2005)., Methods: the environmental parameters that correlate to relevant health effects are the particles with diameters less than or equal to 10 micrometers (PM10), the nitrogen dioxide (NO2) and the ozone (O3). The necessary meteorological data are: temperature, relative humidity, barometric pressure and apparent temperature.We have identified some criteria to select monitoring stations and have taken standard methods of calculation to produce environmental indicators starting from the daily data available after closely evaluating the completeness of the existing data. Furthermore, we have checked the homogeneity of the selected data to ensure that it represents the population's exposure., Results: close examination of descriptive statistics shows a critical situation of the considered pollutants. The analysis of the yearly state underlines for PM10 values higher than 40 microg/m3 in the area of Mestre-Venice and in Milan, Turin, Bologna e Taranto. For NO2, values are consistently above 40 microg/m3 in Milan, Turin, Bologna, Florence, Rome and Palermo. For ozone, the concentrations were stable, with the exception of Summer 2003 when we recorded, on average, an increase of 13% compared to the mean value estimated for the ten cities during the study period, especially in Mestre-Venice, Turin and Palermo., Conclusions: it is important to ensure the consistency of the methods and instruments in environmental monitoring. To evaluate health effects and perform interventions over the longterm, it is therefore fundamental that the data be homogenous, especially during the periodic reorganizations and rationalizations of air quality management. It is also necessary to include daily meteorological data that influence pollutant dispersion and population health status.

Background: Several time-series studies have established the relationship between particulate matter (PM10) and mortality. We adopted a case-crossover design to evaluate whether individual socio-demographic characteristics and chronic or acute medical conditions modify the PM10-mortality association., Methods: We selected all natural deaths (321,024 subjects) occurring among adult (aged 35+ years) residents of 9 Italian cities between 1997 and 2004. We had access to individual information on socio-demographic variables, location of death, and chronic conditions (hospital admissions in the preceding 2-year period). For in-hospital deaths, we collected information on treatment wards at time of death and acute medical conditions. In a case-crossover analysis we adjusted for time, population changes, and meteorological conditions., Results: PM10 was associated with mortality among subjects age 65 years and older (0.75% increase per 10 microg/m3 [95% confidence interval = 0.42% to 1.09%]), with a more pronounced effect among people age 85 and older. A weaker effect was found among the most affluent people. The effect was present for both out-of-hospital and in-hospital deaths, especially among those treated in general medicine and other less specialized wards. PM10 effects were stronger among people with diabetes (1.03% [0.28% to 1.79%]) and chronic obstructive pulmonary disease (0.84% [0.17% to 1.52%]). The acute conditions with the largest effect estimates were acute impairment of pulmonary circulation (4.56% [0.75% to 8.51%]) and heart failure (1.67% [0.30% to 3.04%])., Conclusions: Several factors, including advanced age, type of hospital ward, and chronic and acute health conditions, modify the PM10-related risk of death. Altered pulmonary circulation and heart failure are important effect modifiers, suggesting that cardiac decompensation is a possible mechanism of the fatal PM10 effect.

Aim: development of an algorithm to estimate asthma prevalence by record linkage of different health databases: causes of death (CM), hospital discharges (SDO), drug prescriptions archive (PF), health tax exemptions (ET) in three Italian areas., Setting: Venezia AULSS 12, city of Torino, Firenze ASL 10., Participants: residents aged between 0 and 34 years in the above three centres in the three year period 2002-2004, for a total of 661,275 inhabitants on 30 June 2003., Main Outcome: annual crude and standardized prevalence (per 100 inhabitants) with 95% confidence intervals by gender and age groups (0-14, 15-34, total: 0-34 years)., Methods: for each year of interest, we selected the following: cases with asthma as primary cause of death from CM; all persons discharged from hospitals with diagnosis (primary or secondary) of asthma (ICD9-CM code = 493*); selected prescriptions of anti-asthma drugs (ATC code = R03A, R03CC02, R03CC04, R03CK, R03DC01, R03DC03), and health-tax exemptions for asthma (code = 007.493) from ET. We defined as prevalent case a subject who was present every single year in at least one of four health databases. We reported the absolute and relative contribution of each information system by area, age, gender and year of interest. A sensitivity analysis using more restrictive criteria to identify prevalent cases (two or more prescriptions per year) was also performed., Results: the PF archive is the most important information source in identifying prevalent cases (from 92.5% of Torino to 95.4% of Firenze). The standardized prevalence of asthma in 0-34 years of age is higher in Venezia (6.37%; 2003 year) than in the other two areas, which show similar values (4.01% in Firenze, 3.77% in Torino; 2003 year). In both genders, the standardized prevalence of asthma is, for all centers, clearly higher in the 0-14 age group than in the 15-34 age group. However, Venezia has a prevalence almost twice (11.21%) that of Firenze (6.20%) and Torino (5.60%) in the 0-14years age group. The use of more restrictive criteria in case identification consistently reduces the estimated prevalence; however, in the 0-14 age group the prevalence estimated in Venice (3.3%) is still almost twice as high as those observed in the other centres (1.8% in Florence and 1.6% in Turin)., Conclusions: the algorithm used to estimate asthma prevalence in the 0-34 years age group provides values which differ considerably between the centres that contributed to the study. A validation study is required to evaluate the diagnostic quality of the identified cases, in particular among younger subjects.

Objective: development of an algorithm to estimate the prevalence of obstructive lung diseases (OLD) through record linkage of administrative health data sources in three Italian areas., Setting: AULSS 12 Veneziana, city of Torino, ASL10 Firenze., Participants: all residents in the three areas in the period 2002-2004 (N = 1,944,471 on 30th June 2003)., Main Outcome: crude prevalence, standardized prevalence with 95% confidence intervals., Methods: the following data sources were used to identify OLD cases: hospital discharges (HD), health-tax exemptions (HTE), death causes (DC) and drug prescriptions (DP). All patients diagnosed with (from HD) or dead because of chronic bronchitis, emphysema and asthma have been included in the analysis. We defined as a prevalent case a subject found in each year in at least one of the four data sources. We reported the absolute and relative contribution of each information system by area, age, gender and year of interest. We performed a sensitivity analysis using more restrictive criteria to identify prevalent cases (two or more DPs per year)., Results: DP was the most relevantsource in identifying cases (from 86 to 88%). The relative contribution ofHD ranged from 3 to 5%. In 2003, standardized prevalence of OLD ranged from 5.35% in Firenze to 6.02% in Venezia. Venezia showed a higher prevalence in children aged 0-14years and a lower prevalence in older age groups (> 64 years) compared to other centers. Overall, the prevalence was higher among males. The use of more restrictive criteria in case identification substantially reduces the estimated prevalence, particularly in younger age-groups and to a lesser extent, in older age-groups., Conclusions: the algorithm provides estimates with differences between centres. The validity of this algorithm (in terms of sensitivity and positive predictive value) needs to be evaluated through further ad hoc studies.

Aim: to define an algorithm to estimate prevalence of ischemic heart disease from health administrative datasets., Setting: four Italian areas: Venezia, Treviso, Torino, Firenze., Participants: resident population in the four areas in the period 2002-2004 (only 2003 for Firenze) for a total of 2,350,000 inhabitants in 2003., Main Outcomes: annual crude and standardized prevalence rate (x100 inhabitants), 95% confidence intervals by area. Quality (comparability and coherence) indicators are also reported, Methods: the algorithm is based on record linkage of hospital discharges (SDO), pharmacological prescriptions (PF), exemptions from health-tax exemptions (ET) and causes of mortality (CM). From SDO we extracted discharges for ICD9-CM codes 410*-414* in all diagnoses in the estimation year and during the four years immediately preceding. We selected from PF subjects with at least two prescriptions of organic nitrates (ATC = C01DA*) in the estimation year. From ET subjects with a new exemption for ischemic heart disease (002.414) or who obtained exemption in the three years preceding, were selected. We also considered all deaths in the year for ischemic heart disease (ICD9 CM 410-414). Cases were defined as ischemic heart disease prevalent cases if they were extracted at least once from one of the datasets and if they were alive on January 1 of the estimation year., Results: estimated crude prevalence ranges from 2.5 to 4%. The standardized prevalence led to a narrower range of values (2.8-3.3%). Venezia and Firenze show a higher standardized prevalence in both sexes (men 4.7% and 4.4%; women 2.3% and 2.2% respectively); Treviso and Torino present a lower standardized prevalence (men: 3.9%; women: 1.9%). The hospital discharges are the main source to identify prevalent subjects (34-48% of subjects are solely identified by SDO), pharmacological prescriptions are a relevant source in Firenze and Torino (27-28%), while they are less relevant in Venezia and Treviso (13-15%). ET shows a different contribution to prevalent case identification in the four areas: Venezia (8%), Treviso (3.2%), Firenze (1.3%), whereas in Torino this source was not available at all. Subjects classified as prevalent cases only through causes of death are less than 2%. The percentage of subjects simultaneously identified by multiple sources is high in Venezia (43%) and low in Torino (30%)., Conclusions: patterns in use of pharmaceuticals and exemptions from prescription charges appear to be heterogeneous in the different areas under study. These two aspects make a proper comparison between areas difficult. The algorithm could be applied only in areas with a similar use of organic nitrates and with a good comparability of the exemptions dataset.

Aim: to estimate the prevalence of chronic obstructive pulmonary disease (COPD) by integrating various administrative health information systems., Methods: prevalent COPD cases were defined as those reported in the hospital discharge registry (HDR) and cause of mortality registry (CMR) with codes 490*, 491*, 492*, 494* and 496* of the International diseases classification 9th revision. Annual prevalence was estimated in 35+ year-old residents in six Italian areas ofb different sizes, in the period 2002-2004. We included cases observed in the previous four years who were alive at the beginning of each year., Results: in 2003, age-standardized prevalence rates varied from 1.6% in Venice to 5% in Taranto. Prevalence was higher in males and increased with age. The highest rates were observed in central (Rome) and southern (Taranto) cities, especially in the 35-64 age group. HDR contributed 91% of cases. Health-tax exemption registry would increase the prevalence estimate by 0.2% if used as a third data source., Conclusions: with respect to the National Health Status survey, COPD prevalence is underestimated by 1%-3%; this can partly be due to the selection of severe and exacerbated COPD by the algorithm used. However, age, gender and geographical characteristics of prevalent cases were comparable to national estimates. Including cases observed in previous years (longitudinal estimates) increased the point estimate (yearly) of prevalence two or three times in each area.

Aims: the goal of this study was to estimate the prevalence of diabetes through record linkage of various data sources in four Italian areas., Setting: Aulss 12 Veneziana, Aulss 4 Alto vicentino, Torino, ASL10 of Firenze., Participants: all 2002 to 2004 residents in the four areas (n = 2,123,913 on 30th June 2003)., Main Outcome: crude prevalence by age and gender and standardized prevalence by gender., Methods: we used three different data sources. The first was the set of files of all persons discharged from hospitals with a primary or secondary diagnosis of diabetes (ICD-9-CM code 250*) in the year of interest or in the four previous years. The second data source was the set of files of all prescriptions of antidiabetic drugs (ATC code: A10A* and A10B*) prescribed in the year of interest; we considered as persons with diabetes only those who had at least two prescriptions of antidiabetic drugs at two different times. The third source was the set of files of all subjects who obtained exemption from payment of drugs or laboratory testing due to a diagnosis of diabetes mellitus in the year of interest or in the 3 previous years. All data sources were matched by a deterministic linkage procedure. We defined as "prevalent case" those persons who were present in at least one of the three data sources. We compared the estimated prevalence in the four different areas., Results: in 2003, the prevalence of diabetes in the four areas ranged from 3.93% to 5.55% among men, and from 3.55% to 4.52% among women. After adjustment for age, differences among men were reduced and were no longer present among women. Prevalence is higher among the elderly and among men., Conclusions: using routinely collected data we were able to identify large cohorts of persons with known diabetes and to estimate the prevalence of the disease, which was shown to be highly homogeneous among participating centres, and similar to that reported in other studies conducted in Italy with more costly and time consuming methods.