Clinical Characteristics And Health Care Resources In Patients Treated With Oral Anticoagulants: Evidences From Italian Administrative Databases.

OBJECTIVES: 1) To evaluate anticoagulation treatment patterns and health care resource use in adult patients with a discharge diagnosis of non-valvular atrial fibrillation (NVAF) in an Italian real-world setting and 2) to describe the characteristics of NVAF patients in relation to treatment. DESIGN: A retrospective cohort study in a "real-world" setting. SETTING: Data were analysed by integrating administrative databases that included approximately 2,000,000 individuals assisted by the National Health System from two Italian Local Health Units. PARTICIPANTS: All adult patients with at least one hospital discharge or ≥2 outpatient visits with a diagnosis code for NVAF from 1/01/2011 to 31/12/2015 were included. MAIN OUTCOME MEASURES: Anticoagulation treatment patterns, health care resource use and major bleeding events that occurred during the follow-up period were evaluated. RESULTS: 32,863 NVAF patients were included, of whom 7,831 had at least one prescription of oral anticoagulants. Among them, 6,876 patients were vitamin K antagonists (VKA) users and 955 were non-vitamin K antagonist oral anticoagulant (NOAC) users at index date (ID). During the follow-up period, the use of antiplatelet drugs was higher among VKA-naïve users than the NOAC-naïve users. Among NOAC users, 76.1% showed an adherence level ≥80% during follow-up. The rate of bleeding events resulted higher for VKA patients compared to NOAC patients. The unadjusted incidence rate was 10.46 per 1000 person-year for VKA patients and 4.55 per 1,000 person-years for NOAC patients. The overall annual cost (in term of drugs, hospitalisations and outpatient specialist services) was € 5,156.13 for VKA and € 4,630.57 for NOAC. CONCLUSION: This unselected cohort study, on NVAF patients being prescribed oral anticoagulants, highlights that VKA was largely prescribed and the great majority of patients on NOACs were adherent to treatment. Most of the OAC patients still received antiplatelet agents in combination, and in NOAC patients, we registered a lower number of bleeding events compared with VKA.

Microbial safety status of Serro artisanal cheese produced in Brazil.

Considering the growing consumption of artisanal foods worldwide, we aimed to evaluate the microbial safety of Serro artisanal cheese (SAC), produced in Minas Gerais State, Brazil. This cheese is produced with raw milk using 1 of 2 natural starter cultures: "pingo" and "rala." A total of 53 SAC samples (pingo = 8; rala = 45) were obtained from different farmers and subjected to conventional and molecular assays to detect and enumerate Listeria monocytogenes, Salmonella spp., coagulase-positive staphylococci (CPS), diarrheagenic Escherichia coli, Mycobacterium tuberculosis, and Brucella abortus. The SAC samples were also subjected to an ELISA to detect classical staphylococcal enterotoxins (CSE: SEA, SEB, SEC, SED, SEE) and to PCR assays to detect staphylococcal enterotoxin-related genes (sea, seb, sec, sed, see). Coagulase-positive staphylococci isolates were obtained and tested by the same assays to detect their potential in CSE production and presence of CSE-related genes. None of the SAC samples showed any of the screened food-borne pathogens and zoonotic agents, and none showed the presence of CSE by phenotypic and genotypic approaches. Despite the absence of microbial hazards, mean counts of CPS in SAC samples were 5.2 log cfu/g (pingo starter) and 4.6 log cfu/g (rala starter), indicating poor hygiene practices during production. None of the tested CPS isolates (n = 116) produced CSE or presented CSE-related genes. Despite the relative microbial safety, hygienic conditions during SAC production must be improved to meet official guidelines established in Brazil.

Study of antidepressant use in 5 European settings. Could economic, sociodemographic and cultural determinants be related to their use?

BACKGROUND: We aimed at describing the trends in antidepressants use (AD) by age and sex, during 2007-2011, in 5 European settings (Sweden, Norway, Denmark, Catalonia and Veneto), and to assess whether the differences found across settings could be related to economic, social and cultural determinants. METHODS: We collected data of AD use expressed in defined daily doses (DDD). Data were retrieved from population-based databases. We calculated DDD/1000 inhabitants/day. We analysed which economic, social, and cultural covariates determined between-settings differences in AD consumption. RESULTS: The use of AD showed an increasing trend during the study period, being Selective Serotonin Reuptake Inhibitors the most consumed, followed "others AD". Women and the elderly showed the highest AD consumption. Between-settings variability in AD consumption showed a positive correlation with pharmaceutical expenditure and a negative one with general practitioner's rate. After adjusting by pharmaceutical expenditure and general practitioners rate Masculinity, Long-Term Orientation and Individualism cultural dimensions were associated with AD use by using the Hofstede´s cultural dimensions model. LIMITATIONS: This study has been conducted in administrative databases, with no information on AD use by indication; differences among AD use could be related to their prescription for other disorders. Analyses were based on a small dataset and none of the results reached statistical significance. CONCLUSIONS: AD use increased through 2007-2011. Pharmaceutical expenditure and General Practitioners rate, Masculinity, Long-Term Orientation and Individualism explained the differences in AD use between countries. People's attitude should be considered when designing national campaigns to improve antidepressant use.

[Sjögren's syndrome: comparison among the main imaging techniques in the study of major salivary glands]. / Sindrome di Sjögren: confronto fra le principali tecniche di imaging per lo studio delle ghiandole salivari maggiori.

Sjögren's syndrome (SS) is a chronic inflammatory disease with an autoimmune etiology, that affects exocrine glands, in particular salivary and lacrimal glands. Among the diagnostic criteria of SS, imaging techniques play an important role. The aim of our study is to compare three imaging techniques, such as sonography, scintigraphy and sialography in the evaluation of major salivary glands. The use of the these techniques is of great importance for the diagnosis of SS. Sonography is the most frequently used for its prompt execution, non invasivity, great acceptance by the patient and low cost. In the diagnostic patient management of SS, sonography results are eventually confirmed by the other imaging techniques, sialography and scintigraphy.

Current opinions in sialolithiasis diagnosis and treatment.

The introduction, 15 years ago, of extracorporeal shock wave lithotripsy in the treatment of salivary gland calculi, has changed the therapeutic approach in these patients. Aim of this study was to evaluate the efficacy of lithotripsy in sialolithiasis, after 10 years follow-up. A review has been made of the literature to establish current opinions in diagnosis and treatment of sialolithiasis. The role of ultrasonography, radiography and, in particular, of sialomagnetic resonance imaging in diagnosis of salivary lithiasis has been evaluated. The greater efficiency of the extracorporeal shock wave lithotripsy treatment for parotid, compared to submandibular calculi, has been demonstrated (57% versus 33%). In 68% of our patients, lithotripsy was resolutive after 10 years. Ultrasonograpy should be considered first choice examination in diagnosis of salivary calculi. Sialo-magnetic resonance imaging is a recent, non-invasive diagnostic procedure with the advantage of no radiation exposure, and with better definition of anatomical and functional state of glandular parenchyma and duct, compared to other available techniques.

[Current opinion on diagnosis of primary Sjögren's syndrome]. / Attualità nella diagnosi della sindrome di Sjögren.

For many years, Sjögren's syndrome was a purely descriptive diagnosis of symptoms such as xerostomia and dry eye (sicca syndrome). The different classification criteria proposed for Sjögren's syndrome comprise a rather variable spectrum of diagnostic possibilities, at one extreme of which we find an array of exclusively objective parameters while, at the other extreme, the objective parameters and patients' symptoms balance out. Improved accuracy in the diagnosis of Sjögren's syndrome can be attained only through the combination of a symptoms questionnaire, histopathology, scintigraphy or sialography or evaluation of the unstimulated salivary flow and specific autoantibodies. In these last few years, further methods have been proposed to increase diagnostic accuracy: the analysis of various salivary constituents, saliva and tear ferning tests, the search for new autoantigens and, above all the use of ultrasonography and magnetic resonance imaging. Color-power Doppler and magnetic resonance sialography have recently been proposed as promising techniques to improve sensitivity and diagnostic specificity. This study discusses the data present in the literature and personal experience regarding diagnostic methods in a group of 350 patients affected by primary Sjögren's syndrome.

[Comparison of ultrasonography and sialography vs. magnetic resonance in the diagnosis of the primary Sjogren's syndrome]. / La risonanza magnetica nucleare nella diagnosi della sindrome di Sjögren primitiva. Confronto con le metodiche ecografica e scialografica.

To date there is no agreement as to which imaging technique is best for the evaluation of the oral component of primary Sjögren's Syndrome (SS). The purpose of the present study has, therefore, been to determine the reliability of Magnetic Resonance (MR) in the evaluation of salivary alterations in patients with SS. The study involved 23 patients suffering from SS according to the European criteria. All the patients underwent ultrasonography and MR of the major salivary glands, parotid sialography and biopsy of the minor salivary glands. The first control group was made up of 50 healthy subjects who underwent parotid ultrasonography. The second control group comprised 23 subjects who underwent MR of the head and neck for other non parotid pathology. The ultrasonography, MR and sialography images were evaluated by a single observer during a single session and scored from 0 to 4. In the SS patients ultrasonography was abnormal in all 23 cases (100%): 3 patients showed grade 1 alterations (13%); 5 grade 2 (21.7%); 9 grade 3 (39.1%); 6 grade 4 (26.1%). In the healthy controls, grade 0 was found in 36 subjects (72%) while the remaining 14 subjects revealed grade 1 alterations (28%). Using MR imaging only one of the SS patients showed grade 0 alterations (4.3%), 7 showed grade 1 alterations (30.4%), 9 grade 2 (39.1%), 5 grade 3 (21.7%) and only 1 grade 4 (4.3%). MR imaging sensitivity was 95.8% while specificity was 100%. For ultrasonography, considering grade 1 as non pathological, we found a sensitivity of 88.4% and specificity of 100%. The MR score for SS patients was compared to that obtained with sialography and ultrasonography. There was a good correlation between MR and sialography (r = 0.528, p = 0.010) while the correlation between MR and ultrasonography was not statistically significant. This study confirms that, of the diagnostic procedures available for evaluation of salivary gland involvement in SS, the most useful initial examination is ultrasonography. When there is some doubt or there are subtleties, MR is a valid alternative to classical sialography.

[Imaging in major salivary gland diseases] / Diagnostica per immagini nelle malattie delle ghiandole salivari maggiori.

Most of the salivary glands diseases are characterized only by a few distinct clinical patterns. Medical history and clinical examination are still considered of great relevance. However, in order to obtain a definite diagnosis, imaging techniques are required in most of the cases. Salivary glands ultrasonography (US) is the technique to be used as the first because US can easily differentiate calculosis, inflammatory diseases and tumors. Sonography is also frequently needed to perform needle aspiration or biopsy (FNAC). Sialography should be used essentially for assessing chronic sialoadenitis as well as Sjögren's syndrome. At present, Magnetic Resonance sialography should be preferred because of the greater sensibility in diagnosing inflammatory diseases of the salivary glands. It allows to evaluate both intraglandular oedema and nodules, so that incannulation of the salivary duct is not required. Computer Tomography (CT) and Magnetic Resonance imaging (MR) are useful when neoplasm are suspected, particularly if deep areas of the gland, which cannot be visualized by US, are involved. Sequential scintigraphy is currently employed for assessing the functional status of all the 4 major salivary glands and evaluating the chronic evolution of glandular damage.

[Primary Sjögren's syndrome. A longitudinal study of 68 patients]. / Sindrome di Sjögren primitiva. Studio longitudinale di 68 pazienti.

There are only few studies, regarding primary Sjögren's syndrome (pSS) long-term clinical course. Moreover, it has been often studied in a restricted number of patients, employing different recruitment and diagnostic criteria. During a 10 years follow-up, we longitudinally evaluate clinical course as well as severe complications and mortality rates in 68 patients with pSS, diagnosed according to the Fox's criteria. Patients were divided into 2 groups according to the autoantibodies pattern detected at the diagnosis: anti-Ro and/or La positive and anti-Ro La negative. Glandular manifestations of pSS were distinctively present in the majority of patients already at time of the diagnosis and serological findings remained typically constant during the whole follow-up. Increased IgG, IgA and ESR as well as low C4 serum levels were significantly prevalent in the Ro and/or La positive group. Finally, we did not found any significant increase in the mortality rate of pSS patients in comparison with the general population.

Juvenile onset of primary Sjögren's syndrome: report of 10 cases.

OBJECTIVE: Ten new cases with primary Sjögren's syndrome (pSS) whose disease began before age 16 are described. Special attention is paid both to the follow-up and treatment of this condition. METHODS: Cases with juvenile pSS were retrospectively identified from our series of 180 pSS patients. Ocular, salivary, and extraglandular manifestations as well as a full laboratory evaluation including HLA-DR typing were retrieved. RESULTS: A disease prevalence of 5.5% (10 cases, 8 female and 2 male) was found in our series. The mean age at onset was 11.0 years, but the disease started at the age of 4 in 2 patients. At onset, parotid swelling was found in 6 cases and extraglandular manifestations in 3. Throughout the follow-up period (mean 48.6 months from the time of diagnosis), the clinical picture was similar to that of pSS in adults, but oral involvement was generally milder. Extraglandular manifestations were always present but never severe. Pertinent laboratory abnormalities (e.g. rheumatoid factor, polyclonal hypergammaglobulinemia, leukopenia, increased ESR, ANA and anti-SSA/SSB antibodies) were found in all patients. Specifically, ANA and anti-SSA were always positive. Moreover, in our cases histocompatibility antigens HLA-DR3 and DR 52 were closely associated with the disease. Clinical outcome was difficult to predict; however, no serious complications have been observed so far. We obtained good results with low-dose steroids and/or hydroxychloroquine, especially with regard to the extraglandular manifestations and laboratory abnormalities. CONCLUSION: We confirm that juvenile pSS is not a rare condition. It closely resembles pSS in adults except for the extremely high prevalence of recurrent parotitis and immunological findings.

[Diagnostic value of labial salivary biopsy in Sjogren's syndrome: report of 182 cases]. / Valore diagnostico della biopsia delle ghiandole salivari minori nella sindrome di Sjögren (Studio su 182 casi).

Various sets of criteria have been suggested in order to establish a diagnosis of Sjögren's syndrome (SS) in as much as evaluation of the salivary component is highly controversial. Our study was aimed at investigating both sensitivity and specificity of labial salivary gland biopsy (LSGB), as well as at comparing this method with other diagnostic procedures commonly employed in SS. LSGB was performed in 182 patients (174 female and 8 male, mean age 51.2) with xerostomia, dry eyes, parotid swelling and/or serological abnormalities such as positive rheumatoid factors, antinuclear antibodies, leukopenia and hypergammaglobulinemia. Diagnosis of SS was made according to the criteria recently proposed by Vitali et al. (1993). Severity of histologic changes was graded according to the Chisholm and Mason scoring system. Bioptic samples were considered abnormal when at least one focus of mononuclear cells/4mm2 was observed. The following parameters were also assessed in each patient: questionnaire of symptoms, Saxon test, sialography, salivary dynamic scintiscan, Schirmer-I-test, rose Bengal score, ANA, anti-SSA/SSB antibodies and rheumatoid factors. According to the above diagnostic criteria, 108 out of 182 patients had SS, 90 primary and 18 secondary. For 74 there were not enough data for a definite diagnosis of SS. In 9 cases (4 with and 5 without SS) LSGB was excluded because no glandular tissue was found in the specimens. Among the remaining 173, Grades 3 or 4 were found in 74 patients (71.2%) with SS and only in 1 case (1.4%) without SS. LSGB showed a very high specificity (98.6%) and a rather good sensitivity (72.5%). However, biopsy was crucial for diagnosis in only 11 cases (14.6%).(ABSTRACT TRUNCATED AT 250 WORDS)

Lacrimo-auricolo-dento-digital syndrome mimicking primary juvenile Sjögren's syndrome.

We describe a 24 year old female patient affected with symptoms of severe xerostomia and keratoconjunctivitis sicca since her childhood. She also had several malformations involving face and digits as well as cup shaped ears, enamel dysplasia and absence of lacrimal puncta. Hence, the diagnosis of Lacrimo-Auricolo-Dento-Digital (LADD) syndrome was made. The main differences between this rare, inherited disease and primary juvenile Sjögren's syndrome are pointed out.

Phosphorylation of synthetic fragments of inhibitor-2 of protein phosphatase-1 by casein kinase-1 and -2. Evidence that phosphorylated residues are not strictly required for efficient targeting by casein kinase-1.

The major phosphorylation site for both casein kinase-2 (CK2) and casein kinase-1 (CK1) in protein phosphatase-1 (PP-1) inhibitor-2 (I-2) is Ser86. Minor phosphorylation sites affected by either CK2 or CK1 are Ser120/Ser121 and Ser174, respectively. A synthetic peptide of 25 amino acids encompassing residues 67-93 of I-2 is phosphorylated by either CK2 or CK1 at its seryl residue corresponding to Ser86 with higher Vmax and Km values similar to those of the intact protein (9 vs 7.2 microM and 14.2 vs 5.3 microM with CK2 and CK1, respectively). No detectable phosphorylation of this peptide which also includes the glycogen synthase kinase-3 (GSK-3) site (Thr72), could be observed with either GSK-3 or p34cdc2 kinase whether or not its seryl residue equivalent to Ser86 had been previously phosphorylated by CK2. Shorter derivatives of I-2(67-93), encompassing residues 72-93 and 78-93, are also readily phosphorylated by both CK1 and CK2, with phosphorylation efficiencies similar to those of the parent peptide. A synthetic heptadecapeptide reproducing the phosphoacceptor site around Ser120/Ser121 is phosphorylated by CK2, but not to any detectable extent by CK1, with a Km value fivefold higher than that of the corresponding pentadecapeptide including Ser86 (78-93). A synthetic pentadecapeptide (166-180) reproducing the phosphoacceptor site around Ser174 is phosphorylated by CK1 less efficiently than the pentadecapeptide including its main phosphorylation site (78-93) (Km 280 microM vs 33 microM). This peptide is readily phosphorylated by CK2 as well, although it lacks the canonical consensus sequence for CK2 and its Ser174 is almost unaffected by CK2 in intact I-2. These data provide the clear-cut demonstration that the consensus sequence with N-terminal prephosphorylated residue(s), SerP/ThrP-Xaa-Xaa-Ser/Thr, [Flotow, H., Graves, P. R., Wang, A., Fiol, C. J., Roeske, R. W. & Roach, P. J. (1990) J. Biol. Chem. 265, 14264-14269; Meggio, F., Perich, J. W., Reynolds, E. C. & Pinna, L. A. (1991) FEBS Lett. 283, 303-306] is not always required to achieve efficient and high-affinity phosphorylation by CK1. They also show that the specificity determinants for I-2 phosphorylation by either CK2 or CK1, but not by GSK3, are entirely grounded on local structural features of the phosphoacceptor site, being only marginally affected by the overall structure of I-2.

Non-occupational recurrent bilateral pneumoparotitis in an adolescent.

This is a case report of recurrent bilateral parotid swelling with intraglandular gaseous bubbles in a 14-year-old boy, together with a review of the literature on this condition, which is usually called pneumoparotitis. The disorder has been reported as an occupational hazard in wind instrument players and glass-blowers and also as a rare non-occupational disease, mainly in adolescents and often associated with psychological problems.

Implantation of parotid pleomorphic adenoma in the upper neck.

This paper presents a case of pleomorphic adenoma from an abnormal site in the right upper neck in a patient surgically treated 4 years previously for pleomorphic adenoma of the right parotid gland. The lack of normal salivary tissue in the neck growth oriented us towards a diagnosis of implantation tumor, resulting from surgery of the parotid mass, rather than towards one of heterotopic tumor. The literature concerning salivary heterotopias and salivary tumors arising from heterotopic foci is also reviewed.

Compensation mechanisms after acute peripheral disorders of the labyrinth as a function of age.

Nowadays opinions on the complexity of the central vestibular compensation mechanisms are still divergent, but it is correct to believe that biochemical and morphological changes appearing in various sites of the central nervous system during aging have a negative reflection on the integrity of such a process. The present paper is a clinical-descriptive study on 26 patients affected with a sudden loss of the vestibular function, examined at the ENT Department at the University of Padua, from 1981 to 1983. The study's results are reported, and several problems connected to the interference of the aging process on the mechanism of vestibular compensation are examined.