External validation of the DASH prediction rule: a retrospective cohort study.

Essentials Predicting recurrences may guide therapy after unprovoked venous thromboembolism (VTE). We evaluated the DASH score in 827 patients with unprovoked VTE to verify prediction accuracy. A DASH score ≤ 1 had a cumulative recurrence risk at 1 year of 3.6%, as predicted by the model. The DASH score performed better in younger (< 65 years old) subjects. SUMMARY: Background The DASH prediction model has been proposed as a guide to identify patients at low risk of recurrence of venous thromboembolism (VTE), but has never been validated in an independent cohort. Aims To validate the calibration and discrimination of the DASH prediction model, and to evaluate the DASH score in a predefined patient subgroup aged > 65 years. Methods Patients with a proximal unprovoked deep vein thrombosis (DVT) or pulmonary embolism (PE) who received a full course of vitamin K antagonist or direct oral anticoagulant (> 3 months) and had D-dimer measured after treatment withdrawal were eligible. The DASH score was computed on the basis of the D-dimer level after therapy withdrawal and personal characteristics at the time of the event. Recurrent VTE events were symptomatic proximal or distal DVT/PE, and were analyzed with a time-dependent analysis. Observed 12-month and 24-month recurrence rates were compared with recurrence rates predicted by the DASH model. Results We analyzed a total of 827 patients, of whom 100 (12.1%) had an objectively documented recurrence. As compared with the original DASH cohort, there was a greater proportion of subjects with a 'low-risk' (≤ 1) DASH score (66.3% versus 51.6%, P < 0.001). The slope of the observed versus expected cumulative incidence at 2 years was 0.71 (95% confidence interval 0.51-1.45). The c-statistic was lower for subjects aged > 65 years (0.54) than for younger subjects (0.72). Conclusions These results confirm the validity of DASH prediction model, particularly in young subjects. The recurrence risk in elderly patients (> 65 years) was, however, > 5% even in those with the lowest DASH scores.

Three scenarios of clinical claim reimbursement for nosocomial infection: the good, the bad, and the ugly.

We studied the extent to which hospitals can expect to receive reimbursement for costs relating to nosocomial infections (NI) under the diagnosis-related groups (DRG) system of clinical claims and calculated the loss of reimbursement due to missed or incorrect registration of infective complications on hospital discharge records (HDR). We calculated clinical claim reimbursement in three scenarios: the good, in which all NI are recorded on HDR; the bad, in which a proportion of NI recorded on HDR observed at the 41 participating hospitals; the ugly, in which none of the NI are recorded on HDR. We analysed in which patients the recording of infective complications changed the DRG clinical claim and the economic consequences on reimbursements. Compared with the ugly scenario, the bad scenario, which is closest to what actually occurs, with only 55.9% of NI (180/322) properly recorded, produced an increased DRG clinical claim in 30 cases, of on average 403 for every NI. Compared with the ugly scenario, the good scenario, produced an increased DRG clinical claim in 45 cases with an average reimbursement of 618. The difference between the bad and the good scenarios shows an average loss of 215 for every case. Our calculated good scenario could cover only 3.8% of direct costs per case attributable to NI. Real, tangible benefits in health, both social and economic, will only accrue from the monitoring and control of NI in hospitals.

Mycobacterium tuberculosis isolates belonging to katG gyrA group 2 are associated with clustered cases of tuberculosis in Italian patients.

Fifty-one consecutive isolates of Mycobacterium tuberculosis, collected during a 2-year period in the north-east of Italy, were subjected to IS6110-RFLP analysis to detect the presence of clusters and assigned to one of the three genotypic groups delineated by single nucleotide polymorphisms in the genes katG and gyrA. All the isolates collected from the local population belonged to group 2 or 3, while group 1 isolates were found only in specimens collected from African immigrants. Clustered cases of tuberculosis, which are likely to be related to recently transmitted infection, were found to be significantly associated with katG gyrA group 2. In the local situation, strains belonging to this group may therefore present a higher risk of transmission.

Prevalence of nosocomial infections in Italy: result from the Lombardy survey in 2000.

A one-day survey was carried out in 88 out of 113 public hospitals in Lombardy to obtain prevalence rates of hospital-acquired infections (HAIs) by hospital departments and to identify the pathogens more frequently involved. In total 18667 patients were surveyed, representing 72% of the average daily total of occupied beds in public hospitals in Lombardy. The overall prevalence of HAI was 4.9%. The highest prevalence was observed in intensive care units and in spinal units. The prevalence of bloodstream infections was 0.6%; pneumonia 1.1%; urinary tract infections 1.6% and gastrointestinal infections 0.4%. In surgical patients the prevalence of surgical site infections was 2.7%. The most frequently isolated pathogen from all sites of infections was Escherichia coli (16.8%), followed by Staphylococcus aureus (15.0%), Pseudomonas aeruginosa (13.2%) and Candida spp. (8.7%). Methicillin-resistant S. aureus accounted for 23% of all isolated S. aureus. The results provide baseline data for rational priorities in allocation of resources, for further studies and for infection control activities.

New plant-origin food allergens.

Plant-origin foods, especially nuts and seeds, are the most important sources of food allergic reactions. An important characteristic is the quantitative and qualitative variability of their content in allergenic molecules, depending on plant growth, ripening, environmental stresses or industrial processing. In this review we will focus on newly identified allergens. Recent research have characterized and extensively studied their biochemistry, structure and immunological properties.

Antimycobacterial activity of N1-[1-[3-aryl-1-(pyridin-2-, 3- or 4-yl)-3-oxo] propyl]-2-pyridinecarboxamidrazones.

Infections caused by non-tuberculous mycobacteria and multidrug-resistant Mycobacterium tuberculosis are difficult to treat, and so new compounds potentially active against these bacteria are being sought. A series of 2-pyridinecarboxamidrazone derivatives, recently synthesized, have been evaluated for their inhibitory activity against 17 Mycobacterium avium isolates; the agar dilution method showed different degrees of susceptibility to the new molecules. Four molecules, three of which are chlorine derivatives, inhibited 94% of the strains tested with an MIC of 32 mg/L. These data indicate that these new pyridine-2-carboxamidrazones merit further study as antimycobacterial agents.

Synthesis and antimycobacterial activity of [5-(pyridin-2-yl)-1,3,4-thiadiazol-2-ylthio]acetic acid arylidene-hydrazide derivatives.

[5-(Pyridin-2-yl)-1,3,4-thiadiazol-2-ylthio]acetic acid arylidene-hydrazide derivatives were synthesized and tested for their in vitro antimycobacterial activity. Some compounds showed a feable activity against a strain of Mycobacterium tuberculosis and a strain of Mycobacterium avium.

Synthesis and antimycobacterial activity of 5-aryl-1-isonicotinoyl-3-(pyridin-2-yl)-4, 5-dihydro-1H-pyrazole derivatives.

5-Aryl-1-isonicotinoyl-3-(pyridin-2-yl)-4,5-dihydro-1H-pyrazole derivatives were synthesized and tested for their in vitro antimycobacterial activity. The compounds showed an interesting activity against a strain of Mycobacterium tuberculosis and a human strain of M. tuberculosis H4.

Antimycobacterial activity of ionic fullerene derivatives.

Positively charged fullerene derivatives, moderately soluble in water:DMSO 9:1, have been tested using three strains of Mycobacterium spp. Some compounds inhibit the growth of Mycobacterium tuberculosis, a human clinical isolate, particularly virulent and resistant, at doses as low as 5 microg/mL.

Infection of macrophage-like THP-1 cells with Mycobacterium avium results in a decrease in their ability to phosphorylate nucleolin.

This study of the phosphorylation ability of macrophage-like cells upon infection with Mycobacterium avium was undertaken to establish potential targets of the interference with host response mechanisms. Cytosolic and membrane fractions from noninfected and infected cells were incubated with [gamma-(32)P]ATP, in the presence of Mg(2+) and the absence of Ca(2+), and the patterns of phosphoproteins synthesized were analyzed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Lower levels of a 110-kDa phosphoprotein were observed in association with cytosolic fractions from mycobacterium-infected cells compared to noninfected cells or cells treated with lipopolysaccharide or having ingested Escherichia coli or killed M. avium. The 110-kDa phosphoprotein was present in the soluble fraction (230,000 x g supernatant) after the kinase incubation, from where it was partially purified and identified as phosphonucleolin by amino acid sequencing. The decrease in nucleolin phosphorylation observed was not related to changes in the cytosolic or membrane levels of this protein, and was detected also in the cytosolic fraction of (32)P-labeled intact cells.

Synthesis and antimycobacterial activity of some 4H-1,2,4-triazin-5-one derivatives.

6-[(Arylmethylenamino)carbonyl]-3-(pyridin-2-yl)-4H-1,2,4-triazin-5-one derivatives were synthesized and tested for their in vitro antimycobacterial activity. Some compounds showed interesting activity against a strain of Mycobacterium tuberculosis.

Myeloperoxidase exerts microbicidal activity against Mycobacterium tuberculosis.

We investigated the antimycobacterial role of myeloperoxidase (MPO), one of the most abundant granule proteins in human neutrophils. Our data indicate that purified MPO, in the presence of hydrogen peroxide, exerts a consistent killing activity against Mycobacterium tuberculosis H37Rv and against a clinical isolate. The activity is time and dose dependent and requires the presence of chloride ions in the assay medium.

Synthesis and antimycobacterial activity of some N1-[1-[3-aryl-1-(pyridin-2-, 3-, or 4-yl)-3-oxo]propyl]-2- pyridinecarboxamidrazones.

N1-[1-[3-aryl-1-(pyridin-2,3-, and 4-yl)-3-oxo[propyl]-2- pyridinecarboxamidrazone derivatives were synthesized and tested for their in vitro antimycobacterial activity. Some compounds showed interesting activity against a strain of Mycobacterium tuberculosis and a strain of Mycobacterium avium.

Synthesis and antimycobacterial activity of some indole derivatives of pyridine-2-carboxamidrazone and quinoline-2-carboxamidrazone.

A series of pyridine-2-carboxamidrazone and quinoline-2-carboxamidrazone derivatives containing the indole moiety was prepared. Some of the synthesized compounds showed an interesting in vitro antimycobacterial activity against a strain of Mycobacterium tuberculosis.

Synthesis and antimicrobial activity of some 2,5-disubstituted 1,3,4,-thiadiazole derivatives.

A series of 5-substituted 2-arylamino-1,3,4-thiadiazole derivatives was prepared. The antimicrobial activity of these compounds against some strains of bacteria and a strain of Candida albicans was determined, together with that of the corresponding thiosemicarbazone derivatives, which are intermediates in the synthetical procedure.

A new flow cytometric assay for the evaluation of phagocytosis and the oxidative burst in whole blood.

Phagocytes play an important role in host defence against microorganisms and different techniques are needed to evaluate their functional activities. Here we describe a rapid, simple and reliable one step procedure to measure the phagocytosis rate and oxidative burst activation of both polymorphonuclear leukocytes (PMN) and monocytes, by means of flow cytometry using only small quantities of whole blood. The two species of bacteria employed as test microorganisms, Staphylococcus aureus and Candida albicans showed a somewhat different behaviour. We found that the present method could be used as an alternative test in the diagnosis of chronic granulomatous disease (CGD). Moreover we were able to analyse, in a one step procedure, defective phagocyte functions in a group of paediatric patients suffering from recurrent microbial infections.

In-vitro antimycobacterial activity of new synthetic amidrazone derivatives.

After preliminary in vitro screening of 15 newly synthesized compounds belonging to the chemical class of N1-(aryliden)-4-pyridinecarboxyamidrazones against Mycobacterium tuberculosis reference strain H37 Rv, we determined the minimum inhibitory concentrations (MICs) of the six most promising chemicals against different species of Mycobacterium and different strains of M. tuberculosis. The agar dilution method was employed against M. gordonae, M. bovis, M. kansasi, M. avium, M. fortuitum and on eighteen different strains of M. tuberculosis, isolated from human bronchial aspirates. The results obtained confirmed that the newly synthesized chemicals possessed a very interesting antitubercular activity, their MICs ranging from 4 micrograms/ml to 16 micrograms/ml.

Synthesis and antimycobacterial activity of some 4-pyridinecarboxyamidrazone derivatives.

A series of N1-aryliden-4-pyridinecarboxyamidrazone derivatives was prepared. Some of the synthesized compounds showed interesting in vitro antimycobacterial activity against some strains of Mycobacterium and clinical isolates of Mycobacterium tuberculosis.

Evaluation of an immunoenzymatic test (ELISA) for the diagnosis of leptospirosis in Italy.

An enzyme-linked immunosorbent assay (ELISA) was assessed to detect in humans IgM and IgG against the main serogroups/serovars of Leptospira present in Italy. Sonicated antigens from strain Wijnberg, serogroups Icterohaemorrhagiae and Riccio 2, serogroup Australis, were used in ELISA and the results were compared to microagglutination test (MAT). IgM were confirmed to be the predominant class of antibodies; the total sensitivity obtained by Wijnberg/ELISA with the sera of patients infected by different serogroups was 81.5% in relation to MAT, better sensitivity was achieved by the use of Riccio 2/ELISA; no reaction occurred with the control sera. Cross-reactivity was noted with some sera of patients with Lyme disease (IgM) and with few sera of patients with autoimmune disease (IgM and IgG). To improve the sensitivity of the ELISA both antigens Wijnberg and Riccio 2 must be employed in the immunoenzymatic assay, since serogroup Australis must be considered as a new emerging serogroup causing human leptospirosis in our country.