Effective immunosuppression with dexamethasone phosphate in the Galleria mellonella larva infection model resulting in enhanced virulence of Escherichia coli and Klebsiella pneumoniae.

The aim was to evaluate whether immunosuppression with dexamethasone 21-phosphate could be applied to the Galleria mellonella in vivo infection model. Characterised clinical isolates of Escherichia coli or Klebsiella pneumoniae were employed, and G. mellonella larvae were infected with increasing doses of each strain to investigate virulence in vivo. Virulence was then compared with larvae exposed to increasing doses of dexamethasone 21-phosphate. The effect of dexamethasone 21-phosphate on larval haemocyte phagocytosis in vitro was determined via fluorescence microscopy and a burden assay measured the growth of infecting bacteria inside the larvae. Finally, the effect of dexamethasone 21-phosphate treatment on the efficacy of ceftazidime after infection was also noted. The pathogenicity of K. pneumoniae or E. coli in G. mellonella larvae was dependent on high inoculum numbers such that virulence could not be attributed specifically to infection by live bacteria but also to factors associated with dead cells. Thus, for these strains, G. mellonella larvae do not constitute an ideal infection model. Treatment of larvae with dexamethasone 21-phosphate enhanced the lethality induced by infection with E. coli or K. pneumoniae in a dose- and inoculum size-dependent manner. This correlated with proliferation of bacteria in the larvae that could be attributed to dexamethasone inhibiting haemocyte phagocytosis and acting as an immunosuppressant. Notably, prior exposure to dexamethasone 21-phosphate reduced the efficacy of ceftazidime in vivo. In conclusion, demonstration of an effective immunosuppressant regimen can improve the specificity and broaden the applications of the G. mellonella model to address key questions regarding infection.

[Emergency care of patients with upper gastrointestinal bleeding in regional hospitals in Catalonia]. / Asistencia urgente a los pacientes con hemorragia digestiva alta en los hospitales comarcales catalanes.

OBJECTIVE: To evaluate the resources available in Catalan regional hospitals for the emergency care of upper gastrointestinal hemorrhage. METHODS: We analyzed a survey sent to 32 hospitals on the availability, composition and resources of a duty endoscopy service for the year 2009. RESULTS: Responses were obtained from 24 centers, covering 3,954,000 inhabitants. Duty endoscopists were available in 12 hospitals. A total of 1,483,000 inhabitants were unable to access a duty endoscopist in the referral center. Centers with duty endoscopists had more beds and had a larger catchment area. Duty services were composed of 4.5 endoscopists (range 2-11), covering 82.1 (33.2-182.5) duty shifts/year. Seventeen centers reported 1,571 episodes (51%, range: 3-280, 39.68/100,000 inhabitants). Centers with a duty service reported a greater number of cases (76 vs. 43, p=0.047). Centers without this service referred a greater number of patients (147 vs. 17, p=0.001). Patients in the emergency department were under the care of the internal medicine department in four centers, the surgery department in 14 centers and under the care of both departments in six. Admitted patients were under the care of the gastroenterology department in only six hospitals. The most widely used procedures were ligation of varicose bleeding and injection therapies in non-varicose bleeding. Twenty-one percent of centers did not perform combined treatment. CONCLUSIONS: A significant proportion of the population does not have access to a duty endoscopist in referral centers. Duty shifts represent significant workload in regional hospitals. Coordination among health professionals and centers would allow the efficient application of therapeutic resources and a duty endoscopy service to be established in centers lacking this resource.

Prevalence and factors related to hepatitis B and C in inflammatory bowel disease patients in Spain: a nationwide, multicenter study.

OBJECTIVES: Limited information suggests the existence of a high prevalence of hepatitis B (HBV) and C virus (HCV) infection in inflammatory bowel disease (IBD). This knowledge is relevant because the viruses may reactivate under immunosuppressive therapy. The objectives of this study are to assess the prevalence of HBV and HCV infection in IBD, in a nationwide study, and to evaluate associated risk factors. METHODS: This cross-sectional multicenter study included 2,076 IBD patients, consecutively recruited in 17 Spanish hospitals. Factors related to IBD (severity, invasive procedures, etc.) and to infection (transfusions, drug abuse, etc.) were registered. Independent risk factors for viral infection were evaluated using logistic regression analysis. RESULTS: Present and/or past HBV and HCV infection was found in 9.7% of patients of both ulcerative colitis (UC) and Crohn's disease (CD) (UC: HBsAg 0.8%, anti-HBc 8%, anti-HCV 1.3%; CD: HBsAg 0.6%, anti-HBc 7.1%, anti-HCV 2.3 %). Effective vaccination (anti-HBs, without anti-HBc) was present in 12% of patients. In multivariate analysis, age (odds ratio (OR) 1.04; 95% confidence interval (CI) 1.02-1.06; P=0.000), family history of hepatitis (OR 2.48; 95% CI 1.3-4.74; P=0.006) and moderate-to-severe IBD disease (OR 2.5; 95% CI 1.02-6.15; P=0.046) were significantly related to HBV, whereas transfusions (OR 2.66; 95% CI 1.2-5.87; P=0.015) and antibiotic use (OR 2.66; 95% CI 1.1-6.3; P=0.03) were significantly related to HCV. The significance for transfusions was lost if they were administered after 1991, when HCV markers became mandatory in blood banks. CONCLUSIONS: Prevalence of HBV and HCV infection in IBD is similar to that of the general population of reference and lower than that in previously published series. This fact, in addition to the lack of association with invasive procedures, suggests the existence of adequate preventive measures in centers attending to these patients. The low percentage of effective vaccination makes it mandatory to intensify B virus vaccination in IBD.

[Needlestick injuries in health care workers: analysis of non preventable risk factors through standard precautions]. / Accidentes biológicos percutáneos en el personal sanitario: análisis de factores de riesgo no prevenibles mediante precauciones estándares.

OBJECTIVE: To identify potential risk factors of occupational needlestick injuries that were not prevented despite adherence to standard precautions. PATIENTS AND METHOD: Multicentre case control study. Cases were defined as any workers who reported a needlestick injury despite documented use of standard precautions. Controls were workers of the same hospital who had performed procedures similar to matched cases and who reported a needlestick injury without correct use of standard precautions (control 1) or who did not report a needlestick injury during the previous 6 months (control 2). RESULTS: A total of 512 injuries were included (256 cases and 256 controls 1), and 256 controls 2. Analyses based on controls 1 showed an increased risk for physicians (ORa 2.22; 95% CI: 1.07-4.60) and those working in the operating theatre (ORa 2.87; 95% CI: 1.26-6.55). Regarding controls 2, increased risks were found for those younger than 25 years (ORa 2.58; 95% CI: 1.20-5.58), physicians (ORa 5.24; 95% CI: 1.50-18.28), those working in operating theatres (ORa 6.00; 95% CI: 2.07-17.36), emergency services, intensive and life-support units (ORa 3.48; 95% CI: 1.37-8.85) and those exposed to poor lighting (ORa 1.67; 95% CI: 1.02-2.82). Education in occupational risk prevention was found to be a protecting factor when controls 1 were analyzed (ORa 0.61; 95% CI: 0.39-0.97). CONCLUSIONS: Despite adherence to standard precautions, working as a physician, in operating theatres, emergency and life-support units, being younger than 25 years, and being exposed to poor visibility and training in occupational risk prevention appear to be independent risk factors for occupational needlestick injuries.

How many patients with rheumatic diseases and TNF inhibitors treatment have latent tuberculosis?

OBJECTIVES: Spanish clinical guidelines recommend screening patients for tuberculosis (TB) before TNF inhibitors (TNFi) treatment. Our objective was to estimate the prevalence of TST seroconversion as an estimation of the prevalence of latent TB in patients with rheumatic diseases and TNFi treatment that have already been screened for tuberculosis. METHODS: TST, booster and chest x-ray were performed to patients with rheumatic diseases, TNFi treatment, negative tuberculin skin tests before treatment and that were attending the rheumatology Department of three different hospitals in Barcelona. According to the Spanish Society Rheumatology guidelines, these patients had not received TB prophylaxis treatment. RESULTS: One hundred and forty patients were included in the study. The tuberculin skin test was positive in 4.28% (n=6) of the patients. 50% of the patients were undergoing TNFi ≤ 2 years, being two of the patients only one year on the TNFi when a positive TST was detected. This shows that a conversion of the TST can occur even few months or years after the TNFi is started. CONCLUSIONS: The present study observed that 4.28% of patients with rheumatic diseases on TNFi who did not have performed a pre-treatment TB prophylaxis, had a conversion of the TST. Moreover, the conversion of the TST had been within the first two years of treatment in half of the patients of our cohort. In spite of these results, false TST positives in the diagnosis of latent TB cannot be excluded as an explanation for our results.

Alerts in electronic medical records to promote a colorectal cancer screening programme: a cluster randomised controlled trial in primary care.

BACKGROUND: Participation rates in colorectal cancer screening are below recommended European targets. AIM: To evaluate the effectiveness of an alert in primary care electronic medical records (EMRs) to increase individuals' participation in an organised, population-based colorectal cancer screening programme when compared with usual care. DESIGN AND SETTING: Cluster randomised controlled trial in primary care centres of Barcelona, Spain. METHOD: Participants were males and females aged 50-69 years, who were invited to the first round of a screening programme based on the faecal immunochemical test (FIT) (n = 41 042), and their primary care professional. The randomisation unit was the physician cluster (n = 130) and patients were blinded to the study group. The control group followed usual care as per the colorectal cancer screening programme. In the intervention group, as well as usual care, an alert to health professionals (cluster level) to promote screening was introduced in the individual's primary care EMR for 1 year. The main outcome was colorectal cancer screening participation at individual participant level. RESULTS: In total, 67 physicians and 21 619 patients (intervention group) and 63 physicians and 19 423 patients (control group) were randomised. In the intention-to-treat analysis screening participation was 44.1% and 42.2% respectively (odds ratio 1.08, 95% confidence interval [CI] = 0.97 to 1.20, P = 0.146). However, in the per-protocol analysis screening uptake in the intervention group showed a statistically significant increase, after adjusting for potential confounders (OR, 1.11; 95% CI = 1.02 to 1.22; P = 0.018). CONCLUSION: The use of an alert in an individual's primary care EMR is associated with a statistically significant increased uptake of an organised, FIT-based colorectal cancer screening programme in patients attending primary care centres.

[Induction therapy with interferon alfa-2a in compensated hepatitis C virus-related cirrhosis. Randomized, multicenter study]. / Terapia de inducción con interferón alfa-2a en la cirrosis por el virus de la hepatitis C compensada. Estudio multicéntrico aleatorizado.

BACKGROUND: Although standard dose interferon (IFN) is successful in only 5% of patients with compensated hepatitis C virus (HCV)-related cirrhosis, it has been suggested that this therapy might decrease the risk of complications or the incidence of hepatocellular carcinoma. Based on HCV kinetics, daily IFN may improve response rates. PATIENTS AND METHOD: Forty cirrhotic patients were randomised to receive (Group I: 19) or not (Group II: 21) treatment with IFN (4.5 MU/daily for 24 weeks, followed by 4.5 MU/48 hours for a further 24 weeks period, only if ALT was within normal values). RESULTS: Dose reduction and discontinuation for adverse events was required in 11 (58%) and 6 (31.5%) cases, respectively. End-of-treatment response was not observed in any of the 21 controls but in 4 of the 19 (21%) treated patients (p = 0.04); a sustained response was achieved in only 2 treated patients (10.5%). The 3-year probability of developing any of the following: ascites, hepatocellular carcinoma, transplantation or death was lower in Group I than in Group II (6% vs 27%; p = 0.05). CONCLUSION: Although induction IFN therapy is associated with common side effects and poor sustained response in compensated HCV-related cirrhosis, it might improve the outcome of patients at the medium-term.

Can we predict the severity of pulmonary hypertension in patients with scleroderma?

OBJECTIVES: To describe the clinical-biological characteristics of patients with scleroderma (SSc) and pulmonary artery hypertension (PAH). To establish the relationship between pulmonary functional tests (PFT), Doppler echocardiography (ECHO) and the severity of the PAH. MATERIAL AND METHODS: Retrospective study of patients with scleroderma treated at a tertiary center. All participants received a protocol study, which included a complete analysis and additional tests: Doppler Echocardiography and pulmonary functional tests (PFT) with carbon monoxide diffusing capacity (DLCO). RESULTS: Overall, 331 patients were treated, including 68 (20.5%) with PAH. The limited subtype of Scleroderma was the most prevalent. The Person's correlation coefficient was used for the following variables: FVC-sPAP, FVC/DLCO-sPAP, DLCO-sPAP and TRV-sPAP, showed a significant moderate linear association in the relationship DLCO-sPAP and TRV-sPAP. 29 deaths occurred, with 12 of them related to PAH. The median time between the PAH diagnosis and death was 1.8 years. CONCLUSIONS: The decrease in DLCO and the increase in TRV are negative predictor factor of PAH which, at the same time, means a worsening prognosis for patients with Scleroderma.

[Susceptibility to varicella among health care workers. Acceptability and response to vaccination]. / Susceptibilidad a la varicela en personal sanitario. Aceptación y respuesta a la vacunación.

BACKGROUND AND OBJECTIVE: To determine the prevalence of health care workers (HCW) susceptibility to varicella zoster virus (VZV). As a secondary objective, we describe the immunogenicity and reactogenicity of the vaccine. SUBJECTS AND METHODS: A multicenter analytic cross-sectional study was conducted in 5 hospitals in Catalonia, Spain, in a total of 1,111 HCW, aged between 18-60 years. We studied the prevalence of anti-VZV antibodies (IgG) and obtained demographic, occupational and health related variables that were expected to be associated with immunogenicity, as well as past history of varicella. All susceptible HCW were vaccinated and we studied the immunogenicity (antibody detection) and reactogenicity of the 1st and 2nd doses of the vaccine. Detection of antibodies against VZV was obtained by ELISA. All negative results were confirmed with FAMA. RESULTS: Forty two subjects (3.8%) were negative. Susceptibility to VZV was associated (p<0.05) with decreased age (29.6 years ± 8.5 vs. 32,5 ± 9,3 in non-susceptible individuals), having fewer siblings and having no previous clinical history of varicella. Postvaccination detection tests with ELISA showed a seroconversion rate of 52 and 86% after the 1st and 2nd doses of the vaccine respectively, and 100% when using FAMA. There were no significant adverse events. CONCLUSIONS: Susceptibility to varicella among HCW is low. Positive past history of varicella is a good predictor of previous exposure to VZV, since 99% (687/696) of the individuals that declared having experienced the disease were immune. This would avoid prevaccination screening in nearly two thirds of HCW.