Maria Sala

Effectiveness and safety of colistin for the treatment of multidrug-resistant Pseudomonas aeruginosa infections

Purpose:To describe the clinical and microbiological outcomes of patients infected with multidrug-resistant Pseudomonas aeruginosa (MDRP) treated with colistin (colistimethate sodium) and the adverse events observed with this treatment.Methods:Retrospective study of MDRP infections treated with colistin from 1997 to 2006.Results:121 episodes were identified. The median daily intravenous dose was 240 mg/day; 28.9% of patients received intravenous and nebulized colistin. Clinical outcome was favorable in ten cases of bacteremia (62.5%, n = 16), 43 cases of bronchial infection (72.9%, n = 59), 13 cases of pneumonia (65%, n = 20), 11 cases of urinary infection (84.6%, n = 13), eight cases of skin and soft tissues (72.7%, n = 11), and in the one case of arthritis and one case of otitis. Eradication was achieved in 31 (34.8%) of the 89 patients with available bacteriologic data. Factors associated with bacteriological failure were smoking, chronic obstructive pulmonary disease (COPD), and previous infection with P. aeruginosa. Nephrotoxicity occurred in ten cases (8.3%), with the associated factors being previous chronic renal insufficiency, diabetes mellitus, and aminoglycoside use. Crude mortality was 16.5%, and related MDRP was 12.4%, and was higher in patients with pneumonia or bacteremia (36.1%) than in other types of infections (8.2%).Conclusions:Colistin is a safe option for the treatment of MDRP infections, with acceptable clinical outcomes. However, bacteriological eradication is difficult to achieve, especially in COPD patients.

Hospital costs of nosocomial multi-drug resistant Pseudomonas aeruginosa acquisition

BackgroundWe aimed to assess the hospital economic costs of nosocomial multi-drug resistant Pseudomonas aeruginosa acquisition.MethodsA retrospective study of all hospital admissions between January 1, 2005, and December 31, 2006 was carried out in a 420-bed, urban, tertiary-care teaching hospital in Barcelona (Spain). All patients with a first positive clinical culture for P. aeruginosa more than 48 h after admission were included. Patient and hospitalization characteristics were collected from hospital and microbiology laboratory computerized records. According to antibiotic susceptibility, isolates were classified as non-resistant, resistant and multi-drug resistant. Cost estimation was based on a full-costing cost accounting system and on the criteria of clinical Activity-Based Costing methods. Multivariate analyses were performed using generalized linear models of log-transformed costs.ResultsCost estimations were available for 402 nosocomial incident P. aeruginosa positive cultures. Their distribution by antibiotic susceptibility pattern was 37.1% non-resistant, 29.6% resistant and 33.3% multi-drug resistant. The total mean economic cost per admission of patients with multi-drug resistant P. aeruginosa strains was higher than that for non-resistant strains (15,265 vs. 4,933 Euros). In multivariate analysis, resistant and multi-drug resistant strains were independently predictive of an increased hospital total cost in compared with non-resistant strains (the incremental increase in total hospital cost was more than 1.37-fold and 1.77-fold that for non-resistant strains, respectively).ConclusionsP. aeruginosa multi-drug resistance independently predicted higher hospital costs with a more than 70% increase per admission compared with non-resistant strains. Prevention of the nosocomial emergence and spread of antimicrobial resistant microorganisms is essential to limit the strong economic impact.

Effect of protocol-related variables and women's characteristics on the cumulative false-positive risk in breast cancer screening

BACKGROUND Reducing the false-positive risk in breast cancer screening is important. We examined how the screening-protocol and womens characteristics affect the cumulative false-positive risk. METHODS This is a retrospective cohort study of 1565364 women aged 45-69 years who underwent 4739498 screening mammograms from 1990 to 2006. Multilevel discrete hazard models were used to estimate the cumulative false-positive risk over 10 sequential mammograms under different risk scenarios. RESULTS The factors affecting the false-positive risk for any procedure and for invasive procedures were double mammogram reading [odds ratio (OR)=2.06 and 4.44, respectively], two mammographic views (OR=0.77 and 1.56, respectively), digital mammography (OR=0.83 for invasive procedures), premenopausal status (OR=1.31 and 1.22, respectively), use of hormone replacement therapy (OR=1.03 and 0.84, respectively), previous invasive procedures (OR=1.52 and 2.00, respectively), and a familial history of breast cancer (OR=1.18 and 1.21, respectively). The cumulative false-positive risk for women who started screening at age 50-51 was 20.39% [95% confidence interval (CI) 20.02-20.76], ranging from 51.43% to 7.47% in the highest and lowest risk profiles, respectively. The cumulative risk for invasive procedures was 1.76% (95% CI 1.66-1.87), ranging from 12.02% to 1.58%. CONCLUSIONS The cumulative false-positive risk varied widely depending on the factors studied. These findings are relevant to provide women with accurate information and to improve the effectiveness of screening programs.Background: Reducing the false-positive risk in breast cancer screening is important. We examined how the screening-protocol and womens characteristics affect the cumulative false-positive risk. Methods: This is a retrospective cohort study of 1 565 364 women aged 45–69 years who underwent 4 739 498 screening mammograms from 1990 to 2006. Multilevel discrete hazard models were used to estimate the cumulative false-positive risk over 10 sequential mammograms under different risk scenarios. Results: The factors affecting the false-positive risk for any procedure and for invasive procedures were double mammogram reading [odds ratio (OR) = 2.06 and 4.44, respectively], two mammographic views (OR = 0.77 and 1.56, respectively), digital mammography (OR = 0.83 for invasive procedures), premenopausal status (OR = 1.31 and 1.22, respectively), use of hormone replacement therapy (OR = 1.03 and 0.84, respectively), previous invasive procedures (OR = 1.52 and 2.00, respectively), and a familial history of breast cancer (OR = 1.18 and 1.21, respectively). The cumulative false-positive risk for women who started screening at age 50–51 was 20.39% [95% confidence interval (CI) 20.02–20.76], ranging from 51.43% to 7.47% in the highest and lowest risk profiles, respectively. The cumulative risk for invasive procedures was 1.76% (95% CI 1.66–1.87), ranging from 12.02% to 1.58%. Conclusions: The cumulative false-positive risk varied widely depending on the factors studied. These findings are relevant to provide women with accurate information and to improve the effectiveness of screening programs.

Risk factors for multidrug-resistant Pseudomonas aeruginosa acquisition. Impact of antibiotic use in a double case-control study

Multidrug-resistant strains of Pseudomonas aeruginosa(MDRPA) have been increasing in some hospitals [1] andmay become a public health problem [2].The emergence of MDRPA has been related to exposureto antibiotics against P. aeruginosa [3, 4]. Most of thesestudies have focussed on particular environments such asthe intensive care unit (ICU) [5] or particular antibioticresistances, mainly quinolone-resistant P. aeruginosa andcarbapenem-resistant P. aeruginosa or specific infectionsites such ventilator-associated pneumonia or bacteraemia[6, 7]. Most studies have used case–control methodology orhave investigated outbreaks, and the case–control studieshave usually compared susceptibility to resistant micro-organisms. This methodology may overestimate the associ-ation between the resistance-defining antibiotic or may befalsely implicated as a potential risk factor for theacquisition of this pattern of susceptibility [8, 9].The aim of this study was to assess the factors related toMDRPA acquisition, especially previous antibiotic expo-sure, using a double case–control methodology [10],analysing all types of infections and all hospital wardsduring a long period of follow-up.We conducted a double case–control epidemiologicalstudy, exploring the risk factors (host characteristics,invasive procedures and, especially, previous antibioticexposure) associated with the acquisition of MDRPA inhospitalised patients from 1 January 2001 to 31 December2006 in a University Hospital with 450 beds. P. aeruginosawas isolated and identified by the microbiology laboratoryby means of routine techniques. The susceptibility of

Effect of false-positive results on reattendance at breast cancer screening programmes in Spain.

BACKGROUND Mammography is the only breast screening method, we are aware of today, which is able to reduce mortality from breast cancer. Nevertheless, this procedure carries an inherent risk of false-positive screening mammogram. The association between these results and reattendance at the next scheduled screening mammogram is controversial. The aim of this study was to examine the effect of a false-positive screening mammogram and womens characteristics on reattendance in eight regional population-based breast cancer screening programmes in Spain. METHODS This study included 1 383 032 women aged 44-67 years who were initially screened for breast cancer between 1990 and 2004. To investigate factors associated with reattendance, logistic regression models were used. RESULTS The mean age of women at first screening was 53.6 years (SD = 6.1 years). Of 120 800 women with a false-positive screening mammogram, 78.3% returned for a subsequent screening mammogram compared with 81.9% of those with a negative result (P < 0.001). Multivariate analysis showed that women with a false-positive result at first screening mammogram were less likely to reattend (OR = 0.71; 95% CI 0.70-0.73) and that the likelihood was lower in those who had undergone invasive additional tests (OR = 0.56; 95% CI 0.53-0.59). CONCLUSION A false-positive screening mammogram in the first screening negatively affected attendance at the subsequent screening. The results of this study could be useful to improve the screening process and to increase womens compliance.

Cost-effectiveness of early detection of breast cancer in Catalonia (Spain)

BackgroundBreast cancer (BC) causes more deaths than any other cancer among women in Catalonia. Early detection has contributed to the observed decline in BC mortality. However, there is debate on the optimal screening strategy. We performed an economic evaluation of 20 screening strategies taking into account the cost over time of screening and subsequent medical costs, including diagnostic confirmation, initial treatment, follow-up and advanced care.MethodsWe used a probabilistic model to estimate the effect and costs over time of each scenario. The effect was measured as years of life (YL), quality-adjusted life years (QALY), and lives extended (LE). Costs of screening and treatment were obtained from the Early Detection Program and hospital databases of the IMAS-Hospital del Mar in Barcelona. The incremental cost-effectiveness ratio (ICER) was used to compare the relative costs and outcomes of different scenarios.ResultsStrategies that start at ages 40 or 45 and end at 69 predominate when the effect is measured as YL or QALYs. Biennial strategies 50-69, 45-69 or annual 45-69, 40-69 and 40-74 were selected as cost-effective for both effect measures (YL or QALYs). The ICER increases considerably when moving from biennial to annual scenarios. Moving from no screening to biennial 50-69 years represented an ICER of 4,469€ per QALY.ConclusionsA reduced number of screening strategies have been selected for consideration by researchers, decision makers and policy planners. Mathematical models are useful to assess the impact and costs of BC screening in a specific geographical area.

Breast cancer detection risk in screening mammography after a false-positive result

BACKGROUND False-positives are a major concern in breast cancer screening. However, false-positives have been little evaluated as a prognostic factor for cancer detection. Our aim was to evaluate the association of false-positive results with the cancer detection risk in subsequent screening participations over a 17-year period. METHODS This is a retrospective cohort study of 762,506 women aged 45-69 years, with at least two screening participations, who underwent 2,594,146 screening mammograms from 1990 to 2006. Multilevel discrete-time hazard models were used to estimate the adjusted odds ratios (OR) of breast cancer detection in subsequent screening participations in women with false-positive results. RESULTS False-positives involving a fine-needle aspiration cytology or a biopsy had a higher cancer detection risk than those involving additional imaging procedures alone (OR = 2.69; 95%CI: 2.28-3.16 and OR = 1.81; 95%CI: 1.70-1.94, respectively). The risk of cancer detection increased substantially if women with cytology or biopsy had a familial history of breast cancer (OR = 4.64; 95%CI: 3.23-6.66). Other factors associated with an increased cancer detection risk were age 65-69 years (OR = 1.84; 95%CI: 1.67-2.03), non-attendance at the previous screening invitation (OR = 1.26; 95%CI: 1.11-1.43), and having undergone a previous benign biopsy outside the screening program (OR = 1.24; 95%CI: 1.13-1.35). CONCLUSION Women with a false-positive test have an increased risk of cancer detection in subsequent screening participations, especially those with a false-positive result involving cytology or biopsy. Understanding the factors behind this association could provide valuable information to increase the effectiveness of breast cancer screening.

Seventeen-years overview of breast cancer inside and outside screening in Denmark.

Abstract Background. Long-term data on breast cancer detection in mammography screening programs are warranted to better understand the mechanisms by which screening changes the breast cancer pattern in the population. We aimed to analyze 17 years of breast cancer detection rates inside and outside screening in two Danish regions, emphasizing the influence of organizational differences of screening programs on the outcomes. Material and methods. We used data from two long-standing population-based mammography screening programs, Copenhagen and Fyn, in Denmark. Both programs offered biennial screening to women aged 50–69 years. We identified targeted, eligible, invited and participating women. We calculated screening detection and interval cancer rates for participants, and breast cancer incidence in non-screened women (= targeted women excluding participants) by biennial invitation rounds. Tumor characteristics were tabulated for each of the three groups of cancers. Results. Start of screening resulted in a prevalence peak in participants, followed by a decrease to a fairly stable detection rate in subsequent invitation rounds. A similar pattern was found for breast cancer incidence in non-screened women. In Fyn, non-screened women even had a higher rate than screening participants during the first three invitation rounds. The interval cancer rate was lower in Copenhagen than in Fyn, with an increase over time in Copenhagen, but not in Fyn. Screen-detected cancers showed tumor features related with a better prognosis than tumors detected otherwise, as more than 80% were smaller than 20 mm and estrogen receptor positive. Conclusion. Data from two long-standing population-based screening programs in Denmark illustrated that even if background breast cancer incidence and organization were rather similar, performance indicators of screening could be strongly influenced by inclusion criteria and participation rates. Detection rates should be interpreted with caution as they may be biased by selection into the screening population.

Pandemic A/H1N1 influenza: Transmission of the first cases in Spain

INTRODUCTION Pandemic A/H1N1 influenza emerged in Mexico at the end of March 2009. Since then, it is still important to provide evidences that contributed to the international spread of the virus and to ascertain the attack rate of this new strain of influenza among the first cases in Spain that led to identify the first transmission in Europe. METHODS Three pandemic A/H1N1 influenza groups related to an overseas flight were studied: 71 student group, 94 remaining passengers, and 68 contacts of confirmed cases. The attack rate with their 95% confidence interval (CI) among the student group and contacts was calculated. On April 26th, when the first cases were notified, strong preventive measures were implemented among the student group and the contacts of the confirmed cases. RESULTS On 27th April, the first pandemic A/H1N1 influenza cases confirmed in Spain were three students that came back from Mexico by airplane. A student generated the first native case in Spain and one of the first cases in Europe. Similar attack rates were found between the student group (14.1%; CI: 12.1-16.1) and their contacts (13.2%; CI: 4.4-22.0), but no cases among remaining passengers were detected, suggesting low transmission risk during air travel. CONCLUSION The first cases of pandemic A/H1N1 influenza in Spain were imported by airplane from Mexico. Preventive efforts to reduce the impact of the influenza influenced that primary and secondary rates were lower than first estimations by WHO.

Results of a cervical cancer screening programme from an area of Barcelona (Spain) with a large immigrant population.

BACKGROUND To assess the participation rate and results of cytological assessment in the context of cervical cancer screening activities in an area of Barcelona (Spain) with a large immigrant population. METHODS Descriptive retrospective study of cytologies performed between 2001 and 2006 in women > or =14 years of age living in 2 out of 10 districts of Barcelona (n = 129 327) and participating in cervical cancer screening activities within a sexual and reproductive health care programme. RESULTS Between 2001 and 2006, overall participation among women aged 20- to 64-years old was 50.7%, with higher participation among women aged 20-34 years than among those aged 50-64 years (63.8 and 36.0%, respectively; P < 0.01). The median frequency was 0.5 cytologies/year. The rate of pathological results increased from 11.4 per thousand in 2001 to 29.0 per thousand in 2006 (P < 0.001). This increase was higher among younger women and was mainly due to an increase in the rate of atypical squamous cells of undetermined significance (ASCUS) and low-grade squamous intraepithelial lesions (L-SIL). CONCLUSIONS These results show a low rate of participation in the public cervical cancer screening programme and an increase in the number of pathological results during the study period. These results provide useful information at a time when significant changes in the prevention of cervical cancer are being planned.