Gonzalo Nocea

Consequences of inappropriate initial empiric parenteral antibiotic therapy among patients with community-acquired intra-abdominal infections in Spain

To assess the association between inappropriate antibiotic therapy and clinical outcomes for complicated community-acquired intra-abdominal infections in Spain, patient records from October 1998 to August 2002 in 24 hospitals were reviewed. Initial empiric therapy was classified appropriate if all isolates were sensitive to at least 1 of the antibiotics administered. Multivariate analyses were performed to assess associations between appropriateness of therapy and patient outcomes. Healthcare resource use was measured as hospital length of stay (LOS) and d on intravenous antibiotic therapy. A total of 425 patients were included. Of these, 387 (91%) received appropriate initial empiric therapy. Patients on inappropriate therapy were less likely to have clinical success (79% vs 26%, p<0.001), more likely to require additional antibiotic therapy (40% vs 7%, p<0.01) and more likely to be re-hospitalized within 30 d of discharge (18% vs 3%, p<0.01). Multivariate analyses also showed that inappropriate therapy was associated with an almost 16% increase in LOS (p<0.05) and 26% in d of intravenous antibiotic therapy compared with appropriate therapy (p<0.05). Inappropriate initial antibiotic therapy was associated with a significantly higher proportion of unsuccessful patient outcomes (including death, re-operation, re-hospitalization or additional parental antibiotic therapies), increased length of stay and length on therapy.

Validación de la versión española del Pediatric Quality of Life Questionnaire en la valoración de la calidad de vida del niño asmático

Fundamento Analizar la utilidad clinica y validar el cuestionario de calidad de vida para ninos asmaticos (PAQLQ) en situacion de practica clinica. Pacientes y metodo Se incluyeron 1.012 ninos entre 6 y 14 anos, diagnosticados de asma leve o moderada, atendidos en 48 hospitales espanoles. Ademas de recoger variables sociodemograficas y clinicas de los pacientes, se administraron los cuestionarios PAQLQ y EQ-5D en dos ocasiones: en la visita basal y a los 2-3 meses en pacientes con asma no controlada (grupo A), o en la visita basal y a los 15 dias en pacientes con asma controlada (grupo B). Se valoro la factibilidad, la validez, la fiabilidad y la sensibilidad al cambio del PAQLQ. Resultados El PAQLQ puede aplicarse sin dificultades en ninos con asma leve o moderada a partir de los 7 anos. Este cuestionario no presento una relacion estadisticamente significativa con las variables sociodemograficas ni con la mayoria de las clinicas, a excepcion de la gravedad del asma, el numero de exacerbaciones, los sintomas y el uso de agonistas de s2 de corta duracion a demanda. Las dimensiones mas asociadas entre el PAQLQ y el EQ-5D fueron aquellas que median aspectos similares de la calidad de vida. El coeficiente a de Cronbach de las puntuaciones del PAQLQ oscilo entre 0,88 (limitacion de las actividades) y 0,96 (puntuacion global). El coeficiente de correlacion intraclase de las puntuaciones del PAQLQ obtenido en el grupo B oscilo entre 0,71 (limitacion de las actividades) y 0,83 (puntuacion global). La magnitud del efecto entre ambas visitas oscilo entre 0,49 y 0,69. Conclusiones La version espanola del PAQLQ demostro ser factible y valida para su uso en ninos con asma leve y moderada.

Imipenem/cilastatin versus piperacillin/tazobactam plus amikacin for empirical therapy in febrile neutropenic patients: results of the COSTINE study*

ABSTRACT Background: Combinations of beta-lactams plus aminoglycosides have become standard therapy for suspected infections in patients with profound neutropenia. However, it is not clear whether such combinations are advantageous over therapy with a broad-spectrum antibiotic. Objective: To assess the clinical effectiveness and the cost-effectiveness ratio of empirical therapy of febrile neutropenia with imipenem/cilastatin (I/C) versus piperacillin/tazobactam plus amikacin (P/T+A). Research design and methods: Prospective, multicenter observational study with 2 matched parallel cohorts treated with I/C (500 mg/6 h iv) or P/T+A (P/T: 4 g/6 h iv; A: 20 mg/kg/day iv). Main outcome measures: Therapeutic success was defined as the resolution of fever following ≥ 7 days of unchanged antibiotic treatment. An economic comparison was conducted focusing on the daily treatment costs, and the management of its toxicity. Results: There were 343 eligible patients (180 I/C, 163 P/T+A), of whom 290 were evaluable for the primary clinical effectiveness analysis. Follow-up information beyond 7 days of study inclusion was only available for 52% of all evaluable patients. Treatment success was observed in 42% of I/C patients compared with 31% of P/T+A patients (95% CI: –0.01, 21.4). The incidence of drug-related adverse experiences was 13% for I/C and 6% for P/T+A, with no differences in moderate or severe adverse experiences nor in those causing discontinuation of antibiotic therapy. Treatment costs were 189.55 euros (95% CI: 127.46–251.46) lower per episode of febrile neutropenia for patients treated with I/C. Conclusions: The clinical effectiveness of I/C was similar to that of P/T+A. In both treatment groups toxicity was low and did not limit antibiotic therapy. Resource consumption was lower with I/C.

Observational study of treatment compliance in women initiating antiresorptive therapy with or without calcium and vitamin D supplements in Spain.

ObjectiveThe aims of this study were to evaluate the compliance with antiresorptive therapy (ART) and supplements in Spain and to analyze the validity of the different treatment compliance assessment methods. MethodsA cross-sectional study with retrospective data collection was carried out in women starting ART, evaluating indirect objective compliance, self-reported compliance, and the Morisky-Green questionnaire. ResultsA total of 480 women with a mean (SD) age of 65.8 (9.2) years were studied. Of these women, 62.9% received calcium and/or vitamin D supplements in addition to ART. According to the objective compliance method, 76.9% of the women were compliers (≥80%) with bisphosphonates; 69.4%, with selective estrogen receptor modulators; and 61.8%, with supplements (P < 0.01). Using the self-reported compliance, we identified 91% compliers with antiresorptive drugs and 75% with supplements. Using the Morisky-Green test, we classified 60.8% of the women as compliers with antiresorptive drugs and 48.4% with supplements. Combining the objective and self-reported compliance, 29.5% of the women did not adequately comply with ART and 56% with the drug supplements. ConclusionsWith all three compliance measures, supplements were the treatment yielding the lowest percentage of compliers. Bisphosphonates constituted the treatment offering the best objective compliance: 38.2% of the women with drug supplements and between 23.1% and 30.6% of the women with ART failed to exceed the theoretical value of 80% regarded as representing good compliance.

Calcium and vitamin D intake by postmenopausal women with osteoporosis in France

Abstract Objective: To assess dietary calcium and vitamin D intake and their relationship with prescription medication and nutritional supplement use among postmenopausal women with osteoporosis in France. Research design and methods: Telephone interviews were conducted with 207 postmenopausal women with osteoporosis referred by a random sample of physicians from a French national list. Based on a French food frequency questionnaire, patients reported their daily food intake and frequency as well as their use of prescription medications and nutritional supplements. Results: Average daily dietary vitamin D intake was only 144.8 IU (SD 84.6, p < 0.01 compared to the recommended 800 IU), with 30% of the sample taking a vitamin D supplement. No participant had more than 500 IU vitamin D daily from food alone and 78% had less than 200 IU per day. A total of 51% of patients took no vitamin D supplements and had less than 5 hours of sun exposure in a week. Patients who were receiving osteoporosis medications and those who were not had comparable vitamin D intake. The average daily dietary calcium intake was 966.4 mg (SD 273.7, p < 0.01 compared to the 800 mg recommended). Calcium supplements were taken by 38% of participants and older patients tended to take more. Limitations of the study include convenience sampling and patient self-report. Conclusions: Daily vitamin D intake among this sample of postmenopausal osteoporotic women in France was significantly lower than recommended dosages. At least 50% of these patients might benefit by adding vitamin D to their current therapy.

Validation of a new tool to assess health-related quality of life in psoriasis: the PSO-LIFE questionnaire

BackgroundSeveral questionnaires have been used to measure health related quality of life (HRQoL) in patients with psoriasis, few have been adapted for use in Spain; none of them was developed specifically for the Spanish population. The purpose of the study was to validate and assess the sensitivity to change of a new questionnaire to measure HRQOL in patients with psoriasis (PSO-LIFE).MethodsObservational, prospective, multicenter study performed in centers around Spain. Patients with active or inactive psoriasis completed the PSO-LIFE together with other Dermatology Quality of Life Index (DLQI) and Psoriasis Disability Index (PDI). A control group of patients with urticaria or atopic dermatitis was also included. Internal consistency and test-retest reliability of the PSO-LIFE were assessed by calculating Cronbach’s alpha and Intraclass Correlation Coefficient (ICC). Validity was assessed by examining factorial structure, the capacity to discriminate between groups, and correlations with other measures. Sensitivity to change was measured using effect sizes.ResultsThe final sample included for analysis consisted of 304 patients and 56 controls. Mean (SD) age of psoriasis patients was 45.3 (14.5) years compared to 38.8 (14) years for controls (p < 0.01). Cronbach’s alpha for the PSO-LIFE was 0.95 and test-retest reliability using the ICC was 0.98. Factor analysis showed the questionnaire to be unidimensional. Mean (SD) PSO-LIFE scores differed between patients with psoriasis and controls (64.9 [22.5] vs 69.4 [17.3]; p < 0.05), between those with active and inactive disease (57.4 [20.4] vs 76.4 [20.6]; p < 0.01), and between those with visible and non-visible lesions (63.0 [21.9] vs. 74.8 [23.9]; p < 0.01). The correlation between PSO-LIFE and PASI scores was moderate (r = −0.43) while correlations with DLQI and PDI dimensions ranged from moderate to high (between 0.4 and 0.8). Effect size on the PSO-LIFE in patients reporting ‘much improved’ health status at study completion was 1.01 (large effect size).ConclusionsThe present results provide substantial support for the reliability, validity, and responsiveness of the PSO-LIFE questionnaire in the population for which it was designed.

Cost-effectiveness analysis of raltegravir in treatment-experienced HIV type 1-infected patients in Spain.

Raltegravir, a novel HIV-1 integrase inhibitor, has superior efficacy with optimized background treatment (OBT) vs. placebo + OBT in treatment-experienced HIV-1 patients. This study assessed the long-term cost effectiveness of raltegravir from a Spanish National Healthcare System perspective. A cohort-state-transition model was used to estimate clinical and economic outcomes associated with raltegravir + OBT vs. OBT alone. Subjects were stratified into health states according to HIV RNA level, CD4 count, and opportunistic infection (OI) history, and could transition into different health states over time based on projected long-term efficacy. Each health state was associated with a distinct treatment cost and utility (QoL) score. Model inputs for mortality, resource utilization, unit costs, OI risk, and long-term durability of viral suppression were obtained from clinical trials, published studies, and database analyses. Model outcomes were reported as incremental cost-effectiveness ratios (ICERs) in 2007 Euros per quality-adjusted life-year (euro/QALY) gained. Costs and QALYs were discounted at 6% per year based on Spanish cost-effectiveness guidelines. Extensive sensitivity analyses were conducted. Five years of treatment with raltegravir + OBT resulted in an additional 4.5 years of undiscounted life expectancy vs. OBT alone. The ICER of raltegravir + OBT vs. OBT alone was euro22,908/QALY and euro31,431/QALY for 3- and 5-year use, respectively. Lower ICERs were observed with lower discount rates (3%) for costs and benefits, lower raltegravir price (20%), and shorter treatment duration (3 years). ICER was also sensitive to analytical time horizon and alternative sources of QoL scores. In treatment-experienced Spanish patients, raltegravir was projected to provide survival benefits and be cost effective.

Attainment of normal lipid levels among high cardiovascular risk patients: Pooled analysis of observational studies from the United Kingdom, Sweden, Spain and Canada

BACKGROUND Although low-density lipoprotein cholesterol (LDL-C) is the primary lipid target for cardiovascular disease (CVD) risk reduction, high-density lipoprotein cholesterol (HDL-C) and triglycerides (TG) have also emerged as risk factors. This study evaluated attainment of goal/normal lipid levels in current clinical practice among high-risk patients following lipid-modifying therapy (LMT). METHODS Data for patients aged ≥35years and on LMT for ≥12months were identified from electronic medical records (United Kingdom and Sweden) and extracted from medical charts (Canada and Spain). High CVD risk was defined according to the Adult Treatment Panel III guidelines. An index period was defined, from January 1995-July 2008, during which patients received an initial LMT prescription. Prevalence of lipid abnormalities was assessed 12months before and after the index date. Multivariate logistic regressions evaluated predictors of attaining goal/normal lipid levels. RESULTS Among 12,768 high-risk patients, 75% had elevated LDL-C, 37% low HDL-C, and 30% elevated TG before LMT. Despite therapy (97% statins only), 23% had elevated LDL-C, 36% low HDL-C, 16% elevated TG, and 17% had ≥2 abnormal lipid levels. Framingham risk score >20% (Odds Ratio, 95% confidence interval: 0.37,0.31-0.43), diabetes (0.75,0.64-0.88), hypertension (1.26,1.09-1.46), current smoker (0.82,0.70-0.95) and increased body mass index (0.95,0.94-0.96) were associated with the likelihood of attaining ≥2 normal lipid levels (vs. LDL-C goal only). CONCLUSION Current approaches to lipid management improve LDL-C goal attainment; however, control of multiple lipid risk factors remains poor. Patients may benefit from more comprehensive approaches to lipid management, which treat multiple lipid abnormalities, as suggested in clinical guidelines.

Reduction of urinary levels of N-telopeptide correlates with treatment compliance in women with postmenopausal osteoporosis receiving alendronate.

ObjectiveThe aim of this study was to assess the factors associated with the effectiveness of treatment with alendronate (ALN) quantified by a reduction in urinary excretion of N-telopeptide (NTx). MethodsThe study is an observational, prospective, multicenter trial, with a 6-month follow-up. Postmenopausal osteoporotic women (densitometric criteria), who initiated treatment with ALN (70 mg/weekly) without previous treatment with antiresorptive agents (12 month) and calcitonin (6 month), were included. The assessment of NTx levels (nmol bone collagen equivalents/mmol creatinine) in the urine was performed at baseline and after completion of follow-up. A logistic regression model included “achieving a reduction in urinary NTx of at least 30% (minimal clinically significant change [MCSC])” as a dichotomous dependent variable and the following as independent variables: baseline urinary NTx levels, treatment compliance, years since diagnosis of menopause, ALN treatment duration, and treatment with calcium and vitamin D. Treatment compliance was assessed as the percentage of days of medication prescribed as a function of the time between the beginning and end of treatment. Good compliance was defined as a percentage between 80% and 120%. ResultsThe variables that reached statistical significance were baseline urinary NTx values (odds ratio, 1.052; 95% CI, 1.025-1.079) and compliance (odds ratio, 3.9; 95% CI, 1.5-10.1). Therefore, the women with good treatment compliance were almost 4 times more likely to achieve an MCSC in NTx levels, and the raise in one unit of urinary NTx baseline values increased by 5% of the probability of achieving MCSC. ConclusionsTreatment with ALN (70 mg/week) in women with postmenopausal osteoporosis effectively reduces the urinary excretion of the bone turnover biomarker NTx. The probability of achieving a clinically significant reduction is greater in those women with higher baseline levels of NTx and in women who comply with treatment.

Intensive care unit-related fluconazole use in Spain and Germany: patient characteristics and outcomes of a prospective multicenter longitudinal observational study

Background Candida spp. are a frequent cause of nosocomial bloodstream infections worldwide. Objective To evaluate the use patterns and outcomes associated with intravenous (IV) fluconazole therapy in intensive care units in Spain and Germany. Patients and methods The research reported here was a prospective multicenter longitudinal observational study in adult intensive care unit patients receiving IV fluconazole. Demographic, microbiologic, therapy success, length of hospital stay, adverse event, and all-cause mortality data were collected at 14 sites in Spain and five in Germany, from February 2004 to November 2005. Results Patients (n = 303) received prophylaxis (n = 29), empiric therapy (n = 140), preemptive therapy (n = 85), or definitive therapy (n = 49). A total of 298 patients (98.4%) were treated with IV fluconazole as first-line therapy. The treating physicians judged therapy successful in 66% of prophylactic, 55% of empiric, 45% of preemptive, and 43% of definitive group patients. In the subgroup of 152 patients with proven and specified Candida infection only, 32% suffered from Candida specified as potentially resistant to IV fluconazole. The overall mortality rate was 42%. Conclusion Our study informs treatment decision makers that approximately 32% of the patients with microbiological results available suffered from Candida specified as potentially resistant to IV fluconazole, highlighting the importance of appropriate therapy.