Impact of non-formulary drugs on pharmacological prescription in hospitalised patients.

OBJECTIVES: The growing number of drugs on the market makes it necessary to adapt hospital formularies in order to ensure consistent drug coverage. The aim of this study was to evaluate the impact of the prescription of non-formulary drugs (NFD) on the therapeutic management of admitted patients. METHODS: This retrospective observational study included NFD prescriptions in patients hospitalised in a tertiary university hospital during the period 2012-2015. NFD prescriptions are displayed on the computerised medical order as a pending alert to be reviewed by the clinical pharmacists, who make a notation to the clinical course that includes a recommendation for an available therapeutic alternative when available in the hospital formulary. The degree of acceptance of the recommendation by physicians is recorded. RESULTS: Approximately 0.5% of patients hospitalised during the study period were affected by an NFD prescription. A total of 52 (9.5%) NFD were of doubtful therapeutic efficacy, five (0.9%) were non-replaceable drugs and 490 (89.4%) were prescriptions for drugs with an alternative available in the hospital formulary. The acceptance rate for the recommended alternative was 34.9% in the evaluable NFD prescriptions. No correlation was observed between the number of NFD prescriptions or the number of NFD and the availability index (drugs included in the hospital formulary in relation to the total number of drugs marketed). CONCLUSIONS: The number of patients with a NFD prescription was very low. The lack of correlation between the number of NFD or NFD prescriptions and the availability index demonstrated that the hospital formulary covers practically all therapeutic needs.

Incremental cost of nosocomial bacteremia according to the focus of infection and antibiotic sensitivity of the causative microorganism in a university hospital.

To estimate the incremental cost of nosocomial bacteremia according to the causative focus and classified by the antibiotic sensitivity of the microorganism.Patients admitted to Hospital del Mar in Barcelona from 2005 to 2012 were included. We analyzed the total hospital costs of patients with nosocomial bacteremia caused by microorganisms with a high prevalence and, often, with multidrug-resistance. A control group was defined by selecting patients without bacteremia in the same diagnosis-related group.Our hospital has a cost accounting system (full-costing) that uses activity-based criteria to estimate per-patient costs. A logistic regression was fitted to estimate the probability of developing bacteremia (propensity score) and was used for propensity-score matching adjustment. This propensity score was included in an econometric model to adjust the incremental cost of patients with bacteremia with differentiation of the causative focus and antibiotic sensitivity.The mean incremental cost was estimated at &OV0556;15,526. The lowest incremental cost corresponded to bacteremia caused by multidrug-sensitive urinary infection (&OV0556;6786) and the highest to primary or unknown sources of bacteremia caused by multidrug-resistant microorganisms (&OV0556;29,186).This is one of the first analyses to include all episodes of bacteremia produced during hospital stays in a single study. The study included accurate information about the focus and antibiotic sensitivity of the causative organism and actual hospital costs. It provides information that could be useful to improve, establish, and prioritize prevention strategies for nosocomial infections.

Cost Attributable to Nosocomial Bacteremia. Analysis According to Microorganism and Antimicrobial Sensitivity in a University Hospital in Barcelona.

AIM: To calculate the incremental cost of nosocomial bacteremia caused by the most common organisms, classified by their antimicrobial susceptibility. METHODS: We selected patients who developed nosocomial bacteremia caused by Staphylococcus aureus, Escherichia coli, Klebsiella pneumoniae, or Pseudomonas aeruginosa. These microorganisms were analyzed because of their high prevalence and they frequently present multidrug resistance. A control group consisted of patients classified within the same all-patient refined-diagnosis related group without bacteremia. Our hospital has an established cost accounting system (full-costing) that uses activity-based criteria to analyze cost distribution. A logistic regression model was fitted to estimate the probability of developing bacteremia for each admission (propensity score) and was used for propensity score matching adjustment. Subsequently, the propensity score was included in an econometric model to adjust the incremental cost of patients who developed bacteremia, as well as differences in this cost, depending on whether the microorganism was multidrug-resistant or multidrug-sensitive. RESULTS: A total of 571 admissions with bacteremia matched the inclusion criteria and 82,022 were included in the control group. The mean cost was € 25,891 for admissions with bacteremia and € 6,750 for those without bacteremia. The mean incremental cost was estimated at € 15,151 (CI, € 11,570 to € 18,733). Multidrug-resistant P. aeruginosa bacteremia had the highest mean incremental cost, € 44,709 (CI, € 34,559 to € 54,859). Antimicrobial-susceptible E. coli nosocomial bacteremia had the lowest mean incremental cost, € 10,481 (CI, € 8,752 to € 12,210). Despite their lower cost, episodes of antimicrobial-susceptible E. coli nosocomial bacteremia had a major impact due to their high frequency. CONCLUSIONS: Adjustment of hospital cost according to the organism causing bacteremia and antibiotic sensitivity could improve prevention strategies and allow their prioritization according to their overall impact and costs. Infection reduction is a strategy to reduce resistance.

[Economic impact of nosocomial bacteraemia. A comparison of three calculation methods]. / Impacto económico de las bacteriemias nosocomiales. Comparación de tres metodologías de cálculo.

INTRODUCTION: The excess cost associated with nosocomial bacteraemia (NB) is used as a measurement of the impact of these infections. However, some authors have suggested that traditional methods overestimate the incremental cost due to the presence of various types of bias. The aim of this study was to compare three assessment methods of NB incremental cost to correct biases in previous analyses. METHODS: Patients who experienced an episode of NB between 2005 and 2007 were compared with patients grouped within the same All Patient Refined-Diagnosis-Related Group (APR-DRG) without NB. The causative organisms were grouped according to the Gram stain, and whether bacteraemia was caused by a single or multiple microorganisms, or by a fungus. Three assessment methods are compared: stratification by disease; econometric multivariate adjustment using a generalised linear model (GLM); and propensity score matching (PSM) was performed to control for biases in the econometric model. RESULTS: The analysis included 640 admissions with NB and 28,459 without NB. The observed mean cost was €24,515 for admissions with NB and €4,851.6 for controls (without NB). Mean incremental cost was estimated at €14,735 in stratified analysis. Gram positive microorganism had the lowest mean incremental cost, €10,051. In the GLM, mean incremental cost was estimated as €20,922, and adjusting with PSM, the mean incremental cost was €11,916. The three estimates showed important differences between groups of microorganisms. CONCLUSIONS: Using enhanced methodologies improves the adjustment in this type of study and increases the value of the results.

Patient risk factors for developing a drug-related problem in a cardiology ward.

BACKGROUND: Because of the high incidence of drug-related problems (DRPs) among hospitalized patients with cardiovascular diseases and their potential impact on morbidity and mortality, it is important to identify the most susceptible patients, who therefore require closer monitoring of drug therapy. PURPOSE: To identify the profile of patients at higher risk of developing at least one DRP during hospitalization in a cardiology ward. METHOD: We consecutively included all patients hospitalized in the cardiology ward of a teaching hospital in 2009. DRPs were identified through a computerized warning system designed by the pharmacy department and integrated into the electronic medical record. RESULTS: A total of 964 admissions were included, and at least one DRP was detected in 29.8%. The variables associated with a higher risk of these events were polypharmacy (odds ratio [OR]=1.228; 95% confidence interval [CI]=1.153-1.308), female sex (OR=1.496; 95% CI=1.026-2.180), and first admission (OR=1.494; 95% CI=1.005-2.221). CONCLUSION: Monitoring patients through a computerized warning system allowed the detection of at least one DRP in one-third of the patients. Knowledge of the risk factors for developing these problems in patients admitted to hospital for cardiovascular problems helps in identifying the most susceptible patients.

Design of a score to identify hospitalized patients at risk of drug-related problems.

PURPOSE: The potential impact of drug-related problems (DRP) on morbidity and mortality is a serious concern in hospitalized patients. This study aimed to design a risk score to identify patients most at risk of a DRP. METHODS: Data from patients admitted to a tertiary university hospital between January and August 2009 were used to design the risk score (training set). DRP were detected through a pharmacy warning system integrated in the computerized medical history. The variables associated with developing a DRP were identified through a binary multivariate logistic regression analysis and were used to compute the DRP risk score, which was subsequently validated in patients admitted between September and December 2009 (validation set). RESULTS: Of the 8713 patients included in the training set, at least one DRP was detected in 2425 (27.8%). Prescription of a higher number of drugs, higher comorbidity, advanced age, certain groups of the Anatomical Therapeutic Chemical classification system, and some major diagnostic categories were associated with risk of DRP. These variables were used to compute the DRP risk score. The area under the receiver operator characteristic curve was 0.778 (95%CI [0.768, 0.789]). Of the 4058 admissions included in the validation set, at least one DRP was detected in 876 (21.6%). The area under the receiver operator characteristic curve was 0.776 (95%CI [0.759, 0.792]). CONCLUSIONS: Knowledge of the variables associated with DRP could aid their early detection in at-risk patients. The use of an application that can be continually updated in daily clinical practice helps to optimize resources.

Eosinophil count and neutrophil-lymphocyte count ratio as prognostic markers in patients with bacteremia: a retrospective cohort study.

INTRODUCTION: There is scarce evidence on the use of eosinophil count as a marker of outcome in patients with infection. The aim of this study was to evaluate whether changes in eosinophil count, as well as the neutrophil-lymphocyte count ratio (NLCR), could be used as clinical markers of outcome in patients with bacteremia. METHODS: We performed a retrospective study of patients with a first episode of community-acquired or healthcare-related bacteremia during hospital admission between 2004 and 2009. A total of 2,311 patients were included. Cox regression was used to analyze the behaviour of eosinophil count and the NLCR in survivors and non-survivors. RESULTS: In the adjusted analysis, the main independent risk factor for mortality was persistence of an eosinophil count below 0.0454·10(3)/uL (HR = 4.20; 95% CI 2.66-6.62). An NLCR value >7 was also an independent risk factor but was of lesser importance. The mean eosinophil count in survivors showed a tendency to increase rapidly and to achieve normal values between the second and third day. In these patients, the NLCR was <7 between the second and third day. CONCLUSION: Both sustained eosinopenia and persistence of an NLCR >7 were independent markers of mortality in patients with bacteremia.

Hospital costs of nosocomial multi-drug resistant Pseudomonas aeruginosa acquisition.

BACKGROUND: We aimed to assess the hospital economic costs of nosocomial multi-drug resistant Pseudomonas aeruginosa acquisition. METHODS: A 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. RESULTS: Cost 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). CONCLUSIONS: P. 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.

[Costs associated with nosocomial bacteraemias in a University Hospital]. / Costes asociados a las bacteriemias nosocomiales en un hospital universitario.

OBJECTIVE: To describe the increase in costs due to patients who had any episode of nosocomial bacteraemia (NB) in a University Hospital, compared to the costs of patients with the same illness who did not. METHODS: Descriptive and retrospective study. POPULATION: all hospitalisation episodes between January 2005 and December 2007. We compared the patients who suffered some episode of NB, with the patients who did not. Dependent variable: cost of the hospitalisation episode. Main explanatory variable: presence of nosocomial bacteraemia. A generalized linear model was adjusted, with Gamma distribution and link logarithm function, given the distribution of the costs. RESULTS: There were 640 hospital episodes with NB and 28,459 with no NB. The average incremental cost for the hospitalisations with NB was 14,735.5€, adjusted for the disease. The impact on the costs for the hospital due to patients with NB was 9,430,713€. The most frequent source of infection was the catheter (35.5%), with an average increase in cost of 18,078€. In the multivariable model, the cost of patients with NB and involving a Gram(+) microorganism was 2.1 times more than that of patients without bacteraemia (95% CI; 1.96-2.23), if the microorganism was Gram(-) it was 1.8 times more (95% CI; 1.70-1.93), and for a fungus it was 2.4 time more (95% CI; 1.95-2.89). CONCLUSIONS: This analysis shows the significant impact in the financial costs due to NB, and gives a measure of the cost-benefit of investing in resources to prevent them. Knowing the source cause of the bacteraemia allows priority to be given to these areas and to promote the necessary actions designed to prevent them.

Characterization of new founder Alu-mediated rearrangements in MSH2 gene associated with a Lynch syndrome phenotype.

It has been reported that large genomic deletions in the MLH1 and MSH2 genes are a frequent cause of Lynch syndrome in certain populations. Here, a cohort has been screened and two new founder rearrangements have been found in the MSH2 gene. These mutations have been characterized by break point determination, haplotype analysis, and genotype-phenotype correlation. Mutations have been identified in the MLH1, MSH2, and MSH6 genes in 303 subjects from 160 suspected Lynch syndrome unrelated families. All subjects were tested using heteroduplex analysis by capillary array electrophoresis. Multiplex ligation-dependent probe amplification was used to detect rearrangements in mutation-negative index patients and confirmed by reverse transcriptase PCR. The break point of the deletions was further characterized by the array comparative genomic hybridization method. Immunohistochemical staining and microsatellite instability were studied in tumor samples. Hereditary nonpolyposis colorectal cancer-related phenotypes were evaluated. More than 16% (24 of 160) of the families had pathogenic mutations (8 MLH1, 15 MSH2, and 1 MSH6). Twelve of these families (50%) are carriers of a novel mutation. Seven of the 15 positive MSH2 families (47%) are carriers of a rearrangement. The exon 7 deletion and exon 4 to 8 deletion of MSH2 are new founder mutations. The segregation of a common haplotype, a similar phenotype, and anticipation effects were observed in these families. These findings will greatly simplify the diagnosis, counseling, and clinical care in suspected Lynch syndrome families and not just in specific geographic areas, so wide distribution may be explained by migration patterns.

[Results of a multidisciplinary and multifocal project to reduce bacteraemia caused by central venous catheters in non critical patients in a university hospital]. / Resultados de un proyecto multidisciplinar y multifocal para la disminución de la bacteriemia causada por catéter venoso central, en pacientes no críticos, en un hospital universitario.

OBJECTIVE: To evaluate a multidisciplinary and multifocal intervention in order to reduce catheter related bloodstream infections (CRBI), based on previously identified risk factors in non-critical patients. METHODS: A pre-post-intervention study, 2004-2006. POPULATION: patients with a central venous catheter (CVC). The primary endpoint was the CRBI. Other studied variables were patient characteristics, insertion, maintenance and removal of the catheter. The intervention consisted of baseline knowledge and identifying risk factors. In a second period, there was specific training on these identified risk factors and communication of the results, monitoring and evaluation of the CVC inserted. RESULTS: We analysed 175 and 200 CVC, respectively. The incidence of CRBI was 15.4% during the pre-intervention and 4.0% in the post-intervention period (P<.001). The incidence of BRC by CVC days in the first group was 8.8 infections 1.000 days of CVC and the second 2,3 (P=.0009). The multivariate analysis found an increased risk of CRBI during the first period (OR 4.32; 95% CI: 1.81-10.29) and the use of total parenteral nutrition (OR: 2.37; 95% CI: 1.10-5. 12). CONCLUSION: The application of specific measures directed at all non-critical patients in the entire hospital and involving a large number of professionals has achieved a decrease incidence of 73.9% of CRBI. An acceptable incidence of CRBI was obtained, and, with the completion of the project together with a new awareness, the situation will continue to improve.

[Evaluation of the impact of the introduction of a functional knee arthroplasty unit]. / Evaluación del impacto asistencial de la puesta en funcionamiento de una unidad funcional de artroplastia de rodilla.

OBJECTIVES: To evaluate the impact of a functional knee arthroplasty unit in Hospital de l'Esperança (Barcelona) on resource consumption, quality indicators and the direct costs of the healthcare process. METHOD: We performed a retrospective study based on two cross-sections: the first in 317 patients who underwent surgery in 2004 before the implementation of the functional knee arthroplasty unit and the second in 624 patients who underwent surgery in 2005. Data related to the process, complications and costs were collected. RESULTS: The mean length of hospital stay decreased by 9 days (p<0.001). The number of patients requiring convalescence after the intervention increased by 9.5% (p<0.001). Overall, the total cost of the healthcare process decreased by 16%, from 9,031.34 to 7,591.54 euro (p<0.001). This cost reduction was due to decreases in the length of hospital stay (2,946.0 vs. 1,616.8 euro), surgery costs (2,156.7 vs. 1,776.7 euro) and prosthesis costs (2,730.5 vs. 2,678.1 euro). CONCLUSIONS: The implementation of the functional knee arthroplasty unit reduced overall costs and length of hospital stay and substantially increased activity while maintaining a similar complication rate.

[Community bacteremia ambulatory treated or identified after discharge from the emergency department]. / Bacteriemia comunitaria tratada o identificada de forma ambulatoria tras el alta de un servicio de urgencias.

BACKGROUND AND OBJECTIVE: The patients with bacteremia usually require hospital admission. In occasions they are remitted to their home, due to inappropriate diagnosis or rapid clinical improvement. The study describes the evolution and the interventions carried out in patients with community bacteremia that were remitted to their home. PATIENTS AND METHOD: Prospective observational study carried out in a university hospital, of 450 beds, from March of 2000 until December of 2003. The hospital has a team that daily evaluated all blood cultures practiced; the patients with bacteremia remitted to home from the Emergency Department with inappropriate antibiotic were identified. RESULTS: During the period of study 1,172 episodes of true bacteremia were diagnosed, of these 247 (21.1%) were remitted to their home. In 50 cases (20.2%) it was considered necessary to contact with the patient: 36 for inappropriate empiric antibiotic treatment, 12 without antibiotic treatment and 2 for lack of information. Antibiotic treatment was initiated or modified in 34 cases, and 10 required hospital admission. Excluding the 66 patients who died in the first 48 h, the crude mortality of the patients remitted to home was inferior (4%) to that of the patients that required hospital admission (11.9%). CONCLUSIONS: One fifth of community bacteremia were ambulatory treated, frequently the antibiotic treatment was inappropriate, it is necessary to guarantee an appropriate control of this population.

[Impact of a clinical self-evaluation intervention on the appropriateness of hospital stays]. / Impacto de una intervención de autoevaluación clínica sobre la adecuación de la estancia hospitalaria.

AIM: To assess the impact of an intervention on inappropriate hospital stays (IHS) in acute-care hospitals in Catalonia (Spain) with the aim of testing the hypothesis that a simple intervention (adeQhos) reduces the proportion of IHS. METHODS: A pre-test/post-test study was performed through the <> questionnaire. Two intervention groups (internal medicine and general surgery) and 2 control groups (other medical specialities, orthopedics) were compared in 10 acute-care hospitals in Catalonia. The same evaluators assessed appropriateness of hospital stays before and after the intervention, using the Appropriateness Evaluation Protocol. RESULTS: A total of 1,594 pre-test stays and 1,495 post-test stays were reviewed. Of all the stays reviewed (day before discharge), 41.1% were inappropriate. The intervention was applied to 4,613 stays. There was a significant increase of IHS in the medicine control group (from 39.7 to 48.6%), and no decrease in the intervention groups (internal medicine [from 46.7 to 50.6%] or general surgery [from 27.2 to 31.2%]). The correlation between the intensity of the intervention and the difference in IHS before and after the intervention was r = -0.373 (p = 0.106). The intensity of intervention differed among the hospitals. In hospitals with an intensity of intervention > 60%, the proportion of IHS decreased by 10.7 points in internal medicine and by 4.8 points in general surgery, while the proportion of IHS increased in the control groups. CONCLUSIONS: The prevalanece of IHS the day before discharge in the hospitals studied was high (41.1%). No significant decrease in IHS was observed after a low-intensity intervention.

Impact of immigration on the cost of emergency visits in Barcelona (Spain).

BACKGROUND: The impact of immigration on health services utilisation has been analysed by several studies performed in countries with lower levels of immigration than Spain. These studies indicate that health services utilisation is lower among the immigrant population than among the host population and that immigrants tend to use hospital emergency services at the expense of primary care. We aimed to quantify the relative over-utilisation of emergency services in the immigrant population. METHODS: Emergency visits to Hospital del Mar in Barcelona in 2002 and 2003 were analysed. The country of origin, gender, age, discharge-related circumstances (hospital admission, discharge to home, or death), medical specialty, and variable cost related to medical care were registered. Immigrants were grouped into those from high-income countries (IHIC) and those from low-income countries (ILIC) and the average direct cost was compared by country of origin. A multivariate linear mixed model of direct costs was adjusted by country of origin (classified in five groups) and by the individual variables of age, gender, hospital admission, and death as a cause of discharge. Medical specialty was considered as a random effect. RESULTS: With the exception of gynaecological emergency visits, costs resulting from emergency visits by both groups of immigrants were lower than those due to visits by the Spanish-born population. This effect was especially marked for emergency visits by adults. CONCLUSION: Immigrants tend to use the emergency department in preference to other health services. No differences were found between IHIC and ILIC, suggesting that this result was due to the ease of access to emergency services and to lack of knowledge about the country's health system rather than to poor health status resulting from immigrants' socioeconomic position. The use of costs as a variable of complexity represents an opportunistic use of a highly exhaustive registry, which is becoming ever more frequent in hospitals and which overcomes the lack of clinical information related to outpatient activity.

Importance of appropriateness of empiric antibiotic therapy on clinical outcomes in intra-abdominal infections.

OBJECTIVES: The objective of this study is to describe the frequency of inappropriate empirical antibiotic therapy in secondary intra-abdominal infection and to identify the possible relationship between inappropriateness and some clinical outcomes. METHODS: A retrospective descriptive multicenter study was conducted using hospital secondary databases developed at two university hospitals located in northeast Spain. Participants were patients 18 years of age or older who were diagnosed with community-acquired intra-abdominal infections between January 1, 1998, and December 31, 2000, identified through computerized patient records using ICD-9 codes. Appropriateness of empirical treatment was defined according to the recommendations of the literature. The clinical outcome of each patient was classified as one of the following: (i) resolved with initial therapy, (ii) required second-line antibiotics, (iii) required re-operation, or (iv) in-hospital death. The Fisher's exact test or the Chi-squared test for categorical variables and the t-test or Mann-Whitney test for continuous variables were used for comparing groups. Conditional logistic and linear regression analyses were also applied. RESULTS: Of 376 cases, 51 cases (13.6 percent, 95 percent confidence interval, 10-17 percent) received inappropriate empirical antibiotic therapy according to the scientific literature. Inappropriate initial empirical treatment was significantly associated with the need for a second line of antibiotics (p < .001), although not with re-operation, mortality, or length of hospitalization. CONCLUSIONS: Approximately 14 percent of the patients received inappropriate empirical antibiotic treatment. Worse clinical outcomes consistently were observed in the group of patients receiving inappropriate empirical treatment. The appropriateness of antibiotic treatment for a given infection, in light of the availability of clearly defined clinical guidelines is an easily evaluated aspect of the quality of care.