Outcomes of off-label drug uses in hospitals: a multicentric prospective study.

PURPOSE: The study aims to assess the clinical evidence, outcome and cost of off-label use of medicines in the hospital setting. METHODS: A multicentric prospective cohort study of patients treated with off-label medicines was carried out in five tertiary hospitals from May 2011 to May 2012. Information on clinical characteristics of patients, drugs, outcomes and costs was collected. Patients were followed up to 6 months, and information was assessed by reviewing clinical records and interviewing physicians. RESULTS: A total of 226 patients were included. The median (interquartile range (IQR)) age of patients was 46 (33-62) years; 59 % were women. Patients had received a median of three previous treatments, and a lack of response (or suboptimal) was the main reason for off-label use (72.1 %). A total of 232 off-label medicines were administered for 102 different indications. The most frequent medicines were rituximab (49; 21.1 %), botulinum toxin (25; 10.7 %) and omalizumab (14; 6.0 %). In 117 (51.8 %) cases, the level of clinical evidence for their use was low. A partial clinical response was observed in 82 patients (36.3 %), complete response in 71 (31.4 %) and stabilization in 11 (4.9 %). A total of 58 (26.5 %) patients had adverse effects, which in 11 (4.9 %) were severe. The median (IQR) cost per patient was 2,943.07 (541.9-5,872.54). CONCLUSIONS: There was a high variability of off-label medicines and indications. Although the clinical evidence of off-label medicines was often low, clinical response was observed in many patients with previous multiple treatment failure, but at the expense of some adverse effects and a high cost. Registers of patients would be helpful for clinical decisions, although clinical trials are needed.

Available evidence and outcome of off-label use of rituximab in clinical practice.

PURPOSE: To analyze the therapeutic indications for off-label use of rituximab, the available evidence for its use, the outcomes, and the cost. METHODS: This was a retrospective analysis of patients treated with rituximab for off-label indications from January 2007 to December 2009 in two tertiary hospitals. Information on patient characteristics, medical conditions, and therapeutic responses was collected from medical records. Available evidence for the efficacy of rituximab in each condition was reviewed, and the cost of treatment was calculated. RESULTS: A total of 101 cases of off-label rituximab use were analyzed. The median age of the patients involved was 53 [interquartile range (IQR) 37.5-68.0] years; 55.4 % were women. The indications for prescribing rituximab were primarily hematological diseases (46 %), systemic connective tissue disorders (27 %), and kidney diseases (20 %). Available evidence supporting rituximab treatment for these indications mainly came from individual cohort studies (53.5 % of cases) and case series (25.7 %). The short-term outcome (median 3 months, IQR 2-4 months) was a complete response in 38 % of cases and partial response in 32.6 %. The highest short-term responses were observed for systemic lupus erythematosus and membranous glomerulonephritis, and the lowest was for neuromyelitis optica, idiopathic thrombocytopenic purpura, and miscellaneous indications. Some response was maintained in long-term follow-up (median 23 months IQR 12-30 months) in 69.2 % of patients showing a short-term response. Median cost per patient was €5,187.5 (IQR €5,187.5-7,781.3). CONCLUSIONS: In our study, off-label rituximab was mainly used for the treatment of hematological, kidney, and systemic connective tissue disorders, and the response among our patient cohort was variable depending on the specific disease. The level of evidence supporting the use of rituximab for these indications was low and the cost was very high. We conclude that more clinical trials on the off-label use of rituximab are needed, although these may be difficult to conduct in some rare diseases. Data from observational studies may provide useful information to assist prescribing in clinical practice.

Impact of local guidelines and an integrated dispensing system on antibiotic prophylaxis quality in a surgical centre.

Surgical antibiotic prophylaxis is effective in preventing postoperative wound infections. Guidelines are designed to optimize antimicrobial use in this setting. The aim of this study was to assess antibiotic use in surgical prophylaxis in a surgical hospital before and after the implementation of both local antibiotic prophylaxis guidelines and a specific medication set for various surgical procedures. The appropriateness of surgical antibiotic prophylaxis increased from 50.9% in the pre-implementation stage to 94.9% in the postimplementation stage (P<0.001). The implementation of a multidisciplinary protocol and design of medication sets helped to improve the practice of surgical antibiotic prophylaxis.

[The bacteriological control of TPN mixtures at the Hospital de Bellvitge]. / Control bacteriológico de las mezclas de NPT en el Hospital de Bellvitge.

The complications of sepsis often make it necessary to suspend nutritional therapy. The origin of these is the nutritive mixture as well as the catheter connection and/or point where it has been inserted. The aim of this study is to show the need for bacteriological control of the whole process, in order to evaluate the effectiveness of the methods used, dilucidate the origin of the sepsis and establish an internal quality control. Study of different methods for bacteriological control of the nutritive mixtures, comparing them with the methods used in our Hospital, which is based on systematic culture of the mixtures, the collecting of samples after preparation and prior to perfusing the mixture through the patient, the performing of a further culture control and a bacteriological examination of the catheter. For this purpose, 28,501 nutritive mixtures were studied, corresponding to 1,782 patients. Of these, 185 samples were initially positive (0.65%) and only 59 samples showed positive cultures (0.21%). Of the 6 cases of sepsis discovered and confirmed by haemoculture, 5 corresponded to Enterobacter cloacae and 1 to Klebsiella pneumoniae.

[Bacteriologic control of total parenteral nutrition formulations at the Bellvitge Hospital]. / Control bacteriológico de las mezclas de NPT en el Hospital de Bellvitge.

Septic complications often lead to halting nutritional parenteral therapy. In general, the source of infection lies in the mixture, the connection and/or point of catheter insertion. The objective of this study is to show the need for bacteriological control throughout the parenteral nutrition process in order to assess the efficacy of the methods used, discover the source of infection and establish an in-house quality control. Different methods for bacteriological control of parenteral nutrition mixtures are studied and are compared with the method used at our hospital which is based on routine culture sampling after the mixture is prepared and before it is perfused, on repeating bacteriological control cultures and on performing bacteriological assessments of the catheter. In order to achieve this goal, 28.501 nutritional parenteral samples from 1,782 patients were studied. Only 185 (0.65%) samples were originally positive, and only 59 of them (0.21%) remained positive following a verification culture. Of the 6 culture-verified septic cases, 5 corresponded to Enterobacter cloacae and 1 to Klebsiella pneumoniae.

Use of restricted antibiotics in primary care.

The objective of this study was to detect and evaluate the use of restricted antibiotics (RAs) in our ambulatory care site. We retrospectively analyzed 1084 treatments of a selected group of intramuscularly administered antibiotics that are usually considered restricted for use in hospitals. Five cephalosporins, four aminoglycosides, and one acylureidopenicillin were analyzed. The study was conducted in 47 primary health centers over six months. We reported the information on a special order form for parenteral prescriptions and evaluated the selection and the dosing interval of each antibiotic. Of the 1084 treatments, cefonicid was the antibiotic most frequently prescribed (61.3 percent), followed by tobramycin (15.3 percent), cefotaxime sodium (6.7 percent), amikacin (3.8 percent), cefuroxime (3.8 percent), mezlocillin (3.7 percent), netilmicin sulfate (3.7 percent), ceftizoxime sodium (0.8 percent), cefoxitin (0.5 percent), and streptomycin sulfate (0.4 percent). Based on our survey criteria, 59 percent of the 710 orders that indicated diagnosis had a correct or possibly correct indication; the remaining percentage was considered unnecessary therapy or poor drug choice. Of the 1050 orders that indicated a dosing interval, 75.4 percent showed an appropriate dosing interval. We assume that most of the infections treated in our ambulatory care site could be resolved with or without common antibiotics. In this study we obtained objective data of the use of ten RAs in order to determine if their use in ambulatory patients was justified. We observed that a small number of prescriptions agreed with the recommended criteria stated in this survey for use of these antibiotics in outpatient infections.

[Vaccination against hepatitis B in health workers and other staff in Barcelona]. / Vacunación contra el virus de la hepatitis B del personal sanitario y no sanitario en el área de Barcelona ciudad.

OBJECTIVE: To analyse the results of a hepatitis B vaccination programme, in order to find the levels of acceptance of the programme and adherence to it, as well as the immunological response and the impact of age, gender and the index of corporal mass (ICM). DESIGN: This was a retrospective study. SETTING: Primary Care. PATIENTS AND OTHER PARTICIPANTS: 2,055 Primary Care professionals considered at risk (43.3% of the Area total). MEASUREMENTS AND MAIN RESULTS: Out of the total number of professionals at risk, 1,294 (63%) agreed to have the serological markers. The prevalence of markers of the hepatitis B virus (HBV) was 16.07% (208), which increased with age (p < 0.0001). 87% had three doses (961/1,106). 863 (89.8%) of these went through the post-vaccination controls and levels of HB antibodies above 10 IU/ml were found in 790 (91.5%). The fourth dose produced favorable results (66.7%) in individuals with HB antibodies between 10 and 100 IU/ml and unfavorable ones (3.8%) where the HB antibodies were below 10 IU/ml. CONCLUSIONS: The hepatitis B vaccination programme has not enjoyed total acceptance by Primary Care professionals, although a satisfactory level of adherence has been reached. Age is the variable linked most closely to the risk of a poor immunological response, though ICM and gender should not be ignored.