Epidemiology and clonality of methicillin-resistant and methicillin-susceptible Staphylococcus aureus causing bacteremia in a tertiary-care hospital in Spain.

OBJECTIVES: To describe the relative proportions of nosocomial and community-onset Staphylococcus aureus bacteremia at our institution and the epidemiologic characteristics and clonal diversity of S. aureus isolates, as determined by pulsed-field gel electrophoresis (PFGE) and antimicrobial resistance patterns. DESIGN: Retrospective cohort study of all cases of S. aureus bacteremia between October 2001 and October 2002. SETTING: A 1300-bed, tertiary-care hospital. RESULTS: One hundred sixty-two unique episodes of S. aureus bacteremia were identified. Forty-three cases (26.5%) were caused by methicillin-resistant S. aureus (MRSA). Most cases of S. aureus bacteremia, whether MRSA or methicillin susceptible (MSSA), were nosocomial in origin (77.2%) or were otherwise associated with the healthcare system (16%). Only 11 (6.8%) of the cases (all MSSA) were strictly community acquired. Thirty-five unique macrorestriction patterns were identified among the 154 isolates that were typed by PFGE. Four major genotypes were defined among the isolates of MRSA, with 36 (85.7%) represented by a single PFGE type. Of the isolates within this major clone, all (100%) were ciprofloxacin resistant and 77.8% were erythromycin resistant. In contrast, the 112 isolates of MSSA comprised 31 different PFGE types, 3 of which represented 42.9% of all MSSA isolates and were associated with both nosocomial and community-onset bacteremia. CONCLUSIONS: Most cases of S. aureus bacteremia in our healthcare region are nosocomial in origin or are acquired through contact with the healthcare system and are thus potentially preventable. To preclude dissemination of pathogenic clones, it is therefore necessary to redouble preventive measures in both the hospital and the community.     

Patient's quality of life and hearing outcomes after stapes surgery

Objectives: To determine the quality of life (QOL) after stapes surgery and whether audiological parameters for hearing correlate with specific QOL factors. Design: A retrospective cross‐sectional study. Setting: A tertiary referral centre. Participants: A series of 35 patients who underwent stapes surgery of which three were excluded because they were <18 years of age, chronically or mentally ill, or in a dependant relationship. Response rate was 93% (30/32). Nine were further excluded because they had revision or bilateral surgery, or missing data. Twenty‐one patients were included in this study. Main outcome measures: The Glasgow Benefit Inventory (GBI) was used to evaluate general QOL and the Hearing Disability and Handicap Scale (HDHS) was used as a disease‐specific measure. The Belfast Rule of Thumb and Glasgow Benefit Plot assessed hearing outcomes. Results: Operative success was 86% using the Belfast Rule of Thumb and 95% had closure of the air–bone gap to within 20 dB. 81.8% of patients reported a better overall QOL as surgery. Glasgow Benefit Inventory Social and GBI Physical scores correlated positively with the HDHS speech component (P < 0.05). The duration of hearing loss correlated inversely with the average HDHS score (P < 0.05). Conclusion: The majority of patients report a better QOL as undergoing stapes surgery. Speech impacts on people's physical and social QOL of patients. Quality of life tools, in addition to objective audiologic measurements can provide clinicians with patients’ subjective perspective that helps guide clinical decision‐making and counselling.     

Concomitant boost radiation and concurrent cisplatin for advanced head and neck carcinomas. Preliminary results of a phase II, single-institutional trial

INTRODUCTION: This study aims to asses the effectiveness and toxicity of boost radiotherapy concomitant and concurrent cisplatin for patients with locally advanced head and neck cancer (LAHNC). MATERIAL AND METHODS: There were 30 patients included in a prospective, phase II single-institution trial and of whom, 29 were at AJCC stage IV and 1 at stage III. Treatment consisted of radiotherapy acceleration fractionation with concomitant boost, 72 Gy, and 2 cycles of concomitant cisplatin (20 mg/m2/day continuous infusion; days 1-5 and 29-33). Amifostine, (i.v. 200 mg/m2) was administered to 26 prior to the first fraction of radiotherapy. Endpoints of the study were quality-of-life (QL), overall survival, and local control of disease. RESULTS: Complete response (CR) was achieved in 23 patients (77%), 2 patients had partial response (PR) (7%), 4 had no response (13%), and 1 was not evaluated for response. The 2-year overall survival and loco-regional control were 60% and 56%, respectively. Main toxicity was grade 3 or 4 mucositis in 93% of the patients. QL scores (questionnaire QLQC30; version 3.0) and the HN cancer module QLQ-HN35) showed a worsening in areas related to the treatment e.g. dry mouth, problems stretching the mouth, and sticky saliva. CONCLUSIONS: this combination modality is active, but toxic, in the treatment for LAHNC. Concomitant boost radiotherapy is probably, not the best radiotherapy schema for combining with chemotherapy in LAHNC.     

Upfront high-dose sequential therapy (HDS) versus VACOP-B with or without HDS in aggressive non-Hodgkin's lymphoma: long-term results by the NHLCSG.

BACKGROUND: There is not univocal concordance for using high-dose sequential therapy (HDS) as first-line treatment for aggressive non-Hodgkin's lymphoma (NHL). We designed this study to evaluate the usefulness of HDS followed by high-dose therapy (HDT) with autologous stem cell transplantation as front-line treatment in different subsets of aggressive NHL. PATIENTS AND METHODS: Among 223 patients aged 15-60 years with aggressive, advanced stage NHL, 106 patients were randomized to VACOP-B (etoposide, doxorubicin, cyclophosphamide, vincristine, prednisone, bleomycin) for 12 weeks (plus HDS/HDT in case of persistent disease) (arm A), and 117 patients to VACOP-B for 8 weeks plus upfront HDS/HDT (arm B). RESULTS: According to the intention-to-treat analysis, the complete response rate was 75% for arm A and 72.6% for arm B. With a median follow-up of 62 months there was no difference in 7-year probability of survival (60% and 57.8%; P = 0.5), disease-free survival (DFS) (62% and 71%; P = 0.2) and progression-free survival (PFS) (44.9% and 40.9%; P = 0.7) between the two arms. Subgroup analyses confirmed that the best results in terms of survival, DFS and PFS were achieved by patients with large B-cell NHL without bone marrow (BM) involvement, independently of the treatment arm. Results were poorer in other categories of patients and poorest in patients with BM involvement. CONCLUSIONS: Aggressive NHL patients do not benefit from upfront HDS/HDT.     

Phase II trial of fortnightly irinotecan (CPT-11) in the treatment of colorectal cancer patients resistant to previous fluoropyrimidine-based chemotherapy

Introduction This phase II study investigated the anti-tumour activity and toxicity of CPT-11 (250 mg/m2 i.v. infusion over 60 minutes) administered every 2 weeks as second-line chemotherapy in patients with advanced colorectal cancer (CRC). Material and methods Patients (n=63) with histology diagnosis of advanced CRC and proven resistance to previous fluoropyrimidine therapy were enrolled. Results A total of 510 CPT-11 cycles were administered, with a mean of 8 cycles per patient (range: 1–32). The median relative dose intensity was 93%. Partial response (PR) was obtained in 11 patients (17.5%; 95%CI: 8.1%–26.7%) and 29 patients (46.0%) showed stable disease (clinical benefit of 63.5%). The median duration of response was 6.8 months (95%CI: 6.1–7.5 months), median survival was 8.8 months (95%CI: 6.3–11.5 months) and median time to disease progression was 4.5 months (95%CI: 3.9–5.0 months). Overall, this schedule of CPT-11 chemotherapy was well tolerated by the patient. Neutropenia was the most frequent grade 3/4 haematological toxicity (20.6% of patients and 4.1% of cycles). Neutropenia with concurrent fever or infection occurred in 7 patients (11.1%). Late onset diarrhoea was the most frequent grade 3/4 non-haematological toxicity (19.0% of patients and 2.3% of cycles). Other, lower-incidence, toxicities were anaemia, fever, infection, mucositis, nausea and vomiting. There were no toxic deaths. Conclusions We found that CPT-11, administered as 250 mg/m² i.v. infusion over 60 minutes every 2 weeks, was active and well tolerated schedule in the second-line chemotherapy of advanced CRC patients. This bi-weekly scheme could be used as an alternative to the weekly or the every-three-week schedule as well as in combined therapies with other chemotherapeutic agents for the treatment of advanced, metastatic, CRC.     

Allogeneic transplant with reduced intensity conditioning regimens may overcome the poor prognosis of B-cell chronic lymphocytic leukemia with unmutated immunoglobulin variable heavy-chain gene and chromosomal abnormalities (11q- and 17p-).

PURPOSE: To evaluate the efficacy of reduced intensity conditioning (RIC) allogeneic transplant in 30 patients with poor-prognosis chronic lymphocytic leukemia (CLL) and/or high-risk molecular/cytogenetic characteristics. EXPERIMENTAL DESIGN: Eighty-three percent of patients had active disease at the moment of transplant. That is, 14 of the 23 patients analyzed (60%) had unmutated immunoglobulin variable heavy-chain gene (IgV(H)) status; 8 of 25 patients (32%) had 11q-, with four of them also displaying unmutated IgV(H); and six (24%) had 17p- (five were also unmutated). RESULTS: After a median follow-up of 47.3 months, all 22 patients alive are disease free; overall survival and event-free survival (EFS) at 6 years were 70% and 72%, respectively. According to molecular/cytogenetic characteristics, overall survival and EFS for unmutated CLL and/or with 11q- aberration (n = 13) were 90% and 92%, respectively, not significantly different to those with normal in situ hybridization, 13q- and +12, or mutated CLL (n = 7). All six patients with 17p deletion were transplanted with active disease, including three with refractory disease; all except one reached complete remission after the transplant and two are alive and disease free. Nonrelapse mortality (NRM) was 20%; more than two lines before transplant is an independent prognostic factor for NRM (P = 0,02), EFS (P = 0.02), and overall survival (P = 0.01). Patients older than 55 years have a higher risk of NRM (hazard ratio, 12.8; 95% confidence interval, 1.5-111). Minimal residual disease was monitored by multiparametric flow cytometry in 21 patients. Clearance of CD79/CD5/CD19/CD23 cells in bone marrow was achieved in 68% and 94% of the patients at days 100 and 360, respectively. CONCLUSION: According to these results, RIC allogeneic transplant could overcome the adverse prognosis of patients with unmutated CLL as well as those with 11q- or 17p-.     

Pharmacological Prevention of Reperfusion Injury in Acute Myocardial Infarction

The concept of reperfusion injury, although first recognized from animal studies, is now recognized as a clinical phenomenon that may result in microvascular damage, no-reflow phenomenon, myocardial stunning, myocardial hibernation and ischemic preconditioning. The final consequence of this event is left ventricular (LV) systolic dysfunction leading to increased morbidity and mortality. The typical clinical case of reperfusion injury occurs in acute myocardial infarction (MI) with ST segment elevation in which an occlusion of a major epicardial coronary artery is followed by recanalization of the artery. This may occur either spontaneously or by means of thrombolysis and/or by primary percutaneous coronary intervention (PCI) with efficient platelet inhibition by aspirin (acetylsalicylic acid), clopidogrel and glycoprotein IIb/IIIa inhibitors. Although the pathophysiology of reperfusion injury is complex, the major role that neutrophils play in this process is well known. Neutrophils generate free radicals, degranulation products, arachidonic acid metabolites and platelet-activating factors that interact with endothelial cells, inducing endothelial injury and neutralization of nitrous oxide vasodilator capacity. Adenosine, through its multi-targeted pharmacological actions, is able to inhibit some of the above-mentioned detrimental effects. The net protective of adenosine in in vivo models of reperfusion injury is the reduction of the infarct size, the improvement of the regional myocardial blood flow and of the regional function of the ischemic area. Additionally, adenosine preserves the post-ischemic coronary flow reserve, coronary blood flow and the post-ischemic regional contractility. In small-scale studies in patients with acute MI, treatment with adenosine has been associated with smaller infarcts, less no-reflow phenomenon and improved LV function. During elective PCI adenosine reduced ST segment shifts, lactate production and ischemic symptoms. During the last years, three relatively large placebo-controlled clinical trials have been conducted: Acute Myocardial Infarction Study of Adenosine Trial (AMISTAD) I and II and Attenuation by Adenosine of Cardiac Complications (ATTACC). In the AMISTAD trials, the final infarct size was reduced and the LV systolic function was improved by adenosine treatment, mainly in patients with anterior MI localization. However, morbidity and mortality were not affected. In the ATTACC study, the LV systolic function was not affected by adenosine, however, trends towards improved survival were observed in patients with anterior MI localization. The possibility of obtaining a Thrombolysis in Myocardial Infarction (TIMI) grade 3 flow in the infarct-related artery in up to 95% of patients with acute MI (increasing the occurrence of reperfusion injury) has turned back the interest towards the protection of myocardial cells from the impending ischemic and reperfusion injury in which adenosine alone or together with other cardio-protective agents may exert important clinical effects.     

Patterns and determinants of psychoactive drug use in Lisbon University students – a population-based study

OBJECTIVE: To study the patterns and determinants of psychoactive drug use by Lisbon University students. MATERIALS AND METHODS: A cross-sectional survey was conducted, from January to April 2000, in a probabilistic sample of 1,147 students. Information about use of psychoactive drugs and co-variates was collected by a questionnaire administered by trained interviewers. Psychoactive drugs were considered to be all medicines classified in group N (nervous system) of the ATC system except the anesthetics (subgroup N01) and the analgesics (subgroup N02). RESULTS: 91 students (7.9%) had taken psychoactive drugs during the fortnight before the interview, 39 of whom (42.8%) mentioned continuous use. The prevalence of use was significantly higher in females (9.6%), older than 25 years (13.1%), married (16%), who considered themselves to have a weak health status (21.7%), as under intense stress (15.5%). After adjustment by multivariate analysis the variables sex, self-evaluation of health status and daily stress retained a higher significant association with psychoactive drug use. A total of 132 drugs were reported as being used in that period. Tranquilizers (ATC = N05B or N05C) were used by 82 students (7.2%), while 22 (1.9%) consumed psychoactive stimulants (N06B) and 19 (1.7%) antidepressants (N06A). In all of these therapeutical subgroups, females had higher consumption prevalence than males, but the difference was statistically significant only for tranquilizers (P < 0.001). Anxiety, depression and insomnia were the most frequently stated health problems. More than 90% of drug consumers considered they had a compliant attitude and about 60% considered themselves well-informed about adverse effects of the drug used. The reported prevalence of self-medication for psychoactive drugs used was 12.8%. CONCLUSIONS: The prevalence of psychoactive drug use among students of Lisbon University was higher than expected, considering age group and the usual health status of this population. The administration of a questionnaire was a very useful tool to characterise the pattern of use and the consumer's knowledge about the drugs consumed.     

Deprescripción en personas mayores: es el momento de pasar a la acción

El uso de fármacos conlleva innegables beneficios en las personas mayores, pero no está exento de efectos indeseables. La deprescripción es el proceso de revisión sistemática de la medicación con el objetivo de lograr la mejor relación riesgo-beneficio en base a la mejor evidencia disponible. Este proceso es especialmente importante en mayores polimedicados, sobretratados, frágiles, con enfermedades terminales y en el final de la vida.La deprescripción debe hacerse de forma escalonada, estableciendo un seguimiento estrecho por si aparecen problemas tras la retirada. En la toma de decisiones es muy importante contar con la opinión del paciente y de los cuidadores, valorando los objetivos del tratamiento según la situación clínica, funcional y social del enfermo.Existen múltiples herramientas para facilitar a los clínicos la tarea de seleccionar qué fármacos deprescribir (criterios Beers, STOPP-START…). Los grupos farmacológicos más susceptibles de intervención son: antihipertensivos, antidiabéticos, estatinas, benzodiacepinas, antidepresivos, anticolinérgicos, anticolinesterásicos y neurolépticos.Palabras clave: Polifarmacia, Envejecimiento, Comorbilidad, Prescripción inadecuada, Efectos adversos, Deprescripción