Experience with Sunitinib in metastatic renal cell carcinoma (mRCC) patients: pooled analysis from 3 Spanish observational prospective studies

Background: A pivotal, randomized, phase III trial demonstrated a statistically significant superiority of sunitinib over interferon-α in metastatic renal cell carcinoma (mRCC) patients.

Objective: To evaluate the effectiveness and safety of sunitinib in patients with advanced or mRCC in routine clinical practice.

Methods: Retrospective pooled analysis of clinical data from three observational and prospective studies carried out between 2007 and 2011 in 33 Spanish hospitals. Tumor response, Progression-free survival (PFS) and overall survival (OS), and main sunitinib-related toxicities were registered.

Results: 224 patients were analyzed. Median PFS 10.6 months (95% CI: 9.02–12.25), median OS 21.9 months (95% CI: 17.2–26.6). Objective response rate (ORR) 43.8% (95% CI: 36.8–50.7). Median time to PR was 3.8 months (95% CI: 3.86–5.99) and to CR 8.2 months (95% CI: 4.75–9.77). The most common ≥ grade-3 AEs were asthenia/fatigue (18.7%), hand-foot syndrome (6.2%), hypertension (5.8%) and neutropenia (4.8%). Hand-foot syndrome, diarrhea and mucositis were confirmed as independent predictors for PFS and/or OS in a multivariate analysis (p < 0.05)

Conclusions: Outcomes with sunitinib in daily clinical practice resemble those obtained in clinical trials. Long-term benefit with sunitinib is possible in advanced RCC patients but the appropriate management of toxicities is mandatory to enable patients to remain on treatment.     

Antimicrobial use in a critical care unit: a prospective observational study

Objective The purpose of this study was to describe antimicrobial utilization, consumption, indications and microbial resistance in a medical‐surgical‐trauma intensive care unit (ICU) of a teaching hospital to identify potential targets for antimicrobial stewardship. Methods This was a 30‐day prospective observational study enrolling adults admitted to the ICU for at least 24 h and having received antimicrobial therapy. Primary endpoints included utilization as percentage use of antimicrobials by class and agent, consumption measured as days of therapy per 1000 patient days (DOT/1000PD), indications for use and prescriber. Secondary endpoints included reasons for modifications to therapy and microbial resistance. Key findings Eighty‐three patients were screened and 61 enrolled, receiving 133 courses of antimicrobial therapy, mainly intravenously and prescribed by ICU staff. The most frequently prescribed agents were piperacillin/tazobactam (20%), cefazolin (17%) and vancomycin (13%). The indications for therapy were empirical (50%), directed (27%) and prophylactic (23%). Overall consumption was 1368.54 DOT/1000PD and was mainly attributed to empirical therapy (734.25). Prolonged durations were noted for carbapenems and for surgical prophylaxis. There were 86 therapy modifications involving indication (36), efficacy (25), safety (18) and route (7). Suboptimal or excessive dosing were common contributors to efficacy and safety modifications, respectively. Infections due to microorganisms with notable resistance included methicillin‐resistant Staphylococcus aureus (5), Pseudomonas aeruginosa (1) and Streptococcus pneumoniae (1). Conclusions Antimicrobial utilization and consumption based on DOT/1000PD were prospectively determined providing a comparator for other ICUs. Potential targets identified for antimicrobial stewardship initiatives include empirical therapy, treatment duration, dosing and route.     

The use of analgesic drugs in postoperative patients: the neglected problem of pain control in intensive care units. An observational, prospective, multicenter study in 128 Italian intensive care units

OBJECTIVE: The use of analgesic drugs in patients admitted to Italian intensive care units (ICUs) was assessed. METHODS: An observational, prospective, cohort study was conducted, involving all adult patients admitted during a 1-month period in 128 Italian general ICUs. The use of analgesic drugs was evaluated for the first 2 postoperative days in surgical patients who stayed in ICU for at least 2 days. RESULTS: We observed 661 postoperative patients who underwent elective (72%) or emergency surgery. Of the patients with an ICU stay of at least 2 days, 49% did not receive any opioids in the first 48 postoperative hours, and more than 35% did not receive any analgesic at all. The most used opioid was fentanyl, followed by morphine and buprenorphine. Among the 336 patients who received at least one opioid, as many as 42% had only a single bolus per day. Pain control was reported as the reason for drug use in 54.5% of opioid administrations, while control of anxiety covered 10.3% of them. The probability of receiving an opioid was lower for patients in coma. CONCLUSION: Management of postoperative pain in Italian ICUs was insufficient, particularly in neurosurgical and comatose patients. A general lack of knowledge about pain and misconceptions about pain drugs may be at the basis of these results.     

Paroxetine in the treatment of post-traumatic stress disorder: pooled analysis of placebo-controlled studies

Post-traumatic stress disorder (PTSD) is increasingly understood to be a medical disorder characterised by particular psychobiological dysfunctions that respond to specific treatments. Paroxetine is a selective serotonin re-uptake inhibitor that has been found effective in the treatment of major depression as well as a range of anxiety disorders. This paper reviews data on the use of paroxetine for the treatment of adult PTSD. There have been three 12-week, placebo-controlled studies of paroxetine in PTSD. As these followed a partly similar design, a pooled analysis of the studies is possible and is reported here. Paroxetine is effective in the short-term treatment of PTSD, resulting in significantly better response and remission rates than placebo, improving sleep disturbance and reducing each of the symptom clusters of PTSD, as well as the disability associated with this condition. The medication is effective in both male and female PTSD patients and whether or not there are comorbid disorders such as depression.     

Paroxetine in the treatment of post-traumatic stress disorder: pooled analysis of placebo-controlled studies

Post-traumatic stress disorder (PTSD) is increasingly understood to be a medical disorder characterised by particular psychobiological dysfunctions that respond to specific treatments. Paroxetine is a selective serotonin re-uptake inhibitor that has been found effective in the treatment of major depression as well as a range of anxiety disorders. This paper reviews data on the use of paroxetine for the treatment of adult PTSD. There have been three 12-week, placebo-controlled studies of paroxetine in PTSD. As these followed a partly similar design, a pooled analysis of the studies is possible and is reported here. Paroxetine is effective in the short-term treatment of PTSD, resulting in significantly better response and remission rates than placebo, improving sleep disturbance and reducing each of the symptom clusters of PTSD, as well as the disability associated with this condition. The medication is effective in both male and female PTSD patients and whether or not there are comorbid disorders such as depression.     

Usefulness of subacute care for older patients discharged from acute care hospitals: a prospective observational study in Crema

Three hundred and eighteen elderly patients admitted to our acute care hospital, were then transferred to a subacute care unit (SCU) and then followed for 6 months after having been discharged. We measured laboratory and functional parameters at admission and discharge from the SCU and we found that both of them were significantly better at discharge, with the exception of haemoglobin level. Distinctive patterns at discharge could be identified in the patients who needed hospital readmissions in the following 6 months: female gender, younger age, lower haemoglobin, higher creatinine and poorer functional status. We conclude that subacute care is useful for the frail patient, can help in readmission avoidance and might prove to be very cost-effective, provided that certain requirements are met.     

Efficacy of zofenopril in combination with amlodipine in patients with acute myocardial infarction: a pooled individual patient data analysis of four randomized,double-blind,controlled, prospective studies

Objective: In the four SMILE (Survival of Myocardial Infarction Long-Term Evaluation) studies, early administration of zofenopril in acute myocardial infarction (AMI) showed beneficial effects as compared to placebo and other angiotensin converting enzyme inhibitors (ACEIs). This study investigated whether the concomitant administration of the dihydropyridine calcium channel-blocker amlodipine may improve zofenopril efficacy to prevent cardiovascular events in post-AMI patients.

Methods: This was a post-hoc analysis of pooled individual patient data from the four large randomized SMILE studies. The primary endpoint was the 1-year combined occurrence of death or hospitalization for cardiovascular causes.

Results: In total, 3488 patients were considered, 303 (8.7%) treated with concomitant amlodipine. Baseline systolic blood pressure and prevalence of metabolic syndrome were higher in amlodipine treated patients. The 1-year occurrence of major cardiovascular outcomes was significantly reduced in patients receiving concomitant treatment with amlodipine (hazard ratio, HR?=?0.66; and 95% confidence interval, CI?=?0.44–0.98; p?=?.039). After accounting for treatment with amlodipine, the risk of cardiovascular events was significantly reduced with zofenopril compared to placebo (HR?=?0.78; 95% CI?=?0.63–0.97; p?=?.026]. Among ACEI-treated patients, the zofenopril plus amlodipine combination reduced the risk of cardiovascular events by 38%, compared to the combination of other ACEIs plus amlodipine [HR?=?0.76; 95% CI?=?0.61–0.94); p?=?.013). The prognostic benefit of concomitant treatment with zofenopril plus amlodipine was independent from blood pressure lowering.

Conclusions: Zofenopril had a positive impact on prognosis in post-AMI patients, compared to other ACEIs. Concomitant administration of amlodipine may help to reduce the risk of cardiovascular events at 1?year.     

Short-term treatment with topical diclofenac epolamine plaster in patients with symptomatic knee osteoarthritis: pooled analysis of two randomised clinical studies

ABSTRACT

Background: Data from two randomised, double-blind, placebo-controlled studies were considered in order to investigate the efficacy and safety of a bio-adhesive plaster for topical administration containing diclofenac epolamine (DHEP) in patients with symptomatic knee osteoarthritis (OA).

Methods: Patients with radiologically confirmed symptomatic knee OA were included. The 14‐day treatment consisted of two daily applications of either DHEP or placebo plaster. The algofunctional Lequesne index and pain intensity, measured by means of the Huskisson's visual analogue scale (VAS), were considered as main efficacy parameters. The main analysis of the pooled data was by intention-to-treat.

Results: Of the 258 patients included, 235 completed the study. At the end of the study, the mean decrease in the Lequesne index was 35% in the DHEP group and 15% in the placebo group (?p < 0.0001). The mean decrease in pain intensity was 59.5% in the DHEP group and 29.9% in the placebo group. No interaction resulted between treatment and study effects (?p ≥ 0.2 whatever the test). The non-parametric Hodges–Lehmann estimator of the treatment effect resulted in a reduction of 21.9% for the Lequesne index and of 30.0% in pain intensity.

The number needed to treat (NNT) for at least a 50% reduction of pain was 3.0 and the effect size for pain was 0.75.

Conclusions: Topical application of DHEP plaster was shown to be an efficacious and safe short-term treatment for symptomatic knee OA, reducing pain and increasing physical function and may be similar in efficacy to oral non-steroidal anti-inflammatory drugs (as indicated by relative benefit data and NNT value).     

Varenicline treatment for smoking cessation in Asian populations: a pooled analysis of placebo-controlled trials conducted in six Asian countries

Abstract

Objective:

A pooled analysis to evaluate the efficacy and safety of varenicline versus placebo for smoking cessation in Asian populations. A secondary objective was to compare the data to pooled trials among predominantly Western populations.     

Healthcare costs with tiotropium plus usual care versus usual care alone following 1 year of treatment in patients with chronic obstructive pulmonary disorder (COPD)

BACKGROUND: Healthcare costs for chronic obstructive pulmonary disease (COPD) have continued to increase with the increasing prevalence of the disease. New interventions that can reduce the medical costs of COPD are needed. Tiotropium bromide, a once-daily inhaled anticholinergic, has been evaluated in patients with COPD enrolled in two 1-year randomised, double-blind, placebo-controlled (usual care) trials which showed the drug reduced exacerbations and improved spirometry, dyspnoea, and health status. OBJECTIVE: To retrospectively assess the direct costs of medical care for COPD in a US healthcare setting for patients treated with tiotropium in addition to usual care compared with usual care alone over a 1-year timeframe. The study was based on resource utilisation in the two previously described trials. METHODS: Resource utilisation and clinical data were prospectively collected for the two 1-year, randomised, double-blind trials of tiotropium plus usual care versus usual care alone (placebo) in 921 patients with COPD. Usual care was defined as any medication for COPD used prior to the trial except anticholinergics and long-acting beta-adrenoceptor agonists. Medical care resource utilisation was recorded at every scheduled visit in each trial. Mean total costs were calculated retrospectively by combining the resources utilised with the appropriate unit costs (1999 US dollars), excluding study drug (tiotropium) costs. RESULTS: Compared with usual care, patients receiving tiotropium in addition to usual care had significantly fewer COPD exacerbations (20% decrease), hospitalisations (44% reduction) and hospital days (50% reduction). Utilisation of resources other than hospitalisation did not differ between study groups. As a consequence, patients receiving tiotropium had significantly lower mean per- patient costs of hospitalisation compared with patients receiving usual care alone (tiotropium US 1,738 dollars +/- US 259 dollars; placebo US 2,793 dollars +/- US 453 dollars). The mean difference in the cost of hospitalisation (resulting from all causes, including COPD) between treatment groups was -US 1,056 dollars (95% CI -US 2,078 dollars, -US 34 dollars), and the difference in total healthcare costs (excluding study drug acquisition cost) was -US 1,043 dollars (95% CI -US 2,136 dollars, US 48 dollars) in favour of tiotropium. The cost of hospital admissions accounted for 48% of the total direct medical costs in this trial. CONCLUSIONS: As hospitalisation is a large contributor to the cost of COPD, the addition of tiotropium to usual care therapy may have the potential to reduce the economic burden of COPD in a US healthcare setting. However, as our study did not consider the acquisition cost of tiotropium, further economic evaluation including this cost is needed to address whether tiotropium is cost saving compared with usual care (placebo).     

Craving predicts use during treatment for methamphetamine dependence: a prospective, repeated-measures, within-subject analysis.

Clinical lore dictates that craving drives the compulsive use of drugs and alcohol - the core feature of substance dependence. Yet limited research has yielded mixed results, suggesting that craving is neither necessary nor sufficient for continued use or relapse to addictive substances. To investigate the role of craving in compulsive methamphetamine use, 31 men and women in treatment for methamphetamine dependence were asked to indicate, once each week for 12 weeks, the severity of craving that they had experienced during the previous 24 h, using a 100-mm visual analog scale. In a prospective, repeated-measures, within-subject analysis, craving intensity significantly predicted methamphetamine use in the week immediately following each craving report. Craving remained a highly significant predictor in multivariate models controlling for pharmacological intervention, and for methamphetamine use during the prior week. Craving scores that preceded use were 2.7 times higher than scores that preceded abstinence. Risk of subsequent use was 2.5 times greater for scores in the upper half of the scale relative to scores in the lower half. The results obtained demonstrate that, while craving alone may be neither necessary nor sufficient to explain substance addiction, when measured prospectively in a carefully-designed study craving emerges as a salient predictive factor in continued methamphetamine use for patients in treatment for methamphetamine dependence.     

Factors influencing the length of hospitalisation in intensive care units: a prospective observational study

INTRODUCTION: The length of stay (LOS) in patients admitted to intensive care units (ICUs) is influenced by the clinical history of the patient, so the main factors affecting clinical outcome are logical candidates to be predictors of LOS. Since there is still limited information about which factors can influence LOS in these patients, we undertook this observational study in Italian hospitals. MATERIALS AND METHODS: From 1 August to 31 October 2001 we enrolled a maximum of 10 consecutive patients admitted to ICUs in 16 Italian hospitals. The following information was recorded from each patient: date of admission; APACHE II score on admission; active sepsis and/or septic shock on admission; sepsis and/or septic shock developed during the stay in ICU; Glasgow coma scale on the third day; date and clinical outcome upon discharge from the hospital (alive or dead). RESULTS: In the study 131 patients were enrolled; 31 (23.7%) had active sepsis upon admission to ICU and 10 (7.6%) had septic shock; 12 (9.2%) developed sepsis during hospitalization and 12 (9.2%) developed septic shock. At the end of the study, 101 patients were alive and 30 had died. The overall mean LOS was 12 days. The mean LOS was 18.3 days for the subgroup with sepsis and 8.3 days in the subgroup without sepsis. Sepsis was the only factor that significantly influenced the LOS (P = 0.016). CONCLUSIONS: Our study was aimed to analyse the factors that influence the LOS in ICU patients and found that among the variables that affected LOS, sepsis had the greatest impact. Other studies had evaluated the impact of some variables on LOS and identified sepsis and infection as a determinant prolonging LOS.     

Antipsychotic switching: results from a one-year prospective,observational study of patients with schizophrenia

ABSTRACT

Objective: The Health Outcomes of a Canadian Community Cohort (HOCCC) study is a 1-year prospective observational study of outpatients with schizophrenia or related psychotic disorders. The purpose of the study was to compare effectiveness of antipsychotic treatment as measured by 1-year treatment completion rates.

Design and methods: Patients (N?=?929) were enrolled if in the course of usual clinical practice they switched to a second-generation antipsychotic (SGA). Observational data were collected for up to 1 year. The primary analysis compared 1-year treatment-completion rates for the olanzapine cohort with the other SGA cohort (quetiapine, risperidone, clozapine), using a chi-squared test.

Results: Of 929 patients enrolled, 64.8% (516/796) of evaluable patients completed 1 year of treatment. There was no statistically significant difference in the proportion of treatment completers between the olanzapine cohort (67.4%, 256/380) and the other SGA cohort (62.5%, 260/416). Treatment-completion rates were risperidone 62.0% (127/205), quetiapine 63.7% (123/193) and clozapine 55.6% (10/18). Antipsychotic polypharmacy was common. Patients treated with olanzapine or risperidone had significantly higher increases in BMI than quetiapine-treated patients. There were no major differences between olanzapine monotherapy and pooled other SGA monotherapy groups in status of extrapyramidal symptoms from baseline to endpoint.

Conclusions: Olanzapine and other SGAs exhibited similar rates of 1-year treatment completion. Further study of medication combinations is needed, given their perceived clinical value, and the high frequency of antipsychotic polypharmacy in clinical practice.

Limitations: As most patients received several psychotropics and power was reduced in monotherapy analyses, comparisons between cohorts must be interpreted cautiously. Comparisons between individual antipsychotics were post hoc and not powered a priori. Accuracy and completeness of adverse event information for drugs other than olanzapine is limited.