Cost-utility of direct transfer to angiography suite (DTAS) bypassing conventional imaging for patients with acute ischemic stroke in Spain: results from the ANGIOCAT trial.

Background: The ANGIOCAT trial showed a clinical benefit of direct to angiography suite (DTAS) for patients with large vessel occlusion (LVO) stroke admitted within 6 hours after symptom onset in decreased hospital workflow time and improved clinical outcome. However, the impact of DTAS implementation on hospital costs is unknown. This economic evaluation aims to assess the cost-utility of DTAS from the provider (hospital) perspective.

Delays in pulmonary decline in eteplirsen-treated patients with Duchenne muscular dystrophy.

Introduction/aims: Pulmonary decline is a major issue in patients with Duchenne muscular dystrophy (DMD). Eteplirsen is a United States-approved treatment for patients with DMD and exon 51 skip-amenable mutations. Previous analyses have shown that eteplirsen is associated with a statistically significant attenuation of pulmonary decline.

Treatment strategies for polycythemia vera: Observations in a Dutch "real-world" cohort study.

Objectives: Assessment of "real-world" treatment strategies and outcome in Dutch polycythemia vera (PV) patients.

Methods: Retrospective chart review in 150 patients with PV (WHO 2008 diagnostic criteria) from 10 major non-academic hospitals in the Netherlands.

Results: Patients (median age 64 years, 49% male) frequently had cardiovascular risk factors (56%) and prior vascular events (31%).

Economic burden of hypoglycemia with basal insulin in type 2 diabetes.

Objectives: To assess the impact of hypoglycemia and potential underlying factors of economic burden in patients with type 2 diabetes (T2D) who are initiating basal insulin therapy.

Study Design: This retrospective cohort study combined commercial insurance and Medicare Advantage data from the Clinformatics Data Mart.

Methods: Adults with T2D on oral antidiabetes drugs initiating basal insulin (n = 18,918) were assessed at baseline (12 months prior to insulin initiation) and follow-up (1 and 2 years).

Safety and efficacy of insulin glargine 300 u/mL compared with other basal insulin therapies in patients with type 2 diabetes mellitus: a network meta-analysis.

Objective: To compare the efficacy and safety of a concentrated formulation of insulin glargine (Gla-300) with other basal insulin therapies in patients with type 2 diabetes mellitus (T2DM).

Design: This was a network meta-analysis (NMA) of randomised clinical trials of basal insulin therapy in T2DM identified via a systematic literature review of Cochrane library databases, MEDLINE and MEDLINE In-Process, EMBASE and PsycINFO.

Outcome Measures: Changes in HbA1c (%) and body weight, and rates of nocturnal and documented symptomatic hypoglycaemia were assessed.

Comparative effectiveness without head-to-head trials: a method for matching-adjusted indirect comparisons applied to psoriasis treatment with adalimumab or etanercept.

The absence of head-to-head trials is a common challenge in comparative effectiveness research and health technology assessment. Indirect cross-trial treatment comparisons are possible, but can be biased by cross-trial differences in patient characteristics. Using only published aggregate data, adjustment for such biases may be impossible.

Detection of spironolactone-associated hyperkalaemia following the Randomized Aldactone Evaluation Study (RALES).

Introduction: A population-based analysis has suggested that the publication of the RALES (Randomized Aldactone Evaluation Study) in late 1999 was associated with both the wider use of spironolactone to treat heart failure and a corresponding increase in hyperkalaemia-associated morbidity and mortality in patients also being treated with ACE inhibitors.

Objectives: To gain further insight into the reporting of spironolactone-associated hyperkalaemia in an independent dataset by analysing the spontaneous reporting experience in relation to the publication of RALES, and to determine whether the implementation of a commonly used data mining algorithm (DMA) might have directed the attention of safety reviewers to the spironolactone/hyperkalaemia association in advance of epidemiological findings.

Methods: We calculated the reporting rate of spironolactone-associated hyperkalaemia per 1,000 reports per year from 1970 through to the end of 2005 by identifying relevant cases in the US FDA Adverse Event Reporting System.

Down syndrome associated with hypothyroidism and chronic pericardial effusion: echocardiographic follow-up.

We present a 39-year-old male patient with Down syndrome who was evaluated for fatigue, palpitations and bouts of cyanosis. Physical examination showed features of trisomy-21(Down syndrome), with a slow pulse rate, distant cardiac sounds and absent apex beat. He had normal jugular venous pressure without pulsus paradoxus.

Illusions of objectivity and a recommendation for reporting data mining results.

Objective: Data mining algorithms (DMAs) are being applied to spontaneous reporting system (SRS) databases in the hope of obtaining timely insights into post-licensure safety data. Some DMAs have been characterized as "objective" screening tools. However, there are numerous available modifiable configuration parameters to choose from, including choice of vendor, that may affect results.

Reports of hyperkalemia after publication of RALES--a pharmacovigilance study.

Purpose: A population-based study and anecdotal reports have indicated that the publication of the Randomized Aldactone Evaluation Study (RALES) was associated with not merely a broader use of spironolactone in the treatment of heart failure, but also with a coinciding sharp increase in hyperkalemia-associated morbidity/mortality in patients also being treated with ACE-inhibitors. Data mining algorithms (DMAs) are being applied to spontaneous reporting system (SRS) databases in hopes of obtaining early warnings/additional insights into post-licensure safety data. We applied two DMAs (i.

Randomised Phase III study of biweekly 24-h infusion of high-dose 5FU with folinic acid and oxaliplatin versus monthly plus 5-FU/folinic acid in first-line treatment of advanced colorectal cancer.

Background: A phase III study was started to compare oxaliplatin/5FU/LV in the first-line with bolus FU/LV in metastatic colorectal cancer.

Patients And Methods: 302 patients were randomised and received bolus 5-FU 425 mg/m(2) day 1-5, FA 20 mg/m(2) day 1-5, q 4 wk or oxaliplatin 85 mg/m(2), 2 h-infusion, FA 200 mg/m(2), 1-h infusion. 5-FU 2600 mg/m(2), 24-h infusion day 1, q 2 wk.

Perspectives on the use of data mining in pharmaco-vigilance.

In the last 5 years, regulatory agencies and drug monitoring centres have been developing computerised data-mining methods to better identify reporting relationships in spontaneous reporting databases that could signal possible adverse drug reactions. At present, there are no guidelines or standards for the use of these methods in routine pharmaco-vigilance. In 2003, a group of statisticians, pharmaco-epidemiologists and pharmaco-vigilance professionals from the pharmaceutical industry and the US FDA formed the Pharmaceutical Research and Manufacturers of America-FDA Collaborative Working Group on Safety Evaluation Tools to review best practices for the use of these methods.

Data mining in pharmacovigilance: the need for a balanced perspective.

Data mining is receiving considerable attention as a tool for pharmacovigilance and is generating many perspectives on its uses. This paper presents four concepts that have appeared in various professional venues and represent potential sources of misunderstanding and/or entail extended discussions: (i) data mining algorithms are unvalidated; (ii) data mining algorithms allow data miners to objectively screen spontaneous report data; (iii) mathematically more complex Bayesian algorithms are superior to frequentist algorithms; and (iv) data mining algorithms are not just for hypothesis generation. Key points for a balanced perspective are that: (i) validation exercises have been done but lack a gold standard for comparison and are complicated by numerous nuances and pitfalls in the deployment of data mining algorithms.

The role of data mining in pharmacovigilance.

A principle concern of pharmacovigilance is the timely detection of adverse drug reactions that are novel by virtue of their clinical nature, severity and/or frequency. The cornerstone of this process is the scientific acumen of the pharmacovigilance domain expert. There is understandably an interest in developing database screening tools to assist human reviewers in identifying associations worthy of further investigation (i.

Persistence with inhaled corticosteroid therapy in daily practice.

Objective: To quantify persistence with inhaled corticosteroids (ICS) among new users in daily practice and identify determinants of persistence.

Methods: A retrospective cohort study was performed with data from the Dutch PHARMO system. This system consists of medication and hospital admission records of 325,000 inhabitants of 12 Dutch cities.

N-acetylcysteine reduces the risk of re-hospitalisation among patients with chronic obstructive pulmonary disease.

The aim of this study was to evaluate the effect of oral N-acetylcysteine in the prevention of re-hospitalisation for chronic obstructive pulmonary disease (COPD) exacerbations. Using the PHARmacoMOrbidity linkage (PHARMO) system the authors included all patients aged > or = 55 yrs who had been dispensed medication, labelled for respiratory indications (anatomical therapeutic chemical (ATC) classification system: R03), between 1986-1998 and who had also been hospitalised for COPD (International Classification of Diseases (ICD)-9: 491, 492, 496) in this time frame. These subjects were subsequently divided into two groups, those who had received N-acetylcysteine following discharge from their first admission between 1986-1998 and those who had not.

Asthma exacerbations during first therapy with long acting beta 2-agonists.

Long-acting beta 2-agonists (LBA) have become an important therapeutic strategy in the treatment of asthma. There is, however, debate whether LBA increase the risk of asthma exacerbations (AE). We studied whether the risk of AE was increased in patients starting LBA therapy and whether the risk was associated with severity.

A comparison of clinical pharmacodynamics of different administration schedules of oral topotecan (Hycamtin).

Prolonged exposure to topotecan in in vitro and in vivo experiments has yielded the highest antitumor efficacy. An oral formulation of topotecan with a bioavailability of 32-44% in humans enables convenient prolonged administration. Pharmacokinetic/pharmacodynamic relationships from four Phase I studies with different schedules of administration of oral topotecan in 99 adult patients with malignant solid tumors refractory to standard forms of chemotherapy were compared.

Five days of oral topotecan (Hycamtin), a phase I and pharmacological study in adult patients with solid tumours.

Topotecan is a specific inhibitor to topoisomerase I. An oral formulation of topotecan is available with a bioavailability of 32-44% in humans. A phase I and pharmacological study of the oral formulation of topotecan administered daily for 5 days every 21 days was performed in adult patients with solid tumours to determine the maximum tolerated dose (MTD).

Oral topotecan given once or twice daily for ten days: a phase I pharmacology study in adult patients with solid tumors.

Prolonged exposure to topotecan (TPT) in in vitro experiments and in vivo studies in animals yielded the highest antitumor efficacy. An oral bioavailability of TPT of 32-44% enables convenient prolonged administration. Because of unpredictable diarrhea in the third week of the twice daily (b.

Phase I and pharmacologic study of oral topotecan administered twice daily for 21 days to adult patients with solid tumors.

Purpose: Topotecan is a specific inhibitor of topoisomerase I. Recently bioavailability of an oral formulation of approximately 30% with limited variability was reported. We conducted a phase I and pharmacokinetic study of the oral formulation of topotecan to characterize the maximum-tolerated dose (MTD), toxicities, pharmacokinetics, and antitumor effects in patients with refractory malignancies.

Topoisomerase I inhibitors: the relevance of prolonged exposure for present clinical development.

Topoisomerase I inhibitors constitute a new class of anti-cancer agents. Recently, topotecan and irinotecan were registered for clinical use in ovarian cancer and colorectal cancer respectively. Cytotoxicity of topoisomerase I inhibitors is S-phase specific, and in vitro and in vivo studies have suggested that, for efficacy, prolonged exposure might be more important than short-term exposure to high concentration.

The bioavailability of oral GI147211 (GG211), a new topoisomerase I inhibitor.

Topoisomerase I inhibitors are new compounds of interest for cancer chemotherapy. We performed a study with GI147211, a new semisynthetic camptothecin analogue, to determine the absolute bioavailability of the drug given orally. Patients with a histologically confirmed diagnosis of a solid tumour refractory to standard forms of therapy were eligible for the study.