Australian data do not support current pharmaceutical benefits scheme criteria for use of tumour necrosis factor-α inhibitors in ankylosing spondylitis

On the basis of local data, we write in support of the conclusions of Smith and Ahern that current Pharmaceu- tical Benefits Scheme (PBS) criteria for tumour necrosis factor (TNF)-a inhibitors in ankylosing spondylitis (AS) are not evidence-based. 1 As a prerequisite to the appropriate use of biological therapy in AS, three aspects of the disease need to be defined: (i) diagnosis, (ii) activity and (iii) therapeutic failure (Table 1)....

Produtos naturais como candidatos a fármacos úteis no tratamento do mal de Alzheimer

Alzheimer's disease (AD) is a progressive neurodegenerative pathology with severe economic and social impact. There is currently no cure, although cholinesterase inhibitors provide effective temporary relief of symptoms in some patients. Nowadays drug research and development are based on the cholinergic hypothesis that supports the cognition improvement by regulation of the synthesis and release of acetylcholine in the brain. There are only four commercial medicines approved for treatment of AD and natural products have played an important role in the research for new acetylcholinesterase inhibitors.

Hysteroscopic myomectomy in a submucous fibroid 3 mm from the serosa: A case report - Case report from the endoscopy service of Ginendo-RJ

This is a case report of a 39-year-old black woman, nulliparous, married who presented a heavy menstrual flow with clots and dysmenorrhea. Gynaecological examination of the uterus revealed RVF, mobility, no pain, slight enlargement, and right displacement. Magnetic resonance imaging (MRI) of the pelvis showed a 40 mm submucous fibroid with intramural component less than 50%, type 1, with a 3 mm distance from serosa. In an office hysteroscopy, it was noted a 40 mm submucous fibroid with an intramural component with less than 50%, type 1, classified in STEP-W submucous fibroids classification as a Score 6, Group II. The patient was submitted to partial hysteroscopic myomectomy, removing 60% of the fibroid volume in a 48.75-minute surgery. GnRH analogue was indicated for 3 months before another intervention. In the second evaluation MRI revealed a 22 mm-fibroid with intramural component more than 50%, type 2, with a 7 mm distance from serosa. Hysteroscopy found a 20 mm submucous fibroid, with intramural component more than 50%, type 2, Score 4, Group I on STEP-W classification. The patient was submitted to a second hysteroscopic myomectomy with complete removal and 10.5 minutes operating time, without complications. © 2006 Springer-Verlag.

Treatment of pulmonary thromboembolism in patients with systemic blood pressure stability and right ventricular dysfunction

Pulmonary thromboembolism (PTE) ranges from incidental, clinically unimportant thromboembolism to massive embolism with sudden death. Its treatment is well established in two groups of patients: heparin for those with normal systemic blood pressure without right ventricular dysfunction (RVD) and thrombolysis for those with RVD and circulatory shock. In an intermediate group of patients with systemic blood pressure stability combined with RVD, which is usually associated with worse outcome, the treatment is controversial. There are authors who strongly suggest thrombolysis while others contraindicate this procedure and recommend anticoagulation with heparin. This is a narrative review that includes clinical trials comparing thrombolysis and heparin for the treatment of PTE patients with systemic blood pressure stability and RVD published since 1973. The results show that there are only four trials on this subject with less than 500 patients. Many PTE patients with systemic blood pressure stability and RVD might benefit from thrombolysis but, on the other hand, the risk for hemorrhagic events may be increased. Large randomized clinical trials are required to clarify this. © 2008 Bentham Science Publishers Ltd.

Bromocriptine:old drug, new formulation and new indication

Bromocriptine is an ergot alkaloid dopamine D receptor agonist that has been used extensively in the past to treat hyperprolactinaemia, galactorrhoea and Parkinsonism. It is known that hypothalamic hypodopaminergic states and disturbed circadian rhythm are associated with the development of insulin resistance, obesity and diabetes in animals and humans. When administered in the early morning at the start of the light phase, a new quick release (QR) formulation of bromocriptine appears to act centrally to reset circadian rhythms of hypothalamic dopamine and serotonin and improve insulin resistance and other metabolic abnormalities. Phase II and III clinical studies show that QR-bromocriptine lowers glycated haemoglobin by 0.6-1.2% (7-13 mmol/mol) either as monotherapy or in combination with other antidiabetes medications. Apart from nausea, the drug is well tolerated. The doses used to treat diabetes (up to 4.8 mg daily) are much lower than those used to treat Parkinson's disease and have not been associated with retroperitoneal fibrosis or heart valve abnormalities. QR-bromocriptine (Cycloset™) has recently been approved in the USA for the treatment of type 2 diabetes mellitus (T2DM). Thus, a QR formulation of bromocriptine timed for peak delivery in the early morning may provide a novel neurally mediated approach to the control of hyperglycaemia in T2DM. © 2010 Blackwell Publishing Ltd.

Deterring drug drivers : a study into the initial impact of oral random roadside drug testing in Queensland

Objective: The global implementation of oral random roadside drug testing is relatively limited, and correspondingly, the literature that focuses on the effectiveness of this intervention is scant. This study aims to provide a preliminary indication of the impact of roadside drug testing in Queensland. Methods: A sample of Queensland motorists’ (N= 922) completed a self-report questionnaire to investigate their drug driving behaviour, as well as examine the perceived affect of legal sanctions (certainty, severity and swiftness) and knowledge of the countermeasure on their subsequent offending behaviour. Results: Analysis of the collected data revealed that approximately 20% of participants reported drug driving at least once in the last six months. Overall, there was considerable variability in respondent’s perceptions regarding the certainty, severity and swiftness of legal sanctions associated with the testing regime and a considerable proportion remained unaware of testing practices. In regards to predicting those who intended to drug driving again in the future, perceptions of apprehension certainty, more specifically low certainty of apprehension, were significantly associated with self-reported intentions to offend. Additionally, self-reported recent drug driving activity and frequent drug consumption were also identified as significant predictors, which indicates that in the current context, past behaviour is a prominent predictor of future behaviour. To a lesser extent, awareness of testing practices was a significant predictor of intending not to drug drive in the future. Conclusion: The results indicate that drug driving is relatively prevalent on Queensland roads, and a number of factors may influence such behaviour. Additionally, while the roadside testing initiative is beginning to have a deterrent impact, its success will likely be linked with targeted intelligence-led implementation in order to increase apprehension levels as well as the general deterrent effect.

Pediatric drug-related problems: a multicenter study in four French-speaking countries.

BACKGROUND: Pediatric intensive care patients represent a population at high risk for drug-related problems. There are few studies that compare the activity of clinical pharmacists between countries. OBJECTIVE: To describe the drug-related problems identified and interventions by four pharmacists in a pediatric cardiac and intensive care unit. SETTING: Four pediatric centers in France, Quebec, Switzerland and Belgium. METHOD: This was a six-month multicenter, descriptive and prospective study conducted from August 1, 2009 to January 31, 2010. Drug-related problems and clinical interventions were compiled from four pediatric centers in France, Quebec, Switzerland and Belgium. Data on patients, drugs, intervention, documentation, approval and estimated impact were compiled. MAIN OUTCOME MEASURE: Number and type of drug-related problems encountered in a large pediatric inpatient population. RESULTS: A total of 996 interventions were recorded: 238 (24 %) in France, 278 (28 %) in Quebec, 351 (35 %) in Switzerland and 129 (13 %) in Belgium. These interventions targeted 270 patients (median 21 months old, 53 % male): 88 (33 %) in France, 56 (21 %) in Quebec, 57 (21 %) in Switzerland and 69 (26 %) in Belgium. The main drug-related problems were inappropriate administration technique (29 %), untreated indication (25 %) and supra-therapeutic dose (11 %). The pharmacists' interventions were mostly optimizing the mode of administration (22 %), dose adjustment (20 %) and therapeutic monitoring (16 %). The two major drug classes that led to interventions were anti-infectives for systemic use (23 %) and digestive system and metabolism drugs (22 %). Interventions mainly involved residents and all clinical staff (21 %). Among the 878 (88 %) proposed interventions requiring physician approval, 860 (98 %) were accepted. CONCLUSION: This descriptive study illustrates drug-related problems and the ability of clinical pharmacists to identify and resolve them in pediatric intensive care units in four French-speaking countries.

Effect of drug utilization reviews on the quality of in-hospital prescribing: a quasi-experimental study

Affiliation: Louise Potvin: Groupe de recherche interdisciplinaire en santé, Faculté de médecine, Université de Montréal

Qualitative methods in early-phase drug trials : data and methods from a trial of N-acetylcysteine in schizophrenia

Objective: The pharmacokinetic profile of a drug often gives little indication of its potential therapeutic application, with many therapeutic uses of drugs being discovered serendipitously while being studied for different indications. As hypothesis-driven, quantitative research methodology is exclusively used in early-phase trials, unexpected but important phenomena may escape detection. In this context, this study aimed to examine the potential for integrating qualitative research methods with quantitative methods in early-phase drug trials. To our knowledge, this mixed methodology has not previously been applied to blinded psychopharmacologic trials.

Method: We undertook qualitative data analysis of clinical observations on the dataset of a randomized, double-blind, placebo-controlled trial of N-acetylcysteine (NAC) in patients with DSM-IV-TR–diagnosed schizophrenia (N = 140). Textual data on all participants, deliberately collected for this purpose, were coded using NVivo 2, and emergent themes were analyzed in a blinded manner in the NAC and placebo groups. The trial was conducted from November 2002 to July 2005.

Results: The principal findings of the published trial could be replicated using a qualitative methodology. In addition, significant differences between NAC- and placebo-treated participants emerged for positive and affective symptoms, which had not been captured by the rating scales utilized in the quantitative trial. Qualitative data in this study subsequently led to a positive trial of NAC in bipolar disorder.

Conclusions: The use of qualitative methods may yield broader data and has the potential to complement traditional quantitative methods and detect unexpected efficacy and safety signals, thereby maximizing the findings of early-phase clinical trial research.

Application of an in vitro drug screening assay based on the release of phosphoglucose isomerase to determine the structure-activity relationship of thiazolides against Echinococcus multilocularis metacestodes

OBJECTIVES: The disease alveolar echinococcosis (AE), caused by the larval stage of the cestode Echinococcus multilocularis, is fatal if treatment is unsuccessful. Current treatment options are, at best, parasitostatic, and involve taking benzimidazoles (albendazole, mebendazole) for the whole of a patient's life. In conjunction with the recent development of optimized procedures for E. multilocularis metacestode cultivation, we aimed to develop a rapid and reliable drug screening test, which enables efficient screening of a large number of compounds in a relatively short time frame. METHODS: Metacestodes were treated in vitro with albendazole, the nitro-thiazole nitazoxanide and 29 nitazoxanide derivatives. The resulting leakage of phosphoglucose isomerase (PGI) activity into the medium supernatant was measured and provided an indication of compound efficacy. RESULTS: We show that upon in vitro culture of E. multilocularis metacestodes in the presence of active drugs such as albendazole, the nitro-thiazole nitazoxanide and 30 different nitazoxanide derivatives, the activity of PGI in culture supernatants increased. The increase in PGI activity correlated with the progressive degeneration and destruction of metacestode tissue in a time- and concentration-dependent manner, which allowed us to perform a structure-activity relationship analysis on the thiazolide compounds used in this study. CONCLUSIONS: The assay presented here is inexpensive, rapid, can be used in 24- and 96-well formats and will serve as an ideal tool for first-round in vitro tests on the efficacy of large numbers of antiparasitic compounds.

Comparison of long versus short ("spot") drug-eluting stenting for long coronary stenoses

We compared spot drug-eluting stenting (DES) to full stent coverage for treatment of long coronary stenoses. Consecutive, consenting patients with a long (>20 mm) coronary lesion of nonuniform severity and indication for percutaneous coronary intervention were randomized to full stent coverage of the atherosclerotic lesion with multiple, overlapping stenting (full DES group, n = 90) or spot stenting of hemodynamically significant parts of the lesion only (defined as diameter stenosis >50%; spot DES group, n = 89). At 1-year follow-up, 14 patients with full DES (15.6%) and 5 patients (5.6%) with spot DES had a major adverse cardiac event (MACE; p = 0.031). At 3 years, MACEs occurred in 18 patients with full DES (20%) and 7 patients (7.8%) with spot DES (p = 0.019). Cox proportional hazard model showed that the risk for MACEs was almost 60% lower in patients with spot DES compared to those with full DES (hazard ratio 0.41, 95% confidence interval 0.17 to 0.98, p = 0.044). This association remained even after controlling for age, gender, lesion length, and type of stent used (hazard ratio 0.42, 95% confidence interval 0.17 to 1.00, p = 0.05). In conclusion, total lesion coverage with DES is not necessary in the presence of diffuse disease of nonuniform severity. Selective stenting of only the significantly stenosed parts of the lesion is an appropriate therapeutic alternative in this setting, offering a favorable clinical outcome.