Discriminative stimulus properties in rats of the novel antipsychotic quetiapine

Rats discriminated the novel antipsychotic quetiapine (Seroquel). Full generalization was seen with the novel ("atypical") antipsychotics, clozapine, olanzapine, and risperidone. Generalization was not seen with the older "typical" antipsychotics, haloperidol, chlorpromazine, and loxapine, or with the novel atypical antipsychotic, amisulpride. The pattern of generalization resembled that seen in rats trained to discriminate a low dose (1.25 mg/kg) of clozapine, which dissociates most novel antipsychotics from typical antipsychotics. However, the failure of the novel antipsychotic amisulpride to generalize demonstrates that this bioassay does not detect all novel antipsychotics. These data suggest that the discrimination of antipsychotics such as quetiapine may be of value in the development of novel antipsychotics, although the relationship between the discriminative properties of such drugs and their clinical actions is unclear.     

Cost effectiveness of tinzaparin sodium versus unfractionated heparin in the treatment of proximal deep vein thrombosis

OBJECTIVE: To evaluate economic and health implications of tinzaparin sodium, a once a day low-molecular-weight heparin (LMWH), versus unfractionated heparin (UFH) in the treatment of acute deep vein thrombosis (DVT) from a US healthcare payer perspective. STUDY DESIGN: An economic model, composed of two submodules, was created: A short-term module based on clinical trial data covering the first 3 months and a long-term module that projects trial results based on published data for up to 50 years. METHODS: Clinical trial results were combined with data from long-term follow-up studies of DVT in a model that estimates the health and economic consequences of treatment. Both short- and long-term costs with tinzaparin sodium were compared with UFH, as were health outcomes and quality-adjusted life-years (QALYs). RESULTS: Patients treated with tinzaparin sodium are estimated to live a mean of 0.9 years longer on average (0.6 discounted), resulting in an increase of 0.8 QALYs (0.5 discounted). At the same time, lifetime savings are US dollars 621 per patient (1999 values), even when all patients receiving tinzapirin sodium are treated as inpatients. Early discharge of patients receiving tinzaparin sodium, or outpatient treatment, would save between US dollars 3000 and US dollars 5000 per patient. CONCLUSION: Tinzaparin sodium leads to better health outcomes and substantial economic savings compared with UFH treatment when all management costs are considered.     

Aldosterone antagonists in congestive heart failure

The role of aldosterone in the pathophysiology of congestive heart failure (CHF) has long been recognized. The recent RALES (Randomized Aldactone Evaluation Study) trial demonstrated early reduction in morbidity and mortality using spironolactone, an aldosterone receptor antagonist, in combination with angiotensin converting enzyme (ACE) inhibitor and loop diuretic, in patients with heart failure. This effect of spironolactone highlighted the importance of understanding the contributions of the renin-angiotensin-aldosterone system (RAAS) in the progression of CHF, and increased interest in the use of aldosterone antagonists. While ACE inhibitors have had the largest impact on adverse events in CHF, numerous studies have shown that these drugs fail to completely suppress aldosterone. Blocking the effects of residual aldosterone has now been demonstrated to affect prognosis in these patients. This review will discuss the role of aldosterone in the pathophysiology of CHF, with an emphasis on both known and potential therapeutic benefits of aldosterone antagonism.     

Paediatric myelodysplastic syndromes and juvenile myelomonocytic leukaemia in the UK: a population-based study of incidence and survival

We aimed to identify and classify cases of paediatric myelodysplastic syndromes (MDS) occurring in Britain to estimate the incidence of this rare group of diseases, investigate the results of therapy and identify prognostic risk factors. Patients aged below 15 years at diagnosis were collected from England, Scotland and Wales, inclusively between 1990 and 1999. One hundred and thirty-five patients were accepted as de novo MDS or juvenile myelomonocytic leukaemia (JMML). The incidence for this period was 1.35 per million (age standardized rate) which is below that reported outside the UK. The overall survival was 45%[standard error (SE) = 4%] at 5 years: 40% (SE = 6%) for JMML and 50% (SE = 6%) for other MDS. Significant adverse prognostic factors for JMML were a platelet count < 40 x 10(9)/l, raised fetal haemoglobin, FPC score and age above 2 years at diagnosis, for other MDS only monosomy 7 was significant. To conclude, the incidence of MDS/JMML in children in the UK appears to be lower than that reported outside the UK. This may be either a real difference in incidence or variation in reporting. Monosomy 7 is associated with poor outcome in MDS other than JMML. The prognosis of JMML depends on age, platelet count and fetal haemoglobin.