The MALSF synthesis study in the central and eastern English Channel

The need for effective stewardship of the marine environment through integrated management, balancing the requirements for development and exploitation with nature conservation and legislation, has been widely recognised. However, implementing such a strategy requires a significant knowledge of the nature of the sea bed. Acquiring such knowledge in the central and eastern English Channel (Figure 1) has been a focus of the Marine Aggregate Levy Sustainability Fund (MALSF) since 2005. The MALSF has funded a series of surveys to acquire high resolution data and its subsequent interpretation, along with other data, using a multi-disciplinary approach including geologists, biologists and archaeologists. This has produced a great deal of beneficial cooperation and interaction between these disciplines and enhanced the quality of the interpretations and results

Comparison of the effects of thioridazine and mesoridazine on the QT interval in healthy adults after single oral doses

We compared the effects of single doses of thioridazine and mesoridazine on the heart rate-corrected QT (QTc) interval in healthy adult volunteers. QTc intervals and plasma concentrations of thioridazine, mesoridazine, and metabolites were measured after single oral doses of thioridazine hydrochloride 50 mg, mesoridazine besylate 50 mg, or placebo in a double-blind, crossover study. Mean maximum increases in the QTc interval following thioridazine (37.3±4.1 ms, P=0.023) and mesoridazine (46.6±7.4 ms, P=0.021) were similar and significantly greater than following placebo (12.9±8.1 ms). The area under the effect–time curve over 8 h following drug administration was similar between the two drugs (129.3±22.1 vs 148.3±43.0 ms h). In conclusion, thioridazine and mesoridazine are associated with similar effects on the QTc interval

Thioridazine and sudden unexplained death in psychiatric patients

Background Sudden death has been linked to antipsychotic therapy, but the relative risk associated with specific drugs is unknown. Aims To assess the risk of sudden unexplained death associated with antipsychotic drug therapy and its relation to drug dose and individual agents. Method A case—control study of psychiatric in-patients dying suddenly in five hospitals in the north-east of England and surviving controls matched for age, gender and mental disorder. Logistic regression analysis was used to identify significant risk factors, and odds ratios were calculated. Results Sixty-nine case—control clusters were identified. Probable sudden unexplained death was significantly associated with hypertension, ischaemic heart disease and current treatment with thioridazine (adjusted odds ratio=5.3, 95% CI 1.7-16.2, P=0.004). There was no significant association with other individual antipsychotic drugs. Conclusions Thioridazine alone was associated with sudden unexplained death, the likely mechanism being drug induced arrythmia

Enquiries to the UK National Poisons Information Service regarding dextromethorphant toxicity [Abstract]

Objective: Dextromethorphan is a readily accessible antitussive agent. Recreational abuse has been associated with dissociative effects, and deaths have been reported after ingestion of very large doses.1,2 This study examined the clinical features associated with dextromethorphan ingestion in the United Kingdom.  Methods:  The National Poisons Information Service is commissioned by the Health Protection Agency to provide clinical advice on the management of poisoned patients in the United Kingdom. Enquiries concerning dextromethorphan were examined retrospectively.  Results: Data were available between 2004 to 2007. There were data concerning 354 patients with median age 7 years (95% CI 4 to 14 years) of whom 194 were female (55.0%). Cases involved accidental ingestion in 261 (73.9%), deliberate overdose in 87 (24.6%), and adverse effects of therapeutic dose in 5 (1.4%). Median dose was 45 mg (range 3 to 2750 mg). Commonest co-ingested agents were paracetamol in 147 (41.6%), promethazine in 132 (37.4%), diphenhydramine in 73 (20.7%), pseudoephedrine in 67 (19.0%), triprolidine in 53 (15.0%), and menthol in 32 (9.1%). There were no symptoms or signs of toxicity in 257 patients (72.8%). The dose was higher in patients with symptoms; 120 mg (IQR 50 to 225 mg) versus 30 mg (IQR 8 to 90 mg), p<0.0001 by Mann Whitney test. Dextromethorphan dose was predictive of toxicity; receiver operating characteristic AUC 72.5% (95% CI 67.1 to 77.4%). Clinical features were drowsiness in 50 (14.2%), minor haemodynamic effects in 14 (4.0%), nausea or vomiting in 13 (3.7%), dizziness and ataxia in 10 (2.8%), agitation in 7 (2.0%), non-specific abdominal pain in 4 (1.1%), mydriasis in 3 (0.8%), dry mouth in 3 (0.8%), blurred vision in 2 (0.6%), headache in 2 (0.6%), and tremor in 1 (0.3%). None had features of severe poisoning. Conclusion: Dextromethorphan enquiries to the National Poisons Information Service often concern accidental exposures in children. The majority of patients had no clinical features or only minor symptoms

Lung deposition of nebulised pentamidine in children.

BACKGROUND: Nebulised pentamidine is effective for preventing Pneumocystis carinii pneumonia in adults with acquired immunodeficiency syndrome. The nebuliser dose required to produce equivalent lung concentrations of pentamidine in children is unknown. This study was performed to measure pulmonary pentamidine deposition in children and to relate this to age, ventilation pattern, and body size. METHODS: Nebulised pentamidine (50 mg in 6 ml saline) was administered to 12 children (including one with lymphocytic interstitial pneumonitis) and to six adults with human immunodeficiency virus infection using a Respirgard II nebuliser. Technetium-99m labeled colloidal human serum albumin was used as an indirect marker for pentamidine and deposition in the lungs was detected by a gamma camera. RESULTS: Absolute deposition of pentamidine was not related to age, height, weight, spirometry, or ventilation characteristics. Deposition, as a mean (SD) percentage of nebuliser output, was similar in children aged 8-11 years (5.5(2.4)%), teenagers aged 12-15 years (7.2(2.2)%) and adults (7.1(2.6)%). Aerosol concentration within the lungs (% nebuliser output deposited/predicted total lung capacity) was therefore higher in children (1.9(1.5)%/1) and teenagers (1.9(0.7)%/1) than in adults (1.0(0.7%)/1), and was negatively correlated with height (r = -0.69) and weight (r = -0.50). Deposition of aerosol in the region of the large central airways was particularly marked in children. Small reductions in forced expiratory volume in one second and forced vital capacity after treatment did not differ significantly between adults and children and visual analogue scores of subjective adverse effects did not vary with age. CONCLUSIONS: These results suggest that children probably require lower nebuliser pentamidine doses to produce lung pentamidine concentrations equivalent to those found to be effective for preventing P carinii pneumonia in adults using the Respirgard II nebuliser