A UK-based resource to support the monitoring and safe use of anti-TB drugs and second-line treatment of multidrug-resistant TB.

Using the best available evidence and expert consensus, this document provides guidance for adverse effect monitoring in multidrug-resistant TB (MDR-TB). It includes recommendations for baseline tests, routine drug and toxicity monitoring guides as well as individual drug monographs for all drugs currently available in the UK to treat TB. These recommendations provide a structure through which healthcare professionals can better manage the complex drug regimens required for the treatment of MDR-TB; minimising the risk of adverse incidents and helping to improve patients' tolerance, compliance and treatment completion.

Treatment interruptions and inconsistent supply of anti-tuberculosis drugs in the United Kingdom.

SETTING: National Health Service (NHS) centres treating tuberculosis (TB) in the United Kingdom. OBJECTIVES: To describe NHS TB treatment centres' experience of obtaining anti-tuberculosis drugs to treat drug-susceptible and drug-resistant TB between 2007 and 2009. In particular: 1) any difficulties experienced in obtaining different drugs; 2) resulting interruptions or alterations in the prescribed regimen; 3) availability of paediatric formulations; and 4) resources available to identify and manage drug shortages. DESIGN: Questionnaires were sent to pharmacists at 168 treatment centres. RESULTS: Of the 77 (46%) treatment centres that responded, 63% (48/77) reported difficulties in obtaining anti-tuberculosis drugs. Consequently, 27% had to interrupt the prescribed treatment regimen at least once, whilst 19% had to alter the regimen. Of 55 centres treating multidrug-resistant tuberculosis, 36% reported difficulties obtaining second-line drugs, 16% had to interrupt the prescribed treatment regimen at least once and 5% had to alter the regimen. A lack of licensed liquid formulations for children resulted in 26% of treatment centres using unlicensed, variable-strength liquids and locally prepared suspensions. CONCLUSIONS: Difficulties obtaining drugs to treat both drug-susceptible and drug-resistant disease are common in the UK. There are particular risks for children. Our data identify an urgent need for national strategic guidance to ensure a consistent and reliable supply of anti-tuberculosis drugs.

Efficacy of thrombolytic agents in the treatment of pulmonary embolism.

Recent guidelines recommend bolus-dose alteplase for treating massive pulmonary embolism (PE). However, the safest and most effective treatment is as yet unknown. In the present study, a meta-analysis of published studies of alteplase infusion, bolus-dose alteplase and streptokinase was performed. The outcome measures were as follows: objective assessment of thrombolysis; all-cause mortality; deaths due to initial PE, major bleeding episodes and recurrent PE; and morbidity. In total, 26 studies were identified; however, only two comparative studies of alteplase infusion versus either bolus-dose alteplase or streptokinase were found. Meta-analysis revealed no significant difference between the three regimens, but was compromised by a paucity of data. Crude analysis of summated data on thrombolytic efficacy from all studies revealed that alteplase infusion was more effective than bolus-dose alteplase (relative risk (RR): 1.95; 95% confidence interval (CI): 1.19-3.2), whereas streptokinase was more effective than alteplase infusion (RR: 1.27; 95% CI: 1.09-1.47). Alteplase infusion had a lower mortality due to the initial PE than both bolus-dose alteplase and streptokinase (RR: 0.16; 95% CI: 0.05-0.59 and RR: 0.13; 95% CI: 0.04-0.46, respectively). In conclusion, this evidence suggests that the three thrombolytic agents may vary in efficacy. However, large-scale randomised controlled trials are needed to confirm these results.