ObjectiveTo investigate whether antidrug antibodies and/or drug non‐trough levels predict the long‐term treatment response in a large cohort of patients with rheumatoid arthritis (RA) treated with adalimumab or etanercept and to identify factors influencing antidrug antibody and drug levels to optimize future treatment decisions.MethodsA total of 331 patients from an observational prospective cohort were selected (160 patients treated with adalimumab and 171 treated with etanercept). Antidrug antibody levels were measured by radioimmunoassay, and drug levels were measured by enzyme‐linked immunosorbent assay in 835 serial serum samples obtained 3, 6, and 12 months after initiation of therapy. The association between antidrug antibodies and drug non‐trough levels and the treatment response (change in the Disease Activity Score in 28 joints) was evaluated.ResultsAmong patients who completed 12 months of followup, antidrug antibodies were detected in 24.8% of those receiving adalimumab (31 of 125) and in none of those receiving etanercept. At 3 months, antidrug antibody formation and low adalimumab levels were significant predictors of no response according to the European League Against Rheumatism (EULAR) criteria at 12 months (area under the receiver operating characteristic curve 0.71 [95% confidence interval (95% CI) 0.57, 0.85]). Antidrug antibody–positive patients received lower median dosages of methotrexate compared with antidrug antibody–negative patients (15 mg/week versus 20 mg/week; P = 0.01) and had a longer disease duration (14.0 versus 7.7 years; P = 0.03). The adalimumab level was the best predictor of change in the DAS28 at 12 months, after adjustment for confounders (regression coefficient 0.060 [95% CI 0.015, 0.10], P = 0.009). Etanercept levels were associated with the EULAR response at 12 months (regression coefficient 0.088 [95% CI 0.019, 0.16], P = 0.012); however, this difference was not significant after adjustment. A body mass index of ≥30 kg/m2 and poor adherence were associated with lower drug levels.ConclusionPharmacologic testing in anti–tumor necrosis factor–treated patients is clinically useful even in the absence of trough levels. At 3 months, antidrug antibodies and low adalimumab levels are significant predictors of no response according to the EULAR criteria at 12 months.

Forty eight hours later she was profoundly hypoxaemic with an oxygen saturation of 54% breathing air. The chest radiograph showed extensive alveolar shadowing in keeping with a severe pneumonitis (fig 1). She required ventilation with an Fio2 of 95%, 10 cm positive end expiratory pressure (PEEP), and cardiovascular support with adrenaline. Treatment with high dose erythromycin and imipenem was started. At this time the presence of a cytopathic effect suggestive of adenovirus was noted in the viral tissue cultures which had been inoculated with the bronchoalveolar fluid. The same cytopathic effect was also seen in tissue cultures inoculated with a throat swab taken on the same day that the bronchoscopy was performed. The presence of an adenovirus was confirmed by electron microscopy.She was commenced on continuous nebulised ribavirin (20 mg/ml ribavirin via small particle generating nebuliser) but remained critically ill. Twenty four hours later intravenous ribavirin (20 mg/kg loading dose fol- Figure 2 Chest radiograph after treatment with intravenous and nebulised ribavirin showing significant clearing of the pneumonitis.

Detailed review of clinical characteristics of patients with persistently high scores led to the strong impression that, in most cases, persistently high pain was not simply because of inadequate administration of opioids. Instead, the first step in improving pain management of hospitalized children may be the identification of outliers with high pain scores to direct efforts on the development of interventions for patient groups with mechanistically similar pain.

SummaryRoutine pre-operative evaluation of a 58-year-old man scheduled for repair of an inguinal hernia, disclosed a blood pressure of 200/100 mmHg. This decreased to 150/100 mmHg after a period of rest. An electrocardiogram taken as a result of this chance finding showed left bundle branch block. There were no other cardiovascular symptoms or signs. Soon after induction of general anaesthesia, the conduction defect disappeared. The return to sinus rhythm was sudden and sustained and was not related to changes in heart rate or blood pressure. One month later, his electrocardiograph remained normal. Intermittent left bundle branch block is uncommon and its development during anaesthesia more so [1, 2]. It must be distinguished from the more common intermittent bundle branch block, where both normal and abnormal complexes are seen in the same electrocardiogram (ECG) record. Although there are a number of causes of right bundle branch block, left bundle branch block (LBBB) is most frequently associated with ischaemic heart disease [3, 4]. Particular care is needed when anaesthetising patients who have LBBB. They should be managed with the same delicacy as patients who have significant ischaemic heart disease.We present a case of a patient in whom LBBB, an incidental finding during pre-operative screening, reverted to sinus rhythm during anaesthesia. Because myocardial ischaemia is unlikely to lessen during anaesthesia, an asymptomatic patient whose ECG shows LBBB represents a significant dilemma for the anaesthetist. Case historyA 70-kg, 58-year-old Caucasian male, with a body mass index of 23.1, was scheduled for repair of right inguinal hernia under general anaesthesia. Pre-assessment disclosed only a history of a single episode of fainting many years before. Clinical examination was unremarkable. He did not receive any medication and had no known allergies.On admission, the patient's blood pressure was found to be elevated at 200/100 mmHg. This settled within a few hours but he remained mildly hypertensive with a blood pressure of 150/100 mmHg. His pulse rate was 90 beat. min ÿ 1 . Re-examination showed all pulses were normal, that the apex beat was not displaced and heart sounds were normal. There was no evidence of congestive heart failure. A chest X-ray was reported normal. His routine biochemical and haematological tests were within the normal limits. An ECG, obtained because of the chance finding of hypertension, showed normal sinus rhythm with a heart rate of 85 beat.min ÿ 1 and LBBB (Fig. 1). Following reassessment, no further investigations were considered appropriate or necessary because the patient gave no history suggestive of ischaemic heart disease and had an excellent exercise tolerance.He received no premedication. Before induction of anaesthesia, routine monitors (electrocardiography (CM5), oxygen saturation and noninvasive blood pressure) were placed and baseline observations made. He was preoxygenated with 100% oxygen. Anaesthesia was induced 684ᮊ 1997 Blackwell Science Ltd with thiopentone 40...