An evaluation of the drug interaction potential of pazopanib, an oral vascular endothelial growth factor receptor tyrosine kinase inhibitor, using a modified Cooperstown 5+1 cocktail in patients with advanced solid tumors.

Pazopanib, an oral inhibitor of vascular endothelial growth factor receptor, platelet-derived growth factor receptor, and c-kit kinases, inhibits multiple cytochrome P450 (CYP450) enzymes in vitro. This study in patients with advanced cancer evaluated the effect of pazopanib on CYP450 function by comparing the pharmacokinetics of CYP-specific probe drugs in the presence and absence of pazopanib. The probes used included midazolam (CYP3A specific), warfarin (CYP2C9 specific), omeprazole (CYP2C19 specific), caffeine (CYP1A2 specific), and dextromethorphan (CYP2D6 specific). The estimated ratios of the geometric means (90% confidence interval (CI)) for the area under the curve to the last measurable point (AUC(0-t)) for these probe drugs with/without pazopanib were as follows: midazolam, 1.35 (1.18-1.54); omeprazole, 0.81 (0.59-1.12); caffeine, 1.00 (0.77-1.30); and S-warfarin, 0.93 (0.84-1.03). The geometric least-squares (LS) mean ratio of urine dextromethorphan:dextrorphan ranged from 1.33 (0-4-h interval) to 1.64 (4-8-h interval). The data suggest that pazopanib is a weak inhibitor of CYP3A4 and CYP2D6 and has no effect on CYP1A2, CYP2C9, and CYP2C19 in patients with advanced cancer.

Current practice of obtaining informed consent for local steroid injection among the shoulder and elbow surgeons in United Kingdom.

BACKGROUND: Local steroid injection is a common procedure and not without risks. AIM: To establish the current practice of obtaining informed consent for local steroid injection among shoulder and elbow surgeons in the UK. METHODS: A postal questionnaire survey was distributed to 176 orthopaedics surgeons in UK who were members of the British Elbow and Shoulder Society. RESULTS: 68% of the surgeons considered local steroid injection invasive. 88% of the surgeons obtained verbal consent only. Of these, only 19% recorded the discussion. Almost all the surgeons (96%) explained the desired effects and 26% provided statistical evidence of local steroid injection. About 88% of the surgeons mentioned other drugs included in the injection. Only 13% of them mentioned the dose of the steroid used. 82% and 77% of the surgeons offered alternative treatment options and the right to refuse injection respectively. 85% and 59% of the surgeons discussed local and systemic risks of steroid injection, respectively. The most common risk mentioned by the surgeons is short term increase of pain. CONCLUSIONS: Majority of the surgeons used verbal consent only for local steroid injection. The consent discussion was not regularly documented in case notes and the information delivered varies.

Traumatic hip dislocation in a 21-month-old child.

Traumatic hip dislocation in the paediatric population is a relatively rare occurrence and constitutes an orthopaedic emergency. A trivial force is all that is required and non-accidental injury should not be necessarily suspected. A case report involving a hip dislocation in a 21-month-old child, the youngest in the recent English literature is detailed.

Dipstick screening for urinary tract infection before arthroplasty: a safe alternative to laboratory testing?

We performed a prospective study on 247 consecutive patients attending our arthroplasty pre-admission clinic over six months, to compare the accuracy of dipstick urinalysis with the standard microbiological test for excluding urinary tract infection. There were 22 positive culture results and 43 positive dipstick results, with 16 true positives and 198 true negatives. Sensitivity was 72.7%, lower then the 88.0% figure for specificity. The positive predictive value was 37.2%, and the negative predictive value was 97.1%. Dipstick urinalysis is ideally suited to the busy pre-admission setting and would have resulted in a 90% reduction in the number of samples sent for laboratory analysis. In view of these results, we have changed our working practise from performing cultures to dipstick urinalysis on all patients prior to arthroplasty.

Impingement syndrome associated with whiplash injury.

We examined 524 patients with whiplash injuries for delayed onset of shoulder pain in order to establish whether this was due to impingement syndrome. A total of 476 patients (91%) responded to a questionnaire of which 102 (22%) were entered into the study; 43 had both a positive impingement sign and Neer test. The incidence of impingement-type pain was 9%. After treatment 23 patients (5%) had a significant improvement in their symptoms, ten (2%) had a moderate improvement and nine had no improvement. Impingement-type pain can occur after whiplash injuries and can be successfully treated.

Diagnosing shoulder dislocations: time for a change of view.

Posterior shoulder dislocations are uncommon, with frequent delays in the diagnosis. Three missed posterior dislocations within our hospital caused us to review the standard radiographs taken and the knowledge of this condition. A total of 40 radiographers and 40 casualty officers were surveyed. Of the radiographers, 63% felt it unnecessary to perform two views, they complained that laterals were difficult to obtain because of patient distress. All the radiographers surveyed knew of alternative views, but would not perform them unless specifically requested. Casualty officers claimed always to request two views, but did not in 75% of cases. Only 20% were aware of alternative views, all would accept one view for exclusion of a dislocation and none were aware of the radiographic signs associated with a posterior dislocation. Increased education and a change of view would assist in decreasing the rate of missed diagnoses.

'Doctor, have I got a fracture or a break'?

Many patients apparently believe there is a difference between a fracture and a break. In a survey of 100 patients, 81 thought there was a difference. Of these, 71 thought a fracture was better than a break, and 65 believed that bone was undisplaced in a fracture and displaced in a break. These results suggest that greater care, including visual means, should be used in informing patients of their injuries.

Displaced bucket handle tears of the medial meniscus masking anterior cruciate deficiency.

Traditionally, anterior cruciate ligament (ACL) injuries have been difficult to diagnose in the Casualty Department. Studies have shown that the anterior drawer test has a poor sensitivity both in acute and chronic ACL deficient knees [4, 6, 9]; thus, more emphasis has been placed on the pivot shift and Lachman tests [3]. We report four cases of proven ACL rupture where clinical examination revealed an absent pivot shift and a near normal Lachman test following a displaced bucket handle tear of the medial meniscus. This finding has been reproduced in cadaver studies, and we conclude that if the history strongly suggests an ACL injury and examination reveals a stable knee, then the dual pathology of medial meniscus tear and ACL rupture should be suspected.