Evaluation of interventions to prevent injuries: an overview

Overview of issues involved in evaluating the effectiveness of injury interventions is presented. An intervention should be evaluated to show it prevents injuries in the target population, to identify unintended consequences, to correct problems that limit effectiveness, to justify current and future resources from funding agencies, and to guide its replication elsewhere. Problems in conducting evaluations include obtaining sufficient resources, coping with rare events, establishing reliability and validity of measurement instruments, separating effects of multiple simultaneous events, and adjusting for the time lag between an intervention and its effects.

When feasible, changes in injury rates (documented by medical records) should be used. These are more convincing for demonstrating intervention effectiveness than changes in observed or reported behaviors or in knowledge and attitudes (documented by surveys). Quasiexperimental evaluation designs are often useful, such as measuring injury rates before and after an intervention in a time series design, or intervening in one of two comparable communities in a non-equivalent control group design. Evaluations using true experimental designs, in which individuals or groups are randomized to receive or not receive an intervention, are highly desirable but are often difficult due to logistical or ethical considerations. An evaluation component should be integral to the introduction of any new injury intervention.

     

Synthesis and evaluation of 6-[(18)F]fluoro-3-(2(S)-azetidinylmethoxy)pyridine as a PET tracer for nicotinic acetylcholine receptors

Both ABT-594 ((R)-2-chloro-5-(2-azetidinylmethoxy)pyridine) and A-85380 (3-[2(S)-2-azetidinylmethoxy]pyridine), novel nicotinic agonists that possess potent non-opioid analgesic properties, have high affinity for neuronal nicotinic acetylcholine receptors (nAChR) but do not elicit the pronounced toxicity of epibatidine. 6-[(18)F]Fluoro-3-(2(S)-azetidinylmethoxy)pyridine (6-[(18)F]fluoro-A-85380), a F-18 labeled analogue of these two compounds, is therefore a promising radioligand for positron emission tomography (PET) studies in humans. The use of trimethylammonium as a leaving group in nucleophilic aromatic substitution reactions has proven to be a versatile and efficient strategy, and offers several advantages over other leaving groups. Here, we report the synthetic strategy for the preparation of a precursor, as a trimethylammonium iodide salt, and its use in the radiosynthesis to 6-[(18)F]fluoro-A-85380. Preliminary compartative PET studies of 6-[(18)F]fluoro-A-85380 and 2-[(18)F]fluoro-A-85380 were carried out in baboon to examine their suitability as tracers for studying nAChR system.     

Treatment options for perianal Bowen's disease: survery of American Society of Colon and Rectal Surgeons Members

The aim of this study was to determine current management practices of physicians caring for patients with perianal Bowen's disease. A questionnaire was sent to 1,499 members listed in the 1997 American Society of Colon and Rectal Surgeons Directory asking them how many patients they have treated and which operative or nonoperative treatment option they choose for small (< or =3 cm), large (> 3 cm), and microscopic lesions. Of 1,499, 663 (44.2%) surgeons responded. Not all respondents answered each item. Seventy-five per cent of surgeons surveyed (n = 653) devote greater than 75 per cent of their practice to colon and rectal surgery. Of 642 respondents, 552 (86%) managed a total of <10 patients, and 90/642 (14%), > or =10 patients. Ninety-six per cent of respondents use wide local excision for patients with small lesions. Eighty-seven per cent of respondents use wide local excision for patients with large lesions. Seventy-four per cent treat patients with microscopic disease conservatively and without wide excision. The majority of surgeons caring for patients with perianal Bowen's disease are performing wide local excision for both small and large lesions. Microscopic disease was usually treated conservatively with observation alone.     

The effects of sodium valproate on γ-aminobutyrate metabolism and behaviour in naive and ethanolamine-O-sulphate pretreated rats and mice

Sodium valproate was injected acutely (400 mg/kg i.p.) into naive and ethanoloamine-O-sulphate chronically pretreated rats and mice, in an attempt to gain further insight into the effects of this anticonvulsant on GABA metabolism. Sodium valproate significantly enhanced the activity of GAD in the medulla and pons, cerebellum and midhrain regions of rats, and partially relieved the suppression of GAD activity caused by chronic GABA-transaminase inhibition in whole mouse brain. In combination with EOS, sodium valproate caused behavioural excitation in mice which was similar to that sometimes seen with high doses of some GABA-T inhibitors. Pretreatment with EOS potentiated the characteristic abstinence behaviour caused by sodium valproate in rats, though no further significant rise in cerebral GABA levels was observed. In view of the neuronal location of GAD, the elevation of cerebral GABA levels at least in part by potentiation of GAD activity could be involved in the mediation of the anticonvulsant activity of sodium valproate.     

Combination gemcitabine, platinum, and bevacizumab for the treatment of recurrent ovarian cancer

ObjectiveTo describe the response rate (RR), progression-free survival (PFS), and toxicity profile of combination gemcitabine, platinum, and bevacizumab (GPB) for the treatment of recurrent epithelial ovarian cancer (EOC).MethodsA chart review of all patients with recurrent EOC who were treated with D1, D15 GPB in a 28-day cycle at a single institution was performed. Standard doses were gemcitabine 1000 mg/m², cisplatin 30 mg/m² or carboplatin AUC 3, and bevacizumab 10 mg/kg. All patients were analyzed for toxicity. RR and PFS were assessed in all patients who received at least 2 cycles of GPB.ResultsThirty-five patients were identified, and 33 received at least 2 cycles of GPB. The majority of patients (80%) were platinum sensitive. Patients received a median of 6 cycles of GPB (range 1–24). Sixteen patients (48%) had a complete response (CR), and 10 patients (30%) had a partial response (PR), for a total RR of 78%. An additional 5 patients (15%) had stable disease, and only 2 (6%) patients had progressive disease. The median overall PFS was 12 months (95% CI 7–15), with a median follow-up time of 10 months (2–22). Two patients (6%) had bowel perforations, and both survived. Hematologic toxicities were most common, with 29% and 14% of patients experiencing grade 3 or 4 neutropenia and thrombocytopenia respectively.ConclusionsThe combination of GPB demonstrated excellent efficacy for the treatment of recurrent EOC. However, serious toxicities occurred, and the safety profile of this combination requires further study.