Laryngeal cancer treatment and survival differences across regional cancer centres in Ontario, Canada.

AIMS: We conducted a population-based study of practice patterns and outcome across the regional cancer centres providing care to patients with laryngeal cancer in the Province of Ontario, Canada. MATERIALS AND METHODS: : This was a retrospective cohort study of 1547 patients with cancers of the glottic or supraglottic larynx diagnosed between 1982 and 1995. Data were collected via chart review, including: patient and disease characteristics, treatment, waiting times and treatment volumes. Vital status was obtained from the Ontario Cancer Registry. Variations across the nine regional cancer centres are described and their effect on outcome explored. All analyses were stratified by stage I and II separately from stage III and IV. RESULTS: Treatments differed across centres (P<0.0001); for instance, in the stage I and II group, use of a daily dose of >2.54Gy varied from 0 to 87.6% and in the stage III and IV group, total laryngectomy rates varied from a low of 6% to a high of 53%. The percentage of patients waiting more than 6 weeks from diagnosis to first treatment varied from 17 to 49% (P<0.0001). Multivariate analysis revealed cause-specific survival differences that were not explained by control for case mix, treatment or waiting times. Differences ranged from an 82% risk reduction in one centre compared with the reference (stage I and II group, P=0.008) to a 153% increase in risk (stage III and IV group, P=0.02). Centre case volumes were not associated with cause-specific survival. CONCLUSIONS: This study quantifies the degree of variation that can occur in the treatment and outcome of people with cancer. We cannot properly assess whether care delivery is of high quality until we have a better understanding of the factors that drive such variations.

Radiotherapy patterns of practice: T1N0 glottic cancer in Ontario, Canada.

AIMS: To describe the variation in the delivery of radiation therapy to patients with T1N0 glottic cancer who were diagnosed in Ontario, Canada, between 1982 and 1995. MATERIALS AND METHODS: The patient population consisted of a random sample of 461 patients treated with curative intent from the nine cancer centres that administer radiation therapy in the province. Abstracted variables included prescribed dose (Gy) and fractionation (f), beam energy and arrangement, set-up, field size, beam modifiers, positioning and treatment interruptions. RESULTS: Thirteen prescribed dose-fractionation schemes (> or = four cases each) were identified, including 50.0-53.0 Gy/20 f (54.5%), 55.0-61.0 Gy/25 f (30.3%), and 60.0-66.0 Gy/30-33 f (7.7%). All regimens used one fraction per day, 5 days per week. An isocentric set-up was used (94.3%), with megavoltage (MV) beam energies of Cobalt-60 (87.9%), 6 MV (6.1%) and 4 MV (6.1%). A lateral parallel-opposed pair of beams was the predominant technique (76.4%) versus an anterior oblique pair (17.2%) or angle-down pair (caudally directed fields to achieve shoulder clearance, 5.7%). Wedging (96.3%) and bolus (11.8%) were used as beam-modifying devices. Predominant field-width dimensions were 5.0-6.0 cm (43.4%) and 6.5-7.0 cm (43.1%), and field length dimensions were 5.0-6.0 cm (49.5%) and 6.5-7.0 cm (35.0%). Head, neck or chin immobilisation was used in 86.9% of the cases, with 94.6% of these being custom-made. We found that radiotherapy practice was stable over time, except for a trend of increasing field size and increasing use of immobilisation. In contrast, we found practice variations among the province's cancer centres. On the basis of our findings, we defined a predominant technical practice consisting of Cobalt-60 (reflecting machine availability during the period of the study), an isocentric set-up, a lateral parallel-opposed pair technique with wedging, and supine-head neutral positioning with custom immobilisation. Forty-two per cent of the cases had one or more components of treatment that differed from this definition. CONCLUSIONS: Description of practice variation can provoke discussion about unrecognised differences in practice policies, perhaps identifying the need for better evidence, treatment guidelines, or both.

Comparative efficacy and safety of inhaled corticosteroids in asthma.

Current guidelines emphasize the efficacy of inhaled corticosteroids for anti-inflammatory activity in asthma, and recommend higher doses and earlier initiation of therapy than previous guidelines. Concern over possible side effects with long term use has prompted an evaluation of the available literature to determine the optimal dose that may be administered without fear that significant side effects might occur (e.g., growth retardation in children, adrenal suppression, reduction in bone mineral density, cataract formation). Regular treatment with the following drugs in adults and children, respectively, is unlikely to result in any clinically significant effects on the above parameters: beclomethasone dipropionate less than 1500 micrograms and 400 micrograms, budesonide less than 1600 micrograms and 400 micrograms, flunisolide less than 2000 micrograms and 1000 micrograms, fluticasone propionate approximately 500 micrograms and 200 micrograms, and triamcinolone acetonide less than 1600 micrograms and 1200 micrograms. Systemic effects are influenced by potency and bioavailability. Inhaled corticosteroids owe their favourable safety profile to a high topical to systemic potency ratio compared with that of oral corticosteroids. In terms of relative topical potency, fluticasone propionate is more potent than budesonide, which is more potent than beclomethasone dipropionate, which is more potent than flunisolide and triamcinolone acetonide. The delivery device has an important influence on the amount of drug reaching the patient. A spacer device attached to a metered dose inhaler or a Turbuhaler reduces oropharyngeal deposition and increases lung deposition. As a result, a dosage reduction may be possible, and local side effects of dysphonia and oral candidiasis may be reduced. Patients requiring continued high doses by the inhaled route should be monitored for systemic effects and be considered for osteoporosis prevention therapy if appropriate.

Magnetic characteristics of Yasargil aneurysm clips.

BACKGROUND: Metallic bioimplants are subject to great scrutiny in order to ensure that they are totally harmless to patients. Aneurysm clips are no exception to this rule. Considering the number of aneurysm clips used and their potential for injury, they should be evaluated very meticulously. Determining the magnetic characteristics of these clips is an important part of the evaluation process. In this study, a new method for evaluating magnetism is described and the importance of that information is briefly discussed. METHODS: Twenty Yasargil aneurysm clips were analyzed using a vibrating sample magnetometer under 1.5 Tesla. This device is highly sensitive, and is capable of measuring the magnetism of small objects. RESULTS: Our measurements showed magnetism of the aneurysm clips ranged from 0.0334-0.1369 electromagnetic units (emu). CONCLUSIONS: Magnetometer measurements and real life tests under magnetic resonance imaging (MRI) have shown that these clips have a very low magnetism and are safe to use in 1.5 Tesla MRI scanners. This study also proves that the vibrating sample magnetometer is a useful device for analyzing the magnetism of aneurysm clips, and their emu values can be used as another industry standard in the production line to increase the safety of these clips.

Cyclosporin in the treatment of corticosteroid resistant autoimmune chronic active hepatitis.

A 17 year old Asian patient with autoimmune chronic active hepatitis resistant to treatment with high dose corticosteroids and azathioprine was given cyclosporin at a dose of 5 mg/kg/day. Within two weeks of starting the cyclosporin treatment a favourable clinical and biochemical response was obtained and by one month serum aminotransferase activities were within normal limits. An attempted reduction in the daily dose of cyclosporin resulted in a relapse of the patient's disease. Remission was again attained by returning the dose of cyclosporin to 5 mg/kg/day. No significant side effects of the treatment have been shown. Cyclosporin seems to have a role in the treatment of corticosteroid resistant autoimmune chronic active hepatitis and its further evaluation is warranted.

Pressure autoregulation is intact after arteriovenous malformation resection.

The loss of autoregulatory control of cerebral perfusion to changes in perfusion pressure in tissue remote from an arteriovenous malformation (AVM) has been proposed as the mechanism underlying "normal perfusion pressure breakthrough." This study is the first direct test of this mechanism. Studies were performed during the resection of moderate to large AVMs in 25 patients undergoing 28 procedures under isoflurane anesthesia. Cerebral blood flow (CBF) was measured (xenon-133 method) in the hemisphere adjacent to the nidus before resection after dural exposure (pre), after AVM removal before dural closure at spontaneous systemic blood pressure (post), and, finally, with the mean arterial pressure increased by 20 mm Hg, using phenylephrine (post-BP). AVM resection resulted in a significant enhancement of perfusion in the adjacent hemisphere (30 +/- 2 vs. 25 +/- 1 ml/100g/min, P < 0.01), but no further increase of CBF occurred during increased perfusion pressure (30 +/- 2 ml/100g/min). One patient suffered a postoperative hemorrhage and another developed intraoperative brain swelling during the course of the resection that necessitated staging the procedure. These two patients had the highest increases in CBF, but intact pressure autoregulation. Preserved autoregulation to increased mean arterial pressure after resection does not support a hemodynamic mechanism for the observed increase in CBF from before the resection to after the resection. Pathological events, however, do appear to be related to increases in hemispheric perfusion.

Morphometric analysis of osteosclerotic bone resulting from hexachlorobenzene exposure.

Hexachlorobenzene (HCB) exposure has been shown to induce hyperparathyroidism and osteosclerosis in rats. Experiments were undertaken to investigate the effects of HCB-induced hyperparathyroidism and osteosclerosis on femur morphometry as well as femur breaking strength. Fischer 344 rats were dosed 5 d/wk for 15 wk with 0, 0.1, 1, 10, or 25 mg HCB/kg body weight. Hyperparathyroidism was produced in the two higher dose groups as reported previously (Andrews et al., 1989). Femur weight was significantly increased in the rats receiving 0.1, 1, and 25 mg HCB/kg body weight, whereas density was increased significantly at 1, 10, and 25 mg HCB/kg dose levels. Bone strength was also significantly increased at the three higher dose levels. Cross-sectional area of the midpoint of the femur was significantly increased at the 1 mg/kg HCB dose level. Cortical area and the proportion of the total area of the bone that the cortex occupied were significantly increased at the three higher dose levels. Medullary cavity area was significantly increased at the 0.1 mg/kg dose level but significantly decreased at the 2 higher dose levels of HCB. The right femur was significantly predominant to the left femur in weight, volume, and density through all dosing regimens. HCB exposure significantly altered bone morphometry and strength characteristics in the Fischer 344 rat.

Biopsychosocial characteristics of children who later murder: a prospective study.

The authors document the childhood neuropsychiatric and family characteristics of nine male subjects who were clinically evaluated as adolescents and were later arrested for murder. Those subjects are compared with 24 incarcerated delinquents who did not go on to commit violent offenses. The future murderers displayed a constellation of biopsychosocial characteristics that included psychotic symptoms, major neurological impairment, a psychotic first-degree relative, violent acts during childhood, and severe physical abuse. The authors relate this combination of factors to prediction of violence and discuss ethical issues that are involved in intervention to prevent violence.