Is phenytoin contraindicated in patients receiving cranial irradiation ?

Three recent publications have reported the development of erythema multiforme and Stevens-Johnson syndrome in patients receiving cranial irradiation and sodium phenytoin. Some authors have recommended that patients receiving whole brain radiation therapy and who have had seizures should not be prescribed phenytoin but an alternative anticonvulsant. This article reviews the current literature pertaining to the development of this potentially lethal complication in patients receiving whole brain radiation and phenytoin, with reference to the single recorded case of Stevens-Johnson syndrome in a patient receiving cranial irradiation and phenytoin in Auckland, New Zealand. While the clinical picture in the 16 patients reported in the literature and the current case report differed from the classical form of erythema multiforme, a similar pattern of presentation and outcome appeared in all patients reviewed, suggesting that the combination of phenytoin, cranial irradiation and the gradual reduction of concomitant steroids seem to lead to the development of erythema multiforme and/or Stevens-Johnson syndrome. The data presented, although sparse, suggest that phenytoin should not be prescribed in patients receiving cranial irradiation.     

Randomized versus nonrandomized studies of alcohol treatment: participants,methodological features and posttreatment functioning

OBJECTIVE: Randomized trials are widely acknowledged to be the most rigorous method to estimate the comparative efficacy of treatments. Concerns have been raised, however, about the generalizability of findings from randomized trials of alcohol treatments to actual treatment circumstances, and about the internal validity of randomized trials. The purpose of this review was to compare the participants, methodological features and posttreatment functioning in randomized and nonrandomized studies of alcohol treatment. METHOD: Using systematic literature search techniques, 232 randomized and 92 nonrandomized trials published between 1970 and 1998 were identified. Each investigation was scored on a methodological quality scale, participant characteristics were recorded and participants' follow-up abstinence and improvement rates were calculated. RESULTS: Randomized investigations were more likely to use participant selection criteria, to use recognized diagnostic criteria to characterize participants and to stringently implement treatment and assess outcomes. Nonrandomized investigations were more likely to assess outcomes in higher proportions of participants over longer follow-up periods and to have greater statistical power t o detect treatment effects. Abstinence and improvementrates following active treatment were similar for the two types of design (proportion abstinent: 0.35 and 0.39, and proportion improved: 0.52 and 0.54, for randomized and nonrandomized trials, respectively), even when differences in study features were controlled. CONCLUSIONS: The contrasting strengths and weaknesses of randomized and nonrandomized studies suggest that they should be considered as complementary forms of treatment evaluation, in the alcohol treatment field and perhaps more generally.     

More care for a limited budget; a case for a better use of the efficiency criteria

A systematic consideration of the cost-effectiveness in decisions concerning the financing and implementation of healthcare technologies would contribute to the efficiency of the Dutch healthcare system. This consideration applies to the initial decision to finance a project, the periodic testing of this on the basis of practice data and the policy to promote a cost-effective approach in daily practice (via practice guidelines). Bearing in mind that the government has decided to allocate few additional resources to healthcare, it should undertake measures to ensure the systematic use of such information in these steps. The National Institute for Clinical Excellence (NICE) in the United Kingdom can serve as an example, where broadly supported guidelines are drawn up with systematic attention for the cost-effectiveness and the implications for healthcare. Within this context the question arises as to whether a Dutch variant of NICE is needed.     

Interhemispheric reorganization of motor hand function to the primary motor cortex predicted with functional magnetic resonance imaging and transcranial magnetic stimulation

The objective of this study was presurgical assessment of reorganization of motor hand function in an 11-year-old girl with intractable epilepsy and a right-sided hemiplegia resulting from an extensive perinatal left hemispheric stroke. Prior to a left functional hemispherectomy, functional magnetic resonance imaging (MRI) showed that both nonparetic and paretic motor hand function predominantly activated the right primary motor cortex, whereas no activation was found in the left hemisphere. Transcranial magnetic stimulation of the right central area yielded responses in both the nonparetic and the paretic hand, whereas no responses were obtained after stimulation of the affected hemisphere. Both techniques indicated that motor function was mediated by corticospinal fibers originating from the undamaged (primary) motor cortex and predicted no further loss of motor hand function after surgery. Indeed, subsequent functional hemispherectomy induced no new sensorimotor deficits. Functional MRI was repeated 22 months after surgery and matched preoperative sensorimotor functional MRI findings, confirming reorganization of the primary motor cortex. No additional reorganization was introduced by surgery.     

Constitutive overexpression of cyclin D1 but not cyclin E confers acute resistance to antiestrogens in T-47D breast cancer cells

Cyclin D1 and cyclin E are overexpressed in approximately 45% and 30% of breast cancers, respectively, and adverse associations with patient outcome have been reported. The potential roles of cyclin D1 and cyclin E expression as markers of therapeutic responsiveness to the pure steroidal antiestrogen ICI 182780 were investigated using T-47D breast cancer cell lines constitutively overexpressing cyclin D1 or cyclin E. Measurement of S phase fraction, phosphorylation states of the retinoblastoma protein, and cyclin E-cyclin-dependent kinase (Cdk) 2 activity demonstrated that overexpression of cyclin D1 decreased sensitivity to antiestrogen inhibition at 24 and 48 h. Overexpression of cyclin E produced a less pronounced early cell cycle effect indicating only partial resistance to antiestrogen inhibition in the short-term. In ICI 182780-treated cyclin D1-overexpressing cells, sufficient Cdk activity was retained to allow retinoblastoma protein phosphorylation and cell proliferation, despite an increase in the association of p21 and p27 with cyclin D1-Cdk4/6 and cyclin E-Cdk2 complexes. After longer-term (>7 days) treatment, antiestrogens inhibited colony growth in cyclin D1- or cyclin E-overexpressing breast cancer cells, but with an approximately 2-2.5-fold decrease in dose sensitivity. This was associated with a fall in cyclin D1 levels, a reduction in the half-life of cyclin D1 protein and a decline in cyclin E-Cdk2 activity in cyclin D1-overexpressing cells, and the maintenance of cyclin E-p27 association in the cyclin E-overexpressing cells. These data confirm that cyclin D1 expression and cyclin E-p27 association play important roles in antiestrogen action, and suggest that cyclin D1 or cyclin E overexpression has subtle effects on antiestrogen sensitivity. Additional studies to elucidate the contribution of alterations in cyclin D1 stability to antiestrogen action and to assess the relationship between antiestrogen sensitivity and expression of cyclin D1, cyclin E, or p27 in a clinical setting are required.     

Prediction of post-traumatic complaints after mild traumatic brain injury: early symptoms and biochemical markers

OBJECTIVES: To identify parameters at first presentation after mild traumatic brain injury (MTBI) that are predictive of the severity of post-traumatic complaints (PTC) after six months. Early recognition of patients with MTBI who are at risk of developing PTC would be useful because early follow up at the outpatient clinic may help to reduce the severity of these complaints in the long run. METHODS: The presence of symptoms in the emergency room (ER) (headache, dizziness, nausea, vomiting, and neck pain) and biochemical markers (neurone specific enolase and S-100B) in serum were assessed as possible predictive variables for the severity of PTC. Outcome variables were the severity of 16 PTC six months after the trauma. RESULT: After six months, the severity of most complaints had declined to pretrauma levels but medians for headache, dizziness, and drowsiness were still increased. In a series of 79 patients, 22 (28%) reported one or more PTC after six months. After adjustment for baseline variables, an at least twofold increased severity of all PTC subgroups was reported by those patients reporting headache, dizziness, or nausea in the ER. A twofold increased severity of "cognitive" and "vegetative" PTC was also found in those with increased concentrations of biochemical serum markers at first presentation. The prevalence of full recovery after six months increased from 50% in patients with three symptoms to 78% in those with no symptoms in the ER. Inclusion of biochemical markers showed that all 10 patients with no symptoms in the ER and normal markers recovered fully. CONCLUSIONS: The presence of headache, dizziness, or nausea in the ER after MTBI is strongly associated with the severity of most PTC after six months. Identifying MTBI patients in the ER without headache, dizziness, nausea, or increased serum marker concentrations may be a promising strategy for predicting a good outcome.     

Cost effectiveness of combined spa–exercise therapy in ankylosing spondylitis: A randomized controlled trial

Objective

To evaluate the cost effectiveness and cost utility of a 3‐week course of combined spa therapy and exercise therapy in addition to standard treatment consisting of antiinflammatory drugs and weekly group physical therapy in ankylosing spondylitis (AS) patients.

Methods

A total of 120 Dutch outpatients with AS were randomly allocated into 3 groups of 40 patients each. Group 1 was treated in a spa resort in Bad Hofgastein, Austria; group 2 in a spa resort in Arcen, The Netherlands. The control group stayed at home and continued their usual activities and standard treatment during the intervention weeks. After the intervention, all patients followed weekly group physical therapy. The total study period was 40 weeks. Effectiveness of the intervention was assessed by functional ability using the Bath Ankylosing Spondylitis Function Index (BASFI). Utilities were measured with the EuroQoL (EQ‐5D_utility). A time‐integrated summary score defined the clinical effects (BASFI‐area under the curve [AUC]) and utilities (EQ‐5D_utility‐AUC) over time. Both direct (health care and non‐health care) and indirect costs were included. Resource utilization and absence from work were registered weekly by the patients in a diary. All costs were calculated from a societal perspective.

Results

A total of 111 patients completed the diary. The between‐group difference for the BASFI‐AUC was 1.0 (95% confidence interval [95% CI] 0.4–1.6; P = 0.001) for group 1 versus controls, and 0.6 (95% CI 0.1–1.1; P = 0.020) for group 2 versus controls. The between‐group difference for EQ‐5D_utility‐AUC was 0.17 (95% CI 0.09–0.25; P < 0.001) for group 1 versus controls, and 0.08 (95% CI 0.00–0.15; P = 0.04) for group 2 versus controls. The mean total costs per patient (including costs for spa therapy) in Euros (€) during the study period were €3,023 for group 1, €3,240 for group 2, and €1,754 for the control group. The incremental cost‐effectiveness ratio per unit effect gained in functional ability (0–10 scale) was €1,269 (95% CI 497–3,316) for group 1, and €2,477 (95% CI 601–12,098) for group 2. The costs per quality‐adjusted life year gained were €7,465 (95% CI 3,294–14,686) for group 1, and €18,575 (95% CI 3,678–114,257) for group 2.

Conclusion

Combined spa–exercise therapy besides standard treatment with drugs and weekly group physical therapy is more effective and shows favorable cost‐effectiveness and cost‐utility ratios compared with standard treatment alone in patients with AS.

     

氨溴索治疗小儿毛细支气管炎77例

1临床资料2002-01／2004-02收治临床症状典型且无并发症毛细支气管炎患儿116例，发病年龄3-24(平均8．4)mo，男61例，女55例，按就诊时间顺序分为氨溴索雾化吸入组(观察组)、氨溴索静脉点滴组(对照Ⅰ组)和常规治疗组(对照Ⅱ组)，分别为38，39，39例．常规治疗组给予头孢噻肟钠50mg／kg，2／d及穿琥宁80-120mg／d分别静脉滴注及对症治疗(如吸氧、镇静、退热等处理)；观察组在常规治疗的基础上加用氨溴索4mg加生理盐水10mL超声雾化吸入10～15min，2／d；     

Airway and body surface sensors for triggering in neonatal ventilation

Failure of neonatal patient triggered ventilation may reflect a delay in delivery of flow relative to the inspiratory effort of the infant. Transmission of diaphragmatic contraction to the sensor site (patient delay) and further transmission to and within the sensing device (device delay) both contribute to the delay in triggering. Patient and device delays were studied for different sensing systems in 36 infants, 24 of whom were intubated. Device delay was long (<40 ms) with a conventional apnoea monitor compared with sensors placed at the airway opening (2 ms), the inspiratory (12 ms) and expiratory (3 ms) pressure transducers of the ventilator, the Graseby capsule (8 ms), strain gauges (3 ms) and oesophageal pressure (6 ms). In near normal infants, the sum of patient and device delays for the latter sensors was less than 20 ms and a minor component of the total delay. However, in severe lung disease the total delay may be more than 100ms even for airway sensors.