Prognostic index to identify patients who may not benefit from whole brain radiotherapy for multiple brain metastases from lung cancer

Palliative whole brain radiotherapy (WBRT) is often recommended in the management of multiple brain metastases. Allowing for WBRT waiting time, duration of the WBRT course and time to clinical response, it may take 6 weeks from the point of initial assessment for a benefit from WBRT to manifest. Patients who die within 6 weeks (‘early death’) may not benefit from WBRT and may instead experience a decline in quality of life. This study aimed to develop a prognostic index (PI) that identifies the subset of patients with lung cancer with multiple brain metastases who may not benefit from WBRT because of ‘early death’. The medical records of patients with lung cancer who had WBRT recommended for multiple brain metastases over a 10-year period were retrospectively reviewed. Patients were classified as either having died within 6 weeks or having lived beyond 6 weeks. Potential prognostic indicators were evaluated for correlation with ‘early death’. A PI was constructed by modelling the survival classification to determine the contribution of these factors towards shortened survival. Of the 275 patients recommended WBRT, 64 (23.22%) died within 6 weeks. The main prognostic factor predicting early death was Eastern Cooperative Oncology Group (ECOG) status >2. Patients with a high PI score (>13) were at higher risk of ‘early death’. Twenty-three per cent of patients died prior to benefit from WBRT. ECOG status was the most predictive for ‘early death’. Other factors may also contribute towards a poor outcome. With further refinement and validation, the PI could be a valuable clinical decision tool.     

Prospective study of short stature and newly diagnosed asthma in women.

The authors tested the hypothesis that short stature predicts adult-onset asthma independent of obesity among women in the Nurses' Health Study. Height, weight, and physician-diagnosed asthma were assessed with validated questionnaire items. Proportional hazard models adjusted separately for weight and body mass index. The rate of newly diagnosed asthma was 1.55 times greater in the shortest versus the tallest quintile after adjustment for weight (95% CI, 1.26-1.91). After adjustment for body mass index, the rate ratio was 1.16 (95% CI, 0.94-1.42). Short stature predicted adult-onset asthma in a large cohort of women, but this association was not independent of obesity.     

Acetylcholinesterase inhibitors may improve myelin integrity.

Recent clinical trials have revealed that cholinergic treatments are efficacious in a wide spectrum of neuropsychiatric disorders that span the entire human lifespan and include disorders without cholinergic deficits. Furthermore, some clinical and epidemiological data suggest that cholinergic treatments have disease modifying/preventive effects. It is proposed that these observations can be usefully understood in a myelin-centered model of the human brain. The model proposes that the human brain's extensive myelination is the central evolutionary change that defines our uniqueness as a species and our unique vulnerability to highly prevalent neuropsychiatric disorders. Within the framework of this model the clinical, biochemical, and epidemiologic data can be reinterpreted to suggest that nonsynaptic effects of cholinergic treatments on the process of myelination and myelin repair contributes to their mechanism of action and especially to their disease modifying/preventive effects. The ability to test the model in human populations with safe and noninvasive imaging technologies makes it possible to undertake novel clinical trial efforts directed at primary prevention of some of the most prevalent and devastating of human disorders.     

Influence on binding of third-order torque to second-order angulation

Using an earlier model, which described the critical contact angle for binding from second-order angulation alone, a more generalized model is derived that combines the effects of angulation and torque. From this vantage point, the onset of binding is evaluated for 3 scenarios: second-order angulation alone, third-order torque only, and a combination of second-order angulation and third-order torque. These scenarios are detailed by plotting the critical contact angle for binding against the torque angle as a function of 10 wire dimensions (16 x 16, 16 x 22, 17 x 17, 17 x 22, 17 x 25, 18 x 18, 18 x 22, 18 x 25, 19 x 25, and 21 x 25 mil), 4 bracket widths (70, 100, 130, and 160 mil), and 4 bracket slots (18, 20.5, 22, and 24.5 mil). From these plots, we learn that each wire base dimension (eg, an 18-mil base as found in 18 x 18-mil, 18 x 22-mil and 18 x 25-mil archwires) has a common maximum critical contact angle for binding. Moreover, each wire-slot combination has a common maximum torque angle, which is independent of bracket width. Finally, we learn that archwire-bracket combinations that use a metric 0.5-mm slot might have some advantages with regard to torquing--given the current philosophy that light, continuous forces are more favorable.