A robust quantitative structure-activity relationship modelling of influenza neuraminidase a/PR/8/34 (H1N1) inhibitors based on the rank-bridge estimator.

Linear regression model is frequently encountered in quantitative structure-activity relationship (QSAR) modelling. The traditional estimation of regression model parameters is based on the normal assumption of the response variable (biological activity) and therefore, it is sensitive to outliers or heavy-tailed distributions. Robust penalized regression methods have been given considerable attention because they combine the robust estimation method with penalty terms to perform QSAR parameter estimation and variable selection (descriptor selection) simultaneously. In this paper, based on bridge penalty, a robust QSAR model of the influenza neuraminidase a/PR/8/34 (H1N1) inhibitors is proposed as a resistant method to the existence of outliers or heavy-tailed errors. The basic idea is to combine the rank regression and the bridge penalty together to produce the rank-bridge method. The rank-bridge model is internally and externally validated based on Qint2 , QLGO2 , QBoot2 , MSEtrain , Y-randomization test, Qext2 , MSEtest and the applicability domain (AD). The validation results indicate that the rank-bridge model is robust and not due to chance correlation. In addition, the results indicate that the descriptor selection and prediction performance of the rank-bridge model for training dataset outperforms the other two used modelling methods. Rank-bridge model shows the highest Qint2 , QLGO2 and QBoot2 , and the lowest MSEtrain . For the test dataset, rank-bridge model shows higher external validation value ( Qext2 = 0.824), and lower value of MSEtest compared with the other methods, indicating its higher predictive ability.

Long-term pattern of opioid prescriptions after femoral shaft fractures.

BACKGROUND: The use of opioids in non-cancer-related pain following skeletal trauma is controversial due to the presumed risk of dose escalation and dependence. We therefore examined the pattern of opioid prescriptions, that is, those actually dispensed, in patients with femoral shaft fractures. METHODS: We analysed data from the Swedish National Hospital Discharge Register and the Swedish Prescribed Drug Register between 2005 and 2008. RESULTS: We identified 1471 patients with isolated femoral shaft fractures. The median age was 75 (16-102) years and 56% were female. In this cohort, 891 patients (61%) received dispensed opioid prescriptions during a median follow-up of 20 months (interquartile range 11-32). In the age- and sex-matched comparison cohort (7339 individuals) without fracture, 25% had opioid prescriptions dispensed during the same period. The proportions of patients receiving opioid analgesics at 6 and 12 months after the fracture were 45% (95% CI 42-49) and 36% (32-39), respectively. The median daily morphine equivalent dose (MED) was between 15 and 17 mg 1-12 months post-fracture. After 3 months, less than 5% used prescription doses higher than 20 mg MED per day. Older age (≥ 70 compared with < 70 years) was a significant predictor of earlier discontinuation of opioid use (Hazard ratio [HR] 1.9). CONCLUSION: A notable proportion of patients continued to receive dispensed prescriptions for opioids for over 6 months (45%) and more than a third of them (36%) continued treatment for at least 12 months. However, the risk of dose escalation seems to be small in opioid-naïve patients.

Brace treatment in neuromuscular spine deformity.

We reviewed 90 consecutive patients with various neuromuscular diseases and a progressive spine deformity treated with a prefabricated Boston-type underarm corrective brace. Of these, 38 patients had spastic tetraplegia; seven, syndrome-related muscular hypertonia; 24, muscular hypotonia; and 21, myelomeningocele. The mean age at the treatment start was 9.2 years (range, 1.4-17.7 years). Twenty-four were ambulating and 66 wheelchair-bound. Hypotonia was the dominant type of muscle involvement in 49, spasticity in 28, and athetosis in 13 patients. The mean pretreatment Cobb angle was 47 degrees, with a range from 23 to 95 degrees. The mean brace-induced Cobb-angle correction was 60%, thus well comparable to that in idiopathic scoliosis. However, this did not predict favorable treatment results. At the follow-up, on average 3.1 years (range, 1-5.5 years) after weaning from the brace, the brace treatment was successful in 23 patients. Successful was defined as <10 degrees curve progression during the observation time and a good brace compliance. Forty-one patients discontinued the brace treatment, and 19 progressed despite adequate brace wear. Five patients are still in treatment, and two have died. Successful treatment was seen in ambulating patients with muscle hypotonia and short thoracolumbar/lumbar curves measuring <40 degrees as well as in nonambulating patients with spastic short lumbar curves. These types of neuromuscular scoliosis may be the only ones to respond to brace treatment. In other cases, the brace treatment cannot be expected to have a lasting corrective effect although it can be used as sitting support.