Cost-effectiveness of a clinical medication review in vulnerable older patients at hospital discharge,a randomized controlled trial

International Journal of Clinical Pharmacy - Background Drug-related problems (DRP) following hospital discharge may cause morbidity, mortality and hospital re-admissions. It is unclear whether a...     

Larotrectinib for the treatment of TRK fusion solid tumors

Introduction: TRK fusions occur across a wide range of cancers in children and adults. These fusions drive constitutive expression and ligand-independent activation of the TRK kinase and are oncogenic. Larotrectinib is the first highly potent and selective small molecule ATP competitive inhibitor of all three TRK kinases to enter clinical development.

Areas covered: This review covers the current preclinical and clinical evidence for TRK inhibitors for TRK fusion cancers, focusing on larotrectinib.

Expert commentary: Larotrectinib has demonstrated a remarkable 75% centrally confirmed objective response rate in patients with TRK fusion cancers in phase 1 and phase 2 clinical trials with generally mild side effects. Responses appear independent of the patient’s age, underlying histology, and specific fusion partner and are durable in many patients. Larotrectinib is likely to be the first FDA-approved histology-agnostic molecularly targeted therapy. The evolving role of molecular profiling of advanced cancers is discussed.     

Treatment of skeletal open bite using a navigation system: CAD/CAM osteotomy and drilling guides combined with pre-bent titanium plates

Severe skeletal open bite associated with posterior vertical maxillary excess and mandibular deformity is considered a difficult problem in orthodontic and surgical treatment. This study used a navigation system for the correction of severe skeletal open bite in order to accurately transfer the virtual plan to the actual operation and achieve precise rigid internal fixation in bimaxillary osteotomies of the jaws. Twelve patients with a severe skeletal open bite associated with vertical maxillary excess and mandibular deformity were recruited. All patients underwent Le Fort I osteotomy and bilateral sagittal split ramus osteotomy with the guidance of this navigation system. Computed tomography and cephalometric examinations were performed to evaluate the correction of the deformity. Deviations between the simulated plan and actual postoperative outcome were measured to determine the precision of the surgery. Satisfactory and stable results were achieved in all patients postoperatively, without complications or relapse during follow-up. Photographs and cephalometric evaluations showed that the facial profile and occlusion were improved. Assessment of the deviations between the simulated plan and actual postoperative outcome showed that the navigation system can precisely transfer the virtual plan to the actual operation. The results suggest that the navigation system can accurately transfer the virtual plan to the actual operation during bimaxillary jaw osteotomies, without relapse, in patients with a severe skeletal open bite.     

End-organ effects of primary hyperparathyroidism: A population-based study

Background

Patients with primary hyperparathyroidism are at risk for skeletal and renal end-organ damage.

The Chinese National Twin Registry: a ‘gold mine’ for scientific research

The Chinese National Twin Registry (CNTR) currently includes data from 61 566 twin pair from 11 provinces or cities in China. Of these, 31 705, 15 060 and 13 531 pairs are monozygotic, same‐sex dizygotic and opposite‐sex dizygotic pairs, respectively, determined by opposite sex or intrapair similarity. Since its establishment in 2001, the CNTR has provided an important resource for analysing genetic and environmental influences on chronic diseases especially cardiovascular diseases. Recently, the CNTR has focused on collecting biologic specimens from disease‐concordant or disease‐discordant twin pairs or from twin pairs reared apart. More than 8000 pairs of these twins have been registered, and blood samples have been collected from more than 1500 pairs. In this review, we summarize the main findings from univariate and multivariate genetic effects analyses, gene–environment interaction studies, omics studies exploring DNA methylation and metabolomic markers associated with phenotypes. There remains further scope for CNTR research and data mining. The plan for future development of the CNTR is described. The CNTR welcomes worldwide collaboration.     

Associations of Early Age of First Intoxication with Past Year Drinking Contexts and Problems

Background: Mechanisms underlying associations between early drinking and problems are largely unknown. Objectives: We investigated (a) associations between early age of first intoxication (≤15?years) and past year drinking in different contexts and (b) whether early age of first intoxication is differentially associated with problems in these contexts. Methods: We used survey data collected in 2013–2014 from 405 past-year adolescent drinkers in 24 midsized California cities. Data included demographics; drinking behaviors; age of first intoxication; frequency of being at and drinking at restaurants, bars/nightclubs, outdoor places, and home; and problems. We used multilevel logistic and negative binomial models to account for the clustering of adolescents within cities. Probabilities were corrected to maintain family-wise error rates. Results: Early age of first intoxication was associated with a 120% increase in the odds of drinking at outdoor settings (OR = 2.20, p_c < .05). Early age of first intoxication was associated with increased numbers of problems related to drinking in restaurants (IRR = 5.72, p_c < .001), outdoor settings (IRR = 3.40, p_c < .001), and homes (IRR = 2.84, p_c < .001). Later intoxication (≥16?years) was not significantly associated with increased drinking or problems in any of these contexts. Conclusions: Results suggest that underage drinkers who report early intoxication are more likely to drink at outdoor settings, but not other contexts. However, they may differentially experience drinking problems across contexts. To target youths who have experienced intoxication at an early age and to reduce problems, prevention interventions should focus on outdoor settings.