Kilicgiles8421

estigations of other drug-drug interactions for optimising dosing in genetically defined subgroups, particularly during drug development.OBJECTIVES Pharmacogenomic testing (PGX) implementation is rapidly expanding, including pre-emptive testing funded by health systems. PGX continues to develop an evidence base that it saves money and improves clinical outcomes. Identifying the potential impact of pre-emptive testing in specific populations may aid in the development of a business case. METHODS We utilized a software tool that can evaluate patient drug lists and identified groups of patients most likely to benefit from implementation of a PGX testing program in a major medical system population. RESULTS Medication lists were obtained for sixteen patient groups with a total of 82 613 patients. The percent of patients in each group with testing 'Recommended', 'Strongly recommended', or 'Required' ranged from 12.7% in the outpatient pediatric psychiatry group to 75.7% in the any adult inpatient age >50 years group. Some of the highest yield drugs identified were citalopram, simvastatin, escitalopram, metoprolol, clopidogrel, tramadol, and ondansetron. CONCLUSION We demonstrate a significant number of patients in each group may have benefit, but targeting certain ones for pre-emptive testing may result in the initial highest yield for a health system.Injectable biologics have attracted considerable interest in the field of musculoskeletal medicine. Biologics encompass a broad and diverse group of human tissue-derived therapeutics. The most commonly reported biologics for use in musculoskeletal conditions include platelet-rich plasma (PRP), bone marrow aspirate concentrate (BMAC), mesenchymal stem cells (MSCs), micro-fragmented fat, stromal vascular fraction (SVF), amniotic membrane-based products and autologous conditioned serum (ACS). The benefits of biologics in tissue healing and regeneration are thought to be derived from their trophic, paracrine and immunomodulatory functions. The purpose of this review is to define commonly used injectable biologics and to appraise current evidence on its efficacy in the treatment of musculoskeletal disease.OBJECTIVE To evaluate the efficacy of transcutaneous neuromuscular electrical stimulation (NMES) on swallowing disorders. DESIGN MEDLINE/PubMed, Embase, CENTRAL, Web of science and PEDro were searched from their earliest record to 1 August 2019. All randomized controlled trials (RCT) and quasi-RCT were identified, which compared the efficacy of NMES plus traditional therapy (TT) versus TT in swallowing function. The GRADE approach was applied to evaluate the quality of evidence. RESULTS Eight RCTs and three quasi-RCTs were included. These studies demonstrated a significant, moderate pooled effect size (SMD = 0.62; 95% CI = 0.06, 1.17). Studies stimulating suprahyoid muscle groups revealed a negative SMD of 0.17 (95% CI -0.42, 0.08), whereas large effect size was observed in studies stimulating the infrahyoid muscle groups (SMD= 0.89; 95% CI 0.47, 1.30) and stimulating the supra- and infrahyoid muscle groups (SMD= 1.4; 95% CI =1.07, 1.74). Stimulation lasting 45 minutes or less showed a large, significant pooled effect size (SMD= 0.89; 95% CI =0.58, 1.20). The quality of evidences was rated as low to very low. CONCLUSION There is no firm evidence to conclude on the efficacy of NMES on swallowing disorders. Larger scale and well-designed RCTs are needed to reach robust conclusions.OBJECTIVE Evidence is limited regarding clinical factors associated with ambulation status over the lifespan of individuals with myelomeningocele (MMC). We used longitudinal data from the National Spina Bifida Patient Registry to model population-level variation in ambulation over time and hypothesized that effects of clinical factors associated with ambulation would vary by age and motor level. DESIGN A population-averaged generalized estimating equation was used to estimate the probability of independent ambulation. Model predictors included time (age), race, ethnicity, gender, insurance, and interactions between time, motor level, and the number of orthopedic, non-cerebral shunt neurosurgeries, and cerebral shunt neurosurgeries. RESULTS The study cohort included 5,371 participants with MMC. see more A change from sacral to low-lumbar motor level initially reduced the odds of independent ambulation (OR=0.24, 95% CI 0.15-0.38) but became insignificant with increasing age. Surgery count was associated with decreased odds of independent ambulation (orthopedic OR=0.65, 95% CI 0.50-0.85; non-cerebral shunt neurosurgery OR=0.65, 95% CI 0.51-0.84; cerebral shunt OR=0.90, 95% CI0.83-0.98), with increasing effects seen at lower motor levels. CONCLUSION Our findings suggest that effects of several commonly accepted predictors of ambulation status vary with time. As the MMC population ages, it becomes increasingly important that study design account for this time varying nature of clinical reality.The aim of this study is to investigate the association between tumor mutation burden (TMB) and survival in non-small cell lung cancer (NSCLC) patients with anti-programmed cell death protein 1 and anti-programmed death-ligand 1 blockade. Two retrospective cohorts and The Cancer Genome Atlas NSCLC data set were included in this study. The restricted cubic spline analysis was used to explore the association between TMB and survival. The cutoff values for TMB were determined by X-tile software. Primary outcomes were overall survival (OS). The associations between TMB and intratumor heterogeneity, number of segments, fraction of genome alterations, aneuploidy score, and T-cell populations were also investigated. In the restricted cubic spline plots, TMB showed an inverted U-shaped curve with OS. The median OS in the low TMB group was significantly longer than those in the medium TMB group. In The Cancer Genome Atlas NSCLC data set, low TMB was also associated with longer OS in comparison with medium TMB. Furthermore, NSCLC patients with low TMB had significantly lower intratumor heterogeneity, number of segments, fraction of genome alterations, aneuploidy score, T-helper type 2 (Th2) cells, and CD8 T cells, but higher levels of Th1 and Th17 cells. Low TMB might be a prognostic factor for NSCLC patients receiving anti-programmed cell death protein 1/programmed death-ligand 1 immunotherapy.