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[Effect associated with transfer develop menopause age and monthly period duration of professional women].
BACKGROUND Coadministration of artemether-lumefantrine and efavirenz has been shown to result in significant interactions. The influence of functional genetic polymorphisms in selected CYPs on the magnitude of this interaction was investigated in pregnant and nonpregnant adults. METHOD A standard 3-day regimen of artemether-lumefantrine was administered to each patient on steady-state efavirenz-based antiretroviral therapy (ART). Pharmacokinetic parameters were obtained from intensive plasma concentration-time data. Genotyping data were tested for compliance with Hardy-Weinberg equilibrium by Chi-square test. Linear regressions, Mann-Whitney U-test or Kruskal-Wallis tests were conducted to examine the association of lumefantrine plasma level with CYP2B6 c.516G>T, NR1I3 152c-1089T>C, CYP2B6 c.983T>C, CYP3A5*3 and CYP3A4*22. RESULTS Among a total of 69 malaria-HIV coinfected patients (34 nonpregnant and 35 pregnant), median (interquartile range) age was 33 (27-36.5) years and body weight was 59.5 (50-67.5) kg. eles. This warrants further investigations 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. 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.OBJECTIVE In patients with non-Hodgkin lymphoma (NHL), we investigated F FDG PET/computed tomography (CT) parameters, clinical findings, laboratory parameters, and bone marrow involvement (BMI) status for predictive methods in progression-free survival (PFS) and overall survival (OS), and whether F FDG PET/CT could take the place of bone marrow biopsy (BMB). METHODS The performance of F FDG PET/CT (BMPET) was evaluated. The prognostic value of maximum standardized uptake value (SUVmax), metabolic tumor volume (MTV), stage, international prognostic index (IPI) score, IPI risk, lactate dehydrogenase (LDH), B2 microglobulin, Ki67 proliferation index, and the presence of BMI was evaluated for OS and PFS. Kaplan-Meier curves were drawn for each designated cutoff value, and 5-year PFS and 7-year OS were evaluated using log-rank analysis. RESULTS The sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) and accuracy of BMPET and BMB to identify BMI were 69, 100, 86.1, 80, 100%, and 81.6, 100, 92.5, 89, 100%, respectively. Tanespimycin The sensitivity, specificity, PPV, NPV, and accuracy of BMPET in patients with Ki67- proliferation index >25% were all 100%. BMPET, IPI risk, MTV, and LDH were found to be independent prognostic predictors for PFS, whereas BMPET, SUVmax, and MTV for OS. Five-year PFS analysis estimated as follows BMPET (+) = 22%, BMPET (-) = 80%, LDH ≤ 437 (U/L) = 86%, LDH > 437 (U/L) = 51%, MTV ≤ 56 (cm) = 87%, MTV > 56 (cm) = 49%, low IPI risk = 87%, intermediate IPI risk = 69%, high IPI risk = 25%. Seven-year OS analysis was found as SUVmax ≤ 17.6 = 80%, SUVmax > 17.6 = 48%, MTV ≤ 56 (cm) = 84.4%, MTV > 56 (cm) = 45.8%, BMPET (-) = 72.5%, BMPET (+) = 42%. CONCLUSION In the Ki-67 proliferation index > 25% group, F FDG PET/CT was able to differentiate BMI independently from NHL subgroups. We recommend using this method with large patient groups. MTV and BMPET were independent prognostic indicators for OS and PFS and may help to determine high-risk patients.OBJECTIVE Timely pre-hospital diagnosis and treatment of acute coronary syndrome (ACS) are required to achieve optimal outcomes. Clinical decision support systems (CDSS) are platforms designed to integrate multiple data and can aid with management decisions in the pre-hospital environment. The review aim was to describe the accuracy of CDSS and individual components in the pre-hospital ACS management. METHODS This systematic review examined the current literature regarding the accuracy of CDSS for ACS in the pre-hospital setting, the influence of computer-aided decision making and of four components electrocardiogram, biomarkers, patient history and examination findings. The impact of these components on sensitivity, specificity, positive and negative predictive values was assessed. RESULTS A total of 11,439 articles were identified from a search of databases, of which 199 were screened against the eligibility criteria. Eight studies were found to meet the eligibility and quality criteria. There was marked heterogeneity between studies which precluded formal meta-analysis. However, individual components analysis found that patient history led to significant improvement in the sensitivity and negative predictive values. CDSS which incorporated all four components tended to show higher sensitivities and negative predictive values. CDSS incorporating computer-aided electrocardiogram diagnosis showed higher specificities and positive predictive values. CONCLUSIONS Although heterogeneity precluded meta-analysis, this review emphasises the potential of ACS CDSS in pre-hospital environments that incorporate patient history in addition to integration of multiple components. The higher sensitivity of certain components, along with higher specificity of computer-aided decision-making, highlights the opportunity for developing an integrated algorithm with computer-aided decision support.
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