Monoamine oxidase A (MAO A) is located on the X chromosome and metabolizes biogenic amines including dopamine, norepinephrine and serotonin. A functional promoter-region polymorphism of this gene has been described that has been studied in a number of mental illnesses but not in attention deficit hyperactivity disorder (ADHD). In the current study, we examined the MAO A promoter-region polymorphism initially in 133 triads and observed preferential transmission of the long alleles from 74 heterozygote mothers to ADHD probands ( 2 = 4.37, P = 0.036, df = 1). We also examined the role of this polymorphism in a computerized continuous performance test, the TOVA. Significant differences were observed on errors of commission ( 2 = 7.021, P = 0.008) and patients carrying the long MAO A allele made significantly more such errors. Errors of commission are a measure of impulsivity. However, following Ritalin (methylphenidate) administration the association between this polymorphism and errors of commission was markedly attenuated and no longer significant at the P Ͻ 0.05 level. We also analyzed the provisional association by the case-control design. A significant difference in allele frequency was observed between 110 male probands vs 202 male controls (Pearson 2 = 7.94, P = 0.047). Similarly results were obtained when 19 female probands were compared to female controls (genotype 2 = 21.28; P = 0.0032, 3 df and allele 2 = 30.88, P = 0.0007, 2 df). All three complementary approaches employed (family-based, case-control and quantitative trait design) suggest a role for the MAO A promoter-region polymorphism in conferring risk for ADHD in our patient population.
The association between anticholinergic burden and constipation is not well defined and documented; for this reason, a systematic review was carried out in five databases (Medline, Embase, Cochrane Central Register of Controlled Trials, CINAHL, and Scopus), including studies assessing the correlation between anticholinergic burden, and constipation between January 2006 and December 2020. Data extraction was conducted independently by two researchers. Abstracts and titles were reviewed to determine eligibility for review with eligible articles read in full. From 2507 identified articles, 11 were selected for this review: six cross-sectional studies, four retrospective cohort studies, and a post hoc analysis of a randomized clinical trial. Overall, nine studies reported at least one statistical association between anticholinergic burden and constipation, finding 13 positive results out of 24 association measurements. A total of 211,921 patients were studied. The association between constipation and anticholinergic burden could be demonstrated in studies including 207,795 patients. Most studies were not designed to find differences in constipation prevalence and did not adjust the results by confounding factors. Our findings suggest that a correlation between anticholinergic burden and constipation exists. Higher quality-evidence studies are needed, including analysis that considers confounding factors, such as other non-pharmacological causes of constipation.
The KEYNOTE-024 clinical trial showed promising results for pembrolizumab in the first-line of treatment of advanced non-small-cell lung cancer (NSCLC). However, the profile of patients in real-world practice differs from those included in this clinical trial. Here, an observational single-center retrospective study was performed through a comparative analysis of clinical outcomes after pembrolizumab therapy according to the Eastern Cooperative Oncology Group Stage Performance Status (ECOG PS). Moreover, univariate and multivariate analyses were carried out to detect prognostic factors. In our cohort, 63.7% of patients had an ECOG PS of 0–1. Regarding response rate, 31.8% of patients had a partial response (PR), 19.3% had stable disease (SD) and 23.9% had progression disease. On the other hand, patients with ECOG PS ≥ 2 showed a significantly lower rate of PR and SD to pembrolizumab than patients with a PS of 0–1. The rate of response, median overall survival (OS) and progression-free survival (PFS) were significantly higher in patients with ECOG PS 0–1 than in those with ECOG PS ≥ 2. In the current study, we found ECOG PS as the only independent predictor of OS and PFS. Due to the ECOG PS scale being a subjective parameter, other tools are needed to identify treatment effectiveness to each patient.
2.8:1 to 6.3:1. (This does not include the 27% reduction in drug spend observed during the study period. However, more longitudinal data are required to confirm and characterise this phenomenon.). In the third quarter of 2018, 21 medication incidents were reported from the study ward compared with an average of 4 incident reports from the first and second quarters of 2018. This represents a fivefold increase in medication incident reporting, suggestive of an enhanced culture of patient safety. Conclusion and relevance This study assessed and quantified a wide spectrum of pharmacist contributions to medication management and safety. Costing of these contributions estimated the cost-benefit ratio of the clinical pharmacy service, providing compelling support for the extension of this service throughout the hospital.
ICIs have been able to improve overall survival in advanced-stage lung cancer. The benefit of this therapy is limited in patients with poor ECOG PS. However, this scale is imprecise and can be influenced by different factors, such as frailty. Cancer patients have a high risk of frailty independently of age. In this observational, single-center, retrospective study, we investigated the effect of frailty on the effectiveness of pembrolizumab in first-line use in a cohort of 101 patients with metastatic NSCLC. Frailty was determined using a frailty score system developed by Sakakida et al. Univariate and multivariate analysis was performed to determine the prognostic role of frailty on OS and PFS. Median OS was significantly higher in patients with low frailty compared with intermediate and high frailty (23.8 vs. 7.0 and 1.8 months, respectively; p < 0.001). Median PFS was also significantly higher in patients with low frailty compared with intermediate and high frailty (10.5 vs. 3.9 and 1.6 months; p < 000.1, respectively). Frailty was the only variable that showed significant differences in OS and PFS. Multivariate analysis confirms frailty as an independent predictor of OS and PFS. Frailty assessment could help to select which patients are candidates for ICIs in NSCLC.
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