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Herein, we focus on the kinetico‐mechanistic studies of a carboxylate and Cu(II)‐assisted synthesis of imidazo[1,5‐a]pyridines encompassing C(sp3)−H amination and cyclization of imines coupled with C(sp2)−H cyanation using time‐resolved UV‐Vis reaction monitoring and ex‐situ analyses. Thus, kinetic studies have been carried out, providing a proof of the elementary steps involved, allowing for batch analysis of the compounds present in solution via MS. The experimental data obtained are consistent with the formation of a cyclometalated complex (k1) involving a C(sp3)−H bond cleavage followed by a reductive elimination/proton abstraction event (k2), both showing high enthalpy‐demanding transition states. The two processes show a well‐defined Eyring behavior with values of ΔH≠ and ΔS≠ within the expected range. Further insights on the intermediate fast C(sp2)–cyanation are also presented together with control reactions. [ABSTRACT FROM AUTHOR]

The Humanities Institute of Universidad Panamericana, Guadalajara (Mexico), has carefully crafted its own reading canon by incorporating in to its course design a learning outcomes framework that mirrors its Christian institutional mission. The paper presents an overview of this framework and of its implementation within the University's Gen Ed reading canon selection. It uses an excerpt of Bartolomé de las Casas' Apology as a case example of the practice. This text is used within a course of introductory Ethics delivered to 30 different student groups per year. The criteria used in its selection and suggested practices are detailed. Overall, the text shows the value of a learning outcomes approach to text selection in a core-text-based course. [ABSTRACT FROM AUTHOR]

PurposeHarms of prostate cancer treatment on urinary health related quality of life have been thoroughly studied. In this study we evaluated not only the harms but also the potential benefits of prostate cancer treatment in relieving the pretreatment urinary symptom burden.Materials and methodsIn American (1,021) and Spanish (539) multicenter prospective cohorts of men with localized prostate cancer we evaluated the effects of radical prostatectomy, external radiotherapy or brachytherapy in relieving pretreatment urinary symptoms and in inducing urinary symptoms de novo, measured by changes in urinary medication use and patient reported urinary bother.ResultsUrinary symptom burden improved in 23% and worsened in 28% of subjects after prostate cancer treatment in the American cohort. Urinary medication use rates before treatment and 2 years after treatment were 15% and 6% with radical prostatectomy, 22% and 26% with external radiotherapy, and 19% and 46% with brachytherapy, respectively. Pretreatment urinary medication use (OR 1.4, 95% CI 1.0-2.0, p = 0.04) and pretreatment moderate lower urinary tract symptoms (OR 2.8, 95% CI 2.2-3.6) predicted prostate cancer treatment associated relief of baseline urinary symptom burden. Subjects with pretreatment lower urinary tract symptoms who underwent radical prostatectomy experienced the greatest relief of pretreatment symptoms (OR 4.3, 95% CI 3.0-6.1), despite the development of deleterious de novo urinary incontinence in some men. The magnitude of pretreatment urinary symptom burden and beneficial effect of cancer treatment on those symptoms were verified in the Spanish cohort.ConclusionsMen with pretreatment lower urinary tract symptoms may experience benefit rather than harm in overall urinary outcome from primary prostate cancer treatment. Practitioners should consider the full spectrum of urinary symptom burden evident before prostate cancer treatment in treatment decisions.

BackgroundThe Short Physical Performance Battery (SPPB) is a well-established tool to assess lower extremity physical performance status. Its predictive ability for all-cause mortality has been sparsely reported, but with conflicting results in different subsets of participants. The aim of this study was to perform a meta-analysis investigating the relationship between SPPB score and all-cause mortality.MethodsArticles were searched in MEDLINE, the Cochrane Library, Google Scholar, and BioMed Central between July and September 2015 and updated in January 2016. Inclusion criteria were observational studies; >50 participants; stratification of population according to SPPB value; data on all-cause mortality; English language publications. Twenty-four articles were selected from available evidence. Data of interest (i.e., clinical characteristics, information after stratification of the sample into four SPPB groups [0-3, 4-6, 7-9, 10-12]) were retrieved from the articles and/or obtained by the study authors. The odds ratio (OR) and/or hazard ratio (HR) was obtained for all-cause mortality according to SPPB category (with SPPB scores 10-12 considered as reference) with adjustment for age, sex, and body mass index.ResultsStandardized data were obtained for 17 studies (n = 16,534, mean age 76 ± 3 years). As compared to SPPB scores 10-12, values of 0-3 (OR 3.25, 95%CI 2.86-3.79), 4-6 (OR 2.14, 95%CI 1.92-2.39), and 7-9 (OR 1.50, 95%CI 1.32-1.71) were each associated with an increased risk of all-cause mortality. The association between poor performance on SPPB and all-cause mortality remained highly consistent independent of follow-up length, subsets of participants, geographic area, and age of the population. Random effects meta-regression showed that OR for all-cause mortality with SPPB values 7-9 was higher in the younger population, diabetics, and men.ConclusionsAn SPPB score lower than 10 is predictive of all-cause mortality. The systematic implementation of the SPPB in clinical practice settings may provide useful prognostic information about the risk of all-cause mortality. Moreover, the SPPB could be used as a surrogate endpoint of all-cause mortality in trials needing to quantify benefit and health improvements of specific treatments or rehabilitation programs. The study protocol was published on PROSPERO (CRD42015024916).

Background: In response to the rising population of nursing home residents with frailty and multimorbidity, optimizing medication safety through drug utilization review and addressing medication-related problems (MRPs) is imperative. Clinical decision support systems help reduce medication errors and detect potential MRPs, as well as medication reviews performed by a multidisciplinary team, but these combined assessments are not commonly performed. The objective of this study was to evaluate the impact on medication plans of a multidisciplinary team intervention in nursing homes, by analyzing the medication plan before and after the intervention and assessing whether the recommendations given had been implemented. Methods: A multicenter before-after study, involving five nursing homes, assessed the impact of a multidisciplinary team intervention, to estimate effectiveness related to the review of the prescribed medications. The followup period for each patient was 12 months or until death if prior, from July 2020 to February 2022, and involved 483 patients. The clinical pharmacologist coordinated the intervention and reviewed all the prescribed medications to make recommendations, focused on the completion of absent data, withdrawal of a drug, verification of whether a drug was adequate, the substitution of a drug, and the addition of drugs. Since the intervention was performed during the COVID-19 pandemic, optimization of psychotropic drugs and absorbent pads were limited. Results: The intervention had an impact with recommendations given for 398 (82.4%) of the patients and which were followed by 58.5% of them. At least one drug was withdrawn in 293 (60.7%) of the patients, with a mean of 2.3 (SD 1.7). As for the total of 1,097 recommendations given, 355 (32.4%) were followed. From the intervention, antipsychotics, antidepressants, benzodiazepines, statins, and diuretics were the most frequently withdrawn. Conclusion: The findings underscore the impact of targeted interventions to reduce inappropriate medications and enhance medication safety in nursing homes. The proposed recommendations given and followed show the importance of a multidisciplinary team, coordinated by a clinical pharmacologist, for a patient-centered approach to make medication reviews regularly, with the help of clinical decision support systems, to help reduce potential MRPs and polypharmacy. [ABSTRACT FROM AUTHOR]

Background: Aging correlates with increased frailty, multi-morbidity, and chronic diseases. Furthermore, treating the aged often entails polypharmacy to achieve optimal disease management, augmenting medication-related problems (MRPs). Few guidelines and tools address the problem of polypharmacy and MRPs, mainly within the institutionalized elderly population. Routine pharmacological review is needed among institutionalized patients. This pharmacological review may improve with a multidisciplinary approach of a collaboration of multiple health professionals. This study aimed to describe institutionalized patients, systematically review their medication plans, and then give recommendations and identify MRPs. Methods: A cross-sectional study was performed using data obtained from patients living in five nursing homes in the northern area of Barcelona, Spain. The inclusion criteria comprised institutionalized patients with public health coverage provided by the Health Department of Catalonia. A detailed description of the clinical characteristics, chronic diseases, pharmacological treatments, recommendations, incomplete data, and MRPs, such as potential drug-drug interactions, therapeutic duplications, contraindications, and drugs deemed inappropriate or of doubtful efficacy, was made. The clinical pharmacologist was the medical doctor specialist who acted as the coordinator of the multidisciplinary team and actively reviewed all the prescribed medications to make recommendations and detect MRPs. Results: A total of 483 patients were included. Patients had a mean age of 86.3 (SD 8.8) years, and 72.0% were female individuals. All patients had at least three health-related problems, with a mean of 17.4 (SD 5.6). All patients, except one, had a minimum of one prescription, with a mean of 8.22 drugs prescribed (SD 3.5) per patient. Recommendations were made for 82.4% of the patients. Of these recommendations, verification of adequate use was made for 69.3% and withdrawal of a drug for 49.5%. Conclusion: This study demonstrates a high prevalence of health-related problems and several prescribed drugs in nursing homes in Catalonia. Many recommendations were made, confirming the increased proportion of polypharmacy, MRPs, and the need for standardized interventions. A multidisciplinary team approach, including general practitioners, geriatric assessments, a clinical pharmacist, and a clinical pharmacologist, should address this problem. [ABSTRACT FROM AUTHOR]