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Background Meta-analyses of clinical pharmacy services are frequently criticized for restricted data transparency and reproducibility. Objectives To describe the methodological characteristics of meta-analyses of pharmacist-led medication reviews, to identify the elements that limit their replicability and robustness, and to propose recommendations for an appropriate conduction and reporting. Methods A meta-research study was conducted. Systematic searches of the PubMed, Scopus, and Web of Science databases were performed to identify meta-analyses of pharmacist services. Meta-analyses assessing the effect of pharmacist-led medication reviews were selected for data extraction, analysis and replication. Two replication exercises were performed for the two most common outcomes: (i) considering the data provided by authors to construct the meta-analysis and (ii) considering the raw data available in the primary studies included. Prediction intervals (PI), fragility index (FI), and number needed to treat (NNT) were also calculated for each replicated meta-analysis. Results Nine studies reporting meta-analyses about pharmacist-led medication review were found comprising 30 different outcomes. Eleven meta-analyses, including six for hospital admission and five for mortality, were replicated. In five meta-analyses, the pooled effect sizes of the replicated meta-analyses differed from the original ones. Only four meta-analyses mentioned the statistical method used. Other meta-analytic parameters (e.g., q-value, tau2) were omitted in all studies. In nine meta-analyses, the data from primary studies had been incorrectly extracted for at least one variable. The PI demonstrated that the uncertainty intervals of the effect sizes were always underestimated by the authors. NNTs showed wide intervals, ranging from benefit to harm, in almost all meta-analyses. Nine recommendations to facilitate the replication of a meta-analysis were proposed: providing all original data needed to build the analysis; informing about the imputed data or data obtained from different sources; performing sensitivity analyses for imputed or unpublished data; inform about all the statistical methods used; providing all statistical results; and reporting the PI, FI and NNT. Conclusion Errors in data extraction and poor reporting of meta-analytic parameters are common in the pharmacy literature. We proposed nine recommendations to enhance data reproducibility and interpretability. Journal editors and peer reviewers should ensure that authors strictly comply with minimum standards for conduction and reporting of meta-analyses.

Made available in DSpace on 2022-05-01T11:23:34Z (GMT). No. of bitstreams: 0 Previous issue date: 2021-01-01 Ministério da Ciência, Tecnologia, Inovações e Comunicações Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) BACKGROUND: Despite the several options available for supplements containing vitamins C and E, evidence regarding the prevalence of deficiency or insufficiency of these vitamins is weak. OBJECTIVES: To estimate the prevalence of deficiency or insufficiency of vitamins C and E and associated factors among women of childbearing age, in Brazil. DESIGN AND SETTING: Systematic review and meta-analysis conducted at a Brazilian public university. METHODS: A search from index inception until May 2020 was conducted. Meta-analyses were performed using inverse variance for fixed models, with summary proportions calculation using Freeman-Tukey dou-ble arcsine (base case). Reporting and methodological quality were assessed using the Joanna Briggs Institute tool for prevalence studies. RESULTS: Our review identified 12 studies, comprising 1,316 participants, especially breastfeeding wom-en. There was at least one quality weakness in all studies, mainly regarding sampling method (i.e. conve-nience sampling) and small sample size. The prevalence of vitamin C deficiency ranged from 0% to 40%. Only vitamin E deficiency was synthetized in meta-analyses, with mean prevalences of 6% regardless of the alpha-tocopherol cutoff in plasma, and 5% and 16% for cutoffs of

Este é o primeiro de dois artigos, em que se discorre sobre o contexto em que as análises de sensibilidade devem ser realizadas (parte I) e a execução da análise de sensibilidade probabilística no Microsoft Excel (parte II). A análise de custo-efetividade (ACE) e suas variantes são metodologias de análise econômica completa, que apresentam um grau de incerteza inerente à construção de modelos de decisão analítica. Assim, é fundamental demonstrar a adequação e robustez dos resultados obtidos por meio da análise de sensibilidade. Dois métodos de análise de sensibilidade são amplamente utilizados em estudos de ACE: I - análise univariada determinística, que avalia um parâmetro por vez do modelo matemático, alterando o seu valor dentro de um intervalo pré-especificado, e II - análise de sensibilidade probabilística, que é capaz de levar em conta todos os parâmetros do modelo de uma única vez, respeitando a distribuição estatística que corresponde à natureza de cada parâmetro. Nesse primeiro artigo, descrevemos o conceito de análise de sensibilidade probabilística de maneira pragmática no contexto dos estudos de custo-efetividade e ilustramos o racional por trás das duas principais curvas de distribuição estatística utilizadas na farmacoeconomia, curvas Gama e Beta, e como calcular os seus hiperparâmetros

Introduction: The contribution of fluid temperature to the effect of crystalloid fluid bolus therapy (FBT) in post-cardiac surgery patients is unknown. We evaluated the hemodynamic effects of FBT with fluid warmed to 40°C (warm FBT) versus room-temperature fluid. Methods: In this single centre prospective before-and-after study, we evaluated the effects of 500 ml of warm versus room-temperature compound sodium lactate administered over 15% of baseline immediately after FBT and effect dissipation if the CI returned to 10% increase and dissipation as return to Results: Hypotension (56%) and low CI (40%) typically triggered FBT. Temperature decreased >0.3°C in 13 (52%) patients after room-temperature FBT versus 0 (0%) after warm FBT (p 2, p = 0.01). However, dissipation was more common after room-temperature versus warm FBT (9/16 [56%] versus 1/11 [9%], p = 0.02). Conclusion: In postoperative cardiac surgery patients, warm FBT preserved core temperature and induced smaller but more sustained CI increases among responders. Fluid temperature appears to impact both core temperature and the duration of CI response.

Made available in DSpace on 2021-06-25T10:55:23Z (GMT). No. of bitstreams: 0 Previous issue date: 2021-01-01 Introduction: Considering the need for effective postmarketing surveillance of disease-modifying therapies (DMTs) in multiple sclerosis (MS), we analyzed the potential of the spontaneous reports for safety signal detection, verifying the completeness of the reports in the FDA Adverse Event Reporting System (FAERS). Methods: All reports with DMTs for MS considered the primary suspect cause of ADRs and registered between January 2004 and June 2019 were selected. The vigiGrade completeness score was applied and reports with a score greater than 0.80 were considered well documented. Descriptive statistical analysis and comparisons of well-documented reports by DMTs were performed. Results: A total of 297,926 reports were analyzed. The lowest completeness rates were observed for type of report (13.5%), dose (62.7%), and time from treatment start to the ADR (79.0%). Overall, 80.8% of reports were classified as well documented and those related to natalizumab had the highest proportion (92.4%, p

Major surgical societies advised using non-operative management of appendicitis and suggested against laparoscopy during the COVID-19 pandemic. The hypothesis is that a significant reduction in the number of emergent appendectomies was observed during the pandemic, restricted to complex cases. The study aimed to analyse emergent surgical appendectomies during pandemic on a national basis and compare it to the same period of the previous year. This is a multicentre, retrospective, observational study investigating the outcomes of patients undergoing emergent appendectomy in March–April 2019 vs March–April 2020. The primary outcome was the number of appendectomies performed, classified according to the American Association for the Surgery of Trauma (AAST) score. Secondary outcomes were the type of surgical technique employed (laparoscopic vs open) and the complication rates. One thousand five hundred forty one patients with acute appendicitis underwent surgery during the two study periods. 1337 (86.8%) patients met the inclusion criteria: 546 (40.8%) patients underwent surgery for acute appendicitis in 2020 and 791 (59.2%) in 2019. According to AAST, patients with complicated appendicitis operated in 2019 were 30.3% vs 39.9% in 2020 (p = 0.001). We observed an increase in the number of post-operative complications in 2020 (15.9%) compared to 2019 (9.6%) (p 24 h after admission (+ 58%), open surgery (+ 112%) and conversion to open surgery (+ 166%). In Italian hospitals, in March and April 2020, the number of appendectomies has drastically dropped. During the first pandemic wave, patients undergoing surgery were more frequently affected by more severe appendicitis than the previous year's timeframe and experienced a higher number of complications. Trial registration number and date: Research Registry ID 5789, May 7th, 2020

Background Hypocoagulability and impaired platelet function have been associated with a high risk of death in sepsis. The aim of this cohort study was to determine whether sepsis-induced hypocoagulability and platelet dysfunction (assessed by ROTEM® and MULTIPLATE®, respectively) are increased in sepsis patients who died within 28 days after diagnosis compared with patients who died between 29 and 90 days after diagnosis. Methods Consecutive patients admitted to the intensive care unit of Padova University Hospital from March 2015 to March 2018 for severe sepsis were considered. We collected blood samples from all patients to determine ROTEM® and MULTIPLATE® parameters. Each enrolled patient underwent a 90-day follow-up and the mortality rate was recorded. Results Of 120 patients, 36 (30%) died within 28 days post-diagnosis (Group A), 23 (19%) died between days 29 and 90 post-diagnosis (Group B), and 61 (51%) were alive after 90 days (survivors). The clotting time in the ROTEM® test and clot formation time in the EXTEM test were significantly more prolonged in Group A than in B. Both groups showed a significantly higher hypocoagulability than survivors in the EXTEM test. MULTIPLATE® platelet function analysis showed that platelet function was significantly lower in Group A than in Group B. Conclusions The present study showed that the combination of thromboelastometry and impedance aggregometry may help identifying sepsis patients at high risk of short-term death. Larger studies are warranted to corroborate our results.

Background: Suboptimal meta-analyses with misleading conclusions are frequently published in the health areas, and they can compromise decision making in clinical practice. Aim of the review: This systematic review aimed to map the characteristics of published meta-analyses of pharmacy services and their association with the study conclusions. Method: We searched electronic databases (PubMed, Scopus, and Web of Science) to identify published meta-analyses of pharmacy services up to January 2019. Components of meta-analyses were extracted (i.e. studies’ metadata; methods used in the systematic review; description of the statistical model used for the meta-analysis; main results; conflict of interest and funding source). The methodological quality was evaluated using the R-AMSTAR tool. Results: A total of 85 meta-analyses were included, with 2016 as the median publication year. Overall, the methodological quality of meta-analyses of pharmacy services was considered suboptimal. Only one-third of authors registered a protocol; complete search strategy and raw data were provided by 55.3% and 9.4% of studies, respectively. Evidence strength (GRADE) was evaluated in only 19.2% of studies. PRISMA and Cochrane recommendations were stated to be followed in 60% and 27.4% of articles, respectively. Around half of studies performed sensitivity analysis, however, the prediction interval was presented by only one meta-analysis. Studies that favoured the pharmacists’ interventions poorly discussed the methodological quality and heterogeneity of primary trials. Conclusion: Poor conduction and reporting were observed in meta-analyses of pharmacy services, especially in those that favoured the pharmacist’s interventions. Reproducibility and transparency should be rigorously ensured by journal editors and peer-reviewers.

In injection molding, high pressure is required to fill the mold, due to the high viscosity of thermoplastic polymers, the reduced thickness of the cavity and the low mold temperature. In this work, we investigate the functionalization of mold cavities for Injection Molding by means of Laser-Induced Periodic Surface Structures (LIPSS) generated on the ground surface of AISI 420 stainless steel through a picosecond laser. The LIPSS formation is examined with reference to the process parameters, highlighting how they affect the generated pattern. The improvements of the functionalized mold surface on the Injection Molding process are experimentally characterized and discussed. In particular, the slipping of molten PET was investigated as a function of nano-structuring orientation and injection velocity. The results demonstrate that LIPSS parallel to flow induce strong wall slip of the polymer melt, allowing a maximum reduction of the injection pressure of 10%.

Objective: To study the cardiovascular effect over 30 minutes following the end of fluid bolus therapy (FBT) with 20% albumin in patients after cardiac surgery. Design: Prospective observational study. Setting: Intensive care unit of a tertiary university-affiliated hospital. Participants: Twenty post-cardiac surgery mechanically ventilated patients with a clinical decision to administer FBT. Intervention: FBT with a 100 mL bolus of 20% albumin. Main outcome measures: Cardiac index (CI) response was defined by a  15% increase, while mean arterial pressure (MAP) response was defined by a  10% increase. Results: The most common indication for FBT was hypotension (40%). Median duration of infusion was 7 minutes (interquartile range [IQR], 3–9 min). At the end of FBT, five patients (25%) showed a CI response, which increased to almost half in the following 30 minutes and dissipated in one patient. MAP response occurred in 11 patients (55%) and dissipated in five patients (45%) by a median of 6 minutes (IQR, 6–10 min). CI and MAP responses coexisted in four patients (20%). An intrabolus MAP response occurred in 17 patients (85%) but dissipated in 11 patients (65%) within a median of 7 minutes (IQR, 2–11 min). On regression analysis, faster fluid bolus administration predicted MAP increase at the end of the bolus. Conclusion: In post-cardiac surgery patients, CI response to 20% albumin FBT was not congruous with MAP response over 30 minutes. Although hypotension was the main indication for FBT and a MAP response occurred in most of patients, such response was maximal during the bolus, dissipated in a few minutes, and was dissociated from the CI response.

Objectives This study aimed to perform a cost-effectiveness analysis (CEA) of the molecular diagnostic method (MM) associated with conventional diagnostic method (CM) compared with the CM alone, for the detection of resistant profile in bacteremia, from the perspective of the Brazilian Public Health System, in intensive care units setting. Methods The clinical parameters regarding methicillin-resistant Staphylococcus aureus (MRSA), carbapenem-resistant Gram-negative bacteria (CRGNB), and vancomycin-resistant Enterococcus spp. (VRE) infections were collected from searches on PubMed, Scopus, and SciELO, using specific keywords. Data on direct medical costs to treat these infections were collected according to Brazilian Public Health System perspective from Brazilian databases, in tables of 2018 to 2019. CEA was performed after building a dynamic model, which was calibrated and validated according to international recommendations. The incremental cost-effectiveness ratio of the MM + CM compared with the CM was calculated using the outcomes “avoided death” and “avoided resistant infections.” One-way sensitivity analyses were performed. Results This CEA demonstrated that the MM + CM was dominant in all scenarios. Estimates showed that for MRSA, CRGNB, and VRE infections, every avoided death would lead to savings of Brazilian real (R$) 4.9 million ($937 301), R$2.2 million ($419 899), and R$1.3 million ($248 919), respectively. The same infections assessed by avoided resistant infections savings were projected to be R$24 964 ($4686), R$40 260 ($7558), and R$23 867 ($4480). Conclusions MM leads to cost reduction and increased benefits, optimizing the use of financial resources on the health system in the intensive care unit setting, in bacteremia caused by MRSA, CRGNB, and VRE.

Background: Despite current policies of salt iodination, iodine deficiency is still a global public health problem, especially in women. So far, conflicting evidence has been suggested for the prevalence of iodine deficiency in Brazil. Objective: To estimate the prevalence of iodine deficiency and associated factors in women of childbearing age in Brazil. Methods: A systematic review was conducted using databases (PubMed, LILACS, WHO, Scopus, and Capes’ dissertation and thesis), from inception to May 2020. Meta-analyses of proportions were performed using the variance inverse for the fixed model. Reporting and methodological quality were assessed using the Joanna Briggs Institute tool to prevalence studies. Results: Our review identified seven studies published between 2002 e 2017, including 1354 participants, especially pregnant women. All studies presented at least one quality limitation, mainly regarding the sampling method (i.e., convenience) and small sample size. The prevalence of iodine deficiency ranged among studies from 16% to 62%. In contrast, the meta-analysis identified a mean prevalence of 40% (95% confidence interval, CI 37%-43%) for pregnant women and 13% (95% CI 4%-24%) for non-pregnant women. Cumulative meta-analysis suggests a tendency of higher iodine deficiency prevalence from 2018 in pregnant women. Conclusions: Although this systematic review identified studies with poor methodological and reporting quality, a high prevalence of iodine deficiency was identified in pregnant women, reinforcing the importance of national nutritional policies for monitoring iodine status in this population. Future studies should consider random probabilistic sampling, appropriate sample size, and pre-defined subgroup analysis to adequately inform the prevalence of iodine deficiency and associated factors in women of childbearing age and support health policies. Resumen Antecedentes: A pesar de las políticas actuales de yodación de la sal, la deficiencia de yodo sigue siendo un problema de salud pública mundial, especialmente en las mujeres. Hasta ahora, se han sugerido pruebas contradictorias sobre la prevalencia de la deficiencia de yodo en Brasil. Objetivo: Estimar la prevalencia de deficiencia de yodo y factores asociados en mujeres en edad fértil, en Brasil. Métodos: Se realizó una revisión sistemática, buscando en PubMed, LILACS, OMS, Scopus y la base de datos de disertaciones y tesis de Capes desde el inicio hasta mayo de 2020. Se realizaron metanálisis de proporciones utilizando la variancia inversa para el modelo fijo. La calidad de información y metodológica se evaluó utilizando la herramienta del Institute Joanna Briggs para estudios de prevalencia. Resultados: Nuestra revisión identificó siete estudios publicados entre 2002 y 2017, incluyendo 1354 participantes, especialmente mujeres embarazadas. Todos los estudios presentaron al menos una limitación de calidad, principalmente con respecto al método de muestreo (es decir, la conveniencia) y el pequeño tamaño de la muestra. La prevalencia de la deficiencia de yodo varió entre los estudios del 16% y el 62%, mientras que el metanálisis identificó una prevalencia media del 40% (intervalo de confianza del 95%, IC 37%-43%) para las mujeres embarazadas y del 13% (IC del 95% 4%-24%) para mujeres no embarazadas. El metanálisis acumulativo sugiere una tendencia a una mayor prevalencia de deficiencia de yodo a partir de 2018 en mujeres embarazadas. Conclusiones: Si bien esta revisión sistemática identificó estudios con mala calidad metodológica y de reporte, se identificó una alta prevalencia de deficiencia de yodo en mujeres embarazadas, lo que refuerza la importancia de las políticas nutricionales nacionales para monitorear el estado de yodo en esta población. Los estudios futuros deben considerar el muestreo probabilístico aleatorio, el tamaño de muestra apropiado y el análisis de subgrupos predefinidos para informar adecuadamente la prevalencia de la deficiencia de yodo y los factores asociados en mujeres en edad fértil y para respaldar las políticas de salud.

Photovoice was employed as a clinical intervention to engage siblings of children with cancer, provide opportunity for sibling support, and elicit information about their lived experiences. Sibling support groups have been effective, however, none have utilized this intervention. Four teenagers who had a sibling diagnosed with cancer participated in a seven-week intervention group. Themes were identified to inform future clinical practice. Four main themes included: (i) support, (ii) changes, (iii) feelings, and (iv) Photovoice group experience. Photovoice, used as a clinical intervention, elicited valuable information and generated fruitful conversations, enabling siblings to relate to and learn from one another.

The purpose of this study was to evaluate different binding agents for the preparation of salty cereal bars and to characterize them regarding their physical and sensory parameters. Four formulations of cereal bars were developed using collagen, guar gum, xanthan gum and psyllium as binders, which were evaluated for instrumental color and texture. The results of the instrumental analysis revealed that the cereal bars presented characteristic color and crispness for this type of product and the microbiological analyzes ensured food safety. Sensorially, the cereal bars showed good acceptability, especially the bars made with psyllium and xanthan gum binders in the parameters of appearance, texture, flavor and color. The different binders showed technological efficiency in the elaboration of salty cereal bars, but xanthan gum and psyllium were the ones that best corresponded to the expected attributes.

The visual system is primarily affected in sickle cell disease (SCD), and eye examination is recommended starting in late childhood. So far, to our knowledge, all studies have focused on the retina, neglecting the changes that might be present in the cortical portion of the visual system. We performed a multimodal magnetic resonance imaging (MRI) evaluation of the visual cortex in 25 children with SCD (mean age: 12·3 ± 1·9 years) and 31 controls (mean age: 12·7 ± 1·6 years). At ophthalmologic examination, 3/25 SCD children had mild visual acuity deficits and 2/25 had mild tortuosity of the retinal vessels. None showed optic pathway infarcts at MRI or Transcranial Doppler abnormal blood velocities, and 6/25 disclosed posterior cerebral artery stenosis (five mild and one severe) at MR-angiography. Compared to controls, SCD children had increased posterior pericalcarine cortical thickness, with a different trajectory of cortical maturation and decreased connectivity within medial and ventral visual neural networks. Our findings suggest that SCD affects the development and the tuning of the visual cortex, leading to anatomical and functional changes in childhood even in the absence of retinopathy, and set the basis for future studies to determine if these changes can represent useful predictors of visual impairment in adulthood, biomarkers of disease progression or treatment response.

The replication of submicron surface structures by micro injection molding is a crucial factor in achieving advanced functionalities, such as antimicrobial resistance, in mass-produced plastic products. In this work, we investigate and model the replication quality of laser-induced periodic surface structures by micro injection molding of different bio-based polymers. A comprehensive multiscale model was developed to predict the submicron scale polymer flow, using a numerical model to analyze the polymer behavior in the mold macro cavity and determine the boundary conditions for the filling of the surface structures. The replication of the mold topography was modeled considering topographical parameters, polymer rheology and thermal behavior, and the mold surface energy, which was modified by depositing an atomic layer of alumina on the steel surface structures. The modeling approach was validated against injection molding experiments, in which the mold temperature was varied due to its well-known influence on replication. The sensitivity to polymer selection, mold surface properties, and mold temperature, was captured. A maximum error of 8% showed the accuracy of the multi-scale model.

Non-variceal upper gastrointestinal bleeding (non-variceal UGIB) is a frequent and severe adverse drug reaction. Idiosyncratic responses due to genetic susceptibility to non-variceal UGIB has been suggested. A systematic review was conducted to assess the association between genetic polymorphisms and non-variceal UGIB. Twenty-one publications and 7134 participants were included. Thirteen studies evaluated genetic polymorphism in patients exposed to non-steroidal anti-inflammatory drugs, low-dose aspirin, and warfarin. Eight studies present at least one methodological problem. Only six studies clearly defined that the outcome evaluated was non-variceal UGIB. Genetic polymorphisms involved in platelet activation and aggregation, angiogenesis, inflammatory process, and drug metabolism were associated with risk of non-variceal UGIB (NOS3, COX-1; COX-2; PLA2G7; GP1BA; GRS; IL1RN; F13A1; CDKN2B-AS1; DPP6; TBXA2R; TNF-alpha; VKORC1; CYP2C9; and AGT). Further well-designed studies are needed (e.g., clear restriction to non-variceal UGIB; proper selection of participants; and adjustment of confounding factors) to provide strong evidence for pharmacogenetic and personalized medicine.

The ejection phase influences the quality and integrity of micro injection molded parts. The successful design of robust micro mold ejection systems requires studying the tribological interactions at the mold/polymer interface. At the micro-scale, the tooling topography can have a significant impact on the ejection friction. Here we propose a novel approach to the evaluation of ejection friction in micro injection molding. The two main contributors to the ejection force are the normal force due to shrinkage and the static friction coefficient. The former is addressed by developing a procedure for shrinkage characterization at the micro-scale. The latter is studied using experimental measurements of the ejection force in micro injection molding. Comparing the numerical and the experimental results allows identifying the friction coefficient as a function of polymer, process parameters, and mold surface roughness.

Background: The elderly people have high morbimortality associated with respiratory disorders, in addition to the presence of other safety risk factors, such as the use of potentially inappropriate medication and the occurrence of drug interactions. Objective: Considering the current pandemic scenario, it was intended to identify explicit criteria-based tools that reported drug interactions between potentially inappropriate medication and respiratory system disorders and possibly worse prognosis of COVID-19 infection. Methods: A systematic scoping review was conducted until February 2020. Study characteristics of explicit criteria-based tools, and potentially inappropriate medication, drug interactions, and therapeutic management, were extracted. Results: Nineteen explicit criteria-based tools were included. Nineteen drug interactions and 17 potentially inappropriate medications with concerns for three respiratory disorders (asthma, chronic pulmonary obstructive disease, and respiratory failure) were identified. The most frequent pharmacological classes reported were benzodiazepines and beta-blockers. For clinical management, the tools recommend using cardioselective beta-blockers, calcium channel blockers, angiotensin-converting enzyme inhibitors, and angiotensin II type I receptor blockers, and benzodiazepines with a short or intermediate half-life. Conclusion: Considering the increased risk of COVID-19 infection in the elderly, drug interactions and the use of potentially inappropriate medication associated with the occurrence of adverse drug events in the respiratory system may also worsening COVID-19 infection in patients with uncontrolled respiratory disorders. Thus, it is essential to assess drug therapy in use, to identify safety risks, and monitor the elderly in general and those with a worse prognosis concerning COVID-19, promoting patient safety.

Made available in DSpace on 2021-06-25T10:44:53Z (GMT). No. of bitstreams: 0 Previous issue date: 2020-01-01 Objective: To map the clinical pharmacy services conducted in Brazil, their characteristics, outcomes, and process measures in general population, as well as the assessment of the clinical impact on people with cardiometabolic diseases (cardiovascular diseases and metabolic diseases). Methods: A systematic scoping review and meta-analysis were conducted. The electronic searches were re-run in March 2020. To the clinical impact assessment, meta-analyses of cardiometabolic outcomes (i.e., change of systolic (SBP) and diastolic blood pressure (DBP), triglycerides, total cholesterol, glycated hemoglobin (HbA1c), fasting glycemia, LDL-, and HDL-cholesterol) were led. The risk of bias was assessed with the Cochrane Collaboration tools. Results: 71 studies were identified (7,402 patients), being the majority quasi-experimental studies (n=41) and published by research groups of Southeast Brazil (n=33). Medication therapy management (n=62) was the most frequent clinical pharmacy service, performed on outpatient setting (n=45), with adults or elderly people (n=58) with hypertension (n=18) or diabetes (n=10). Process measures (n=58) (e.g. resolution of drug related-problem) were widely used as indicator, followed by clinical (n=44) (e.g. change in SBP), humanistic (n=12) (e.g. change in quality-of-life score assessed by Short-Form 36 Health Survey Questionnaire), and economic outcomes (n=3) (incremental cost-effectiveness ratio for reduction in HbA1c). Regarding the assessment of clinical impact of the services, 20 studies were included in meta-analyses, showing improvement in most cardiometabolic outcomes when considered individual studies. However, the evidence presents high risk of bias, high heterogeneity (median 67-90%) and imprecision, contributing to wide prediction intervals and low reliability. Conclusions: A predominance of studies on cardiometabolic diseases, process measures, and clinical outcomes were identified. Considering the assessment of the clinical impact of clinical pharmacy services in cardiometabolic diseases, an improvement in most cardiometabolic outcomes was showed, however, with low confidence and wide prediction interval. Therefore, development of larger studies with low risk of bias and major homogeneity is necessary for a better comprehension of clinical pharmacy service characteristics, benefits, and the population groups most benefited. Department of Drugs and Medicines School of Pharmaceutical Sciences São Paulo State University (UNESP) Department of Drugs and Medicines School of Pharmaceutical Sciences São Paulo State University (UNESP)

Diseases imply dysregulation of cell’s functions at several levels. The study of differentially expressed genes in case-control cohorts of patients is often the first step in understanding the details of the cell’s dysregulation. A further level of analysis is introduced by noticing that genes are organized in functional modules (often called pathways), thus their action and their dysregulation may be better understood by the identification of the modules most affected by the disease (aka disease modules, or active subnetworks). We describe how an algorithm based on the Core&Peel method developed originally for detecting protein complexes in PPI networks, can be adapted to detect disease modules in co-expression networks of genes. We first validate Core&Peel for the easier general task of functional module detection by comparison with 42 methods participating in the Disease Module Identification DREAM challenge of 2019. Next, we use four specific disease test cases (colorectal cancer, prostate cancer, asthma and rheumatoid arthritis), four state-of-the-art algorithms (ModuleDiscoverer, Degas, KeyPathwayMiner and ClustEx), and several pathway databases to validate the proposed algorithm. Core&Peel is the only method able to find significant associations of the predicted disease module with known validated relevant pathways for all four diseases. Moreover for the two cancer data sets, Core&Peel detects further nine relevant pathways enriched in the predicted disease module, not discovered by the other methods used in the comparative analysis. Finally we apply Core&Peel, along with other methods, to explore the transcriptional response of human cells to SARS-CoV-2 infection, at a modular level, aiming at finding supporting evidence for drug repositioning efforts.

Objective The objective of the review is to explore randomized controlled trials on disease-modifying therapies for relapsing multiple sclerosis to identify and quantify the different outcome measures, instruments and definitions of efficacy, safety outcomes, health-related quality of life instruments and population subgroups. Introduction A wide range of therapies are available for relapsing multiple sclerosis, as well as a wide range of outcome measures and definitions, which can be explained by the absence of a core outcome set for this disease. Establishing a core outcome set is fundamental for guiding future studies as they improve the consistency and relevance of new findings and enable the results of trials to be compared and combined. These features are especially important for relapsing multiple sclerosis due to the limited number of head-to-head studies on this disease. Although many systematic reviews and meta-analyses have focused on the efficacy and safety of disease-modifying therapies in relapsing multiple sclerosis, none have had the specific objective of mapping outcome measures. Inclusion criteria This review will consider randomized controlled trials that explore populational subgroups, efficacy, safety outcomes, health-related quality of life instruments and their definitions in the context of disease-modifying therapies for adults with relapsing multiple sclerosis. Methods Electronic searches will be performed in PubMed, Scopus, the Cochrane Library, ClinicalTrials.gov, and JBI Evidence Synthesis with no time limit. Two researchers will independently select registries (screening and eligibility steps) and extract data on study characteristics, outcome measures, definitions and population subgroups. Data will be presented in graphical or tabular form, accompanied by a narrative summary.

Background This study aimed to map the outcome measures of clinical efficacy reported in Randomized Controlled Trials (RCT) to evaluate disease-modifying therapies (DMT) in patients with relapsing forms of multiple sclerosis (RMS). Methods A systematic scoping review was performed to identify RCT that assessed the efficacy of DMT in adult patients with RMS. Searches were conducted in PubMed, Scopus, and The Cochrane Controlled Register of Trials and complemented by manual search. A descriptive-quantitative analysis of the clinical efficacy outcomes with their respective definitions was performed. Results Of the 5,476 records identified, 226 were included. Among the included studies, 89% reported clinical efficacy outcomes, with 77 different outcomes identified, including five composite outcomes. A total of 36 different definitions for ‘relapse’ were identified. ‘Annualized relapse rate’ was the most prevalent single outcome (n = 56 studies). At the same time, the ‘Proportion of patients with no evidence of radiological and clinic disease activity’ was the most prevalent composite outcome (n = 14 studies) although with six different definitions. Conclusions An absence of consensus on the clinical efficacy outcomes reported in RCT associated with a wide heterogeneity of definitions were identified. The mapped results of this research can be used as a basis for the definition of a core outcome set for clinical efficacy outcomes in adults with RMS.

Saccadi e guida.Guidare non è solo un compito fisico, ma anche mentale. Gli input visivi sono indispensabili per la scansione della strada, la comunicazione con gli altri utenti della strada e il monitoraggio dei dispositivi di bordo. La probabilità di rilevare un oggetto mentre si guida (conspicuity) è molto importante per la valutazione dell’efficacia della guida e la scelta corretta delle informazioni rilevanti per la sicurezza determina l’efficienza di un conducente. Di conseguenza la fissazione visiva e il movimento degli occhi sono essenziali per l’attenzione e la scelta nel prendere decisioni. I movimenti saccadici sono il mezzo più usato ed efficace per mantenere una corretta fissazione durante la guida. Per identificare le caratteristiche dei soggetti più predisposti alle alte prestazioni di guida e quelle degli atleti di alto livello, abbiamo utilizzato il Visual Exploration Training System. Abbiamo studiato con test saccadici e attentivi vari gruppi di conducenti ordinari, di piloti professionisti, di camionisti professionisti e di altri atleti professionisti. I maschi hanno un tempo di reazione più veloce rispetto alle femmine e l’età inferiore ai 30 anni sembra garantire una migliore precisione delle prestazioni e nel raggiungere tutti gli obiettivi visivi. L’effetto dell’attività fisica e lo sport sono confermati. Le performance degli allievi selezionati della Ferrari Driver Academy sono significativamente migliori, in particolare rispetto al gruppo di aspiranti studenti e piloti dilettanti, probabilmente grazie alla predisposizione individuale e sulla cosiddetta ‘efficienza neurale’ dovuta sia ad un utilizzo ridotto delle risorse che al miglioramento nell’elaborazione delle informazioni, grazie a una migliore comunicazione tra le aree del cervello correlate alle attività.Driving is not only a physical task, but is also a mental task. Visual inputs are indispensable in scanning the road, communicating with other road users and monitoring in-vehicle devices. The probability to detect an object while driving (conspicuity) is very important for assessment of driving effectiveness, and correct choice of information relevant to the safety of driving determines the efficiency of a driver. Accordingly, eye fixation and eye movements are essential for attention and choice in decision making. Saccades are the most used and effective means of maintaining a correct fixation while driving. In order to identify the features of the most predisposed subjects at high driving performances and those of the high-level sportsmen, we used a special tool called Visual Exploration Training System. We evaluated by saccade and attentional tests various groups of ordinary drivers, past professional racing drivers, professional truck drivers and professional athletes. Males have faster reaction time compared to females and an age below 30 seems to guarantee better precision of performance and accuracy in achieving all visual targets. The effect on physical activity and sports is confirmed. The performances of the Ferrari Driver Academy (FDA) selected students who were significantly better than those of a group of aspiring students and amateur racing drivers probably thanks to individual predisposition, training and so-called ‘neural efficiency’.

To compare the hemodynamic effect of room temperature (cold) 4% albumin fluid bolus therapy (FBT) with body temperature (warm) albumin FBT.Prospective, before-after trial.A tertiary intensive care unit (ICU).Sixty ventilated, post-cardiac surgery patients prescribed with 4% albumin FBT.Cold or warm 4% albumin 500 ml FBT.We recorded hemodynamic parameters before and for 30 minutes after FBT. Cardiac index (CI) and mean arterial pressure (MAP) responses were defined by a CI increase15% and a MAP increase10%, respectively. Immediately after FBT, median [interquartile range] core temperature changed by -0.3 [-0.4; -0.3] °C with cold albumin vs. 0.0 [0.0; 0.1]°C with warm albumin (P0.001). The median CI increase was 0.3 [0.0; 0.5] L/min/m2 with 14 CI-responders (47%) in both groups (P0.99). The median immediate MAP increase was 9 [3; 15] mmHg with cold albumin vs. 11 [5; 13] mmHg with warm albumin (P=0.79), with a MAP-response in 16 vs. 17 patients (P=0.99). There was an interaction between group and time for MAP (P=0.002), mean pulmonary artery pressure (PAP) (P=0.002) and core temperature (P0.001). In the cold albumin group, after the initial response, MAP and mean PAP decreased more slowly than with warm albumin and, after the initial fall, core temperature increased toward baseline.In postoperative cardiac surgery patients, warm albumin FBT prevents the decrease in core temperature and, after an initial similar increase, is associated with a faster return of MAP and mean PAP toward baseline.

Bauhinia forficata is a medicinal plant that has flavonoid components with hypoglycemic, antioxidant, hepatoprotective, antibacterial, antiviral and anti-inflammatory action. Aim of this study is to evaluate the action of B. forficata alcoholic extract in the male genital system of adult male Wistar rats. For that, 20 adult male Wistar rats were distributed into two experimental groups: the B. forficata group, receiving B. forficata alcoholic extract (0.1 ml/10 g body weight/day) on alternate days, and the control group, receiving just the vehicle for 30 days straight both via gavage. On the 31st day, the animals were euthanized, and the testis and epididymis were collected for histopathological, biochemical, morphometric, and sperm count analysis. Mass spectrometry identified new compounds in the extract: trans-caffeic acid, liquiritigenin, gallocatechin, and 2,4,6-trihydroxyphenanthren-2-glycoside. Biochemical analysis showed higher total cholesterol levels in the testis and lower malondialdehyde levels in the testis and epididymis, in the B. forficata group. The mast cell count showed a reduction in degranulated mast cells in the caput region of the epididymis, in the B. forficata group. The luminal compartment of the caput and the epithelial of the epididymis cauda were reduced, whereas the stromal region of the epididymis caput was increased in the B. forficata group, compared with the control group. The testicular tissue was less impaired, considering that all the histological analyses were similar to the control. We believe that B. forficata alcoholic extract in the male genital system showed antioxidant action, especially in the epididymal tissue.

Guillain-Barré syndrome (GBS) may be complicated by severe hypertension (HT) and in turns severe HT can occur with neurological damage mimicking a GBS, so that underlying causes should be investigated. We describe a case of a 62-year-old woman presented to the emergency department for hypertensive crisis with symmetric flaccid paralysis, hypotonia and hyporeflexia of both upper and lower limbs. Brain computed tomography, magnetic resonance imaging and lumbar puncture were normal. Laboratory investigations revealed severe hypokalemia, renal failure, liver impairment, rabdomyolysis, metabolic alkalosis, and low plasma renin and aldosterone levels. Continuous potassium replacement led to complete clinical resolution. A detailed history revealed chronic intake of 250 g/day black liquorice. Hypokalaemic muscle weakness may simulate a GBS. When serum potassium level falls below 2.5 mmol/l, rhabdomyolysis may occur. In this clinical case, an apparent mineralocorticoid excess syndrome was induced by chronic ingestion of liquorice. This latter contains the glycyrrhetic acid that inhibits the enzyme 11-β-hydroxysteroid dehydrogenase enzyme type-2 leading an aldosterone-like effect and causing hypertension, hypokalemia, metabolic alkalosis and low renin values. The clinical presentation is similar to that observed in the primary aldosteronism, but in this syndrome plasma aldosterone levels are low rather than elevated as in primary aldosteronism. Liquorice-induced hypertension with severe hypokalemia and rhabdomyolysis is a rare condition and the initial presentation with acute muscle paralysis is still more unusual. Before performing instrumental examinations in middle-aged peoples with hypertension crisis and neurological impairment, a detailed clinical history is mandatory.

Jaboticaba (Plinia cauliflora) is a Brazilian native fruit which can be consumed in natura form, and also as processed food. The skin has a significant biological nutritional potential. The present study aimed to evaluate the bioactive compounds of the jaboticaba skin and of the jaboticaba skin flour (JSF), and its application in cookie. Physicochemical analyses to determine the bioactive compounds and antioxidant activity (TEAC and FRAP) of jaboticaba skin and JSF were performed. Skin presented high content of phenolic compounds, anthocyanins, flavonoids and condensed tannins, strengthening that this composition exhibited considerable levels of antioxidant activity. The JSF presented considerable carbohydrate contents, phenolic compounds and antioxidant activity, besides being a source of fibers. The cookies were prepared by replacing 2.5%, 5.0% and 7.5% of the total amount of whole wheat flour in the recipe by JSF. The formulations presented positive increases of bioactive compounds, contributing with the potential of antioxidant activity. All formulations were well accepted in the sensory evaluation.

A broad range of disease-modifying therapies (DMTs) for relapsing–remitting multiple sclerosis (RRMS) is available. However, the efficacy and safety of traditional DMTs compared with the recently developed DMTs remain unclear. Therefore, we have synthesised available evidence of clinical outcomes for DMTs in adults with RRMS. PubMed, Scopus and a manual search were performed. Bayesian network meta-analyses of randomised clinical trials assessing DMTs as monotherapies were conducted. SUCRA and GRADE were used to rank therapies and to assess quality of general evidence, respectively. Thirty-three studies were included in the meta-analyses. The most effective therapies for the outcome of annualised relapse rate were alemtuzumab (96% probability), natalizumab (96%) and ocrelizumab (85%), compared with all other therapies (hazard ratio versus placebo, 0.31, 0.31 and 0.37, respectively; p

To investigate the pharmacokinetics of a 20 mmol magnesium bolus in regards to serum and urinary magnesium concentration, volume of distribution, and half-life.Prospective, experimental study.A university-affiliated teaching hospital.Twenty consecutive cardiac surgery patients treated with magnesium bolus therapy for prevention of arrhythmia.A 20-mmol bolus of magnesium sulfate was administered intravenously.Median magnesium levels increased from 1.04 (interquartile range 0.94-1.23) mmol/L to 1.72 (1.57-2.14) mmol/L after 60 minutes of magnesium infusion (p0.001) but decreased to 1.27 (1.21-1.36) and 1.16 (1.11-1.21) mmol/L after 6 and 12 hours, respectively. Urinary magnesium concentration increased from 6.3 (4.2-14.5) mmol/L to 19.1 (7.4-34.5) mmol/L after 60 minutes (p0.001), followed by 22.7 (18.4-36.7) and 15 (8.4-19.7) mmol/L after 6 and 12 hours, respectively. Over the 12-hour observation period, the cumulative urinary magnesium excretion was 19.1 mmol (95.5% of the dose given). The median magnesium clearance was 10 (4.7-15.8) mL/min and increased to 14.9 (3.8-20.7; p = 0.934) mL/min at 60 minutes. The estimated volume of distribution was 0.31 (0.28-0.34) L/kg.Magnesium bolus therapy after cardiac surgery leads to a significant but short-lived increase of magnesium serum concentration due to renal excretion and distribution, and the magnesium balance is neutral after 12 hours.

To assess the feasibility, biochemical efficacy, and safety of liberal versus conventional glucose control in ICU patients with diabetes.Prospective, open-label, sequential period study.A 22-bed mixed ICU of a tertiary hospital in Australia.We compared 350 consecutive patients with diabetes admitted over 15 months who received liberal glucose control with a preintervention control population of 350 consecutive patients with diabetes who received conventional glucose control.Liberal control patients received insulin therapy if glucose was greater than 14 mmol/L (target: 10-14 mmol/L [180-252 mg/dL]). Conventional control patients received insulin therapy if glucose was greater than 10 mmol/L (target: 6-10 mmol/L [108-180 mg/dL]).We assessed separation in blood glucose, insulin requirements, occurrence of hypoglycemia (blood glucose ≤ 3.9 mmol/L [70 mg/dL]), creatinine and white cell count levels, and clinical outcomes. The median (interquartile range) time-weighted average blood glucose concentration was significantly higher in the liberal control group (11.0 mmol/L [8.7-12.0 mmol/L]; 198 mg/dL [157-216 mg/dL]) than in the conventional control group (9.6 mmol/L [8.5-11.0 mmol/L]; 173 mg/dL [153-198 mg/dL]; p0.001). Overall, 132 liberal control patients (37.7%) and 188 conventional control patients (53.7%) received insulin in ICU (p0.001). Hypoglycemia occurred in 6.6% and 8.6%, respectively (p = 0.32). Among 314 patients with glycated hemoglobin A1c greater than or equal to 7%, hypoglycemia occurred in 4.1% and 9.6%, respectively (p = 0.053). Trajectories of creatinine and white cell count were similar in the groups. In multivariable analyses, we found no independent association between glucose control and mortality, duration of mechanical ventilation, or ICU-free days to day 30.In ICU patients with diabetes, during a period of liberal glucose control, insulin administration, and among patients with hemoglobin A1c greater than or equal to 7%, the prevalence of hypoglycemia was reduced, without negatively affecting serum creatinine, the white cell count response, or other clinical outcomes. (Trial Registration: Australian New Zealand Clinical Trials Registry; ACTRN12615000216516).

The environmental impact of the injection molding process is mostly due to electricity consumption. This is particularly significant for packaging products, which are the largest application sector for the plastics industry. In this work, electricity consumption measurements of the process were performed, considering a large production plant processing polypropylene packaging parts. In particular, the electricity consumption of mold thermal control was analyzed and minimized through a representative case study. The effects of alternative configurations of cooling channels and different process parameters were experimentally and numerically investigated, considering both the electricity consumption and the molded parts quality. The results indicated that the industrial common practice of maximizing the water flow rate and connecting the mold cooling circuits in parallel, to minimize the increase of coolant temperature, can be satisfactory in terms of part quality but not optimal when considering the energy consumption related to mold thermal control. By setting the hot runner and nozzle temperatures to the lowest suitable values, the coolant flow rate could be reduced significantly (−66%) without compromising the quality of the molded parts and reaching a minimum value of the energy consumption.

Rapid heat cycle molding (RHCM) of reinforced thermoplastics is increasingly used in order to obtain high surface quality on structural parts. In this work, the effect of RHCM on both microstructure and ultimate tensile strength of polypropylene reinforced with 30 wt% long glass fibers was investigated. Micro X-ray computed tomography was employed to allow a non-destructive assessment of fibers orientation and internal porosity, while optical measurements were used to evaluate the residual fibers length distribution. The experimental results indicated that an increase of injection velocity always results in a decrease of ultimate tensile stress, due to higher fiber breakage. This effect is partly attenuated at low mold temperature, due to an increase of fiber orientation. On the other hand, when using RHCM an increase of injection velocity results in a greater decrease of ultimate tensile stress, due to the reduction of both fiber length and fiber orientation.

The Hartmann procedure (HP) consists of a sigmoidectomy followed by a terminal colostomy in the left iliac fossa and closure of the rectal stump. Although done as a temporary procedure, up to 74 % of patients will not have stoma reversal with subsequent negative impact on the quality of life. A literature search was performed using MEDLINE (PubMed), The Cochrane Library, and Google Scholar, and the articles from January 2000 until December 2015, edited in English, Italian and French, prospective or retrospective, were analyzed. Outcome variables included number of patients, mean age, sex, etiology of Hartmann's procedure, time interval between initial procedure and reversal procedure (in days), mean operative time (in minutes), number of patients converted to open surgery, causes of conversion, length of hospital stay, mortality, and complication rates. For the purpose of this review, only 21 studies were considered for the final analysis and a total of 681 patients were evaluated. The mean time interval between the initial procedure and the reversal (reported in 18 articles) was 181.6 days (range 95-330 days), while the mean operative time (reported in 20 articles) was 163.2 min (range 62-285). Overall, 80 patients (11.7 %) were converted to open technique. The length of hospitalization was between 3 and 12 days. The mortality rate was reported in 19 articles and was 0.7 % (5 patients). 113 patients (16.6 %) underwent post-operative complications. The HP reversal is a challenging procedure, but it can be safely performed laparoscopically providing various advantages when compared to the open technique and it should be proposed only to a selected group of patients, young and without a severe peritonitis at the first operation.

Photovoice is a novel and promising intervention for working with youth in healthcare settings. Despite this, few studies have examined the efficacy of photovoice as a clinical tool for working with teenagers who are on their cancer journey. To better understand the needs of teenagers with cancer and the ways that photovoice can be utilized to address these needs, a systematic review of the literature was undertaken.Keyword searches of six databases were completed, including MEDLINE, EMBASE, PsycINFO, Social Work Abstracts, Sociological Abstracts, and Health and Psychosocial Instruments. Searches were limited to articles focusing on the psychosocial needs of adolescents, aged 13-17, who were on active cancer treatment.Sixty-four articles were identified that discussed the psychosocial needs of teenagers on active cancer treatment. The needs of these teenagers can be understood as being influenced by the physical changes and symptoms, psychological impact of diagnosis and treatment, short- and long-term social impacts of cancer, impact on holistic well-being, and need for clear, age-appropriate communication. Among these articles, only four articles used photovoice as a methodology and none examined the impact of photovoice as an intervention for teenagers who were currently on active treatment.Photovoice is uniquely positioned among other psychosocial interventions to help address the needs of teenagers on their cancer journey. Despite this, few researchers have examined the efficacy of photovoice as a psychosocial intervention for teenagers who are currently on active treatment.

The friction force developed in the demolding phase of the micro injection molding process is mainly determined by mold surface finish, which affects the tribological phenomena occurring at the polymer–tool interface. In this work, the effects on the ejection force of two cavity surfaces machined with different technologies (viz. micro milling and micro electro discharge machining), but with similar value of Ra , were investigated. The relations between different surface topography parameters and the ejection force were then analyzed, in order to identify the parameters that most appropriately describe the friction at the polymer–tool interface. The experimental results showed the strong interactions between the mold surface texture and the micro injection molding process parameters that promote the replication, such as mold temperature and holding pressure. The different machining technologies generated two mold textures that have a similar value of Ra , but their influence on friction can be properly described only using several other surface topography parameters.