Evaluating the performance of the PRISMA-7 frailty criteria for predicting disability and death after acute ischemic stroke.

OBJECTIVES: We aimed to evaluate the predictive performance of the PRISMA-7 frailty criteria regarding the composite outcome of disability or death in patients with an acute ischemic stroke, and to compare it with the Frailty Index and the National Institutes of Health Stroke Scale (NIHSS). MATERIALS AND METHODS: This prospective cohort study involved all patients aged ≥ 40 years admitted with an acute ischemic stroke between March 2019 and January 2020. We performed survival analyses, calculated risk ratios, sensitivity, specificity, and predictive values for the combined outcome of disability or death according to the presence of frailty as determined by the PRISMA-7 and the Frailty Index, and stroke severity based on the NIHSS. RESULTS: In 174 patients with acute ischemic stroke, being frail in the week before the stroke according to the PRISMA-7 was associated with a Risk Ratio of 4·50 (95%CI 1·77-11·43, P <0·001) and a Positive Predictive Value of 89% (95%CI 77-99%) for being disabled or dead 90 days after the stroke, and a Hazard Ratio of 3·33 (95%CI 1·48-7·51, P = 0·004) for the survival outcome. The predictive performance of the PRISMA-7 was not significantly different from the Frailty Index or the NIHSS. CONCLUSIONS: We provide evidence that the PRISMA-7 frailty criteria may be a useful prognostication tool in acute ischemic stroke.

Why medical schools are tolerant of unethical behavior.

The exposure to unethical and unprofessional behavior is thought to play a major role in the declining empathy experienced by medical students during their training. We reflect on the reasons why medical schools are tolerant of unethical behavior of faculty. First, there are barriers to reporting unprofessional behavior within medical schools including fear of retaliation and lack of mechanisms to ensure anonymity. Second, deans and directors do not want to look for unethical behavior in their colleagues. Third, most of us have learned to take disrespectful circumstances in health care institutions for granted. Fourth, the accreditation of medical schools around the world does not usually cover the processes or outcomes associated with fostering ethical behavior in students. Several initiatives promise to change that picture.

Mindfulness training in medical education as a means to improve resilience, empathy, and mental health in the medical profession.

The high rates of depression, burnout, and increased risk of suicide among medical students, residents, and physicians in comparison with other careers signal a mental health crisis within our profession. We contend that this crisis coupled with the inadequate acquisition of interpersonal skills during medical education results from the interaction between a challenging environment and the mental capital of individuals. Additionally, we posit that mindfulness-based practices are instrumental for the development of major components of mental capital, such as resilience, flexibility of mind, and learning skills, while also serving as a pathway to enhance empathy, compassion, self-awareness, conflict resolution, and relational abilities. Importantly, the evidence base supporting the effectiveness of mindfulness-based interventions has been increasing over the years, and a growing number of medical schools have already integrated mindfulness into their curricula. While we acknowledge that mindfulness is not a panacea for all educational and mental health problems in this field, we argue that there is currently an unprecedented opportunity to gather momentum, spread and study mindfulness-based programs in medical schools around the world as a way to address some longstanding shortcomings of the medical profession and the health and educational systems upon which it is rooted.

Evaluating the Interaction Between Pain Intensity and Resilience on the Impact of Pain in the Lives of People With Fibromyalgia.

OBJECTIVE: Recent theoretical models posit that resilience acts as a resource/mechanism opposing pain catastrophizing and other vulnerability sources against pain adaptation. The aim of this study was to investigate the relationship between resilience, pain, and functionality in people living with fibromyalgia (FM). MATERIALS AND METHODS: We conducted a cross-sectional online survey of people participating in Brazilian fibromyalgia virtual support groups on Facebook in May 2018. Resilience was evaluated by the Connor-Davidson Resilience Scale. Average pain and the degree of interference of pain in the lives of participants (DIPLP) were assessed using the Brief Pain Inventory. The association between these 3 variables was evaluated through multivariable robust linear regression with adjustment for 21 potential confounders. RESULTS: We included 2176 participants with FM. Resilience was associated with a decreased DIPLP (ß: -0.38, 95% CI: -0.54 to -0.22, P <0.001) but not with average pain scores (ß: -0.01, 95% CI: -0.18 to 0.16, P =0.93). A significant interaction between resilience and average levels of pain on the DIPLP was observed so that resilience showed a much stronger protective association among participants with average null-to-mild pain than among those with moderate and severe pain levels. DISCUSSION: Our results provide evidence against beliefs that the pain of people with FM is related to low psychological resilience and shed light on the complex interrelationships between resilience, pain, and functionality. This research signals both the relevance and limits of resilience in the management of FM. Future studies evaluating behavioral interventions for FM should consider how those interventions interact with baseline pain levels and resilience.

Cannabinoid products for pain management: recommendations from the São Paulo State Society of Anesthesiology.

There is growing interest in using cannabinoids across various clinical scenarios, including pain medicine, leading to the disregard of regulatory protocols in some countries. Legislation has been implemented in Brazil, specifically in the state of São Paulo, permitting the distribution of cannabinoid products by health authorities for clinical purposes, free of charge for patients, upon professional prescription. Thus, it is imperative to assess the existing evidence regarding the efficacy and safety of these products in pain management. In light of this, the São Paulo State Society of Anesthesiology (SAESP) established a task force to conduct a narrative review on the topic using the Delphi method, requiring a minimum agreement of 60% among panelists. The study concluded that cannabinoid products could potentially serve as adjuncts in pain management but stressed the importance of judicious prescription. Nevertheless, this review advises against their use for acute pain and cancer-related pain. In other clinical scenarios, established treatments should take precedence, particularly when clinical protocols are available, such as in neuropathic pain. Only patients exhibiting poor therapeutic responses to established protocols or demonstrating intolerance to recommended management may be considered as potential candidates for cannabinoids, which should be prescribed by physicians experienced in handling these substances. Special attention should be given to individual patient characteristics and the likelihood of drug interactions.

The effects of subarachnoid administration of preservative-free S(+)-ketamine on spinal cord and meninges in dogs.

BACKGROUND: The N-methyl-d-aspartate receptor antagonist ketamine and its active enantiomer, S(+)-ketamine, have been injected in the epidural and subarachnoid spaces to treat acute postoperative pain and relieve neuropathic pain syndrome. In this study we evaluated the effects of a single dose of preservative-free S(+)-ketamine, in doses usually used in clinical practice, in the spinal cord and meninges of dogs. METHODS: Under anesthesia (IV etomidate (2 mg/kg) and fentanyl (0.005 mg/kg), 16 dogs (6 to 15 kg) were randomized to receive a lumbar intrathecal injection (L5/6) of saline solution of 0.9% (control group) or S(+)-ketamine 1 mg/kg(-1) (ketamine group). All doses were administered in a volume of 1 mL over a 10-second interval. Accordingly, injection solution ranged from 0.6% to 1.5%. After 21 days of clinical observation, the animals were killed; spinal cord, cauda equina root, and meninges were removed for histological examination with light microscopy. Tissues were examined for demyelination (Masson trichrome), neuronal death (hematoxylin and eosin) and astrocyte activation (glial fibrillary acidic protein). RESULTS: No clinical or histological alterations of spinal tissue or meninges were found in animals from either control or ketamine groups. CONCLUSION: A single intrathecal injection of preservative-free S(+)-ketamine, at 1 mg/kg(-1) dosage, over a concentration range of 6 to 15 mg/mL injected in the subarachnoid space in a single puncture, did not produce histological alterations in this experimental model.

Metformin for the treatment of breast cancer: protocol for a scoping review of randomised clinical trials.

INTRODUCTION: Innovation through the repurposing of generic drugs encloses several advantages when compared with the process of developing new drugs from scratch. Metformin is an established and inexpensive antidiabetic drug for which anticancer properties have been hypothesised. A systematic review of observational studies found promising results for metformin related to breast cancer in women with diabetes. Although the number of randomised clinical trials of metformin for the treatment of breast cancer increased over the last decades, the overall landscape of those studies in this heterogeneous field remains unclear. Hence, we designed the present scoping review protocol to map the literature on randomised clinical trials of metformin in the treatment of breast cancer to determine the value and scope of future systematic reviews on this subject and identify research gaps. METHODS: We will search MEDLINE (via PubMed), EMBASE, CENTRAL, LILACS, Web of Science and sources of grey literature. We will include any randomised clinical trial of metformin for the treatment of breast cancer in adult women, and will not impose restrictions regarding context, language or publication date. Two independent reviewers will screen and select studies, and chart the data. We will structure the presentation of our results based on the molecular types of breast cancer, their stages and treatment modalities. ETHICS AND DISSEMINATION: As a literature review, this study is exempt from ethics approval. Findings will be disseminated through presentations in conferences and a peer-reviewed publication. OPEN SCIENCE FRAMEWORK REGISTRATION: osf.io/yquba.

Evaluation of the Interrater Reliability of End-of-Life Medical Orders in the Physician Orders for Life-Sustaining Treatment Form.

Importance: Despite its spread in much of the United States and increased international interest, the Physician Orders for Life-Sustaining Treatment (POLST) paradigm still lacks supporting evidence. The interrater reliability of the POLST form to translate patients' values and preferences into medical orders for care at the end of life remains to be studied. Objective: To assess the interrater reliability of the medical orders documented in POLST forms. Design, Setting, and Participants: This cross-sectional study was conducted in a public university hospital in southeastern Brazil. Two independent researchers interviewed the same patients or decision-making surrogates (n = 64) during a single episode of hospitalization within a time frame of 1 to 7 days. Eligible participants were hospitalized adults aged 21 years or older who were expected to remain hospitalized for at least 4 days and whose attending physician responded no to the question, Would I be surprised if this patient died in the next year? Data collection occurred between November 1, 2015, and September 20, 2016, and first data analyses were performed on October 3, 2016. Main Outcomes and Measures: Interrater reliability as measured by κ statistics. Results: Of the 64 participants interviewed in the study, 53 (83%) were patients and 11 (17%) were surrogates. Patients' mean (SD) age was 64 (14) years, and 35 patients (55%) and 8 surrogates (73%) were women. Overall, in 5 cases (8%), disagreement in at least 1 medical order for life-sustaining treatment was found in the POLST form, changing from the first interview to the second interview. The κ statistic for cardiopulmonary resuscitation was 0.92 (95% CI, 0.80-1.00); for level of medical intervention, 0.89 (95% CI, 0.76-1.00); and for artificially administered nutrition, 0.92 (95% CI, 0.83-1.00). Conclusions and Relevance: The high interrater reliability of the medical orders in POLST forms appears to offer further support for this advance care planning paradigm; in addition, the finding that this interrater reliability was not 100% underscores the need to ensure that patients or their surrogates have decision-making capacity and to confirm that the content of POLST forms accurately reflects patients' current treatment preferences.

Systematic reviews showed insufficient evidence for clinical practice in 2004: what about in 2011? The next appeal for the evidence-based medicine age.

RATIONALE AND AIM: The aims of the Cochrane systematic reviews are to make readily available and up-to-date information for clinical practice, offering consistent evidence and straightforward recommendations. In 2004, we evaluated the conclusions from Cochrane systematic reviews of randomized controlled trials in terms of their recommendations for clinical practice and found that 47.83% of them had insufficient evidence for use in clinical practice. We proposed to reanalyze the reviews to evaluate whether this percentage had significantly decreased. METHODS: A cross-sectional study of systematic reviews published in the Cochrane Library (Issue 7, 2011) was conducted. We randomly selected reviews across all 52 Cochrane Collaborative Review Groups. RESULTS: We analyzed 1128 completed systematic reviews. Of these, 45.30% concluded that the interventions studied were likely to be beneficial, of which only 2.04% recommended no further research. In total, 45.04% of the reviews reported that the evidence did not support either benefit or harm, of which 0.8% did not recommend further studies and 44.24% recommended additional studies; the latter has decreased from our previous study with a difference of 3.59%. CONCLUSION: Only a small number of the Cochrane collaboration's systematic reviews support clinical interventions with no need for additional research. A larger number of high-quality randomized clinical trials are necessary to change the 'insufficient evidence' scenario for clinical practice illustrated by the Cochrane database. It is recommended that we should produce higher-quality primary studies in active collaboration and consultation with global scholars and societies so that this can represent a major component of methodological advance in this context.

B-type natriuretic peptide in the evaluation of cardiac function / Peptídeo natriurético tipo B na avaliação da função cardíaca

B type natriuretic peptide (BNP) and its precursor, the inactive form of NT-pro-BNP, are currently the most studied laboratory parameters in the heart disease spectrum. The assessment of their blood concentrations provides invaluable information on the likelihood, severity and prognosis of the disease. The present review aims to describe the biological determinants, the factors that influence these peptide concentrations, the suggested cutoff values for the diagnosis of heart failure and the use of this biomarker in the assessment of cardiac function.

O peptídeo natriurético tipo B (BNP) ou o seu precursor, a forma inativa do fragmento N terminal do pró-BNP (NT-pró-BNP), são os parâmetros laboratoriais mais estudados atualmente no espectro da insuficiência cardíaca (IC). Por meio da mensuração de seus níveis no sangue, informações valiosas quanto a probabilidade, gravidade e prognóstico da doença podem ser reunidas. Esta revisão tem como objetivo descrever os determinantes biológicos, os fatores interferentes nas concentrações desses peptídeos, os valores de corte sugeridos para diagnóstico da IC e o uso deste biomarcador na avaliação da função cardíaca.

Efeitos determinados pela amitriotilina, administrada pela via subaracnóidea, sobre a medula e as meninges: estudo experimental em cães / Effects of intraspinal amitriptyline on spinal cord and meninges: Experimental study in dogs

Introdução e Objetivo: A amitriptilina é o protótipo dos antidepressivos tricíclicos, classe de fármaco muito utilizada no tratamento da dor neuropática. Tem por propriedade principal a inibição da recaptação de serotonina e noradrenalina, além de interagir com diversos outros receptores. Estudos recentes demonstraram que os antidepressivos tricíclicos são potentes bloqueadores dos canais de sódio, potássio e cálcio, apresentando propriedades semelhantes aos anestésicos locais. Assim existe potencial para que esta classe farmacológica possa ser utilizada no neuroeixo como adjuvante anestésico local ou no tratamento de síndromes dolorôsas neuropáticas refratárias. Entretanto, até o presente momento, não há consenso quanto a neurotoxicidade desta classe farmacológica sobre a medula e as meninges. O objetivo desta pesquisa foi avaliar a toxicidade da amitriptilina sobre a medula e as meninges quando administrada pela via subaracnóidea em cães. Método: Vinte e um animais foram randomizados em três grupos que receberam pela via subaracnóidea: Grupo 1 - Solução fisiológica 0,9%; Grupo 2 - solução de amitriptilina 5 mmol.ml-1; Grupo 3- solução de amitriptilina 10 mmol.ml-1. A punção subaracnóidea foi realizada no espaço intervertebral L6-L7. O volume da solução injetada foi de 1 ml. Os animais foram avaliados após uma hora da administração do fármaco e durante os 21 dias que permaneceram em cativeiro quanto ao tônus do esfíncter anal, bloqueio motor e sensibilidade dolorosa. Os animais foram sacrificados por eletrocussão sob anestesia. A medula e as meninges fixadas com solução de formalina 10%, coradas pelos métodos hematoxilina-eosina e tricrômico de Masson, para posterior analise histológica, O estudo foi duplamente encoberto. Para avaliação estatística foi utilizada a análise de variância. Resultados: Durante o período de observação de 21 dias os animais mantiveram-se sadios. Todos os animais recobraram a função motora e o tônus esfincteriano...