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Importance: Tranexamic acid reduces bleeding and blood transfusion in many types of surgery, but its effect in patients undergoing liver resection for a cancer-related indication remains unclear. Objective: To determine whether tranexamic acid reduces red blood cell transfusion within 7 days of liver resection. Design, Setting, and Participants: Multicenter randomized clinical trial of tranexamic acid vs placebo conducted from December 1, 2014, to November 8, 2022, at 10 hepatopancreaticobiliary sites in Canada and 1 site in the United States, with 90-day follow-up. Participants, clinicians, and data collectors were blinded to allocation. A volunteer sample of 1384 patients undergoing liver resection for a cancer-related indication met eligibility criteria and consented to randomization. Interventions: Tranexamic acid (1-g bolus followed by 1-g infusion over 8 hours; n = 619) or matching placebo (n = 626) beginning at induction of anesthesia. Main Outcomes and Measures: The primary outcome was receipt of red blood cell transfusion within 7 days of surgery. Results: The primary analysis included 1245 participants (mean age, 63.2 years; 39.8% female; 56.1% with a diagnosis of colorectal liver metastases). Perioperative characteristics were similar between groups. Red blood cell transfusion occurred in 16.3% of participants (n = 101) in the tranexamic acid group and 14.5% (n = 91) in the placebo group (odds ratio, 1.15 [95% CI, 0.84-1.56]; P = .38; absolute difference, 2% [95% CI, -2% to 6%]). Measured intraoperative blood loss (tranexamic acid, 817.3 mL; placebo, 836.7 mL; P = .75) and total estimated blood loss over 7 days (tranexamic acid, 1504.0 mL; placebo, 1551.2 mL; P = .38) were similar between groups. Participants receiving tranexamic acid experienced significantly more complications compared with placebo (odds ratio, 1.28 [95% CI, 1.02-1.60]; P = .03), with no significant difference in venous thromboembolism (odds ratio, 1.68 [95% CI, 0.95-3.07]; P = .08). Conclusions and Relevance: Among patients undergoing liver resection for a cancer-related indication, tranexamic acid did not reduce bleeding or blood transfusion but increased perioperative complications. Trial Registration: ClinicalTrials.gov Identifier: NCT02261415.
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OBJECTIVE: This study aimed to examine the global research trend and frontiers in the field of root caries. METHODS: Two independent investigators searched the Web of Science Core Collection to include journal articles published on root caries from 1994 to 2023. They examined citation trends of the selected publications and performed bibliometric analysis using VOSviewer. Cooccurrence and cocitation analysis were used to calculate the burst strength of the most cited keywords and the most cited publications. RESULTS: This study included 1144 publications (1004 scientific research articles and 140 review articles) for bibliometric analysis. The number of publications from 2018 to 2023 was 404, accounting for 35% (404/1144) over the last 30 years. The annual citation count showed a gradual upward trend with a surge from 2018. The cooccurrence analysis classified the publications into four clusters which were in vitro studies, prevention, microbiology, and epidemiology. Cocitation analysis revealed silver diamine fluoride, systematic review, and randomized clinical trial were the three main keywords; and their citation burst strength (period) were 17.2 (2017-2023), 9.4 (2015-2023), and 6.9 (2018-2023), respectively. Noninvasive treatment of root caries (narrative review), aetiology of root caries (narrative review), and use of silver diamine fluoride in arresting root caries (clinical trial) were the topics (publication type) of the three most cited publications; and their burst strength (period) were 8.9 (2017-2020), 5.9 (2017-2021), and 4.7 (2015-2018), respectively. CONCLUSION: This study highlights the recent growing research interest in root caries, particularly on its microbiology, prevention, and the use of silver diamine fluoride.
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Small cell lung cancers (SCLCs) are composed of heterogeneous subtypes marked by lineage-specific transcription factors, including ASCL1, NEUROD1, and POU2F3. POU2F3-positive SCLCs, â¼12% of all cases, are uniquely dependent on POU2F3 itself; as such, approaches to attenuate POU2F3 expression may represent new therapeutic opportunities. Here using genome-scale screens for regulators of POU2F3 expression and SCLC proliferation, we define mSWI/SNF complexes as top dependencies specific to POU2F3-positive SCLC. Notably, chemical disruption of mSWI/SNF ATPase activity attenuates proliferation of all POU2F3-positive SCLCs, while disruption of non-canonical BAF (ncBAF) via BRD9 degradation is effective in pure non-neuroendocrine POU2F3-SCLCs. mSWI/SNF targets to and maintains accessibility over gene loci central to POU2F3-mediated gene regulatory networks. Finally, clinical-grade pharmacologic disruption of SMARCA4/2 ATPases and BRD9 decreases POU2F3-SCLC tumor growth and increases survival in vivo. These results demonstrate mSWI/SNF-mediated governance of the POU2F3 oncogenic program and suggest mSWI/SNF inhibition as a therapeutic strategy for POU2F3-positive SCLCs.
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Regulação Neoplásica da Expressão Gênica , Neoplasias Pulmonares , Carcinoma de Pequenas Células do Pulmão , Fatores de Transcrição , Humanos , Carcinoma de Pequenas Células do Pulmão/genética , Carcinoma de Pequenas Células do Pulmão/metabolismo , Carcinoma de Pequenas Células do Pulmão/patologia , Carcinoma de Pequenas Células do Pulmão/tratamento farmacológico , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/tratamento farmacológico , Animais , Fatores de Transcrição/metabolismo , Fatores de Transcrição/genética , Camundongos , Linhagem Celular Tumoral , Proliferação de Células , Proteínas Cromossômicas não Histona/metabolismo , Proteínas Cromossômicas não Histona/genética , Fator 3 de Transcrição de Octâmero/metabolismo , Fator 3 de Transcrição de Octâmero/genéticaRESUMO
INTRODUCTION: Surgical stress results in immune dysfunction, predisposing patients to infections in the postoperative period and potentially increasing the risk of cancer recurrence. Perioperative immunonutrition with arginine-enhanced diets has been found to potentially improve short-term and cancer outcomes. This study seeks to measure the impact of perioperative immunomodulation on biomarkers of the immune response and perioperative outcomes following hepatopancreaticobiliary surgery. METHODS AND ANALYSIS: This is a 1:1:1 randomised, controlled and blinded superiority trial of 45 patients. Baseline and perioperative variables were collected to evaluate immune function, clinical outcomes and feasibility outcomes. The primary outcome is a reduction in natural killer cell killing as measured on postoperative day 1 compared with baseline between the control and experimental cohorts. ETHICS AND DISSEMINATION: This trial has been approved by the research ethics boards at participating sites and Health Canada (parent control number: 223646). Results will be distributed widely through local and international meetings, presentation, publication and ClinicalTrials.gov (identifier: NCT04549662). Any modifications to the protocol will be communicated via publications and ClinicalTrials.gov. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov identifier: NCT04549662.
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Neoplasias , Humanos , Projetos de Pesquisa , Imunomodulação , Imunidade , Canadá , Ensaios Clínicos Controlados Aleatórios como Assunto , Ensaios Clínicos Fase II como AssuntoRESUMO
Background: Increasing evidence demonstrates disparities among patients with differing insurance statuses in the field of spine surgery. However, no pooled analyses have performed a robust review characterizing differences in postoperative outcomes among patients with varying insurance types. Methods: A comprehensive literature search of the PUBMED, MEDLINE(R), ERIC, and EMBASE was performed for studies comparing postoperative outcomes in patients with private insurance versus government insurance. Pooled incidence rates and odds ratios were calculated for each outcome and meta-analyses were conducted for 3 perioperative events and 2 types of complications. In addition to pooled analysis, sub-analyses were performed for each outcome in specific government payer statuses. Results: Thirty-eight studies (5,018,165 total patients) were included. Compared with patients with private insurance, patients with government insurance experienced greater risk of 90-day re-admission (OR 1.84, p<.0001), non-routine discharge (OR 4.40, p<.0001), extended LOS (OR 1.82, p<.0001), any postoperative complication (OR 1.61, p<.0001), and any medical complication (OR 1.93, p<.0001). These differences persisted across outcomes in sub-analyses comparing Medicare or Medicaid to private insurance. Similarly, across all examined outcomes, Medicare patients had a higher risk of experiencing an adverse event compared with non-Medicare patients. Compared with Medicaid patients, Medicare patients were only more likely to experience non-routine discharge (OR 2.68, p=.0007). Conclusions: Patients with government insurance experience greater likelihood of morbidity across several perioperative outcomes. Additionally, Medicare patients fare worse than non-Medicare patients across outcomes, potentially due to age-based discrimination. Based on these results, it is clear that directed measures should be taken to ensure that underinsured patients receive equal access to resources and quality care.
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PURPOSE: Children with chronic and complex health conditions frequently need intravenous devices. The current approach to intravenous device selection, insertion, and monitoring is inconsistent, and healthcare consumers are often negatively affected by siloed health information, and poor future planning. Despite child- and family-centred care being recognised as a pillar of paediatric nursing care, limited implementation for vascular access device planning and management is evident. DESIGN AND METHODS: To address this, we conducted a multi-phased approach to co-create, then evaluate, a mobile health (mHealth) application: IV Passport. Co-creation involved a prioritisation survey, followed by a Passport advisory panel consensus meeting. Following confirmation of the required content and features of the Passport, the mHealth application was designed and content validation achieved via survey. RESULTS: The prioritisation survey yielded recommendations for seven features (e.g., graphical presentations of current/past devices). Content for nine device types (e.g., totally implanted ports) was suggested, each with 10 related items (e.g., insertion site). Content items for device-associated complications, future vascular access plans, and educational resources were also suggested. Following design, the application was released through Apple and Android platforms; and adapted to a paper version. Content validation was established; 100% strongly agreed the application was easy to use; 80% agreed/strongly agreed that they would recommend the Passport to others. CONCLUSION: IV Passport embodies effective child- and family-centred care through consumer co-creation to empower patients and families manage vascular access devices. PRACTICE IMPLICATIONS: IV Passport remains active; and can be utilised across many healthcare settings and patient populations.
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Telemedicina , Dispositivos de Acesso Vascular , Humanos , Criança , Aplicativos Móveis , Masculino , Feminino , Doença Crônica , Enfermagem PediátricaRESUMO
PURPOSE: Central venous access devices play a crucial role in healthcare settings. However, there is concern regarding the high incidence of blockages occurring before the completion of treatments and existing guidelines for occlusion management are not consistently followed. To explore the decision-making and problem-solving process of occlusion management and identify enablers and barriers to implementing evidence for occlusion management in pediatric cancer care. METHODS: A qualitative design with individual semi-structured interviews. Participants were selected by purposeful sampling from a tertiary-referral pediatric facility, and semi-structured interviews were conducted. RESULTS: A total of 13 clinicians and 5 parents were interviewed. The thematic analysis revealed four main decision-making/problem-solving themes: 1) clinical reasoning and judgement for central venous access devices occlusion, 2) capability in central venous access devices occlusion management, 3) colleague collaboration in the escalation process and 4) lack of adequate support to manage the occlusion. This study identified positive and negative influences on the problem-solving process, including clinicians' psychological capabilities, social and physical resources, and beliefs about consequences. CONCLUSION: This study found that clinicians in pediatric cancer care were able to manage central venous access device occlusions using clinical reasoning and judgment skills, which may conflict with evidence-based practices. The study confirmed the importance of a team approach and prior experience in managing central venous access devices in pediatric oncology settings and identified potential conflicts between clinician decisions based on the patient's current and anticipated conditions and implementation of evidence-based practice. Improving documentation and providing visual aids could benefit clinicians' problem-solving processes.
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Cateteres Venosos Centrais , Neoplasias , Humanos , Criança , Cateteres Venosos Centrais/efeitos adversos , Neoplasias/terapia , Oncologia , Pesquisa Qualitativa , DocumentaçãoRESUMO
Silver metal and compounds have antibacterial properties, although their action's mechanisms are not fully understood. Scientists generally consider that silver disrupts the bacterial cell wall. It causes a structural change in the bacterial cell membrane and cytoplasm. It also stops deoxyribonucleic acid replication, resulting in inactivating enzymatic activity and cell death. The antimicrobial effect of silver-containing compounds relies on the release of bioactive silver ions. Hence, silver metal and compounds have been used in medicine to prevent infection for hundreds of years. Silver metal and compounds are also used as antibacterial agents in dentistry. Studies have shown that silver compounds are effective in the management of dental caries. Fluoride-containing silver compounds have been found in experiments to be beneficial at remineralising dental cavities. Silver diamine fluoride (SDF) can assist in preventing and arresting tooth cavities. The World Health Organization included SDF in its Model List of Essential Medicine for both adults and children in 2021. Clinicians also use SDF to manage dentine hypersensitivity as well as to inhibit growth of periodontal pathogens. However, traditional silver compounds cause tooth discolouration because of the silver-staining effect. These side effects of their applications depend on the amount applied and the frequency of application. Researchers are developing nanosilver fluoride and silver nanoparticles to overcome the staining. This review gives an overview of the antibacterial mechanism of silver compounds, namely silver nitrate, silver fluoride, SDF, silver nanoparticles, and nano silver fluoride for caries management. The outlook for the future development of silver compounds will be discussed.
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Cárie Dentária , Nanopartículas Metálicas , Criança , Humanos , Cariostáticos/farmacologia , Cariostáticos/uso terapêutico , Fluoretos/uso terapêutico , Cárie Dentária/tratamento farmacológico , Cárie Dentária/prevenção & controle , Suscetibilidade à Cárie Dentária , Prata/uso terapêutico , Fluoretos Tópicos/uso terapêutico , Fluoretos Tópicos/farmacologia , Compostos de Prata/farmacologia , Compostos de Prata/uso terapêutico , Compostos de Prata/química , Nitrato de Prata/uso terapêutico , Compostos de Amônio Quaternário/farmacologia , Compostos de Amônio Quaternário/uso terapêutico , Antibacterianos/uso terapêuticoRESUMO
CONTEXT: Indwelling invasive devices inserted into the body for extended are associated with infections. OBJECTIVE: This study aimed to estimate infection proportion and rates associated with invasive devices in pediatric healthcare. DATA SOURCES: Medline, CINAHL, Embase, Web of Science, Scopus, Cochrane CENTRAL, clinical trial registries, and unpublished study databases were searched. STUDY SELECTION: Cohort studies and trials published from January 2011 to June 2022, including (1) indwelling invasive devices, (2) pediatric participants admitted to a hospital, (3) postinsertion infection complications, and (4) published in English, were included. DATA EXTRACTION: Meta-analysis of observational studies in epidemiology guidelines for abstracting and assessing data quality and validity were used. MAIN OUTCOMES AND MEASURES: Device local, organ, and bloodstream infection (BSIs) pooled proportion and incidence rate (IR) per-1000-device-days per device type were reported. RESULTS: A total of 116 studies (61 554 devices and 3 632 364 device-days) were included. The highest number of studies were central venous access devices associated BSI (CVAD-BSI), which had a pooled proportion of 8% (95% confidence interval [CI], 6-11; 50 studies) and IR of 0.96 per-1000-device-days (95% CI, 0.78-1.14). This was followed by ventilator-associated pneumonia in respiratory devices, which was 19% (95% CI, 14-24) and IR of 14.08 per-1000-device-days (95%CI, 10.57-17.58). CONCLUSIONS: Although CVAD-BSI and ventilator associated pneumonia are well-documented, there is a scarcity of reporting on tissue and local organ infections. Standard guidelines and compliance initiatives similar to those dedicated to CVADs should be implemented in other devices in the future.
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Cateteres Venosos Centrais , Sepse , Criança , Humanos , IncidênciaRESUMO
Homo sapiens adenosine deaminase isoform 1 (HsADA1) hydrolyzes adenosine and 2-deoxyadenosine as a key step in the purine nucleoside salvage pathway. Some HsADA1 mutations have severe deleterious effects, as is the case in a severe combined immunodeficiency resulting from loss of enzyme activity (ADA-SCID). Other mutations that reduce enzyme activity, for instance the Asp8Asn (D8N) variant, do not cause ADA-SCID but are correlated with other consequences to health. To ease further study of HsADA1 and its variants, we optimized an inexpensive, recombinant expression process in an Escherichia coli host through multiplexed parameter testing enabled by a lysate-based microtiter plate assay. We demonstrate the importance of gene codon usage, induction time and temperature, and alcohol supplementation towards improving enzyme yield to a final titer of 5 mg per liter of culture. We further show that use of a double-histidine-tag (his-tag) system greatly improves purity. We then utilize our expression and purification framework to produce the HsADA1 D8N variant, which had previously not been purified to homogeneity. We confirm that the D8N variant is â¼30% less active than the wildtype HsADA1 and show that it better retains its activity in human serum. Additionally, we show that both HsADA1 and the D8N variant have heightened activity in serum, driven in part by a previously undescribed phenomenon involving albumin. Therefore, this work presents a valuable process to produce HsADA1 that allows for insights into it and its variants' behavior. We also confirm the utility of lysate-based activity assays towards finding optimal E. coli expression conditions for enzymes and show how fusing his-tags in tandem can enhance product purity.
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Adenosina Desaminase , Escherichia coli , Imunodeficiência Combinada Severa , Humanos , Adenosina Desaminase/genética , Adenosina Desaminase/metabolismo , Agamaglobulinemia , Escherichia coli/genética , Escherichia coli/metabolismo , Imunodeficiência Combinada Severa/genética , Proteínas Recombinantes/genética , Proteínas Recombinantes/metabolismoRESUMO
OBJECTIVE: Several studies have described disparities between male and female patients following spine surgery, but no pooled analyses have performed a robust review characterizing differences in postoperative outcomes based on gender. The purpose of this study was to broadly assess the effects of gender on postoperative outcomes following elective spine surgery. METHODS: Between November 2022 and March 2023, PubMed, MEDLINE, ERIC, and Embase were queried using artificial intelligence-assisted software for relevant cohort studies. Cohort studies with a minimum sample of 100 patients conducted in the United States since 2010 were eligible. Studies related to trauma, tumors, infections, and spinal cord pathology were excluded. Independent extraction by multiple reviewers was performed using Nested Knowledge software. A fixed- or random-effects model was used if heterogeneity among included studies in a meta-analysis was < 50% or ≥ 50%, respectively. Risk of bias was assessed independently by multiple reviewers using the Newcastle-Ottawa Scale. Pooled effect sizes were calculated for readmission, nonroutine discharge (NRD), length of stay (LOS), extended LOS, reoperation, mortality, all medical complications (individual analyses for cardiovascular, deep venous thrombosis/pulmonary embolism, genitourinary, neurological, respiratory, and systemic infection complications), and wound-related complications. For each outcome, two subanalyses were performed with studies that used either center-based (single- or multi-institution) or high-volume (national or state-wide) databases. RESULTS: Across 124 included studies, male patients had an increased incidence of mortality (OR 0.54, p < 0.0001) and all medical complications (OR 0.80, p = 0.0114), specifically cardiovascular (OR 0.68, p < 0.0001) and respiratory (OR 0.76, p = 0.0008) complications. Female patients were more likely to experience a wound-related surgical complication (OR 1.16, p = 0.0183). These findings persisted in the high-volume database subanalyses. Only center-based subanalyses showed that female patients were at greater odds of experiencing an NRD (OR 1.18, p = 0.0476), longer LOS (SMD 0.23, p = 0.0036), and extended LOS (OR 1.28, p < 0.0001). CONCLUSIONS: Males are more likely to experience death and medical complications, whereas females were more likely to face wound-related surgical complications. At the institution level, females more often experience NRD and longer hospital stays. These findings may better inform preoperative expectation management and provide more detailed postoperative risk assessments based on the patient's gender.
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Procedimentos Cirúrgicos Eletivos , Complicações Pós-Operatórias , Humanos , Procedimentos Cirúrgicos Eletivos/efeitos adversos , Complicações Pós-Operatórias/epidemiologia , Masculino , Feminino , Fatores Sexuais , Tempo de Internação , Coluna Vertebral/cirurgia , Doenças da Coluna Vertebral/cirurgiaRESUMO
Intrinsically disordered regions (IDRs) represent a large percentage of overall nuclear protein content. The prevailing dogma is that IDRs engage in non-specific interactions because they are poorly constrained by evolutionary selection. Here, we demonstrate that condensate formation and heterotypic interactions are distinct and separable features of an IDR within the ARID1A/B subunits of the mSWI/SNF chromatin remodeler, cBAF, and establish distinct "sequence grammars" underlying each contribution. Condensation is driven by uniformly distributed tyrosine residues, and partner interactions are mediated by non-random blocks rich in alanine, glycine, and glutamine residues. These features concentrate a specific cBAF protein-protein interaction network and are essential for chromatin localization and activity. Importantly, human disease-associated perturbations in ARID1B IDR sequence grammars disrupt cBAF function in cells. Together, these data identify IDR contributions to chromatin remodeling and explain how phase separation provides a mechanism through which both genomic localization and functional partner recruitment are achieved.
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Montagem e Desmontagem da Cromatina , Complexos Multiproteicos , Proteínas Nucleares , Humanos , Cromatina , Proteínas de Ligação a DNA/química , Proteínas Intrinsicamente Desordenadas/genética , Proteínas Nucleares/metabolismo , Fatores de Transcrição/metabolismo , Complexos Multiproteicos/química , Complexos Multiproteicos/metabolismoRESUMO
Background: Preclinical medical students commonly perceive shadowing as beneficial for career exploration. However, research is sparse on the broader impact of shadowing as a learning strategy. We explored students' perceptions and lived experiences of shadowing to understand its role and impact on their personal and professional lives. Methods: Between 2020-2021, individual semi-structured video interviews were conducted with 15 Canadian medical students in this qualitative descriptive study. Inductive analysis proceeded concurrently with data collection until no new dominant concepts were identified. Data were iteratively coded and grouped into themes. Results: Participants described internal and external factors that moulded shadowing experiences, arising tensions between intended and perceived experiences, and how these lived experiences impacted their wellness. Internal factors associated with shadowing behaviour included: 1) aspiring to be the best and shadowing to demonstrate excellence, 2) shadowing for career exploration, 3) shadowing as learning opportunities for early clinical exposure and career preparedness, and 4) reaffirming and redefining professional identity through shadowing. External factors were: 1) unclear residency match processes which position shadowing as competitive leverage, 2) faculty messaging that perpetuates student confusion around the intended value of shadowing, and 3) social comparison in peer discourse, fuelling a competitive shadowing culture. Conclusions: The tension between balancing wellness with career ambitions and the unintended consequences of unclear messaging regarding shadowing in a competitive medical culture highlights issues inherent in shadowing culture.
Contexte: De manière générale, les étudiants en médecine préclinique considèrent que l'observation présente une occasion intéressante d'explorer les possibilités de carrière. Cependant, peu de recherches ont été menées sur l'impact plus large de l'observation comme stratégie d'apprentissage. Nous avons exploré les perceptions et les expériences vécues des étudiants en matière d'observation afin de comprendre son rôle et ses répercussions sur leur vie personnelle et professionnelle. Méthodes: Dans le cadre de cette étude qualitative descriptive, entre 2020 et 2021, des entretiens vidéo individuels semi-structurés ont été menés avec 15 étudiants en médecine canadiens. L'analyse inductive s'est déroulée simultanément à la collecte des données jusqu'à ce qu'aucun concept dominant nouveau n'apparaisse. Les données ont été codées de manière itérative et regroupées en thèmes. Résultats: Les participants ont décrit les facteurs internes et externes qui ont façonné leur expérience de l'observation et les tensions qui en ont découlé, ainsi que l'impact de ces expériences sur leur bien-être. Les facteurs internes associés au comportement d'observation sont les suivants : 1) vouloir être le meilleur et faire de l'observation pour montrer son excellence, 2) faire de l'observation dans le but d'explorer les débouchés de carrière, 3) faire de l'observation pour apprendre par l'exposition clinique précoce et pour se préparer à la carrière, et 4) réaffirmer et redéfinir l'identité professionnelle par l'observation. Les facteurs externes sont 1) le manque de clarté dans les processus de jumelage des résidents pouvant donner l'impression que l'observation est un atout, 2) le discours enseignant qui entretient la confusion des étudiants quant à la valeur de l'observation, et 3) la comparaison sociale dans le discours des pairs, alimentant une culture de l'observation compétitive. Conclusions: La difficulté de trouver un équilibre entre le bien-être et les ambitions professionnelles, et les conséquences involontaires d'un discours peu clair concernant l'observation dans le contexte d'un climat compétitif mettent en évidence les problèmes inhérents à la culture de l'observation.
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Estudantes de Medicina , Humanos , Canadá , Aspirações Psicológicas , Confusão , Coleta de DadosRESUMO
OBJECTIVE: Patient-provider discussions about functioning are often outside the scope of usual care for systemic lupus erythematosus (SLE), and tools to facilitate such discussions are lacking. The present study was undertaken to assess the comprehension, utility, and acceptability of a novel, individualized functioning report, the purpose of which is to facilitate patient-provider communication about functioning, in a predominantly Black SLE patient population. METHODS: Individualized reports (including sections with pictorial representations of participants' measured activities of daily living, falls, physical performance, perceived physical functioning, and community mobility from a previous pilot study visit) and surveys were emailed or mailed to 59 SLE patients. Ease of interpretation was dichotomized ("very easy" versus all other responses). Utility and acceptability were assessed by items relating to usefulness for care planning and comfort with discussing the report. RESULTS: Among 47 (79.7%) SLE patients who completed the survey (78.7% Black, 91.5% female, mean age 49.6 years), the reported ease of interpretation ranged from 70.2% to 85.1% across the report sections. Ease of interpretation was lower among those who were older, Black, and female and who had lower cognitive scores (P > 0.05 for all). Most reported that physical functioning domains of the report were useful for treatment or other care planning (70.2-80.5%) and that they felt comfortable discussing the report with a health care provider (93.2-100%). CONCLUSION: We found that a novel functioning report for SLE patients was associated with high comprehension, utility, and acceptability. Future studies can help determine how an individualized functioning report could improve patient-provider communication in the clinic setting.
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Atividades Cotidianas , Lúpus Eritematoso Sistêmico , Humanos , Feminino , Pessoa de Meia-Idade , Masculino , Compreensão , Projetos Piloto , Lúpus Eritematoso Sistêmico/psicologia , Inquéritos e Questionários , Qualidade de VidaRESUMO
OBJECTIVE: The objective of this meta-analysis was to summarize evidence on the therapeutic effects of non-invasive brain stimulation (NIBS) on core symptoms of multiple sclerosis (MS). Specifically, findings from studies deploying transcranial direct current stimulation (tDCS) and repetitive transcranial magnetic stimulation (rTMS) protocols were summarized in this review. METHODS: We systematically searched articles published in four databases, until 31 May 2021, which compared the effects of active tDCS or rTMS with sham intervention in MS patients. We used a random-effects model for this meta-analysis. Meta-regression and subgroup meta-analysis were used to examine the effects of stimulation dose and different stimulation protocols, respectively. RESULTS: Twenty-five randomized controlled trials (RCTs) were included in this review, consisting of 19 tDCS and 6 rTMS studies. tDCS led to a significant and immediate reduction of fatigue with a large effect size (Hedges's g = -0.870, 95% confidence intervals (CI) = [-1.225 to -0.458], number needed to treat (NNT) = 2). Particularly, a subgroup analysis showed that applying tDCS over the left DLPFC and bilateral S1 led to fatigue reductions compared to sham stimulation. Furthermore, tDCS had favorable effects on fatigue in MS patients with low physical disability but not those with high physical disability, and additionally improved cognitive function. Finally, whereas rTMS was observed to reduce muscle spasticity, these NIBS protocols showed no further effect on MS-associated pain and mood symptoms. CONCLUSION: tDCS in MS alleviates fatigue and improves cognitive function whereas rTMS reduces muscle spasticity. More high-quality studies are needed to substantiate the therapeutic effects of different NIBS protocols in MS.
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As of September 1st 2020, over 42 000 COVID-19 cases and 2 800 COVID-19-related deaths have been confirmed in Ontario, Canada. Testing enables quick identification of cases, which results in effective contact tracing and containment of virus spread. Faced with a lack of surge capacity in the public health laboratory system at the start, health officials implemented changes to testing and laboratory infrastructure to significantly expand testing capacity to include 1) the centralization of resources; and 2) the integration of private and independent labs into the COVID-19 testing program. With these changes, testing capacity has grown from approximately 4,000/day in March to 32,000/day by the end of August, 2020. Eligibility criteria for testing has expanded to increase sensitivity and include testing of asymptomatic individuals. Along with previous outbreaks, the COVID-19 pandemic has highlighted the need for integration of testing surge capacity in public health systems before outbreaks occur. This paper details the development and implementation of a COVID-19 testing program in Ontario from January 2020 to September 2020 during the first-wave of the pandemic. The goal of this analysis is to explore the historical precedence, present influences, and future implications of the program.
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COVID-19 , Pandemias , Teste para COVID-19 , Humanos , Ontário , SARS-CoV-2 , Capacidade de Resposta ante EmergênciasRESUMO
Inflammatory biomarkers may be associated with disease severity and increased mortality in COVID-19 patients but have not been studied in North American populations. We sought to determine whether a set of commonly ordered inflammatory biomarkers can predict 28-day mortality. We analyzed a multi-centered (four) COVID-19 registry cohort from March 4th to December 7th, 2020. This cohort included COVID-19-positive patients admitted to medical wards or intensive care units. Patients presenting to the emergency department for COVID-19 symptoms and then subsequently discharged were also included. We performed Cox-regression analysis to measure whether commonly used biomarkers were associated with an increased 28-day mortality. Of 336 COVID-19-positive patients, 267 required hospital admission, and 69 were seen in the emergency room and discharged. The median age was 63 years (IQR 80-50) and the female-to-male ratio was 49:51. Derivation of internally validated cut-offs suggested that C-reactive protein ≥ 78.4 mg/L, neutrophil-to-lymphocyte ratio ≥ 6.1, lymphocyte-to-white blood cell ratio < 0.127, and a modified Glasgow prognostic score equal to 2 vs. 1 or 0 were associated with the highest increased risk of 28-day mortality. We provide early estimates of cut-off values for inflammatory biomarkers and indices measured at the time of admission that may be useful to clinicians for predicting 28-day mortality in North American COVID-19 patients.
Assuntos
Proteína C-Reativa/metabolismo , COVID-19/metabolismo , COVID-19/mortalidade , Linfócitos/metabolismo , Neutrófilos/metabolismo , Idoso , Biomarcadores/metabolismo , Teste para COVID-19 , Estado Terminal/mortalidade , Feminino , Mortalidade Hospitalar , Humanos , Unidades de Terapia Intensiva , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos , Fatores de Risco , Índice de Gravidade de DoençaRESUMO
OBJECTIVES: To examine the gender distribution of authorship of pediatric critical care randomized control trials. DATA SOURCES: The 415 randomized control trials in pediatric critical care published before 2019. STUDY SELECTION: We included all randomized control trials enrolling children in a PICU. We used PICUtrials.net, which uses comprehensive search strategies of multiple databases, to identify published randomized control trials. DATA EXTRACTION: We manually extracted the name and profession of each listed author from each publication and classified each author as male or female based on their name. RESULTS: We included 2,146 authors and were able to classify 1,888 (88%) as men or women. Overall, 38% of authors were women, this varied with the authorship position: 37% of first, 38% of middle, and 25% of last authors were women (p < 0.001). The three most common professions were physician (63%), nonclinician (11%), and nurse (6%)-of which 30%, 45%, and 97%, respectively, were women. The percentage of female authorship overall has increased from 28% in 1985-1989 to 39% in 2015-2018 (p for trend = 0.004). There were no significant differences in the characteristics of randomized control trials published with a female first or last author versus those with both male first and last authors with respect to the median number of children randomized (60 vs. 50; p = 0.41), multicentred trials (17% vs. 24%; p = 0.12), trials at low risk of bias (50% vs. 66%; p = 0.26), reporting any funding (55% vs. 51%; p = 0.66), or median number of citations per year (1.5 vs. 2.4; p = 0.09). CONCLUSIONS: Although increasing over time, the percentage of researchers publishing pediatric critical care randomized control trials who are women still lags behind the percentage clinicians who are women. Trials that female researchers publish are similar in characteristics and impact as male researchers. Further work should identify barriers to gender diversity and potential solutions in pediatric critical care research.