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1.
Anesthesiology ; 2021 Feb 02.
Artigo em Inglês | MEDLINE | ID: mdl-33529334

RESUMO

BACKGROUND: Preoperative frailty is strongly associated with postoperative complications and mortality. However, the pathways between frailty, postoperative complications, and mortality are poorly described. The authors hypothesized that the occurrence of postoperative complications would mediate a substantial proportion of the total effect of frailty on mortality after elective noncardiac surgery. METHODS: Following protocol registration, the authors conducted a retrospective cohort study of intermediate- to high-risk elective noncardiac surgery patients (2016) using National Surgical Quality Improvement Program data. The authors conducted Bayesian mediation analysis of the relationship between preoperative frailty (exposure, using the Risk Analysis Index), serious complications (mediator), and 30-day mortality (outcome), comprehensively adjusting for confounders. The authors estimated the total effect of frailty on mortality (composed of the indirect effect mediated by complications and the remaining direct effect of frailty) and estimated the proportion of the frailty-mortality association mediated by complications. RESULTS: The authors identified 205,051 patients; 1,474 (0.7%) died. Complications occurred in 20,211 (9.9%). A 2 SD increase in frailty score resulted in a total association with mortality equal to an odds ratio of 3.79 (95% credible interval, 2.48 to 5.64), resulting from a direct association (odds ratio, 1.76; 95% credible interval, 1.34 to 2.30) and an indirect association mediated by complications (odds ratio, 2.15; 95% credible interval, 1.58 to 2.96). Complications mediated 57.3% (95% credible interval, 40.8 to 73.8) of the frailty-mortality association. Cardiopulmonary complications were the strongest mediators among complication subtypes. CONCLUSIONS: Complications mediate more than half of the association between frailty and postoperative mortality in elective noncardiac surgery.

2.
Shock ; Publish Ahead of Print2021 Jan 04.
Artigo em Inglês | MEDLINE | ID: mdl-33399356

RESUMO

ABSTRACT: In this mini-review we provide an overview of sex- and gender-dependent issues in both clinical and preclinical sepsis. The increasing recognition for the need to account for sex and gender in biomedical research brings a unique set of challenges and requires researchers to adopt best practices in conducting and communicating sex- and gender-based research. This may be of particular importance in sepsis given the potential contribution of sex bias in the failures of translational sepsis research in adults and neonates. Clinical evidence of sex-dependent differences in sepsis is equivocal. Since clinical studies are limited to observational data and confounded by a multitude of factors, preclinical studies provide a unique opportunity to investigate sex-differences in a controlled, experimental environment. Numerous preclinical studies have suggested that females may experience favourable outcomes in comparison to males. The underlying mechanistic evidence for sex-dependent differences in sepsis and other models of shock (e.g. trauma-hemorrhage) largely centres around the beneficial effects of estrogen. Other mechanisms, such as the immunosuppressive role of testosterone and X-linked mosaicism are also thought to contribute to observed sex- and gender-dependent differences in sepsis. Significant knowledge gaps still exist in this field. Future investigations can address these gaps through careful consideration of sex and gender in clinical studies, and the use of clinically accurate preclinical models that reflect sex differences. A better understanding of sex-and gender-dependent differences may serve to increase translational research success.

3.
Transl Stroke Res ; 2021 Jan 06.
Artigo em Inglês | MEDLINE | ID: mdl-33405011

RESUMO

Remote ischemic conditioning (RIC) is a promising neuroprotective therapy for ischemic stroke. Preclinical studies investigating RIC have shown RIC reduced infarct volume, but clinical trials have been equivocal. Therefore, the efficacy of RIC in reducing infarct volume and quality of current literature needs to be evaluated to identify knowledge gaps to support future clinical trials. We performed a systematic review and meta-analysis of preclinical literature involving RIC in rodent models of focal ischemia. This review was registered with PROSPERO (CRD42019145441). Eligibility criteria included rat or mice models of focal ischemia that received RIC to a limb either before, during, or after stroke. MEDLINE and Embase databases were searched from 1946 to August 2019. Risk of bias was assessed using the SYRCLE risk of bias tool along with construct validity. Seventy-two studies were included in the systematic review. RIC was shown to reduce infarct volume (SMD - 2.19; CI - 2.48 to - 1.91) when compared to stroke-only controls and no adverse events were reported with regard to RIC. Remote ischemic conditioning was shown to be most efficacious in males (SMD - 2.26; CI - 2.58 to - 1.94) and when delivered poststroke (SMD - 1.34; CI - 1.95 to - 0.73). A high risk of bias was present; thus, measures of efficacy may be exaggerated. A limitation is the poor methodological reporting of many studies, resulting in unclear construct validity. We identified several important, but under investigated topics including the efficacy of RIC in different stroke models, varied infarct sizes and location, and potential sex differences.

4.
Crit Care Med ; 49(2): 311-323, 2021 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-33332817

RESUMO

OBJECTIVES: In many jurisdictions, ethical concerns require surrogate humane endpoints to replace death in small animal models of acute lung injury. Heterogenous selection and reporting of surrogate endpoints render interpretation and generalizability of findings between studies difficult. We aimed to establish expert-guided consensus among preclinical scientists and laboratory animal veterinarians on selection and reporting of surrogate endpoints, monitoring of these models, and the use of analgesia. DESIGN: A three-round consensus process, using modified Delphi methodology, with researchers who use small animal models of acute lung injury and laboratory animal veterinarians who provide care for these animals. Statements on the selection and reporting of surrogate endpoints, monitoring, and analgesia were generated through a systematic search of MEDLINE and Embase. Participants were asked to suggest any additional potential statements for evaluation. SETTING: A web-based survey of participants representing the two stakeholder groups (researchers, laboratory animal veterinarians). Statements were rated on level of evidence and strength of support by participants. A final face-to-face meeting was then held to discuss results. SUBJECTS: None. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Forty-two statements were evaluated, and 29 were rated as important, with varying strength of evidence. The majority of evidence was based on rodent models of acute lung injury. Endpoints with strong support and evidence included temperature changes and body weight loss. Behavioral signs and respiratory distress also received support but were associated with lower levels of evidence. Participants strongly agreed that analgesia affects outcomes in these models and that none may be necessary following nonsurgical induction of acute lung injury. Finally, participants strongly supported transparent reporting of surrogate endpoints. A prototype composite score was also developed based on participant feedback. CONCLUSIONS: We provide a preliminary framework that researchers and animal welfare committees may adapt for their needs. We have identified knowledge gaps that future research should address.

5.
J Clin Epidemiol ; 132: 116-124, 2020 Dec 17.
Artigo em Inglês | MEDLINE | ID: mdl-33346013

RESUMO

OBJECTIVES: The objective of the study was to assess the impact of narrative review (NR) vs. systematic review (SR) on expert assessments of a clinical trial. STUDY DESIGN AND SETTING: Experts in colon and rectal surgery were randomized to read an NR or SR for an ongoing clinical trial involving surgery for colorectal cancer. Experts from the United States and Canada completed online or paper surveys between December 2018 and June 2019. After reading the NR or SR, experts predicted the trial's outcome and evaluated the trial under a hypothetical ethical review. RESULTS: Experts who read the NR (n = 55) compared with those who read the SR (n = 56) were more likely to predict a higher absolute risk reduction, 58% vs. 33%, P = 0.018, mean predictions 10.6% vs. 6.6%, mean difference 4.0% [95% confidence interval: 0.3%, 7.8%]. Experts who read the NR were more likely to evaluate the trial more favorably under a hypothetical ethical review, 48% vs. 26%, P = 0.039, 20.0% vs. 8.9% "strongly in favor" of trial being pursued. CONCLUSION: An NR and an SR for the same trial led to different judgments of likely outcomes and ethical appropriateness. These differences point to a potential source of unaddressed bias in ethical review.

6.
Stem Cell Rev Rep ; 2020 Nov 07.
Artigo em Inglês | MEDLINE | ID: mdl-33159616

RESUMO

INTRODUCTION: Treating and preventing graft-versus-host disease (GVHD) after allogeneic hematopoietic cell transplant (HCT) remains a significant challenge. The use of mesenchymal stromal cell-derived extracellular vesicles (MSC-EVs) appears promising and a systematic review of preclinical studies is needed to accelerate the design of translational studies. METHODS: We identified 4 eligible studies from a systematic review performed on December 1, 2018. In brief, eligible studies included the treatment or prevention of GVHD in animal models and the use of MSC-EVs. Study design and outcome data were extracted and reporting was evaluated using the SYRCLE tool to identify potential bias. RESULTS: Two studies assessed the efficacy of MSC-EVs in treatment of GVHD and 2 studies address prevention. Mice treated with MSC-EVs showed improved median survival, GVHD clinical scores and histology scores as compared to untreated mice with GVHD. Prophylactic treatment with MSC-EVs attenuated GVHD severity and improved median survival as compared to no treatment or saline. CONCLUSION: Our systematic review provides important insight regarding the potential of MSC-EVs to treat or prevent GVHD. Although few studies were identified, improved survival and attenuated histologic findings of GVHD were observed in mice after MSC-EV administration for the treatment and prevention of GVHD. Dosing of EVs and route of administration remain inconsistent, however, and scalability of EV isolation for clinical studies remains a challenge. Standardized outcome reporting is needed to pool results for metanalysis. Graphical abstract.

7.
BMC Gastroenterol ; 20(1): 372, 2020 Nov 10.
Artigo em Inglês | MEDLINE | ID: mdl-33167889

RESUMO

BACKGROUND: Inflammatory bowel disease (IBD) is a debilitating chronic disease with limited treatment options. Resistant starches may represent a novel treatment for IBD. However, its efficacy and safety remain unclear. Our objective was to perform a systematic review to summarize the preclinical and clinical effects of resistant starch, which may help guide future studies. METHODS: Medline, EMBASE, and the Cochrane Central Register were searched. Included studies investigated the use of resistant starch therapy in in vivo animal models of IBD or human patients with IBD. Articles were screened, and data extracted, independently and in duplicate. The primary outcomes were clinical remission (clinical) and bowel mucosal damage (preclinical). RESULTS: 21 preclinical (n = 989 animals) and seven clinical (n = 164 patients) studies met eligibility. Preclinically, resistant starch was associated with a significant reduction in bowel mucosal damage compared to placebo (standardized mean difference - 1.83, 95% CI - 2.45 to - 1.20). Clinically, five studies reported data on clinical remission but clinical and methodological heterogeneity precluded pooling. In all five, a positive effect was seen in patients who consumed resistant starch supplemented diets. The majority of studies in both the preclinical and clinical settings were at a high or unclear risk of bias due to poor methodological reporting. CONCLUSIONS: Our review demonstrates that resistant starch is associated with reduced histology damage in animal studies, and improvements in clinical remission in IBD patients. These results need to be tempered by the risk of bias of included studies. Rigorously designed preclinical and clinical studies are warranted. Trial registration The review protocols were registered on PROSPERO (preclinical: CRD42019130896; clinical: CRD42019129513).

8.
F1000Res ; 9: 485, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33123348

RESUMO

Background: The process of translating preclinical findings into a clinical setting takes decades. Previous studies have suggested that only 5-10% of the most promising preclinical studies are successfully translated into viable clinical applications. The underlying determinants of this low success rate (e.g. poor experimental design, suboptimal animal models, poor reporting) have not been examined in an empirical manner. Our study aims to determine the contemporary success rate of preclinical-to-clinical translation, and subsequently determine if an association between preclinical study design and translational success/failure exists. Methods: Established systematic review methodology will be used with regards to the literature search, article screening and study selection process. Preclinical, basic science studies published in high impact basic science journals between 1995 and 2015 will be included. Included studies will focus on publicly available interventions with potential clinical promise. The primary outcome will be successful clinical translation of promising therapies - defined as the conduct of at least one Phase II trial (or greater) with a positive finding. A case-control study will then be performed to evaluate the association between elements of preclinical study design and reporting and the likelihood of successful translation. Discussion: This study will provide a comprehensive analysis of the therapeutic translation from the laboratory bench to the bedside. Importantly, any association between factors of study design and the success of translation will be identified. These findings may inform future research teams attempting preclinical-to-clinical translation. Results will be disseminated to identified knowledge users that fund/support preclinical research.

9.
BMJ ; 371: m4104, 2020 11 25.
Artigo em Inglês | MEDLINE | ID: mdl-33239330

RESUMO

OBJECTIVE: To examine the associations between neuraxial anaesthesia or general anaesthesia and clinical outcomes, length of hospital stay, and readmission in adults undergoing lower limb revascularisation surgery. DESIGN: Comparative effectiveness study using linked, validated, population based databases. SETTING: Ontario, Canada, 1 April 2002 to 31 March 2015. PARTICIPANTS: 20 988 patients Ontario residents aged 18 years or older who underwent their first lower limb revascularisation surgery in hospitals performing 50 or more of these surgeries annually. MAIN OUTCOME MEASURES: Primary outcome was 30 day all cause mortality. Secondary outcomes were in-hospital cardiopulmonary and renal complications, length of hospital stay, and 30 day readmissions. Multivariable, mixed effects regression models, adjusting for patient, procedural, and hospital characteristics, were used to estimate associations between anaesthetic technique and outcomes. Robustness of analyses were evaluated by conducting instrumental variable, propensity score matched, and survival sensitivity analyses. RESULTS: Of 20 988 patients who underwent lower limb revascularisation surgery, 6453 (30.7%) received neuraxial anaesthesia and 14 535 (69.3%) received general anaesthesia. The percentage of neuraxial anaesthesia use ranged from 0.6% to 90.6% across included hospitals. Furthermore, use of neuraxial anaesthesia declined by 17% over the study period. Death within 30 days occurred in 204 (3.2%) patients who received neuraxial anaesthesia and 646 (4.4%) patients who received general anaesthesia. After multivariable, multilevel adjustment, use of neuraxial anaesthesia compared with use of general anaesthesia was associated with decreased 30 day mortality (absolute risk reduction 0.72%, 95% confidence interval 0.65% to 0.79%; odds ratio 0.68, 95% confidence interval 0.57 to 0.83; number needed to treat to prevent one death=139). A similar direction and magnitude of association was found in instrumental variable, propensity score matched, and survival analyses. Use of neuraxial anaesthesia compared with use of general anaesthesia was also associated with decreased in-hospital cardiopulmonary and renal complications (odds ratio 0.73, 0.63 to 0.85) and a reduced length of hospital stay (-0.5 days, -0.3 to-0.6 days). CONCLUSIONS: Use of neuraxial anaesthesia compared with general anaesthesia for lower limb revascularisation surgery was associated with decreased 30 day mortality and hospital length of stay. These findings might have been related to reduced cardiopulmonary and renal complications after neuraxial anaesthesia and support the increased use of neuraxial anaesthesia in patients undergoing these surgeries until the results of a large, confirmatory randomised trial become available.

10.
Res Involv Engagem ; 6: 61, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33072399

RESUMO

Aim: Though patient engagement in clinical research is growing, recent reports suggest few clinical trials report on such activities. To address this gap, we describe our approach to patient engagement in the development of a clinical trial protocol to assess a new immunotherapy for blood cancer (chimeric antigen receptor T-cell therapy, CAR-T cell therapy). Methods: Our team developed a clinical trial protocol by working with patient partners from inception. Two patient partners with lived blood cancer experience were identified through referrals from our team's professional network and patient organization contacts. Our patient partners were onboarded to the team and engaged in several studies conducted to develop the clinical trial protocol, including a systematic review of the existing literature on the therapy, patient interviews and a survey to obtain perspectives on barriers and enablers to participating in the trial, an early economic analysis, and a retrospective cohort study. Results: Engaging patient partners enhanced our research in ways that would not have otherwise occurred. By selecting patient important outcomes for data collection, our partners helped flag that quality of life and health utility measures have not been reported in previous CAR-T cell therapy trials for blood cancer. Our partners also co-developed a non-technical summary of the systematic review that summarized results in an accessible manner. Our patient partners reviewed interview and survey questions, to improve the language and appropriateness; provided recruitment suggestions; and provided a patient perspective on the results, thereby confirming the importance of findings. Input was also obtained on costs for the early economic analysis. Our patient partners identified costs that may be a burden to both patients and caregivers during a trial and helped to confirm that the overall structure of the economic model reflected the patient care pathway. Our patient partners also shared their diagnosis and treatment stories, which helped to provide the research team with insight into this experience. Conclusions: Contributions by our patient partners were invaluable to each component study, as well as the overall development of the trial protocol. We plan to use this approach in the future in order to meaningfully engage patients in the development of other clinical trials; we also hope that by reporting our methods this will help other research teams to do the same. Trial registration: Affiliated with the development of NCT03765177.

11.
Transfus Med Rev ; 34(3): 158-164, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32771272

RESUMO

Many parallel studies of convalescent plasma with modest enrolment projections have been launched for the treatment of COVID-19. By pooling data from multiple parallel studies that are similar, we can increase the effective sample size and achieve enough statistical power to determine effectiveness more quickly through meta-analysis. A scoping review of registered clinical trials of convalescent plasma for COVID-19 was conducted to assess the feasibility of performing a rapid and timely meta-analysis that will support accelerated review for approval and implementation. ClinicalTrials.gov and the WHO International Clinical Trials Registry Platform were searched April 23, 2020. Trials were included if they utilized convalescent plasma to treat or prevent COVID-19. Forty-eight registered trials (projected to enroll more than 5000 subjects) of convalescent plasma were identified and included for analysis. The majority of studies (33 studies with 4440 projected enrolment) will address the treatment of severe and/or critical cases of COVID-19. Twenty-nine studies are controlled and 17 of these are reported as actively recruiting. The combined enrolment of patients from similar studies should be sufficient to determine meaningful improvements in mortality, rates of admission to intensive care and need for mechanical ventilation by the end of 2020-sooner than any individual study could determine effectiveness. Accessing supplemental outcome data from investigators may be needed; however, to align reporting of some outcomes from these studies. Heterogeneity in product potency due to different antibody titers is anticipated and studies using conventional treatment as controls instead of placebo may complicate our understanding of efficacy. Convalescent plasma is being tested in ongoing controlled studies, largely to treat severe and/or critical cases of COVID-19. Sufficient combined power to detect clinically important reductions in multiple outcomes, including mortality, is expected by September 2020. Regulatory approval, funding and implementation by blood operators could be accelerated by planned meta-analysis as study results become available.


Assuntos
Infecções por Coronavirus/terapia , Pneumonia Viral/terapia , Betacoronavirus , Ensaios Clínicos como Assunto , Cuidados Críticos , Saúde Global , Humanos , Imunização Passiva , Pandemias , Sistema de Registros , Reprodutibilidade dos Testes , Projetos de Pesquisa , Respiração Artificial , Tamanho da Amostra , Resultado do Tratamento
12.
Thromb Res ; 195: 103-113, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32683148

RESUMO

OBJECTIVE: The therapeutic effects of low molecular weight heparins (LMWH) may extend past thrombosis prevention, with preclinical evidence demonstrating anti-metastatic properties. Clinical evidence on the topic, however, remains controversial. A systematic review of preclinical evidence may help elucidate reasons for this contradictory evidence. The objective of our systematic review is to assess the anti-metastatic properties of LMWHs in solid tumour animal models. METHODS: MEDLINE, Embase, Web of Science and PubMed were searched from inception to May 12th, 2020. All articles were screened independently and in duplicate. Studies that compared LMWH to a placebo or no treatment arm in solid tumour animal models were included. The primary outcome was the burden of metastasis. Secondary outcomes included primary tumour growth and mortality. The risk of bias was assessed in duplicate using a modified Cochrane Risk of Bias tool. RESULTS: Forty-two studies were included in the review. Administration of a LMWH was associated with a significant decrease in the burden of metastasis (SMD -2.18; 95% CI -2.66 to -1.70). Additionally, the administration of a LMWH was also associated with a significant reduction in primary tumour growth (SMD -1.95; 95% CI -2.56 to -1.34) and risk of death (RR 0.39; 95% CI 0.16-0.97). All included studies were deemed to be at an unclear risk of bias for at least one methodological criterion. CONCLUSIONS: Our results demonstrate that LMWH can effectively reduce metastatic burden and reduce tumour growth in preclinical animal models of solid tumour malignancies. Reasons for the contradiction with clinical evidence require further exploration.

13.
Transfus Med Rev ; 34(3): 165-171, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32684483

RESUMO

The urgent need for safe and effective treatments for COVID-19 has fueled the launch of many parallel complex studies of cellular therapies with small to modest enrolment projections. By pooling data from multiple studies that are similar, we can increase the ability to achieve sufficient power to determine effectiveness more quickly through meta-analysis. A scoping review of registered clinical trials using cell-based interventions for COVID-19 was conducted to identify candidate studies for meta-analysis that could support an accelerated regulatory review. ClinicalTrials.gov and WHO International Clinical Trials Registry Platform were searched April 23, 2020. Trials were included if they utilized cell or cell-derived products to treat or prevent COVID-19. Fifty-four registered cellular therapy trials were identified and included for analysis. Studies of mesenchymal stromal cells (MSCs; 41 studies; 1129 subjects projected to receive cells) and natural killer (NK) cells (5 studies; 135 projected to received cells) were observed most commonly. A subset of studies are controlled (34 studies, or 63%), including 27 studies of MSCs and 3 of NK cells. While heterogeneity in study design exists, the cumulative projected enrolment of patients from similar studies appears sufficient to allow the detection of meaningful differences in clinically important outcomes such as mortality, admission to intensive care and need for mechanical ventilation by September 2020-sooner than any individual study could determine effectiveness. MSCs are the predominant cell type in registered trials for severe or critical COVID-19 and represent the most promising candidates for future meta-analysis. Sufficient pooled sample size to detect clinically important reductions in multiple outcomes, including mortality, is anticipated by September 2020, but may require accessing supplementary data to align outcome reporting. Regulatory approval, funding and implementation by cell manufacturing partners will be accelerated by our framework for rapid meta-analysis.


Assuntos
Infecções por Coronavirus/terapia , Pneumonia Viral/terapia , Betacoronavirus , Ensaios Clínicos como Assunto , Cuidados Críticos , Saúde Global , Humanos , Imunização Passiva , Células Matadoras Naturais/metabolismo , Células-Tronco Mesenquimais/metabolismo , Pandemias , Sistema de Registros , Reprodutibilidade dos Testes , Projetos de Pesquisa , Respiração Artificial , Tamanho da Amostra , Resultado do Tratamento
15.
ACS Nano ; 14(8): 9728-9743, 2020 08 25.
Artigo em Inglês | MEDLINE | ID: mdl-32697573

RESUMO

Mesenchymal stem cell-derived extracellular vesicles (MSC-EVs) can reduce inflammation, promote healing, and improve organ function, thereby providing a potential "cell-free" therapy. Prior to clinical translation, it is critical to synthesize existing evidence on preclinical methods and efficacy. To address these issues, we used gold standard systematic review methodology to consolidate information from all published animal studies investigating MSC-EVs as an intervention. A systematic search of MEDLINE and Embase identified 206 studies. Data were extracted in duplicate for methodology, experimental design, interventional traits, modifications, and outcomes. MSC-EVs were used to treat a variety of diseases and demonstrated benefits in 97% of studies. Adverse effects were reported in only three studies, two demonstrating tumor growth. A quarter of articles modified EVs to enhance efficacy, with 72% leading to markedly improved outcomes as compared to unmodified EVs. However, several key methodological concerns were evident. Only 60% of studies used nomenclature consistent with the size definitions of EVs. Ultracentrifugation (70%) and isolation kits (23%) were the most common isolation techniques with noted differences in yield and purity. EVs were inconsistently dosed by protein (68%) or particle concentration (16%). Two-thirds of studies administered xenogeneic EVs, suggesting immunocompatibility. Less than 25% of studies assessed EV biodistribution. Approaches for determining size, protein markers, and morphology were highly heterogeneous, with only 12 and 4 studies meeting the MISEV 2014 and 2018 recommendations, respectively. Knowledge gaps identified from this systematic review highlight important opportunities to improve preclinical design and methodology in the rapidly growing field of EV therapeutics.

17.
Anesth Analg ; 130(6): 1482-1492, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32384338

RESUMO

BACKGROUND: Frailty strongly predicts adverse outcomes in a variety of clinical settings; however, frailty-related trauma outcomes have not been systematically reviewed and quantitatively synthesized. Our objective was to systematically review and meta-analyze the association between frailty and outcomes (mortality-primary; complications, health resource use, and patient experience-secondary) after multisystem trauma. METHODS: After registration (CRD42018104116), we applied a peer-reviewed search strategy to MEDLINE, EMBASE, and Comprehensive Index to Nursing and Allied Health Literature (CINAHL) from inception to May 22, 2019, to identify studies that described: (1) multisystem trauma; (2) participants ≥18 years of age; (3) explicit frailty instrument application; and (4) relevant outcomes. Excluded studies included those that: (1) lacked a comparator group; (2) reported isolated injuries; and (3) reported mixed trauma and nontrauma populations. Criteria were applied independently, in duplicate to title/abstract and full-text articles. Risk of bias was assessed using the Risk of Bias in Nonrandomized Studies-of Interventions (ROBINS-I) tool. Effect measures (adjusted for prespecified confounders) were pooled using random-effects models; otherwise, narrative synthesis was used. RESULTS: Sixteen studies were included that represented 5198 participants; 9.9% of people with frailty died compared to 4.2% of people without frailty. Frailty was associated with increased mortality (adjusted odds ratio [OR], 1.53; 95% confidence interval [CI], 1.37-1.71), complications (adjusted OR, 2.32; 95% CI, 1.72-3.15), and adverse discharge (adjusted OR, 1.78; 95% CI, 1.29-2.45). Patient function, experience, and resource use outcomes were rarely reported. CONCLUSIONS: The presence of frailty is significantly associated with mortality, complications, and adverse discharge disposition after multisystem trauma. This provides important prognostic information to inform discussions with patients and families and highlights the need for trauma system optimization to meet the complex needs of older patients.


Assuntos
Fragilidade/complicações , Traumatismo Múltiplo/complicações , Idoso , Idoso Fragilizado , Humanos , Estudos Observacionais como Assunto , Razão de Chances , Avaliação de Resultados em Cuidados de Saúde , Alta do Paciente , Prognóstico , Fatores de Risco , Resultado do Tratamento
18.
Thromb Haemost ; 120(5): 832-846, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32369854

RESUMO

BACKGROUND: Low molecular weight heparins (LMWH) are often used as a first-line therapy for the prevention of thrombosis in cancer patients. Preclinical evidence from animal models suggests that LMWH may have antimetastatic properties. Clinical evidence of this effect is inconclusive. The objective of this systematic review is to evaluate the effect of LMWH on overall survival in patients with solid tumor malignancies. METHODS: MEDLINE, Embase, and The Cochrane Central Register of Controlled trials were searched from inception to November 26, 2018. We included randomized controlled trials that compared LMWH to placebo, a no-treatment arm, or a short-term prophylactic course of LMWH in adult patients with solid tumors. The primary outcome was overall survival. Secondary outcomes included progression-free survival, the occurrence of venous thromboembolism, and major bleeding events. The risk of bias was assessed in duplicate using the Cochrane Risk-of-Bias tool. RESULTS: Forty-five articles were included in the review. Overall, no difference in overall survival was observed between groups (risk ratio: 1.00; 95% confidence interval: 0.98-1.02; I2 = 36.5%). In our a priori defined subgroup analyses, the effect was not shown to vary by the type of LMWH, duration of LMWH use, length of study follow-up, comparator used in the study, or the setting in which the LMWH was administered. The majority of studies had an unclear risk of bias for at least one methodological criterion. CONCLUSION: Although LMWH is thought to possess antimetastatic properties and thus have the potential to improve survival in cancer patients, existing data do not support this hypothesis.


Assuntos
Anticoagulantes/administração & dosagem , Heparina de Baixo Peso Molecular/administração & dosagem , Neoplasias/tratamento farmacológico , Trombose/prevenção & controle , Anticoagulantes/efeitos adversos , Heparina de Baixo Peso Molecular/efeitos adversos , Humanos , Neoplasias/sangue , Neoplasias/diagnóstico , Neoplasias/mortalidade , Intervalo Livre de Progressão , Ensaios Clínicos Controlados Aleatórios como Assunto , Medição de Risco , Fatores de Risco , Trombose/sangue , Trombose/diagnóstico , Trombose/mortalidade , Fatores de Tempo
19.
BMC Med ; 18(1): 104, 2020 05 07.
Artigo em Inglês | MEDLINE | ID: mdl-32375818

RESUMO

BACKGROUND: The increase in the number of predatory journals puts scholarly communication at risk. In order to guard against publication in predatory journals, authors may use checklists to help detect predatory journals. We believe there are a large number of such checklists yet it is uncertain whether these checklists contain similar content. We conducted a systematic review to identify checklists that help to detect potential predatory journals and examined and compared their content and measurement properties. METHODS: We searched MEDLINE, Embase, PsycINFO, ERIC, Web of Science and Library, and Information Science & Technology Abstracts (January 2012 to November 2018); university library websites (January 2019); and YouTube (January 2019). We identified sources with original checklists used to detect potential predatory journals published in English, French or Portuguese. Checklists were defined as having instructions in point form, bullet form, tabular format or listed items. We excluded checklists or guidance on recognizing "legitimate" or "trustworthy" journals. To assess risk of bias, we adapted five questions from A Checklist for Checklists tool a priori as no formal assessment tool exists for the type of review conducted. RESULTS: Of 1528 records screened, 93 met our inclusion criteria. The majority of included checklists to identify predatory journals were in English (n = 90, 97%), could be completed in fewer than five minutes (n = 68, 73%), included a mean of 11 items (range = 3 to 64) which were not weighted (n = 91, 98%), did not include qualitative guidance (n = 78, 84%), or quantitative guidance (n = 91, 98%), were not evidence-based (n = 90, 97%) and covered a mean of four of six thematic categories. Only three met our criteria for being evidence-based, i.e. scored three or more "yes" answers (low risk of bias) on the risk of bias tool. CONCLUSION: There is a plethora of published checklists that may overwhelm authors looking to efficiently guard against publishing in predatory journals. The continued development of such checklists may be confusing and of limited benefit. The similarity in checklists could lead to the creation of one evidence-based tool serving authors from all disciplines.

20.
BMC Med ; 18(1): 88, 2020 04 21.
Artigo em Inglês | MEDLINE | ID: mdl-32312313

RESUMO

BACKGROUND: When a journal receives a duplicate publication, the ability to identify the submitted work as previously published, and reject it, is an assay to publication ethics best practices. The aim of this study was to evaluate how three different types of journals, namely open access (OA) journals, subscription-based journals, and presumed predatory journals, responded to receiving a previously published manuscript for review. METHODS: We performed a quasi-experimental study in which we submitted a previously published article to a random sample of 602 biomedical journals, roughly 200 journals from each journal type sampled: OA journals, subscription-based journals, and presumed predatory journals. Three hundred and three journals received a Word version in manuscript format, while 299 journals received the formatted publisher's PDF version of the published article. We then recorded responses to the submission received after approximately 1 month. Responses were reviewed, extracted, and coded in duplicate. Our primary outcome was the rate of rejection of the two types of submitted articles (PDF vs Word) within our three journal types. RESULTS: We received correspondence back from 308 (51.1%) journals within our study timeline (32 days); (N = 46 predatory journals, N = 127 OA journals, N = 135 subscription-based journals). Of the journals that responded, 153 received the Word version of the paper, while 155 received the PDF version. Four journals (1.3%) accepted our paper, 291 (94.5%) journals rejected the paper, and 13 (4.2%) requested a revision. A chi-square test looking at journal type, and submission type, was significant (χ2 (4) = 23.50, p < 0.001). All four responses to accept our article came from presumed predatory journals, 3 of which received the Word format and 1 that received the PDF format. Less than half of journals that rejected our submissions did so because they identified ethical issues such as plagiarism with the manuscript (133 (45.7%)). CONCLUSION: Few journals accepted our submitted paper. However, our findings suggest that all three types of journals may not have adequate safeguards in place to recognize and act on plagiarism or duplicate submissions.

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