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Background: Mesenchymal stem cells (MSCs) are multipotent cells that demonstrate therapeutic potential for the treatment of acute and chronic inflammatory-mediated conditions. Although controversial, some studies suggest that MSCs may lose their functionality with cryopreservation which could render them non-efficacious. Hence, we conducted a systematic review of comparative pre-clinical models of inflammation to determine if there are differences in in vivo measures of pre-clinical efficacy (primary outcomes) and in vitro potency (secondary outcomes) between freshly cultured and cryopreserved MSCs. Methods: A systematic search on OvidMEDLINE, EMBASE, BIOSIS, and Web of Science (until January 13, 2022) was conducted. The primary outcome included measures of in vivo pre-clinical efficacy; secondary outcomes included measures of in vitro MSC potency. Risk of bias was assessed by the SYRCLE ‘Risk of Bias’ assessment tool for pre-clinical studies. Results: Eighteen studies were included. A total of 257 in vivo pre-clinical efficacy experiments represented 101 distinct outcome measures. Of these outcomes, 2.3% (6/257) were significantly different at the 0.05 level or less; 2 favoured freshly cultured and 4 favoured cryopreserved MSCs. A total of 68 in vitro experiments represented 32 different potency measures; 13% (9/68) of the experiments were significantly different at the 0.05 level or less, with seven experiments favouring freshly cultured MSC and two favouring cryopreserved MSCs. Conclusions: The majority of preclinical primary in vivo efficacy and secondary in vitro potency outcomes were not significantly different (p

Background: Characterization of the mesenchymal stromal cell (MSC) safety profile is important as this novel therapy continues to be evaluated in clinical trials for various inflammatory conditions. Due to an increase in published randomized controlled trials (RCTs) from 2012–2019, we performed an updated systematic review to further characterize the MSC safety profile. Methods: MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials and Web of Science (to May 2018) were searched. RCTs that compared intravascular delivery of MSCs to controls in adult populations were included. Pre-specified adverse events were grouped according to: (1) immediate, (2) infection, (3) thrombotic/embolic, and (4) longer-term events (mortality, malignancy). Adverse events were pooled and meta-analyzed by fitting inverse-variance binary random effects models. Primary and secondary clinical efficacy endpoints were summarized descriptively. Findings: 7473 citations were reviewed and 55 studies met inclusion criteria (n = 2696 patients). MSCs as compared to controls were associated with an increased risk of fever (Relative Risk (RR) = 2·48, 95% Confidence Interval (CI) = 1·27–4·86; I2 = 0%), but not non-fever acute infusional toxicity, infection, thrombotic/embolic events, death, or malignancy (RR = 1·16, 0·99, 1·14, 0·78, 0·93; 95% CI = 0·70–1·91, 0·81–1·21, 0·67–1·95, 0·65–0·94, 0·60–1·45; I2 = 0%, 0%, 0%, 0%, 0%). No included trials were ended prematurely due to safety concerns. Interpretations: MSC therapy continues to exhibit a favourable safety profile. Future trials should continue to strengthen study rigor, reporting of MSC characterization, and adverse events. Funding: Stem Cell Network, Ontario Institute for Regenerative Medicine and Ontario Research Fund Keywords: Mesenchymal stem cells, Safety, Adverse events, Systematic review

Introduction. Occupational therapists have shown low adoption rates for many evidence-based practices. One such practice is the limited uptake of standardized outcome measures such as the Canadian Occupational Performance Measure. Use of this measure has not consistently translated into practice despite decades of encouragement. Theory-based approaches to understanding healthcare provider behaviour change are needed if we are to realize the goal of attaining practice that is in keeping with evidence. This study utilized the Theoretical Domains Framework, a theory-based approach for understanding barriers to evidence-based practice, in order to increase our understanding of the limited uptake of the Canadian Occupational Performance Measure in occupational therapy practice. Methods. Theoretical Domains Framework methods were followed. First, primary data was collected from occupational therapists through semistructured interviews that focused on key behaviour change domains as they related to the use of the Canadian Occupational Performance Measure. Two independent researchers coded interview data into domains, derived belief statements from the data, and used belief strength, conflict, and frequency to determine the more and less influential domains for using the Canadian Occupational Performance Measure. Results. Interviews with 15 practicing occupational therapists across a range of practice areas yielded six key behaviour change domains for increasing the use of the Canadian Occupational Performance Measure. The more relevant domains were Social influences, Social professional role and identity, Beliefs about consequences, Beliefs about capabilities, Skills, and Behavioural regulation). The other eight domains were found to be less relevant. Conclusion. We identified important domains and beliefs that influence the use of the Canadian Occupational Performance Measure by occupational therapists. Results inform our understanding of the use of this measure in practice and identify potential targets for behaviour change interventions.

Evaluation of preclinical evidence prior to initiating early-phase clinical studies has typically been performed by selecting individual studies in a non-systematic process that may introduce bias. Thus, in preparation for a first-in-human trial of mesenchymal stromal cells (MSCs) for septic shock, we applied systematic review methodology to evaluate all published preclinical evidence. We identified 20 controlled comparison experiments (980 animals from 18 publications) of in vivo sepsis models. Meta-analysis demonstrated that MSC treatment of preclinical sepsis significantly reduced mortality over a range of experimental conditions (odds ratio 0.27, 95% confidence interval 0.18–0.40, latest timepoint reported for each study). Risk of bias was unclear as few studies described elements such as randomization and no studies included an appropriately calculated sample size. Moreover, the presence of publication bias resulted in a ~30% overestimate of effect and threats to validity limit the strength of our conclusions. This novel prospective application of systematic review methodology serves as a template to evaluate preclinical evidence prior to initiating first-in-human clinical studies.

Incomplete reporting of study methods and results has become a focal point for failures in the reproducibility and translation of findings from preclinical research. Here we demonstrate that incomplete reporting of preclinical research is not limited to a few elements of research design, but rather is a broader problem that extends to the reporting of the methods and results. We evaluated 47 preclinical research studies from a systematic review of acute lung injury that use mesenchymal stem cells (MSCs) as a treatment. We operationalized the ARRIVE (Animal Research: Reporting of In Vivo Experiments) reporting guidelines for pre-clinical studies into 109 discrete reporting sub-items and extracted 5,123 data elements. Overall, studies reported less than half (47%) of all sub-items (median 51 items; range 37-64). Across all studies, the Methods Section reported less than half (45%) and the Results Section reported less than a third (29%). There was no association between journal impact factor and completeness of reporting, which suggests that incomplete reporting of preclinical research occurs across all journals regardless of their perceived prestige. Incomplete reporting of methods and results will impede attempts to replicate research findings and maximize the value of preclinical studies.

The Acute Respiratory Distress Syndrome (ARDS) is a devastating clinical condition that is associated with a 30-40% risk of death, and significant long term morbidity for those who survive. Mesenchymal stromal cells (MSC) have emerged as a potential novel treatment as in pre-clinical models they have been shown to modulate inflammation (a major pathophysiological hallmark of ARDS) while enhancing bacterial clearance and reducing organ injury and death. A systematic search of MEDLINE, EMBASE, BIOSIS and Web of Science was performed to identify pre-clinical studies that examined the efficacy MSCs as compared to diseased controls for the treatment of Acute Lung Injury (ALI) (the pre-clinical correlate of human ARDS) on mortality, a clinically relevant outcome. We assessed study quality and pooled results using random effect meta-analysis. A total of 54 publications met our inclusion criteria of which 17 (21 experiments) reported mortality and were included in the meta-analysis. Treatment with MSCs, as compared to controls, significantly decreased the overall odds of death in animals with ALI (Odds Ratio 0.24, 95% Confidence Interval 0.18-0.34, I2 8%). Efficacy was maintained across different types of animal models and means of ALI induction; MSC origin, source, route of administration and preparation; and the clinical relevance of the model (timing of MSC administration, administration of fluids and or antibiotics). Reporting of standard MSC characterization for experiments that used human MSCs and risks of bias was generally poor, and although not statistically significant, a funnel plot analysis for overall mortality suggested the presence of publication bias. The results from our meta-analysis support that MSCs substantially reduce the odds of death in animal models of ALI but important reporting elements were sub optimal and limit the strength of our conclusions.

The wood frog, Rana sylvatica, has numerous adaptations that allow it to survive freezing of up to 65% of its total body water during the winter. Such adaptations have been found to include the expression of novel freeze responsive genes that are thought to be important for adaptation and survival. In this study, the tissue-specific stress responsive expression of one novel gene, fr47, was assessed in seven wood frog tissues. In response to freezing, the transcript expression of fr47 increased significantly in six tissues: heart, lung, liver, skeletal muscle, kidney, and testes. The expression of fr47 was also strongly upregulated by component stresses of freezing, namely, anoxia and dehydration. A dynamic change in fr47 expression was also observed during tadpole development, with expression low in embryonic stages (Gosner stages 14–20), increasing through intermediate (stages 26–43) and transformation phases (stages 44-45). These results indicated that fr47 potentially has a role to play in development and metamorphosis, in addition to freeze, anoxia, and dehydration tolerance. De novo analysis of FR47 protein structure revealed a likelihood of membrane associated function and possible GRB2 association. It is hypothesized that this interaction may influence inositol 1,4,5-trisphosphate production, known to increase during wood frog freezing.

Teamwork is fundamental to surgical patient safety but is inconsistently measured. While many tools have been developed for elective intraoperative situations, it is unclear which is the most robust. This systematic review aimed to identify tools to measure the teamwork of operating room teams. Studies were included if they examined the measurement properties of these tools. PsycINFO, Embase (via OVID), CINAHL, ERIC, Medline and Medline in Process (via OVID) were searched through to May 3, 2019, as were reference lists of included studies and previously published relevant reviews. Retrieved articles were screened and data extracted in duplicate by two independent reviewers. Quality was assessed using the COSMIN checklist. Of the 2121 references identified, 14 studies of six assessment tools were included. Tools were validated across various specialties, mostly in clinical rather than simulated settings. The Observational Teamwork Assessment for Surgery (OTAS) and Operating Theater Team Non-Technical Skills Assessment Tool (NOTECHS) were the most frequently investigated tools. Though acceptable for assessing teamwork, both NOTECHS and OTAS rely on the questionable assumption that the teamwork of a team is equivalent to the sum of individual performances. Future studies may investigate other assessment tools that assess the whole team as the unit of analysis along with the potential of these tools to provide healthcare providers with meaningful feedback in clinical practice. [ABSTRACT FROM AUTHOR]

Introduction. Occupational therapists have shown low adoption rates for many evidence-based practices. One such practice is the limited uptake of standardized outcome measures such as the Canadian Occupational Performance Measure. Use of this measure has not consistently translated into practice despite decades of encouragement. Theory-based approaches to understanding healthcare provider behaviour change are needed if we are to realize the goal of attaining practice that is in keeping with evidence. This study utilized the Theoretical Domains Framework, a theory-based approach for understanding barriers to evidence-based practice, in order to increase our understanding of the limited uptake of the Canadian Occupational Performance Measure in occupational therapy practice. Methods. Theoretical Domains Framework methods were followed. First, primary data was collected from occupational therapists through semistructured interviews that focused on key behaviour change domains as they related to the use of the Canadian Occupational Performance Measure. Two independent researchers coded interview data into domains, derived belief statements from the data, and used belief strength, conflict, and frequency to determine the more and less influential domains for using the Canadian Occupational Performance Measure. Results. Interviews with 15 practicing occupational therapists across a range of practice areas yielded six key behaviour change domains for increasing the use of the Canadian Occupational Performance Measure. The more relevant domains were Social influences, Social professional role and identity, Beliefs about consequences, Beliefs about capabilities, Skills, and Behavioural regulation). The other eight domains were found to be less relevant. Conclusion. We identified important domains and beliefs that influence the use of the Canadian Occupational Performance Measure by occupational therapists. Results inform our understanding of the use of this measure in practice and identify potential targets for behaviour change interventions. [ABSTRACT FROM AUTHOR]

Background: Congenital malformations of lung, such as congenital lobar emphysema, cystic adenomatoid malformation, bronchial cyst, pulmonary sequestration are of rare occurrence. However, our hospital being in a rural area attracts a large number of patients with complex malformations. Methods: This retrospective analysis is done to evaluate diagnostic accuracy, safety and efficacy and outcomes of open lung resections at a rural hospital. Results: 16 children with congenital lung malformation underwent open resection in a rural hospital, with no mortality and minimal morbidity, no complications and more than 24 months follow-up. Conclusion: Open lung resections are found to be safe, effective in a rural setting also. [ABSTRACT FROM AUTHOR]

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Controversy exists on the optimal age for elective resection of asymptomatic congenital pulmonary airway malformation. Current recommendations vary widely, highlighting the overall lack of consensus. A systematic search of Embase, MEDLINE, CINAL, and CENTRAL was conducted in January 2016. Identified citations were screening independently in duplicate and consensus was required for inclusion. Results were pooled using inverse variance fixed effects meta-analysis. Meta-analysis results indicate no statistically significant differences for complications within the 3-month and 6-month age comparison groups [odds ratio (OR) 4.20, 95% confidence interval (CI) 0.78-22.77, I 2 = 0%; OR 2.39, 95% CI 0.63-9.11, I 2 = 0%, respectively]. Older patients were significantly favoured for 3-month and 6-month age comparison groups for length of hospital stay [mean difference (MD) 4.13, 95% CI 2.31-5.96, I 2 = 0%; MD 3.38, 95% CI 0.44-6.31, I 2 = 0%, respectively]. Borderline statistical significance was observed for chest tube duration in patients ≥6 months of age (MD 1.06, 95% CI 0.02-2.09, I 2 = 0%). No mortalities were recorded. Surgical treatment appears to be safe at all ages, with no mortalities and similar rates of complications between age groups. The included evidence was not sufficient to make a conclusive recommendation on optimal age for elective resection. [ABSTRACT FROM AUTHOR]

Critically ill adults with acute kidney injury (AKI) experience considerable morbidity and mortality. Controversy remains regarding the optimal renal replacement intervention for these patients. Our systematic review aimed to determine the effect(s) of sustained low-efficiency dialysis (SLED) compared with continuous renal replacement (CRRT) therapy on relevant patient outcomes. A systematic search of Medline, Embase, CINAHL and the Cochrane Library was conducted. Identified citations were screened independently in duplicate for relevance, and the methodological quality of included studies was evaluated. Data were extracted on study, patient and intervention characteristics and relevant clinical outcomes. Results were pooled using inverse variance fixed and random effectsmeta-analysis. A total of 1564 patients from 18 studieswere included. Meta-analysis results indicated no statistically significant difference in our primary outcome, overall proportion of renal recovery (risk ratio (RR) 0.87, 95%confidence interval (CI) 0.63-1.20, I2 = 66%). No significant difference was observed for the secondary outcome of time to renal recovery (mean difference 1.33, 95% CI 0.23-2.88, I2=0%). Statistically, SLED was marginally favoured over CRRT for the secondary outcome of mortality (RR 1.21, 95% CI 1.02-1.43, I2= 47%); however, this diminished when sensitivity analysis of only randomized controlled trials was conducted (RR 1.25, 95%CI 1.00-1.57, I2=0%). There appears to be no clear for advantage continuous renal replacement in the hemodynamically unstable patient. Currently, both modalities are safe and effective means of treating AKI in the critically ill adult. [ABSTRACT FROM AUTHOR]

Purpose: To determine whether open or laparoscopic pyloromyotomy is superior for the treatment of hypertrophic pyloric stenosis in infants.Methods: We searched MEDLINE, EMBASE, and CENTRAL for articles comparing laparoscopic and open procedures. We conducted meta-analyses when possible and described other results narratively.Results: Our meta-analyses revealed no significant difference in our primary outcome of major complications [risk difference (RD) 0.03, 95% confidence interval (CI) -0.03 to 0.08, P = 0.35, I 2 = 55%], or in our secondary outcomes of all perioperative complications (RD -0.01, 95% CI -0.06 to 0.04, P = 0.74, I 2 = 0%), operative time [mean difference (MD) 0.68, 95% CI -3.60 to 4.79, P = 0.76, I 2 = 86%], and length of stay (MD -2.60, 95% CI -6.05 to 0.86, P = 0.14, I 2 = 0%). Laparoscopy was associated with a shorter time to full feeds (standardized mean difference -0.25, 95% CI -0.43 to -0.06, P = 0.009, I 2 = 8%) and a slightly higher rate of inadequate pyloromyotomy (RD 0.04, 95% CI 0.00-0.08, P = 0.03, I 2 = 0%). Results from one randomized controlled trial indicate a better cosmetic outcome after laparoscopy compared to open procedure.Conclusion: There is no strong evidence to support a recommendation of one procedure over the other; therefore, the choice of laparoscopic or open procedure should be left to the discretion of the surgeon. [ABSTRACT FROM AUTHOR]

Incomplete reporting of study methods and results has become a focal point for failures in the reproducibility and translation of findings from preclinical research. Here we demonstrate that incomplete reporting of preclinical research is not limited to a few elements of research design, but rather is a broader problem that extends to the reporting of the methods and results. We evaluated 47 preclinical research studies from a systematic review of acute lung injury that use mesenchymal stem cells (MSCs) as a treatment. We operationalized the ARRIVE (Animal Research: Reporting of In Vivo Experiments) reporting guidelines for pre-clinical studies into 109 discrete reporting sub-items and extracted 5,123 data elements. Overall, studies reported less than half (47%) of all sub-items (median 51 items; range 37–64). Across all studies, the Methods Section reported less than half (45%) and the Results Section reported less than a third (29%). There was no association between journal impact factor and completeness of reporting, which suggests that incomplete reporting of preclinical research occurs across all journals regardless of their perceived prestige. Incomplete reporting of methods and results will impede attempts to replicate research findings and maximize the value of preclinical studies. [ABSTRACT FROM AUTHOR]

Background. The Zika virus (ZIKV) outbreak in the Americas has caused international concern due to neurological sequelae linked to the infection, such as microcephaly and Guillain-Barré syndrome (GBS). The World Health Organization stated that there is “sufficient evidence to conclude that Zika virus is a cause of congenital abnormalities and is a trigger of GBS”. This conclusion was based on a systematic review of the evidence published until 30.05.2016. Since then, the body of evidence has grown substantially, leading to this update of that systematic review with new evidence published from 30.05.2016 – 18.01.2017, update 1. Methods. We review evidence on the causal link between ZIKV infection and adverse congenital outcomes and the causal link between ZIKV infection and GBS or immune-mediated thrombocytopaenia purpura. We also describe the transition of the review into a living systematic review, a review that is continually updated. Results. Between 30.05.2016 and 18.01.2017, we identified 2413 publications, of which 101 publications were included. The evidence added in this update confirms the conclusion of a causal association between ZIKV and adverse congenital outcomes. New findings expand the evidence base in the dimensions of biological plausibility, strength of association, animal experiments and specificity. For GBS, the body of evidence has grown during the search period for update 1, but only for dimensions that were already populated in the previous version. There is still a limited understanding of the biological pathways that potentially cause the occurrence of autoimmune disease following ZIKV infection. Conclusions. This systematic review confirms previous conclusions that ZIKV is a cause of congenital abnormalities, including microcephaly, and is a trigger of GBS. The transition to living systematic review techniques and methodology provides a proof of concept for the use of these methods to synthesise evidence about an emerging pathogen such as ZIKV.