Measuring the teamwork performance of operating room teams: a systematic review of assessment tools and their measurement properties.

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.

Self-management interventions for skin care in people with a spinal cord injury: part 2-a systematic review of use of theory and quality of intervention reporting.

STUDY DESIGN: Systematic review. OBJECTIVES: To examine use of theory and quality of reporting in skin care self-management interventions for people with SCI. SETTING: International. METHODS: The Theory Coding Scheme (TCS) and the Template for Intervention Description and Replication (TIDieR) checklist were applied by two independent researchers to 17 interventions identified in a systematic review of self-management interventions for skin care in people with SCI. RESULTS: Six (35%) of the 17 interventions reviewed were reported to have a theoretical basis. Theories used included three of the most commonly featured in health behavior research (the Health Belief Model, Social Cognitive Theory, and the Transtheoretical Model). In these six interventions, theory was used to design content but not to select participants or tailor strategies. None of the interventions were used to test theories in the SCI population, or to propose theoretical refinements. Reporting quality was found to vary by TIDieR item, with 6-100% of interventions including recommended information. Information on two intervention fidelity items was missing in 53 and 82% of descriptions. CONCLUSIONS: Use of theory and reporting quality in SCI self-management research remains suboptimal, potentially slowing down advancements in this area of research. Rehabilitation researchers should direct their efforts toward improving these practices to help build a science of SCI self-management that is cumulative and reproducible by clinicians, scientists, and policy makers. SPONSORSHIP: This work was funded through a postdoctoral fellowship awarded to the first author by the Rick Hansen Institute.

Self-management interventions for skin care in people with a spinal cord injury: part 1-a systematic review of intervention content and effectiveness.

STUDY DESIGN: Systematic review. OBJECTIVES: To review the content and effectiveness of skin care self-management interventions for people with SCI. SETTING: International. METHODS: We searched electronic bibliographic databases, trial registers, and relevant reference lists. Eligibility criteria for the reviews of intervention content and effectiveness were identical with the exception of study design. The review of intervention content included non-randomized and randomized controlled trials (RCTs). The review of effectiveness included RCTs. A Behavior Change Technique (BCT) taxonomy of 93 BCTs was used to code intervention content. Intervention effects on outcomes of interest are summarized descriptively. Effect sizes were calculated, and the Cochrane risk of bias tool applied. RESULTS: In all, 15 studies testing 17 interventions were included in the review of intervention content. Interventions in these studies included 28 BCTs. The most common were "instructions on how to perform behavior" (16 interventions), "credible source" (12 interventions), and "social support (unspecified)" (9 interventions). Ten RCTs were included in the review of intervention effectiveness and they measured knowledge, self-efficacy, and skills relating to skin care/pressure ulcer (PU) prevention, skin care behaviors, skin status (PU prevalence, severity, and time to PU), and health-care utilization for skin problems. Evidence to support intervention effects on these outcomes was limited, particularly for clinical outcomes. Risk of bias assessments was often inconclusive due to poor reporting. CONCLUSIONS: There is potential to design SCI skin care interventions that include currently untested BCTs. Further research and better consistency in outcome measurements and reporting are required to synthesize evidence on effectiveness.

Effect of sustained low efficient dialysis versus continuous renal replacement therapy on renal recovery after acute kidney injury in the intensive care unit: A systematic review and meta-analysis.

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 effects meta-analysis. A total of 1564 patients from 18 studies were 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.

Laparoscopic versus open pyloromyotomy in infants: a systematic review and meta-analysis.

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.

Optimal age for elective surgery of asymptomatic congenital pulmonary airway malformation: a meta-analysis.

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.

Environmental stress responsive expression of the gene li16 in Rana sylvatica, the freeze tolerant wood frog.

Wood frogs (Rana sylvatica) can endure weeks of subzero temperature exposure during the winter with up to 65% of their body water frozen as extracellular ice. Associated with freezing survival is elevated expression of a number of genes/proteins including the unidentified gene, li16, first described in liver. The current study undertakes a broad analysis of li16 expression in response to freezing in 12 tissues of wood frogs as well as expression responses to anoxia and dehydration. Transcript levels of li16 increased significantly after 24h freezing (at -2.5 °C) demonstrating increases of approximately 3-fold in testes, greater than 2-fold in heart, ventral skin and lung, and over 1.5-fold in brain, liver and hind leg muscle as compared to unfrozen controls at 5 °C. Increased li16 transcript levels in brain, muscle and heart were mirrored by elevated Li16 protein in frozen frogs. Significant upregulation of li16 in response to both anoxia and dehydration (both components of freezing) was demonstrated in brain, kidney and heart. Overall, the results indicate that Li16 protein has a significant role to play in cell/organ responses to freezing in wood frogs and that its up-regulation may be linked with oxygen restriction that is a common element in the three stress conditions examined.

Comparison of freshly cultured versus cryopreserved mesenchymal stem cells in animal models of inflammation: A pre-clinical systematic review.

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<0.05) between freshly cultured and cryopreserved MSCs. Our systematic summary of the current evidence base may provide MSC basic and clinical research scientists additional rationale for considering a cryopreserved MSC product in their pre-clinical studies and clinical trials as well as help identify research gaps and guide future related research. Funding: Ontario Institute for Regenerative Medicine.

Long-term Outcomes of Patients Surgically Treated for Hirschsprung Disease.

BACKGROUND: The only curative treatment for Hirschsprung disease (HD) is surgical repair. However, some patients experience poor postoperative outcomes. We determined long-term outcomes of all HD patients in Ontario, Canada's most populous province. METHODS: We conducted a retrospective cohort study including all children with HD born between April 1, 1991 and March 31, 2014 in Ontario using linked health administrative data. Each HD case was matched to five non-HD controls on sex, date of birth, region of residence and income and followed to March 31, 2016. Chronic diarrhea and constipation were identified using combinations of outpatient physician billing codes in both HD patients and non-HD residents of the province. We determined risk factors associated with diarrhea and constipation, including surgery type and sociodemographic characteristics, using multivariable conditional logistic regression, and reported adjusted odds ratios (aORs). RESULTS: There were 3,265,172 children born in the study period, of whom 673 had HD. Compared to controls, chronic constipation was more common in HD patients (27.5% versus 2.1%; aOR 17.2, 95% CI 12.6 to 23.4), as was chronic diarrhea (29.9% versus 6.9%, aOR 5.22, 95% CI 4.19 to 6.50). In HD patients, older age at surgery was associated with increased risk of chronic constipation (OR 2.71, 95% CI 1.75 to 4.20). Surgery type, sex, rural/urban residence and income were not associated with risk of chronic constipation or diarrhea. CONCLUSION: Chronic constipation and diarrhea were common following surgery for HD. Older age at surgery was associated with subsequent risk of chronic constipation. Surgery type was not associated with increased risk of chronic constipation or diarrhea.

Behaviour Change Domains Likely to Influence Occupational Therapist Use of the Canadian Occupational Performance Measure.

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.

Cell therapy with intravascular administration of mesenchymal stromal cells continues to appear safe: An updated systematic review and meta-analysis.

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.

Optimal timing for inguinal hernia repair in premature infants: a systematic review and meta-analysis.

BACKGROUND: The optimal timing of repair for inguinal hernia in premature infants remains a controversial topic. Our objective was to assess the clinical effects of inguinal hernia repair done before or after neonatal intensive care unit (NICU) discharge. METHODS: MEDLINE, Embase, CINAHL, and CENTRAL were searched in July 2018. Publications comparing clinical outcomes of the premature infants with inguinal hernia repair before (early) and after (delayed) NICU discharge were identified. Two reviewers independently screened studies, extracted data, and assessed for quality. Results were pooled using random effects meta-analysis. RESULTS: Of 640 publications identified, six comparative studies assessing a total of 1761 premature infants were included. Meta-analysis indicated no statistically significant difference in incarceration rate (odds ratio (OR) 2.15, 95% confidence interval (CI) 0.83-5.58, I2 = 0%), surgical complications (OR 2.36, 95% CI 0.66-8.41, I2 = 0%) and other secondary complications. However, the odds of recurrence and respiratory difficulty was significantly increase in the early group compared to delayed (OR 4.12, 95% CI 1.17-14.45, I2 = 0%; OR 3.59, 95% CI 1.10-11.75, I2 = 42%). CONCLUSIONS: Repair of inguinal hernia in premature infants before NICU discharge may increase the odds of recurrence, but not incarceration or surgical complications. LEVEL OF EVIDENCE: Level III.

Barriers and facilitators to the implementation of evidence-based practice by pediatric surgeons.

BACKGROUND/PURPOSE: Evidence-based practice (EBP) has been identified as a foundation of mainstream medical practice, yet pediatric surgery has been slow in the acceptance and implementation of EBP. METHODS: Semi-structured interviews of 14 pediatric surgeons were conducted to determine barriers and facilitators to EBP. Resulting data were analyzed using a systematic 3-step approached of coding, generation of specific beliefs, and identification of domains relevant to practice change. RESULTS: Six domains were identified as relevant to changing pediatric surgeons' use of evidence in practice: environmental context and resources, goals, knowledge, skills, social influence, and social/professional role and identity. Important barriers to EBP implementation included time constrains and resource limitations, the general poor quality of evidence in pediatric surgery, a lack of required skills, and a culture that continues to rely on an apprenticeship style of teaching. Facilitators include working in a research hospital, and having a local champion/ peers that support EBP implementation. There were conflicting thoughts as to whether working as a group facilitated or impeded EBP. CONCLUSIONS: Pediatric surgeons' use of research evidence in practice is influenced by a number of domains. These results may be used to inform the design of behavior change interventions intended to encourage EBP implementation. LEVELS OF EVIDENCE: Level V.

Validation of algorithms to determine incidence of Hirschsprung disease in Ontario, Canada: a population-based study using health administrative data.

OBJECTIVE: Incidence rates of Hirschsprung disease (HD) vary by geographical region, yet no recent population-based estimate exists for Canada. The objective of our study was to validate and use health administrative data from Ontario, Canada to describe trends in incidence of HD between 1991 and 2013. STUDY DESIGN: To identify children with HD we tested algorithms consisting of a combination of diagnostic, procedural, and intervention codes against the reference standard of abstracted clinical charts from a tertiary pediatric hospital. The algorithm with the highest positive predictive value (PPV) that could maintain high sensitivity was applied to health administrative data from April 31, 1991 to March 31, 2014 (fiscal years 1991-2013) to determine annual incidence. Temporal trends were evaluated using Poisson regression, controlling for sex as a covariate. RESULTS: The selected algorithm was highly sensitive (93.5%) and specific (>99.9%) with excellent predictive abilities (PPV 89.6% and negative predictive value >99.9%). Using the algorithm, a total of 679 patients diagnosed with HD were identified in Ontario between 1991 and 2013. The overall incidence during this time was 2.05 per 10,000 live births (or 1 in 4,868 live births). The incidence did not change significantly over time (odds ratio 0.998, 95% confidence interval 0.983-1.013, p = 0.80). CONCLUSION: Ontario health administrative data can be used to accurately identify cases of HD and describe trends in incidence. There has not been a significant change in HD incidence over time in Ontario between 1991 and 2013.

Value of upper endoscopic biopsies in predicting medical refractoriness in pediatric patients with ulcerative colitis.

Refractory ulcerative colitis (UC) occurs in patients who experience a severe disease manifestation that is unresponsive to medical therapy. The assessment of upper endoscopic microscopic findings and its correlation with refractory UC has not been fully studied in pediatric patients and is the focus of this study. Medical records of UC patients treated at a tertiary pediatric center between 2000 and 2014 were reviewed. Endoscopic biopsies of the upper gastrointestinal (GI) tract of patients meeting a priori inclusion criteria were compared between refractory UC patients and nonrefractory UC patients for active inflammation. Statistically significant differences were determined between groups, and tissues shown to have significant differences were further evaluated for their diagnostic performance. A total of 52 patients were included, 26 in each group. Significant differences were observed in intraepithelial neutrophil infiltration and percentage involvement of crypts/glands for the antrum, body, and duodenal bulb (P ≤ .001, .005, and .01 [intraepithelial neutrophil infiltration] and P = .001, .009, and .015 [% involvement], respectively). Microabscesses of mucosal glands/crypts were also experienced in a greater number of refractory UC patients in the stomach (ie, antrum and/or body of stomach; P = .005) and duodenum (ie, duodenum and/or duodenal bulb; P = .023). The sensitivity and specificity of upper GI tissues to predict refractory UC were moderate, with sensitivities ranging from 38% to 67% and specificities ranging from 81% to 100%. Our results suggest that children with refractory UC are more likely to have active inflammation in the upper GI tract, and thus, this may represent a predictor of responsiveness to current medical therapy.

Infant nephrolithiasis and nephrocalcinosis: Natural history and predictors of surgical intervention.

INTRODUCTION: Renal stone disease diagnosed in the first year of life is relatively uncommon. While risk factors such as low birth weight, furosemide exposure, and metabolic disorders are well established, there exists little information regarding resolution rates and need for surgical intervention. Our study objective was to evaluate urolithiasis and renal calcification resolution rates, time to resolution, and need for surgical intervention in children diagnosed in their first year of life. MATERIAL AND METHODS: REB approved retrospective chart review of children younger than 12 months of age (corrected for prematurity) diagnosed with nephrolithiasis and/or nephrocalcinosis in a tertiary pediatric hospital between April 2000 and August 2015 with a minimum 1-year follow-up period. Exact logistic regression was performed to assess the relationship between size of the largest stone (on either side) and the need for surgical intervention. Kaplan-Meier curves were constructed to examine time to stone resolution among those not requiring surgical intervention. RESULTS: 62 patients (61% male) were diagnosed with stones or nephrocalcinosis by ultrasound at a median age of 2.9 months. Of these, 37% had been admitted to the NICU because of prematurity, low birth weight or comorbidities. A total of 45 patients were found to have stones (Table); 35 of these had a stone at initial ultrasound and 10 initially diagnosed as nephrocalcinosis were later confirmed to have a stone. 67% of all stones were asymptomatic on presentation. Metabolic anomalies were present in 56% (35/62), and 16% (10/62) required medical treatment. Seven patients ultimately required surgical intervention. Stone size was found to predict the eventual need for surgical intervention (OR 3.52, 95% CI 1.47-12.78) for each 0.1 mm increase in diameter). Among patients not requiring surgical intervention (n = 38), the estimated median time to spontaneous resolution of urolithiasis was 1.1 years (95% CI 0.89-1.53, range 2 months-6 years) and 1.2 years for nephrocalcinosis (95% CI 0.59-2.13). CONCLUSIONS: Spontaneous resolution was a common outcome for newborns and infants diagnosed with urolithiasis in the first year of life, but high variability in time-to-resolution was observed. Only a small proportion who had confirmed stones on ultrasound required surgical intervention (15%), and large stone size was a predictive factor for surgery.

Feeding Post-Pyloromyotomy: A Meta-analysis.

CONTEXT: Postoperative emesis is common after pyloromyotomy. Although postoperative feeding is likely to be an influencing factor, there is no consensus on optimal feeding. OBJECTIVE: To compare the effect of feeding regimens on clinical outcomes of infants after pyloromyotomy. DATA SOURCES: Cumulative Index to Nursing and Allied Health Literature, The Cochrane Central Register of Controlled Trials, Embase, and Medline. STUDY SELECTION: Two reviewers independently assessed studies for inclusion based on a priori inclusion criteria. DATA EXTRACTION: Data were extracted on methodological quality, general study and intervention characteristics, and clinical outcomes. RESULTS: Fourteen studies were included. Ad libitum feeding was associated with significantly shorter length of stay (LOS) when compared with structured feeding (mean difference [MD] -4.66; 95% confidence interval [CI], -8.38 to -0.95; P = .01). Although gradual feeding significantly decreased emesis episodes (MD -1.70; 95% CI, -2.17 to -1.23; P < .00001), rapid feeding led to significantly shorter LOS (MD 22.05; 95% CI, 2.18 to 41.93; P = .03). Late feeding resulted in a significant decrease in number of patients with emesis (odds ratio 3.13; 95% CI, 2.26 to 4.35; P < .00001). LIMITATIONS: Exclusion of non-English studies, lack of randomized controlled trials, insufficient number of studies to perform publication bias or subgroup analysis for potential predictors of emesis. CONCLUSIONS: Ad libitum feeding is recommended for patients after pyloromyotomy as it leads to decreased LOS. If physicians still prefer structured feeding, early rapid feeds are recommended as they should lead to a reduced LOS.

Congenital mesoblastic nephroma: a study of 19 cases using immunohistochemistry and ETV6-NTRK3 fusion gene rearrangement.

Mesoblastic nephroma (MN) is the most common renal tumour in the first 3 months of life and accounts for 3-5% of all paediatric renal neoplasms. To further understand the morphological variants of MN, we identified 19 cases of MN (five classic, eight cellular and six mixed) and examined each case for markers known to be important in urogenital embryological development (PAX8, WT1 and RCC), stem cell associated markers (Oct 4, CD34 and c-kit), muscle/myofibroblastic markers (muscle specific actin, calponin and h-caldesmon), aberrant transcription factors, cell cycle regulation and other oncogenic proteins (p16, cyclin D1 and beta-catenin). Fluorescence in situ hybridisation (FISH) testing for ETV6-NTRK3 gene fusion/rearrangement revealed further differentiation between the subtypes with ETV6-NTRK3 gene fusion detected in 0/5 of the classic MN, 8/8 of the cellular MN and 5/6 of the mixed MN cohorts, respectively. Our results conclude that cyclin D1 and beta-catenin may be useful markers for differentiating between cellular MN and classic MN when the histology is not conclusive. The absence of expression of stem cell markers and markers involved in urogenital development suggests that MN is not a nephroma and most likely represents a soft tissue tumour, with congenital infantile fibrosarcoma representing cellular MN with a predilection to arise in the kidney. In addition, the immunophenotype and genetic fingerprint of mixed MN most likely represents a heterogenous group of tumours that are mostly cellular type, with areas that are phenotypically less cellular.

Evaluating mesenchymal stem cell therapy for sepsis with preclinical meta-analyses prior to initiating a first-in-human trial.

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.

The Devil Is in the Details: Incomplete Reporting in Preclinical Animal Research.

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.