Quality improvement strategies for diabetes care: Effects on outcomes for adults living with diabetes.

BACKGROUND: There is a large body of evidence evaluating quality improvement (QI) programmes to improve care for adults living with diabetes. These programmes are often comprised of multiple QI strategies, which may be implemented in various combinations. Decision-makers planning to implement or evaluate a new QI programme, or both, need reliable evidence on the relative effectiveness of different QI strategies (individually and in combination) for different patient populations. OBJECTIVES: To update existing systematic reviews of diabetes QI programmes and apply novel meta-analytical techniques to estimate the effectiveness of QI strategies (individually and in combination) on diabetes quality of care. SEARCH METHODS: We searched databases (CENTRAL, MEDLINE, Embase and CINAHL) and trials registers (ClinicalTrials.gov and WHO ICTRP) to 4 June 2019. We conducted a top-up search to 23 September 2021; we screened these search results and 42 studies meeting our eligibility criteria are available in the awaiting classification section. SELECTION CRITERIA: We included randomised trials that assessed a QI programme to improve care in outpatient settings for people living with diabetes. QI programmes needed to evaluate at least one system- or provider-targeted QI strategy alone or in combination with a patient-targeted strategy. - System-targeted: case management (CM); team changes (TC); electronic patient registry (EPR); facilitated relay of clinical information (FR); continuous quality improvement (CQI). - Provider-targeted: audit and feedback (AF); clinician education (CE); clinician reminders (CR); financial incentives (FI). - Patient-targeted: patient education (PE); promotion of self-management (PSM); patient reminders (PR). Patient-targeted QI strategies needed to occur with a minimum of one provider or system-targeted strategy. DATA COLLECTION AND ANALYSIS: We dual-screened search results and abstracted data on study design, study population and QI strategies. We assessed the impact of the programmes on 13 measures of diabetes care, including: glycaemic control (e.g. mean glycated haemoglobin (HbA1c)); cardiovascular risk factor management (e.g. mean systolic blood pressure (SBP), low-density lipoprotein cholesterol (LDL-C), proportion of people living with diabetes that quit smoking or receiving cardiovascular medications); and screening/prevention of microvascular complications (e.g. proportion of patients receiving retinopathy or foot screening); and harms (e.g. proportion of patients experiencing adverse hypoglycaemia or hyperglycaemia). We modelled the association of each QI strategy with outcomes using a series of hierarchical multivariable meta-regression models in a Bayesian framework. The previous version of this review identified that different strategies were more or less effective depending on baseline levels of outcomes. To explore this further, we extended the main additive model for continuous outcomes (HbA1c, SBP and LDL-C) to include an interaction term between each strategy and average baseline risk for each study (baseline thresholds were based on a data-driven approach; we used the median of all baseline values reported in the trials). Based on model diagnostics, the baseline interaction models for HbA1c, SBP and LDL-C performed better than the main model and are therefore presented as the primary analyses for these outcomes. Based on the model results, we qualitatively ordered each QI strategy within three tiers (Top, Middle, Bottom) based on its magnitude of effect relative to the other QI strategies, where 'Top' indicates that the QI strategy was likely one of the most effective strategies for that specific outcome. Secondary analyses explored the sensitivity of results to choices in model specification and priors.  Additional information about the methods and results of the review are available as Appendices in an online repository. This review will be maintained as a living systematic review; we will update our syntheses as more data become available. MAIN RESULTS: We identified 553 trials (428 patient-randomised and 125 cluster-randomised trials), including a total of 412,161 participants. Of the included studies, 66% involved people living with type 2 diabetes only. Participants were 50% female and the median age of participants was 58.4 years. The mean duration of follow-up was 12.5 months. HbA1c was the commonest reported outcome; screening outcomes and outcomes related to cardiovascular medications, smoking and harms were reported infrequently. The most frequently evaluated QI strategies across all study arms were PE, PSM and CM, while the least frequently evaluated QI strategies included AF, FI and CQI. Our confidence in the evidence is limited due to a lack of information on how studies were conducted.  Four QI strategies (CM, TC, PE, PSM) were consistently identified as 'Top' across the majority of outcomes. All QI strategies were ranked as 'Top' for at least one key outcome. The majority of effects of individual QI strategies were modest, but when used in combination could result in meaningful population-level improvements across the majority of outcomes. The median number of QI strategies in multicomponent QI programmes was three.  Combinations of the three most effective QI strategies were estimated to lead to the below effects:  - PR + PSM + CE: decrease in HbA1c by 0.41% (credibility interval (CrI) -0.61 to -0.22) when baseline HbA1c < 8.3%; - CM + PE + EPR: decrease in HbA1c by 0.62% (CrI -0.84 to -0.39) when baseline HbA1c > 8.3%;  - PE + TC + PSM: reduction in SBP by 2.14 mmHg (CrI -3.80 to -0.52) when baseline SBP < 136 mmHg; - CM + TC + PSM: reduction in SBP by 4.39 mmHg (CrI -6.20 to -2.56) when baseline SBP > 136 mmHg;  - TC + PE + CM: LDL-C lowering of 5.73 mg/dL (CrI -7.93 to -3.61) when baseline LDL < 107 mg/dL; - TC + CM + CR: LDL-C lowering by 5.52 mg/dL (CrI -9.24 to -1.89) when baseline LDL > 107 mg/dL. Assuming a baseline screening rate of 50%, the three most effective QI strategies were estimated to lead to an absolute improvement of 33% in retinopathy screening (PE + PR + TC) and 38% absolute increase in foot screening (PE + TC + Other). AUTHORS' CONCLUSIONS: There is a significant body of evidence about QI programmes to improve the management of diabetes. Multicomponent QI programmes for diabetes care (comprised of effective QI strategies) may achieve meaningful population-level improvements across the majority of outcomes. For health system decision-makers, the evidence summarised in this review can be used to identify strategies to include in QI programmes. For researchers, this synthesis identifies higher-priority QI strategies to examine in further research regarding how to optimise their evaluation and effects. We will maintain this as a living systematic review.

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.

Functional analysis of the Arabidopsis thaliana MUTE promoter reveals a regulatory region sufficient for stomatal-lineage expression.

MAIN CONCLUSION: The MUTE promoter contains a 175-bp region rich in Dof regulatory elements (AAAG) that is necessary and sufficient for initiation of transcription in meristemoids and the stomatal lineage. The molecular mechanism underlying the decision to divide or differentiate is a central question in developmental biology. During stomatal development, expression of the master regulator MUTE triggers the differentiation of meristemoids into stomata. In this study, we carried out MUTE promoter deletion analysis to define a regulatory region that promotes the initiation of expression in meristemoids. Expression constructs with truncated promoter fragments fused to ß-glucuronidase (GUS) were developed. The full-length promoter and promoter truncations of at least 500 bp from the translational start site exhibited normal spatiotemporal expression patterns. Further truncation revealed a 175-bp promoter fragment that was necessary and sufficient for stomatal-lineage expression. Known cis-elements were identified and tested for functional relevance. Comparison of orthologous MUTE promoters suggested DNA binding with one finger (Dof) regulatory elements and novel motifs may be important for regulation. Our data highlight the complexity and combinatorial control of gene regulation and provides tools to further investigate the genetic control of stomatal development.

A mutation in the canine gene encoding folliculin-interacting protein 2 (FNIP2) associated with a unique disruption in spinal cord myelination.

Novel mutations in myelin and myelin-associated genes have provided important information on oligodendrocytes and myelin and the effects of their disruption on the normal developmental process of myelination of the central nervous system (CNS). We report here a mutation in the folliculin-interacting protein 2 (FNIP2) gene in the Weimaraner dog that results in hypomyelination of the brain and a tract-specific myelin defect in the spinal cord. This myelination disruption results in a notable tremor syndrome from which affected dogs recover with time. In the peripheral tracts of the lateral and ventral columns of the spinal cord, there is a lack of mature oligodendrocytes. A genome-wide association study of DNA from three groups of dogs mapped the gene to canine chromosome 15. Sequencing of all the genes in the candidate region identified a frameshift mutation in the FNIP2 gene that segregated with the phenotype. While the functional role of FNIP2 is not known, our data would suggest that production of truncated protein results in a delay or failure of maturation of a subpopulation of oligodendrocytes.

Quantification of quaternary ammonium compounds by liquid chromatography-mass spectrometry: Minimizing losses from the field to the laboratory.

Quaternary Ammonium Compounds (QACs) are widely used in household, medical and industrial settings. As a consequence, they are ubiquitously found in the environment. Although significant efforts have been put into the development of sensitive and reproducible analytical methods, much less effort has been dedicated to the monitoring of QACs upon sample storage and sample preparation. Here we studied the effect of storage, concentration, and extraction procedures on the concentrations of QACs in samples. Thirteen QACs selected amongst benzalkonium compounds (BACs), dialkyldimethylammonium compounds (DADMACs) and alkyltrimethylammonium compounds (ATMACs) were quantified in aqueous and solid samples using LC-MS/MS. Most QACs adsorbed on container walls could be recovered using a short washing step with MeOH containing 2 % v/v formic acid. Concentrations of QACs from aqueous solutions using solid phase extraction (SPE) with Strata-X cartridges and elution with acidified MeOH utilized to wash the emptied containers gave highly satisfactory recoveries (101-111 %). Good recoveries (89-116 %) were also obtained when extracting a spiked organic-rich synthetic soil using accelerated solvent extraction (ASE) with acidified MeOH at low solid/solvent ratio (0.4 g/20 mL). Applying the recommended methodologies to real samples collected from a Canadian wastewater treatment plant (WWTP) gave QAC concentrations in the ranges of 0.01-30 µg/L, < 1.2 µg/L, and 0.05-27 mg/kg for the influent, effluent and biosolids samples, respectively.

Long-term Kidney Transplant Survival Across the Globe.

BACKGROUND: The outcomes after kidney transplantation (KT), including access, wait time, and other issues around the globe, have been studied. However, issues do vary from one country to another. METHODS: We obtained data from several countries from North America, South America, Europe, Asia, and Australia, including the number of patients awaiting KT from 2015, transplant rate per million population (pmp), proportion of living donor and deceased donor (LD/DD) KT, and posttransplant survival. We also sought opinions on key difficulties faced by each of these countries with respect to KT and long-term survival. RESULTS: Variation in access to KT across the globe was noted. Countries with the highest rates of KT pmp included the United States (79%) and Spain (71%). A higher proportion of LD transplants was noted in Japan (93%), India (85%), Singapore (63%), and South Korea (63%). A higher proportion of DD KTs was noted in Spain (90%), Brazil (90%), France (85%), Italy (85%), Finland (85%), Australia-New Zealand (80%), and the United States (77%). The 5-y graft survival for LD was highest in South Korea (95%), Singapore (94%), Italy (93%), Finland (93%), and Japan (93%), whereas for DD, it was South Korea (93%), Italy (88%), Japan (86%), and Singapore (86%). The common issues surrounding KTs are access and a limited number of LDs and DDs. Key issues identified for long-term survival were increasing age of donors and recipients, higher recipient comorbidity, and posttransplant events, such as alloimmune injury to the kidney, infection, cancer, and suboptimal adherence to therapy. CONCLUSIONS: A unified approach is necessary to improve issues surrounding KT as the demand continues to increase.

Changes in the incubation by American kestrels (Falco sparverius) during exposure to the polybrominated diphenyl ether (PBDE) mixture DE-71.

Polybrominated diphenyl ethers (PBDE) are persistent environmental pollutants that have been detected in wildlife globally. American kestrels exposed to the commercial PBDE mixture DE-71 have previously demonstrated reduced reproductive success and behaviors during courtship and brood rearing; however, it remains unknown whether DE-71 affects incubation. During breeding, captive kestrels were exposed to the DE-71 mixture dissolved in safflower oil at two environmentally relevant concentrations (low: 283.5 ± 48.2, high: 1104.8 ± 124.5 ng/g wet weight [ww]) via diet for an average of 75 d. Unexpected low in ovo concentrations of hexabromocyclododecane (HBCD) were also detected (low: 3 ± 1 ng/g ww, high: 16 ± 3 ng/g ww). All comparisons are made to control pairs. Kestrel pairs in the low- and high-exposure groups experienced longer incubation periods with increasing exposure to ΣPBDE and some individual congeners. As incubation progressed, pairs exposed to DE-71 had significantly lower nest temperatures, which were on average 19% lower in low-exposure nests and 35% lower in high-exposure nests during late incubation. The DE-71 exposed pairs (low and high) also demonstrated significantly reduced incubation constancy (defined as percent of temperature readings above the maximum daily ambient temperature) during early incubation compared to controls. Nest temperatures (all pairs) and incubation constancy (high pairs) during early incubation (d 1-3) were significantly and positively associated with the proportion of eggs that hatched per pair. Higher incubation constancy and incubating nest temperatures in the low-exposure group were associated with markedly less egg weight loss by mid-incubation. These findings demonstrate that exposure to PBDE significantly affected kestrels during incubation, a critical period for embryonic development.

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.

Changes in plasma retinol of American kestrels (Falco sparverius) in response to dietary or in ovo exposure to environmentally relevant concentrations of a penta-brominated diphenyl ether mixture, DE-71.

Polybrominated diphenyl ethers (PBDE) are ubiquitous, lipophilic, and bioaccumulative brominated flame retardants. Plasma retinol concentrations of captive adult American kestrels were assessed at the beginning of the breeding season following 3 wk of daily dietary exposure to vehicle (control), low (0.3 ng/g wet weight [ww]), or high (1.6 ng/g ww) concentrations of DE-71 and in their 25-d-old nestlings following embryonic exposure by maternal deposition to environmentally relevant low (291 ± 48 ng/g ww) or high (1111 ± 160 ng/g ww) sum (Σ) PBDE concentrations. Unexpectedly, low in ovo concentrations of total-α-hexabromocyclododecane (HBCD) were detected. Plasma retinol concentrations of adult males exposed to higher DE-71 concentrations were negatively correlated with in ovo ΣPBDE, BDE-100, and HBCD levels. Maternal (13%) and nestling (11%) retinol levels were lower in the low-exposure group compared to respective controls, and biologically significant since their retinol levels were correlated with hatching success and growth, respectively. Maternal retinol levels were also correlated with BDE-153. The underlying mechanisms may involve (1) PBDE exposure, hydroxylated (OH-) metabolites, and subsequent changes in retinol mobilization; (2) decreased maternal food consumption; and (3) reduced maternal retinol yolk deposits. The apparent lack of retinol changes in the high-exposure kestrel may reflect compensation occurring, either by increased mobilization and transportation of retinol, and/or higher food consumption in these birds. When highly mobile as evidenced during reproduction or development, retinol concentrations of adult and nestling kestrels are sensitive to environmentally relevant PBDE and HBCD levels.

Comparison of freshly cultured versus freshly thawed (cryopreserved) mesenchymal stem cells in preclinical in vivo models of inflammation: a protocol for a preclinical systematic review and meta-analysis.

BACKGROUND: Mesenchymal stem cells (MSCs) are multipotent cells that demonstrate therapeutic potential for the treatment of acute and chronic inflammatory-mediated conditions. Especially for acute conditions, it is critical to have a readily available freshly thawed (cryopreserved) MSC product for rapid administration. Although controversial, some studies suggest that MSCs may lose their functionality with cryopreservation which in turn could render them non-efficacious. OBJECTIVE: In controlled preclinical in vivo models of inflammation, to determine if there are differences in surrogate measures of preclinical efficacy between freshly cultured and freshly thawed MSCs METHODS/DESIGN: A systematic search for pre-clinical in vivo inflammatory model studies will compare freshly cultured to freshly thawed MSCs from any source. The primary outcomes will include measures of in vivo preclinical efficacy; secondary outcomes will include measures of in vitro MSC potency. Electronic searches for MEDLINE and EMBASE will be constructed and reviewed by the Peer Review of Electronic Search Strategies (PRESS) process. If applicable, study outcomes will be meta-analyzed using a random effects model. Risk of bias will be assessed by the SYRCLE "Risk of Bias" assessment tool for preclinical in vivo studies. DISCUSSION: The results of this systematic review will provide translational scientists, clinical trialists, health regulators, and the clinical and public community with the current pre-clinical evidence base related to the efficacy and potency of freshly cultured versus freshly thawed MSCs, help identify evidence gaps, and guide future related research. SYSTEMATIC REVIEW REGISTRATION: Protocol is submitted to PROSPERO for registration (pending confirmation) and will be submitted to Collaborative Approach to Meta-Analysis and Review of Animal Data from Experimental Studies (CAMARADES) for public posting.

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.