37 research outputs found
Effectiveness and meaningful use of paediatric surgical safety checklists and their implementation strategies: a systematic review with narrative synthesis
Objective: To examine the effectiveness and meaningful use of paediatric surgical safety checklists (SSCs) and their implementation strategies through a systematic review with narrative synthesis. Summary background data Since the launch of the WHO SSC, checklists have been integrated into surgical systems worldwide. Information is sparse on how SSCs have been integrated into the paediatric surgical environment. Methods: A broad search strategy was created using Pubmed, Embase, CINAHL, Cochrane Central, Web of Science, Science Citation Index and Conference Proceedings Citation Index. Abstracts and full texts were screened independently, in duplicate for inclusion. Extracted study characteristic and outcomes generated themes explored through subgroup analyses and idea webbing. Results: 1826 of 1921 studies were excluded after title and abstract review (kappa 0.77) and 47 after full-text review (kappa 0.86). 20 studies were of sufficient quality for narrative synthesis. Clinical outcomes were not affected by SSC introduction in studies without implementation strategies. A comprehensive SSC implementation strategy in developing countries demonstrated improved outcomes in high-risk surgeries. Narrative synthesis suggests that meaningful compliance is inconsistently measured and rarely achieved. Strategies involving feedback improved compliance. Stakeholder-developed implementation strategies, including team-based education, achieved greater acceptance. Three studies suggest that parental involvement in the SSC is valued by parents, nurses and physicians and may improve patient safety. Conclusions: A SSC implementation strategy focused on paediatric patients and their families can achieve high acceptability and good compliance. SSCs’ role in improving measures of paediatric surgical outcome is not well established, but they may be effective when used within a comprehensive implementation strategy especially for high-risk patients in low-resource settings
Management of Gastroschisis: Results From the NETS2G Study, a Joint British, Irish, and Canadian Prospective Cohort Study of 1268 Infants.
OBJECTIVE: In infants with gastroschisis, outcomes were compared between those where operative reduction and fascial closure were attempted ?24?hours of age (PC), and those who underwent planned closure of their defect >24?hours of age following reduction with a pre-formed silo (SR). SUMMARY OF BACKGROUND DATA: Inadequate evidence exists to determine how best to treat infants with gastroschisis. METHODS: A secondary analysis was conducted of data collected 2006-2008 using the British Association of Pediatric Surgeons Congenital Anomalies Surveillance System, and 2005-2016 using the Canadian Pediatric Surgery Network.28-day outcomes were compared between infants undergoing PC and SR. Primary outcome was number of gastrointestinal complications. Interactions were investigated between infant characteristics and treatment to determine whether intervention effect varied in sub-groups of infants. RESULTS: Data from 341 British and Irish infants (27%) and 927 Canadian infants (73%) were used. 671 infants (42%) underwent PC and 597 (37%) underwent SR. The effect of SR on outcome varied according to the presence/absence of intestinal perforation, intestinal matting and intestinal necrosis. In infants without these features, SR was associated with fewer gastrointestinal complications [aIRR 0.25 (95% CI 0.09-0.67, P = 0.006)], more operations [aIRR 1.40 (95% CI 1.22-1.60, P < 0.001)], more days PN [aIRR 1.08 (95% CI 1.03-1.13, P < 0.001)], and a higher infection risk [aOR 2.06 (95% CI 1.10-3.87, P = 0.025)]. In infants with these features, SR was associated with a greater number of operations [aIRR 1.30 (95% CI 1.17-1.45, P < 0.001)], and more days PN [aIRR 1.06 (95% CI 1.02-1.10, P = 0.003)]. CONCLUSIONS: In infants without intestinal perforation, matting, or necrosis, the benefits of SR outweigh its drawbacks. In infants with these features, the opposite is true. Treatment choice should be based upon these features
Appendectomy versus non-operative treatment for acute uncomplicated appendicitis in children: Study protocol for a multicentre, open-label, non-inferiority, randomised controlled trial
Background Appendectomy is considered the gold standard treatment for acute appendicitis. Recently the need for surgery has been challenged in both adults and children. In children there is growing clinician, patient and parental interest in non-operative treatment of acute appendicitis with antibiotics as opposed to surgery. To date no multicentre randomised controlled trials that are appropriately powered to determine efficacy of nonoperative treatment (antibiotics) for acute appendicitis in children compared with surgery (appendectomy) have been performed. Methods Multicentre, international, randomised controlled trial with a non-inferiority design. Children (age 5–16 years) with a clinical and/or radiological diagnosis of acute uncomplicated appendicitis will be randomised (1:1 ratio) to receive either laparoscopic appendectomy or treatment with intravenous (minimum 12 hours) followed by oral antibiotics (total course 10 days). Allocation to groups will be stratified by gender, duration of symptoms (≫ or \u3c48 hours) and centre. Children in both treatment groups will follow a standardised treatment pathway. Primary outcome is treatment failure defined as additional intervention related to appendicitis requiring general anaesthesia within 1 year of randomisation (including recurrent appendicitis) or negative appendectomy. Important secondary outcomes will be reported and a cost-effectiveness analysis will be performed. The primary outcome will be analysed on a non-inferiority basis using a 20% non-inferiority margin. Planned sample size is 978 children. Discussion The APPY trial will be the first multicentre randomised trial comparing non-operative treatment with appendectomy for acute uncomplicated appendicitis in children. The results of this trial have the potential to revolutionise the treatment of this common gastrointestinal emergency. The randomised design will limit the effect of bias on outcomes seen in other studies. Trial registration number clinicaltrials.gov:NCT02687464. Registered on Jan 13th 2016
Invitro alteration of rat pancreatic islet immunogenicity in an allogeneic transplant model
Allograft rejection remains the fundamental stumbling block to tissue transplantation. Traditional assumption has been that transplanted tissue alone provides an antigen source (alloantigen), which directly stimulates a host response resulting in graft rejection; accordingly, traditional attempts at circumventing the allograft response have focussed on techniques of recipient immunosuppression. Recently, increasing attention has been given to a subset of non-parenchymal, bone marrow derived lymphoid cells (characterized by their surface expression of class II MHC antigen) which are carried passively with the allograft into an immune competent recipient. A current hypothesis is that these cells, called antigen presenting cells (APCs), participate in the sensitization of the immunologically naive but responsive host to the transplanted tissue, leading ultimately to graft rejection. Therefore, it has been suggested that depletion of APCs from donor tissue prior to transplantation may permit allogeneic transplantation to occur, without host immunosuppression. In contrast to solid organs, pancreatic islets are well suited to this type of immunomodulation prior to transplantation, since they can be maintained in a functional ex vivo state by cell culture.
The purpose of this thesis was to evaluate donor islet APC depletion by pre-transplant cell culture and APC-ablative photodynamic therapy (PDT), and to see whether either in vitro technique could prevent rejection in a rat, allogeneic transplant model.
Briefly, a donor (Sprague Dawley, RTlu) -recipient (Wistar Furth, RTla) pair with a major histo-incompatible barrier was selected. After collagenase digestion of donor pancreata, islets were isolated from A the digested tissue by centrifugation through a discontinuous dextran gradient followed by hand picking using a dissecting microscope. Once isolated, the islets were either used fresh, placed in tissue culture (Ham's F-12 media, 11 mM glucose, 5% C02/room air at 37 C) for variable periods, or subjected to APC-ablative PDT. Islet APC depletion was assessed by fluorescent immunocytochemistry. Fresh, cultured and PDT treated islets were frozen in liquid N2 then cryostat sectioned and stained for class II MHC + cells (APCs), using an anti-class II mouse monoclonal antibody (OX-6), followed by a fluorescent (fluorescein indothiocyanate) labelled anti-mouse monoclonal. Using this technique, APCs could be identified by fluorescent microscopy on the basis of their enhanced surface staining. While fresh islets demonstrated between 1 and 5 APCs per cryostat section, a culture period of at least 10 days resulted in complete islet APC elimination. Islet allograft studies with fresh and cultured islets were then performed to determine: 1) if pre-transplant islet culture could sufficiently reduce donor tissue immunogenicity to allow successful allografting in immune-competent recipients, and if so, 2) what duration of culture was necessary to permit consistently successful allografting. Allografts of fresh and cultured (4, 7, 10, 14, and 21 day) islets were placed under the renal capsule of immune-competent, recipient rats and after 12 days the grafts were removed and studied histologically for evidence of rejection. While all grafts which were cultured for 10 days or less prior to transplantation were rejected, 4/10-14 day cultured islets, and 4/5-21 day cultured islets demonstrated engraftment. In vivo function of 21 day cultured islet allografts was demonstrated by transplantation of islets via the portal vein, into recipients which had been rendered hyperglycemic by IV streptozotocin. This resulted in an immediate and sustained reversion to euglycemia (as assessed by daily plasma glucose determinations using a glucose analyser) over a 30 day period of study. In contrast, streptozotocin "diabetic" recipients of fresh and 14 day cultured islet allografts demonstrated a brief (7-10 day) period of graft function (euglycemia) prior to a return of hyperglycemia, consistent with graft rejection.
Photodynamic therapy (PDT) achieves selective cell ablation by the stimulated emission of singlet oxygen from a light-activated compound (benzoporphyrin) which has been delivered to the cell target. In these experiments, APC elimination was attempted by in vitro islet treatment with OX-6, followed by a specific, secondary antibody (RAMIg) to which BPD had been conjugated. After UV lightactivation the treated islets were frozen, cryostat sectioned and immunostained for Class II MHC + cells. In contrast to control islets which underwent a secondary incubation with either BPD alone or BPD conjugated to an irrelevant secondary antibody, islets which underwent PDT using the specific RAMIg-BPD conjugate demonstrated elimination of APCs as assessed by immunocytochemistry. When syngeneic and allogeneic transplants were performed using islets which had undergone APC "photoablation", the histologic appearance of the grafts was compatible with either inflammation in response to non-viable tissue, or allograft rejection.
The temporal disparity between the duration of tissue culture necessary to deplete islet APCs and that required to allow successful islet allografting can be variably explained. One possibility is that failure to stain APCs after a 7-10 day period of culture is not proof that these cells have been destroyed. It is conceivable that culture alters the surface of the APC such that it is no longer identified by anti-Class II MHC immunostains, but nevertheless retains its ability to present alloantigen. Alternatively, one can hypothesize that in vitro culture causes some donor tissue alteration other than APC depletion which renders it less immunogenic. The failure of PDT to permit successful syngeneic or allogeneic transplantation despite its apparent ability to eliminate islet APCs suggests that the treatment itself may cause irreversible islet injury, and that the inflammatory reaction observed is merely in response to non-viable transplanted tissue.Surgery, Department ofMedicine, Faculty ofGraduat