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Introduction: No worldwide, standardised definitions exist for documenting, reporting and comparing data from severely injured trauma patients. This study evaluated the feasibility of collecting the data variables of the international consensus-derived Utstein Trauma Template.Methods: Trauma centres from three different continents were invited to submit Utstein Trauma Template core data during a defined period, for up to 50 consecutive trauma patients. Directly admitted patients with a New Injury Severity Score (NISS) equal to or above 16 were included. Main outcome variables were data completeness, data differences and data collection difficulty.Results: Centres from Europe (n = 20), North America (n = 3) and Australia (n = 1) submitted data on 965 patients, of whom 783 were included. Median age was 41 years (interquartile range (IQR) 24 to 60), and 73.1% were male. Median NISS was 27 (IQR 20 to 38), and blunt trauma predominated (91.1%). Of the 36 Utstein variables, 13 (36%) were collected by all participating centres. Eleven (46%) centres applied definitions of the survival outcome variable that were different from those of the template. Seventeen (71%) centres used the recommended version of the Abbreviated Injury Scale (AIS). Three variables (age, gender and AIS) were documented in all patients. Completeness > 80% was achieved for 28 variables, and 20 variables were > 90% complete.Conclusions: The Utstein Template was feasible across international trauma centres for the majority of its data variables, with the exception of certain physiological and time variables. Major differences were found in the definition of survival and in AIS coding. The current results give a clear indication of the attainability of information and may serve as a stepping-stone towards creation of a European trauma registry. [ABSTRACT FROM AUTHOR]

Background: Most in vitro cancer cell experiments have been performed using 2D models. However, 3D spheroid cultures are increasingly favored for being more representative of in vivo tumor conditions. To overcome the translational challenges with 2D cell cultures, 3D systems better model more complex cell-to-cell contact and nutrient levels present in a tumor, improving our understanding of cancer complexity. Despite this need, there are few reports on how 3D cultures differ metabolically from 2D cultures., Methods: Well-described cell lines from colorectal cancer (HCT116 and SW948) and pancreatic ductal adenocarcinoma (Panc-1 and MIA-Pa-Ca-2) were used to investigate metabolism in 3D spheroid models. The metabolic variation under normal glucose conditions were investigated comparing 2D and 3D cultures by metabolic flux analysis and expression of key metabolic proteins., Results: We find significant differences in glucose metabolism of 3D cultures compared to 2D cultures, both related to glycolysis and oxidative phosphorylation. Spheroids have higher ATP-linked respiration in standard nutrient conditions and higher non-aerobic ATP production in the absence of supplemented glucose. In addition, ATP-linked respiration is significantly inversely correlated with OCR/ECAR (p = 0.0096). Mitochondrial transport protein, TOMM20, expression decreases in all spheroid models compared to 2D, and monocarboxylate transporter (MCT) expression increases in 3 of the 4 spheroid models., Conclusions: In this study of CRC and PDAC cell lines, we demonstrate that glucose metabolism in 3D spheroids differs significantly from 2D cultures, both in terms of glycolytic and oxidative phosphorylation metrics. The metabolic phenotype shift from 2D to 3D culture in one cell line is greater than the phenotypic differences between each cell line and tumor source. The results herein emphasize the need to use 3D cell models for investigating nutrient utilization and metabolic flux for a better understanding of tumor metabolism and potential metabolic therapeutic targets., (© 2022. The Author(s).)

The aim of this paper was to review the recent literature to create recommendations for the day-to-day diagnosis and surgical management of small bowel and colon injuries. Where knowledge gaps were identified, expert consensus was pursued during the 8th International Congress of the World Society of Emergency Surgery Annual (September 2021, Edinburgh). This process also aimed to guide future research., (© 2022. The Author(s).)

Background: Adhesive small bowel obstruction (ASBO) is a common surgical emergency, causing high morbidity and even some mortality. The adhesions causing such bowel obstructions are typically the footprints of previous abdominal surgical procedures. The present paper presents a revised version of the Bologna guidelines to evidence-based diagnosis and treatment of ASBO. The working group has added paragraphs on prevention of ASBO and special patient groups., Methods: The guideline was written under the auspices of the World Society of Emergency Surgery by the ASBO working group. A systematic literature search was performed prior to the update of the guidelines to identify relevant new papers on epidemiology, diagnosis, and treatment of ASBO. Literature was critically appraised according to an evidence-based guideline development method. Final recommendations were approved by the workgroup, taking into account the level of evidence of the conclusion., Recommendations: Adhesion formation might be reduced by minimally invasive surgical techniques and the use of adhesion barriers. Non-operative treatment is effective in most patients with ASBO. Contraindications for non-operative treatment include peritonitis, strangulation, and ischemia. When the adhesive etiology of obstruction is unsure, or when contraindications for non-operative management might be present, CT is the diagnostic technique of choice. The principles of non-operative treatment are nil per os, naso-gastric, or long-tube decompression, and intravenous supplementation with fluids and electrolytes. When operative treatment is required, a laparoscopic approach may be beneficial for selected cases of simple ASBO.Younger patients have a higher lifetime risk for recurrent ASBO and might therefore benefit from application of adhesion barriers as both primary and secondary prevention., Discussion: This guideline presents recommendations that can be used by surgeons who treat patients with ASBO. Scientific evidence for some aspects of ASBO management is scarce, in particular aspects relating to special patient groups. Results of a randomized trial of laparoscopic versus open surgery for ASBO are awaited., Competing Interests: Not applicableThe authors declare that they have no competing interests.Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Background: Patients with early colorectal cancer (stages I-II) generally have a good prognosis, but a subgroup of 15-20% experiences relapse and eventually die of disease. Occult metastases have been suggested as a marker for increased risk of recurrence in patients with node-negative disease. Using a previously identified, highly accurate epigenetic biomarker panel for early detection of colorectal tumors, we aimed at evaluating the prognostic value of occult metastases in sentinel lymph nodes of colon cancer patients., Results: The biomarker panel was analyzed by quantitative methylation-specific PCR in primary tumors and 783 sentinel lymph nodes from 201 patients. The panel status in sentinel lymph nodes showed a strong association with lymph node stage ( P  = 8.2E-17). Compared with routine lymph node diagnostics, the biomarker panel had a sensitivity of 79% (31/39). Interestingly, among 162 patients with negative lymph nodes from routine diagnostics, 13 (8%) were positive for the biomarker panel. Colon cancer patients with high sentinel lymph node methylation had an inferior prognosis (5-year overall survival P  = 3.0E-4; time to recurrence P  = 3.1E-4), although not significant. The same trend was observed in multivariate analyses ( P  = 1.4E-1 and P  = 6.7E-2, respectively). Occult sentinel lymph node metastases were not detected in early stage (I-II) colon cancer patients who experienced relapse., Conclusions: Colon cancer patients with high sentinel lymph node methylation of the analyzed epigenetic biomarker panel had an inferior prognosis, although not significant in multivariate analyses. Occult metastases in TNM stage II patients that experienced relapse were not detected.

[This corrects the article DOI: 10.1186/s13017-017-0141-6.].

Background: Antimicrobial Stewardship Programs (ASPs) have been promoted to optimize antimicrobial usage and patient outcomes, and to reduce the emergence of antimicrobial-resistant organisms. However, the best strategies for an ASP are not definitively established and are likely to vary based on local culture, policy, and routine clinical practice, and probably limited resources in middle-income countries. The aim of this study is to evaluate structures and resources of antimicrobial stewardship teams (ASTs) in surgical departments from different regions of the world., Methods: A cross-sectional web-based survey was conducted in 2016 on 173 physicians who participated in the AGORA (Antimicrobials: A Global Alliance for Optimizing their Rational Use in Intra-Abdominal Infections) project and on 658 international experts in the fields of ASPs, infection control, and infections in surgery., Results: The response rate was 19.4%. One hundred fifty-six (98.7%) participants stated their hospital had a multidisciplinary AST. The median number of physicians working inside the team was five [interquartile range 4-6]. An infectious disease specialist, a microbiologist and an infection control specialist were, respectively, present in 80.1, 76.3, and 67.9% of the ASTs. A surgeon was a component in 59.0% of cases and was significantly more likely to be present in university hospitals (89.5%, p  < 0.05) compared to community teaching (83.3%) and community hospitals (66.7%). Protocols for pre-operative prophylaxis and for antimicrobial treatment of surgical infections were respectively implemented in 96.2 and 82.3% of the hospitals. The majority of the surgical departments implemented both persuasive and restrictive interventions (72.8%). The most common types of interventions in surgical departments were dissemination of educational materials (62.5%), expert approval (61.0%), audit and feedback (55.1%), educational outreach (53.7%), and compulsory order forms (51.5%)., Conclusion: The survey showed a heterogeneous organization of ASPs worldwide, demonstrating the necessity of a multidisciplinary and collaborative approach in the battle against antimicrobial resistance in surgical infections, and the importance of educational efforts towards this goal.

Intra-abdominal infections (IAIs) are common surgical emergencies and have been reported as major contributors to non-trauma deaths in the emergency departments worldwide. The cornerstones of effective treatment of IAIs are early recognition, adequate source control, and appropriate antimicrobial therapy. Prompt resuscitation of patients with ongoing sepsis is of utmost important. In hospitals worldwide, non-acceptance of, or lack of access to, accessible evidence-based practices and guidelines result in overall poorer outcome of patients suffering IAIs. The aim of this paper is to promote global standards of care in IAIs and update the 2013 WSES guidelines for management of intra-abdominal infections.

The TNM-system fails to accurately predict disease recurrence in a considerate number of patients. While node-negative (stage II) colon cancer is considered to have an overall good prognosis, the 5-year cancer-specific survival is reported at 81-83% in patients who did not have adjuvant chemotherapy. Thus, reliance on node-status alone has lead to under-treatment in a subgroup of stage II patients with an unfavorable prognosis. The search for new and better prognosticators in stage II colon cancer has suggested several proposed biomarkers of better prognostication and prediction. However, few such biomarkers have reached widespread clinical utility. For the clinician swimming in the sea of emerging biomarkers, it may be hard to recognize the true floating aid from the surrounding debris in the search for more precise decision-making. Proposed markers include microsatellite instability (MSI), KRAS mutations and BRAF mutations, but a number of gene panels and consensus molecular subtypes are proposed for clinical prediction and prognostication as well. While several studies suggest such biomarkers or panels to have a prognostic role in subgroups of patients, a number of studies are reported in heterogeneous groups with in part discordant findings, which again distorts the predictive and prognostic ability of each marker. Lack of homogeneous cohorts, underpowered studies in strict subgroups and challenges in analytical and clinical validity may hamper the progress towards widespread clinical utility. The harvest of prognostic biomarkers in colon cancer has yielded a huge number of candidates for which it is now time to separate the wheat from the chaff.

Background: More accurate predictive and prognostic biomarkers for patients with colorectal cancer (CRC) primaries or colorectal liver metastasis (CLM) are needed. Outside clinical trials, the translational integration of emerging pathways and novel techniques should facilitate exploration of biomarkers for improved staging and prognosis., Methods: An observational study exploring predictive and prognostic biomarkers in a population-based, consecutive cohort of surgically treated colorectal cancers and resected colorectal liver metastases. Long-term outcomes will be cancer-specific survival, recurrence-free survival and overall survival at 5 years from diagnosis. Beyond routine clinicopathological and anthropometric characteristics and laboratory and biochemistry results, the project allows for additional blood samples and fresh-frozen tumour and normal tissue for investigation of circulating tumour cells (CTCs) and novel biomarkers (e.g. immune cells, microRNAs etc.). Tumour specimens will be investigated by immunohistochemistry in full slides. Extracted DNA/RNA will be analysed for genomic markers using specific PCR techniques and next-generation sequencing (NGS) panels. Flow cytometry will be used to characterise biomarkers in blood. Collaboration is open and welcomed, with particular interest in mutual opportunities for validation studies., Status and Perspectives: The project is ongoing and recruiting at an expected rate of 120-150 patients per year, since January 2013. A project on circulating tumour cells (CTCs) has commenced, with analysis being prepared. Investigating molecular classes beyond the TNM staging is under way, including characteristics of microsatellite instability (MSI) and elevated microsatellite alterations in selected tetranucleotides (EMAST). Hot spot panels for known mutations in CRC are being investigated using NGS. Immune-cell characteristics are being performed by IHC and flow cytometry in tumour and peripheral blood samples. The project has ethical approval (REK Helse Vest, #2012/742), is financially supported with a Ph.D.-Grant (EMAST project; Folke Hermansen Cancer Fund) and a CTC-project (Norwegian Research Council; O. Nordgård). The ACROBATICC clinical and molecular biobank repository will serve as a long-term source for novel exploratory analysis and invite collaborators for mutual validation of promising biomarker results. The project aims to generate results that can help better discern prognostic groups in stage II/III cancers; explore prognostic and predictive biomarkers, and help detail the biology of colorectal liver metastasis for better patient selection and tailored treatment. The project is registered at http://www.ClinicalTrials.gov NCT01762813.

Background: The increasing incidence of prosthesis revision surgery in the Western world has led to an increased focus on the capacity for stem removal. We previously reported on a femoral stem implanted in goats with an approximate 15% reduction in retention force by drilling longitudinally orientated grooves on the side of the stem. In this current study, we aimed to histologically evaluate the bony apposition towards this stem and correlate this apposition with the pullout force., Methods: We analyzed the femora of 22 goats after stem removal. All stems remained in place for 6 months, and the goats were allowed regular loading of the hip during this time. For histological evaluation, all femora were immersed in EDTA and decalcified until sufficiently soft for standard technique preparation. We evaluated bone apposition, the presence of foreign particle debris and other factors. The apposition was evaluated with a scoring system based on semi-quantitative bone apposition in four quadrants. Kappa statistics were calculated for the score. We correlated the retention force with the amount of bone apposition., Results: The stem drilling was the only significant factor influencing the retention force (p = 0.020). The bone apposition Kappa score comparing poor and good apposition scores was fair (κ = 0.4, 95% CI 0.00-0.88). Signs of foreign body reaction were noted in 5 of 22 goats., Conclusions: Based on the current findings in an experimental goat model, it appears that the effect of drilling tissue/bone out of the longitudinal grooves has a more significant impact on the retention force required to remove the stem than the amount of bone apposition outside the stem grooves. This observation may be further explored in the research of stem designs that are potentially easier to remove.

Becoming old is considered a privilege and results from the socioeconomic progress and improvements in health care systems worldwide. However, morbidity and mortality increases with age, and even more so in acute onset disease. With the current prospects of longevity, a considerable number of elderly patients will continue to live with good function and excellent quality of life after emergency surgical care. However, mortality in emergency surgery may be reported at 15-30%, doubled if associated with complications, and notably higher in patients over 75 years. A number of risks associated with death are reported, and a number of scores proposed for prediction of risk. Frailty, a decline in the physiological reserves that may make the person vulnerable to even the most minor of stressful event, appears to be a valid indicator and predictor of risk and poor outcome, but how to best address and measure frailty in the emergency setting is not clear. Futility may sometimes be clearly defined, but most often becomes a borderline decision between ethics, clinical predictions and patient communication for which no solid evidence currently exists. The number and severity of other underlying condition(s), as well as the treatment alternatives and their consequences, is a complex picture to interpret. Add in the onset of the acute surgical disease as a further potential detrimental factor on function and quality of life - and you have a perfect storm to handle. In this brief review, some of the challenging aspects related to emergency surgery in the elderly will be discussed. More research, including registries and trials, are needed for improved knowledge to a growing health care challenge.

Background: Since the introduction of uncemented hip implants, there has been a search for the best surface coating to enhance bone apposition in order to improve retention. The surface coating of the different stems varies between products. The aim was to assess the retention force and bone adaption in two differently coated stems in a weight-bearing goat model., Materials and Methods: Hydroxyapatite (HA) and electrochemically deposited calcium phosphate (CP; Bonit) on geometrically comparable titanium-based femoral stems were implanted into 12 (CP group) and 35 (HA group) goats. The animal model included physiological loading of the implants for 6 months. The pull-out force of the stems was measured, and bone apposition was microscopically evaluated., Results: After exclusion criteria were applied, the number of available goats was 4 in the CP group and 11 in the HA group. The CP-coated stems had significantly lower retention forces compared with the HA-coated ones after 6 months (CP median 47 N, HA median 1,696 N, p = 0.003). Bone sections revealed a lower degree of bone apposition in the CP-coated stems, with more connective tissue in the bone/implant interface compared with the HA group., Conclusion: In this study, HA had better bone apposition and needed greater pull-out force in loaded implants. The application of CP on the loaded titanium surface to enhance the apposition of bone is questioned.

Lymph node (LN) harvest is influenced by several factors, including tumor genetics. Microsatellite instability (MSI) is associated with improved node harvest, but the association to other genetic factors is largely unknown. Research methods included a prospective series of stage I-III colon cancer patients undergoing ex vivo sentinel-node sampling. The presence of MSI, KRAS mutations in codons 12 and 13, and BRAF V600E mutations was analyzed. Uni- and multivariate regression models for node sampling were adjusted for clinical, pathological and molecular features. Of 204 patients, 67% had an adequate harvest (≥ 12 nodes). Adequate harvest was highest in patients whose tumors exhibited MSI (79%; odds ratio [OR] 2.5, 95% confidence interval [CI] 1.2-4.9; P = 0.007) or were located in the proximal colon (73%; 2.8, 1.5-5.3; P = 0.002). In multiple linear regression, MSI was a significant predictor of the total LN count (P = 0.02). Total node count was highest for cancers with MSI and no KRAS/BRAF mutations. The independent association between MSI and a high LN count persisted for stage I and II cancers (P = 0.04). Tumor location in the proximal colon was the only significant predictor of an adequate LN harvest (adjusted OR 2.4, 95% CI 1.2-4.9; P = 0.01). An increase in the total number of nodes harvested was not associated with an increase in nodal metastasis. In conclusion, number of nodes harvested is highest for cancers of the proximal colon and with MSI. The nodal harvest associated with MSI is influenced by BRAF and KRAS genotypes, even for cancers of proximal location. Mechanisms behind the molecular diversity and node yield should be further explored.

Background: Patients with perforated peptic ulcer (PPU) often present with acute, severe illness that carries a high risk for morbidity and mortality. Mortality ranges from 3-40% and several prognostic scoring systems have been suggested. The aim of this study was to review the available scoring systems for PPU patients, and to assert if there is evidence to prefer one to the other., Material and Methods: We searched PubMed for the mesh terms "perforated peptic ulcer", "scoring systems", "risk factors", "outcome prediction", "mortality", "morbidity" and the combinations of these terms. In addition to relevant scores introduced in the past (e.g. Boey score), we included recent studies published between January 2000 and December 2012) that reported on scoring systems for prediction of morbidity and mortality in PPU patients., Results: A total of ten different scoring systems used to predict outcome in PPU patients were identified; the Boey score, the Hacettepe score, the Jabalpur score the peptic ulcer perforation (PULP) score, the ASA score, the Charlson comorbidity index, the sepsis score, the Mannheim Peritonitis Index (MPI), the Acute physiology and chronic health evaluation II (APACHE II), the simplified acute physiology score II (SAPS II), the Mortality probability models II (MPM II), the Physiological and Operative Severity Score for the enumeration of Mortality and Morbidity physical sub-score (POSSUM-phys score). Only four of the scores were specifically constructed for PPU patients. In five studies the accuracy of outcome prediction of different scoring systems was evaluated by receiver operating characteristics curve (ROC) analysis, and the corresponding area under the curve (AUC) among studies compared. Considerable variation in performance both between different scores and between different studies was found, with the lowest and highest AUC reported between 0.63 and 0.98, respectively., Conclusion: While the Boey score and the ASA score are most commonly used to predict outcome for PPU patients, considerable variations in accuracy for outcome prediction were shown. Other scoring systems are hampered by a lack of validation or by their complexity that precludes routine clinical use. While the PULP score seems promising it needs external validation before widespread use.

Background: Triage and interhospital transfer are central to trauma systems. Few studies have addressed transferred trauma patients. This study investigated transfers of variable distances to OUH (Oslo University Hospital, Ullevål), one of the largest trauma centres in Europe., Methods: Patients included in the OUH trauma registry from 2001 to 2008 were included in the study. Demographic, injury, management and outcome data were abstracted. Patients were grouped according to transfer distance: ≤20 km, 21-100 km and > 100 km., Results: Of the 7.353 included patients, 5.803 were admitted directly, and 1.550 were transferred. The number of transfers per year increased, and there was no reduction in injury severity during the study period. Seventy-six per cent of the transferred patients were severely injured. With greater transfer distances, injury severity increased, and there were larger proportions of traffic injuries, polytrauma and hypotensive patients. With shorter distances, patients were older, and head injuries and injuries after falls were more common. The shorter transfers less often activated the trauma team: ≤20 km -34%; 21-100 km -51%; > 100 km -61%, compared to 92% of all directly admitted patients. The mortality for all transferred patients was 11%, but was unequally distributed according to transfer distance., Conclusion: This study shows heterogeneous characteristics and high injury severity among interhospital transfers. The rate of trauma team assessment was low and should be further examined. The mortality differences should be interpreted with caution as patients were in different phases of management. The descriptive characteristics outlined may be employed in the development of triage protocols and transfer guidelines.

Background: Musculoskeletal trauma represents a considerable global health burden, however reliable population-based incidence data are scarce. A fracture and dislocation registry was established within a well-defined population. An audit of the establishment process, feasibility of the registry work and report of the collected data is given., Methods: Demographic data, fracture type and location, mode of treatment, and the reasons for the secondary procedures were collected and scored using recognized systems, such as the AO/OTA classification and the Gustilo-Anderson classification for open fractures. The reporting was done in the operation planning program by the involved orthopaedic surgeon. Both inpatient and day-case procedures were collected. Data were collected prospectively from 2006 until 2010. Compliance among the surgeons and completeness and accuracy of the data was continuously assured by an orthopaedic surgeon., Results: During the study period, 39 orthopaedic surgeons were involved in the recording of a total of 8,188 procedures, consisting of primary treatment of 4,986 long bone fractures, 467 non long bone fractures, 123 dislocations and 2,612 secondary treatments. In the study period 532 fractures or dislocations were treated at least once for one or more serious complications. For the index year of 2009, a total of 5710 fractures or dislocations were treated in the emergency department or hospitalized, of which the 1594 (28%) were treated at the inpatient or day-case operation rooms, thus registered in the FDR. Quality assurance, educational incentives and continuous feedback between coders and controller in the integrated electronic system are available and used through the features of the electronic database., Conclusions: Implementing an integrated registry of fractures and dislocations with the electronic hospital system has been possible despite several users involved. The electronic system and the data controller provide for completeness and validity. The FDR has become an indispensable tool for the department for planning and education and will serve as a prerequisite for the conduct and execution of future prospective trials within the department. Further, other departments with similar electronic patient files may fairly easily adopt this system for implementation.

Background: Trauma is the most prevalent cause of death in the young. Insight into cause and time of fatal pediatric and adolescent trauma is important for planning trauma care and preventive measures. Our aim was to analyze cause, severity, mode and seasonal aspects of fatal pediatric trauma., Methods: Review of all consecutive autopsies for pediatric fatal trauma during a 10-year period within a defined population., Results: Of all pediatric trauma deaths (n = 36), 70% were males, with the gender increasing with age. Median age was 13 years (range 2-17). Blunt trauma predominated (by road traffic accidents) with most (n = 15; 42%) being "soft" victims, such as pedestrians/bicyclist and, 13 (36%) drivers or passengers in motor vehicles.Penetrating trauma caused only 3 deaths. Prehospital deaths (58%) predominated. 15 children (all intubated) reached hospital alive and had severely deranged vital parameters: 8 were hypotensive (SBP < 90 mmHg), 13 were in respiratory distress, and 14 had GCS < 8 on arrival. Emergency procedures were initiated (i.e. neurosurgical decompression, abdominal surgery or pelvic fixation for hemorrhage) in 12 patients. Probability of survival (Ps) was < 33% in over 75% of the fatalities. A bimodal death pattern was evident; the initial peak by CNS injuries and exsanguinations, the latter peak by CNS alone. Most fatalities occurred during spring (53%) or summertime (25%)., Conclusion: Fatal pediatric trauma occurs most frequently in boys during spring/summer, associated with severe head injuries and low probability of survival. Preventive measures appear mandated in order to reduce this mortality in this age group.

The Advanced Trauma Life Support (ATLS) Program was developed to teach doctors one safe, reliable method to assess and initially manage the trauma patient. The ATLS principles represents an organized approach for evaluation and management of seriously injured patients and offers a foundation of common knowledge for all members of the trauma team. After 3 decades of teaching (1978-2008) of ATLS worldwide one should intuitively perceive that the evidence for the effect of ATLS teaching on the improved management of the injured patient be well established. This editorial addresses aspects of trauma education with needs for further development of better evidence of best practice.