Challenges in evaluating surgical innovation

Research on surgical interventions is associated with several methodological and practical challenges of which few, if any, apply only to surgery. However, surgical evaluation is especially demanding because many of these challenges coincide. In this report, the second of three on surgical innovation and evaluation, we discuss obstacles related to the study design of randomised controlled trials and non-randomised studies assessing surgical interventions. We also describe the issues related to the nature of surgical procedures—for example, their complexity, surgeon-related factors, and the range of outcomes. Although difficult, surgical evaluation is achievable and necessary. Solutions tailored to surgical research and a framework for generating evidence on which to base surgical practice are essential.The Balliol Colloquium has been supported by Ethicon UK with unrestricted educational grants and by the National Institute of Health Research Health Technology Assessment Programme. The Balliol Colloquium was administratively and financially supported by the Nuffield Department of Surgery at the University of Oxford and the Department of Surgery at McGill University. JAC holds a Medical Research Council UK special training fellowship. The University of Aberdeen’s Health Services Research Unit is core funded by the Chief Scientist Offi ce of the Scottish Government Health Directorates. IB is supported by a grant from the Société Française de Rhumatologie and Lavoisier Program (Ministère des Aff aires Etrangères et Européennes). PLE is a DPhil Candidate in Evidence-Based Health Care at Oxford University

Frequency and Clinical Presentation of Mucocutaneous Disease Due to Mycoplasma pneumoniae Infection in Children With Community-Acquired Pneumonia

Importance The diagnosis of Mycoplasma pneumoniae infection as the cause of mucocutaneous disease is challenging because current diagnostic tests are not able to differentiate M pneumoniae infection from carriage. Objective To examine the frequency and clinical presentation of M pneumoniae-induced mucocutaneous disease in children with community-acquired pneumonia (CAP) using improved diagnostics. Design, Setting, and Participants This prospective, longitudinal cohort study included 152 children aged 3 to 18 years with CAP enrolled in a CAP study from May 1, 2016, to April 30, 2017, at the University Children's Hospital Zurich. Children were inpatients or outpatients with clinically defined CAP according to the British Thoracic Society guidelines. Data analysis was performed from July 10, 2017, to June 29, 2018. Main Outcomes and Measures Frequency and clinical presentation of M pneumoniae-induced mucocutaneous disease in childhood CAP. Mycoplasma pneumoniae infection was diagnosed by polymerase chain reaction (PCR) of oropharyngeal samples and confirmed with the measurement of specific peripheral blood IgM antibody-secreting cells by enzyme-linked immunospot assay to differentiate M pneumoniae-infected patients from carriers with CAP caused by other pathogens. Mucocutaneous disease was defined as any eruptive lesion that involved skin and/or mucous membranes occurring during the CAP episode. Results Among 152 enrolled children with CAP (median [interquartile range] age, 5.7 [4.3-8.9] years; 84 [55.3%] male), 44 (28.9%) tested positive for M pneumoniae by PCR; of these, 10 children (22.7%) developed mucocutaneous lesions. All 10 patients with mucocutaneous eruptions tested positive for specific IgM antibody-secreting cells. Skin manifestations were found in 3 cases (2.8%) of M pneumoniae PCR-negative CAP (P < .001). The spectrum of M pneumoniae-induced mucocutaneous disease included M pneumoniae-induced rash and mucositis (3 cases [6.8%]), urticaria (2 cases [4.5%]), and maculopapular skin eruptions (5 cases [11.4%]). Two patients had ocular involvement as the sole mucosal manifestation (bilateral anterior uveitis and nonpurulent conjunctivitis). Patients with M pneumoniae-induced mucocutaneous disease had longer duration of prodromal fever (median [interquartile range], 10.5 [8.3-11.8] vs 7.0 [5.5-9.5] days; P = .02) and higher C-reactive protein levels (median [interquartile range], 31 [22-59] vs 16 [7-23] mg/L; P = .04) than patients with CAP due to M pneumoniae without mucocutaneous manifestations. They were also more likely to require oxygen (5 [50%] vs 1 [5%]; P = .007), to require hospitalization (7 [70%] vs 4 [19%]; P = .01), and to develop long-term sequelae (3 [30%] vs 0; P = .03). Conclusions and Relevance Mucocutaneous disease occurred significantly more frequently in children with CAP due to M pneumoniae than in children with CAP of other origins. Mycoplasma pneumoniae-induced mucocutaneous disease was associated with increased systemic inflammation, morbidity, and a higher risk of long-term sequelae

Genetic Polymorphisms in Genes Related to Oxidative Stress (GSTP1, GSTM1, GSTT1, CAT, MnSOD, MPO, eNOS) and Survival of Rectal Cancer Patients after Radiotherapy

Radiotherapy exerts part of its antineoplastic effect by generating oxidative stress, therefore genetic variation in oxidative stress-related enzymes may influence survival of rectal cancer patients. We hypothesized that genetic polymorphisms associated with higher amounts of reactive oxygen species (ROS) that exaggerate cytotoxic activity could improve survival after radiotherapy. We followed 114 rectal cancer patients who received radiotherapy for an average of 42.5 months. Associations between genotypes (GSTP1, GSTM1, GSTT1, CAT, MnSOD, MPO and eNOS) and overall survival were assessed using Kaplan-Meier curves and Cox proportional hazards regression. As hypothesized, patients carrying low ROS producing eNOS Glu298Asp asparagine allele showed an increased hazard of death compared to homozygous carriers of the glutamine allele (hazard ratio (HR): 2.10, 95% confidence interval (CI): 1.01–4.38). However, carriers of low ROS producing MPO G463A A allele had a decreased hazard of death compared to patients homozygous for the G allele (HR: 0.44, 95% CI: 0.21–0.93) although patients homozygous for the A allele had a slightly increased hazard (HR: 1.12, 95% CI: 0.25–5.08). This explorative study provides first results and highlights the need for further, larger studies to investigate association between genetic variation in oxidative stress genes and survival of rectal cancer patients who received radiotherapy

Clustering in surgical trials : database of intracluster correlations

PMID: 22217216 [PubMed - indexed for MEDLINE] PMCID: PMC3311136 Free PMC ArticlePeer reviewedPublisher PD

To whom do the results of the multicenter, randomized, controlled INSECT trial (ISRCTN 24023541) apply? - assessment of external validity

A response to Seiler et al: Interrupted or continuous slowly absorbable sutures for closure of primary elective midline abdominal incisions: a multicenter randomized trial (INSECT: ISRCTN24023541). Ann Surg 2009, 249(4):576-582

LigaSure Impact™ versus conventional dissection technique in pylorus-preserving pancreatoduodenectomy in clinical suspicion of cancerous tumours on the head of the pancreas: study protocol for a randomised controlled trial

<p>Abstract</p> <p>Background</p> <p>The pp-Whipple procedure requires extensive preparation. The conventional preparation technique is done with scissors for dissection and ligatures, and with clips and sutures for hemostasis. This procedure is very time-consuming and requires numerous changes of instruments. The LigaSure™ device allows dissection and hemostasis for preparation with one instrument. Up to now there has been no comparison of the two techniques with regard to operating time and the patients' outcome. It is still unclear which technique has the optimal benefit/risk ratio for the patient.</p> <p>Methods/Design</p> <p>A single-center, randomized, single-blinded, controlled superiority trial to compare two different techniques for dissection in a pp-Whipple procedure. 102 patients will be included and randomized pre-operatively. All patients aged 18 years or older scheduled for primary elective pp-Whipple procedure who signed the informed consent will be included. The primary endpoint is the operating time of the randomized technique. Control Intervention: Conventional dissection technique; experimental intervention: LigaSureTM dissection technique. Duration of study: Approximately 15 months; follow up time: 3 years. The trial is registered at German ClinicalTrials Register (DRKS00000166).</p

Stent thrombosis following bare-metal stent implantation: success of emergency percutaneous coronary intervention and predictors of adverse outcome

Aims To investigate the efficacy and outcome of emergency percutaneous coronary interventions (PCI) in patients with stent thrombosis. Methods and results Between 1995 and 2003, 6058 patients underwent bare-metal stent implantation, of which 95 (1.6%) patients suffered from stent thrombosis. The timing of stent thrombosis was acute in 10 (11%), subacute in 61 (64%), and late in 24 (25%) patients. Procedural and clinical outcomes of emergency PCI for treatment of stent thrombosis were investigated. Emergency PCI was successful in 86 (91%), complicated by death in 2 (2%), and coronary artery bypass grafting in 2 (2%) patients. Myocardial infarction occurred in 77 (81%) patients with a peak creatine kinase level of 1466±1570 U/L. Left ventricular ejection fraction declined from 0.54±0.19 prior to 0.48±0.16 (P<0.05) at the time of stent thrombosis after emergency PCI. A 6 month major adverse clinical events comprised death (11%), reinfarction (16%), and recurrent stent thrombosis (12%) after emergency PCI. Multivariable logistic regression analysis identified the achievement of TIMI 3 flow (OR=0.1, CI 95% 0.01-0.54, P<0.001) and diameter stenosis <50% (OR=0.06, CI 95% 0.01-0.32, P<0.001) during emergency PCI to be independently associated with a reduced risk of cardiac death. Recurrent stent thrombosis was independently predicted by the omission of abciximab (OR=4.3, CI 95% 1.1-17.5). Conclusion Emergency PCI for treatment of stent thrombosis effectively restores vessel patency and flow. Patients presenting with stent thrombosis are at risk for recurrent myocardial infarction and recurrent stent thrombosi

A concept for trial institutions focussing on randomised controlled trials in surgery

<p>Abstract</p> <p>Background</p> <p>Although considered the reference standard for generating valid scientific evidence of a treatment's benefits and harms, the number of Randomised Controlled Trials (RCT) comparing surgical techniques remains low. Much effort has been made in order to overcome methodological issues and improve quality of RCTs in surgery. To the present there has been, however, only little emphasis on development and maintenance of institutions for implementation of adequately designed and conducted surgical RCTs.</p> <p>Mehods/Design</p> <p>Description of the developments in surgical RCT infrastructure in Germany between 2001 and 2006. Cross sectional evaluation of completed and ongoing surgical RCTs within the German Surgical Society and the Clinical Study Centre, Department of Surgery, University of Heidelberg.</p> <p>Results</p> <p>Foundation of a national Clinical Trial Centre (CTC) for the organisation of multi-centre RCTs in the surgical setting (Study Center of the German Surgical Society, SDGC). Establishment of a network of CTCs with affiliated Clinical Sites (CSs) to enhance patient recruitment and shorten the duration of RCTs. Since its foundation four surgical RCTs with a total sample size of 1650 patients (1006 of these randomised) have been supervised by the SDGC with 35 CSs involved in patient recruitment. Five further CTCs were set up in 2006. Together with their affiliated CSs a network has been organised providing improved conditions for the conduction of surgical RCTs.</p> <p>Conclusion</p> <p>Improvement of infrastructure substantially facilitates integration of RCTs into routine surgical practice. A network of collaborating CTCs and CSs can provide an adequate infrastructure for the conduction of multi-centre RCTs.</p