Clinical and laboratory follow-up for treating and monitoring patients with ankylosing spondylitis: development of recommendations for clinical practice based on published evidence and expert opinion

ObjectiveTo develop French recommendations about the clinical and laboratory follow-up of patients with axial ankylosing spondylitis (AS) seen in everyday practice.MethodsThe recommendations were developed based on evidence from the literature and on expert opinion. A Delphi consensus procedure was used by a scientific committee to select five focal points, about which evidence was obtained by searching Medline and the databases maintained by the French Society for Rheumatology, European League against Rheumatism, and American College of Rheumatology. The results of the literature review were used by a panel of experienced rheumatologists to draft and to validate the recommendations, using expert opinion if needed to supplement gaps in published knowledge. For each recommendation, the level of evidence and the level of agreement among the experts were specified.ResultsThe three focal points selected using the Delphi procedure dealt with choosing the best clinical and laboratory parameters for monitoring patients with AS; whether follow-up benefits from the use of composite indices (e.g., the Bath Ankylosing Spondylitis Disease Activity Index [BASDAI], the BAS Functional Index [BASFI] and the BAS Metrology Index [BASMI]); and the clinical and laboratory parameters that predict functional or structural outcomes in patients with AS. The literature search retrieved 1510 relevant articles based on titles and abstracts, of which 322 were selected for in-depth review. Five recommendations about the clinical and laboratory follow-up of patients with AS were developed then validated by having all panel participants vote during a final meeting.ConclusionRecommendations about the clinical and laboratory follow-up of patients with AS were developed. They can be expected to improve clinical practice uniformity and, in the longer term, to optimize the management of patients with AS.     

Pharmacological treatment (biotherapy excluded) of peripheral psoriatic arthritis: Development of recommendations for clinical practice based on data from the literature and experts opinion

ObjectivesTo develop recommendations about treatment (except anti-TNF agents) of psoriatic arthritis with peripheral joint involvement (PsA) seen in everyday practice, using evidence from the literature, supplemented with expert opinion when needed.MethodsThe recommendations were based on evidence from the literature. First, a scientific committee used a Delphi procedure to select five focal points of interest. Then, a literature task force looked for relevant publications in the following: Cochrane, Pubmed, and Ovid databases and abstracts from the French Society for Rheumatology, European League against Rheumatism and American College of Rheumatology. Based on the data from these publications, recommendations were drafted and then validated by a group of 68 experts. The strength of each recommendation was determined, as well as the extent of agreement among the experts.ResultsThe evidence extracted from 73 selected papers was presented to experts during interactive workshops. At the end of the workshops, the experts drafted six recommendations, which were then validated by a final vote including all participants. These six recommendations displayed various strength from B to D.ConclusionThese recommendations should help to improve practice uniformity and, ultimately, to improve the management of PsA in France.     

Pharmacotherapy (excluding biotherapies) for ankylosing spondylitis: development of recommendations for clinical practice based on published evidence and expert opinion

ObjectivesTo develop recommendations about pharmacotherapy (excluding biotherapeutic agents) in patients with axial forms of ankylosing spondylitis (AS) seen in everyday clinical practice.MethodsThe recommendations were based on evidence from the literature. First, a scientific committee used a Delphi procedure to select five focal points about which recommendations were needed. Then, a literature task force looked for relevant publications in the following: Cochrane, PubMed, and Ovid databases; and abstracts from the French Society for Rheumatology, European League against Rheumatism, and American College of Rheumatology. Based on the data in these publications, recommendations were drafted then validated by a group of experts. The strength of each recommendation was determined, as well as the extent of agreement among the experts.ResultsThe four focal points were the best strategy for using nonsteroidal anti-inflammatory drugs, role for systemic glucocorticoid therapy, role for glucocorticoid injections into the sacroiliac joints and entheses, and role for slow-acting drugs (e.g., methotrexate, sulfasalazine, leflunomide, thalidomide, and pamidronate). Of the 661 promising publications identified by the literature search, 173 were found to be relevant. The evidence in these 173 papers was reported to experts during interactive workshops. At the end of the workshops, the experts drafted recommendations, which were then validated by having all panel participants vote during a final meeting. There were seven recommendations, whose strength ranged from A to D.ConclusionSeven recommendations about pharmacotherapy in patients with AS were developed. They can be expected to improve clinical practice uniformity and, in the longer term, to optimize the management of patients with AS in France.     

Structural evaluation in the management of patients with rheumatoid arthritis: development of recommendations for clinical practice based on published evidence and expert opinion

OBJECTIVES: To develop French evidence-based recommendations for the structural evaluation of rheumatoid arthritis (RA) in everyday practice. METHODS: A scientific committee selected 10 questions using the Delphi consensus procedure. Evidence-based responses to each question were sought by searching the PubMed and Ovid databases and the abstract databases for the 2002, 2003, and 2004 annual meetings of the French Society for Rheumatology, the EULAR, and the American College of Rheumatology. The following indexing terms were used: rheumatoid arthritis, arthritis, patient, diagnostic imaging, radiography, joint, erosion, and joint space width. All articles published in French or English prior to May 2004 were identified. The evidence from these articles was reported to a panel of 77 rheumatologists working in hospital or office practice. The panel developed detailed recommendations, filling gaps in evidence with their expert opinion. The strength of each recommendation was determined. RESULTS: The 10 questions probed the structural evaluation of RA by plain radiography, magnetic resonance imaging (MRI), and ultrasonography, both for diagnostic and monitoring purposes. The literature search retrieved 673 publications, of which 166 were selected and reviewed. The panel developed 10 recommendations, one for each question, which were accepted by consensus. CONCLUSION: Recommendations relative to the diagnosis or monitoring of structural involvement in patients with RA in everyday practice were developed. They should help to improve practice uniformity and, ultimately, to improve the management of RA.     

Role and modalities of information and education in the management of patients with rheumatoid arthritis: development of recommendations for clinical practice based on published evidence and expert opinion

OBJECTIVES: To develop recommendations for the information and education of patients with rheumatoid arthritis (RA) seen in everyday practice, using evidence from the literature, supplemented with expert opinion when needed. METHODS: A scientific committee developed eight questions using the Delphi consensus procedure. A task force reviewed the literature for answers to these questions, using the PubMed Medline database (1980-2004) and the 2002-2004 databases of the annual meetings held by the French Society for Rheumatology (SFR), the European League Against Rheumatism (EULAR), and the American College of Rheumatology (ACR); the indexing terms for the search were rheumatoid, arthritis, patient, education, information, knowledge, general practitioner, family doctor, and continuing medical education. Only articles in French or English were included. A panel of rheumatologists used the evidence thus compiled to develop recommendations for each question; gaps in evidence were filled by calling on the panelists' expert opinion. For each recommendation, the level of evidence and extent of agreement among panelists were specified. RESULTS: There were four general questions about the objectives, supports, and mode of delivery (group or one-on-one) of patient information and education, as well as on evaluating knowledge, and four specific questions on program content. The search identified 1235 articles; 144 were selected on the title and 118 of those on the abstract. Three abstracts presented at meetings were also kept. The evidence from the literature was presented to the panelists during interactive workshops. The panelists then developed eight recommendations, all of which were grade D because no published studies specifically addressed everyday clinical practice. Agreement among panelists ranged across recommendations from 85.7% to 100%. CONCLUSION: Recommendations about educating and informing patients with RA in everyday practice were developed. They should increase practice uniformity and ultimately optimize the management of patients with RA.     

Use of glucocorticoids in rheumatoid arthritis – Pratical modalities of glucocorticoid therapy: Recommendations for clinical practice based on data from the literature and expert opinion

ObjectiveTo develop recommendations about the use of glucocorticoids in patients with established rheumatoid arthritis (RA) managed in everyday practice, using the evidence-based approach and expert opinion.MethodsA three-step procedure was used: a scientific committee used a Delphi procedure to select five questions, which formed the basis for developing the recommendations; a systematic literature review was conducted by searching the Medline and Embase databases and the abstracts of meetings held by the Société Française de Rhumatologie (SFR), American College of Rheumatology (ACR), and European League Against Rheumatism (EULAR); and recommendations were developed and validated by a panel of experts based on the data from the literature review and on their experience. For each recommendation, the level of evidence and extent of agreement among experts were determined.ResultsThe five questions pertained to the use of glucocorticoids in RA patients: role for intravenous glucocorticoid bolus therapy, role for intraarticular injections, and practical modalities of glucocorticoid administration and discontinuation. From the literature search, 93 articles were selected based on their titles and abstracts. Of these, 50 were selected for the literature review. Eight recommendations about the use of glucocorticoid therapy in everyday practice in patients with established RA were validated by a vote among all participating experts: bolus glucocorticoid therapy should be reserved for highly selected situations; triamcinolone hexacetonide is the preferred glucocorticoid for intraarticular therapy, and the joint should be rested for about 24 h after the injection; for oral glucocorticoid therapy, agents with a short half-life taken once daily should be preferred; and when discontinuing glucocorticoid therapy, the patient and usual physician should be informed of the risk of adrenal insufficiency.     

Diagnosis of peripheral psoriatic arthritis: Recommendations for clinical practice based on data from the literature and experts opinion

ObjectiveTo propose French recommendations for the clinical, biological and radiological diagnosis of peripheral psoriatic arthritis (PsA) in daily practice based on data from the literature and expert opinion.MethodThe strategy was the following: the choice of four questions, concerning this topic by the scientific committee according to the Delphi method, forming the basis of the recommendations. The Systematic literature research based on Medline, Cochrane and abstracts from the annual meetings of the French society of rheumatology (SFR), American college of rheumatology (ACR) and European ligue against rheumatism (EULAR). An experts committee of rheumatologists elaborated, validated specifying the strength and the degree of agreement of each recommendation.ResultsThe questions selected were: (1) What clinical data should be collected to assist in the diagnosis of psoriatic arthritis? (2) What laboratory tests, immunological tests, and genetic tests should be performed to assist in the diagnosis of psoriatic arthritis? (3) What are the radiological investigations useful in the diagnosis of psoriatic arthritis? (4) What classification and/or diagnosis criteria can assist in the diagnosis of psoriatic arthritis? A literature search identified 1627 abstracts and 33 articles were included and analyzed. Four recommendations relative to the diagnosis were drafted and validated by a final vote of the experts committee.ConclusionRecommendations concerning the diagnosis of PsA for daily practice were developed and validated on the basis of data from the literature and expert opinion. They should help to establish the diagnosis of PsA in daily practice.     

Prevention and treatment of bile duct injuries during laparoscopic cholecystectomy: the clinical practice guidelines of the European Association for Endoscopic Surgery (EAES)

Background

Laparoscopic cholecystectomy is one of the most common surgical procedures in Europe (and the world) and has become the standard procedure for the management of symptomatic cholelithiasis or acute cholecystitis in patients without specific contraindications. Bile duct injuries (BDI) are rare but serious complications that can occur during a laparoscopic cholecystectomy. Prevention and management of BDI has given rise to a host of publications but very few recommendations, especially in Europe.

Methods

A systematic research of the literature was performed. An international expert panel was invited to appraise the current literature and to develop evidence-based recommendations. Statements and recommendations were drafted after a consensus development conference in May 2011, followed by presentation and discussion at the annual congress of the EAES held in Torino in June 2011. Finally, full guidelines were consented and adopted by the expert panel via e-mail and web conference.

Results

A total of 1,765 publications were identified through the systematic literature search and additional submission by panellists; 671 publications were selected as potentially relevant. Only 46 publications fulfilled minimal methodological criteria to support Clinical Practice Guidelines recommendations. Because the level of evidence was low for most of the studies, most statements or recommendations had to be based on consensus of opinion among the panel members. A total of 15 statements and recommendations were developed covering the following topics: classification of injuries, epidemiology, prevention, diagnosis, and management of BDI.

Conclusions

Because BDI is a rare event, it is difficult to generate evidence for prevention, diagnosis, or the management of BDI from clinical studies. Nevertheless, the panel has formulated recommendations. Due to the currently limited evidence, a European registry should be considered to collect and analyze more valid data on BDI upon which recommendations can be based.     

Physical examination and laboratory tests in the management of patients with rheumatoid arthritis: development of recommendations for clinical practice based on published evidence and expert opinion

OBJECTIVES: To develop recommendations for the physical and laboratory-test follow-up of patients with rheumatoid arthritis (RA) seen in everyday practice, using evidence from the literature, supplemented with expert opinion when needed. METHODS: A scientific committee selected 7-10 questions using the Delphi consensus procedure. Evidence-based responses to each question were sought in the literature and were then used by a panel to develop recommendations. To fill in gaps in knowledge from the literature, the panelists relied on their personal opinion. RESULTS: The seven questions dealt with the physical and laboratory-test follow-up of RA and the factors predicting disease severity. The literature review identified 799 articles whose title and abstract suggested relevance to the study. Elimination of articles that provided no data on the study topic left 128 original articles. The panel developed seven recommendations, one for each question, which were accepted by consensus. CONCLUSION: Recommendations about the physical and laboratory-test follow-up of patients with RA seen in everyday practice were developed. Because they constitute an objective foundation built by consensus among experts, should improve the uniformity and quality of care provided to RA patients in everyday practice.     

Guidelines for the prevention of venous thromboembolism in hospitalized patients with pelvi-acetabular trauma

BackgroundVenous thromboembolism is a dreaded complication leading to increased morbidity and mortality in patients having pelvi-acetabular fractures.ObjectivesThese evidence based guidelines aim to provide the decision making ability in the prevention of venous thromboembolism in patients with pelvi-acetabular trauma planned for operative or non operative treatment.MethodsThe patients were subclassified into 5 categories. The PICO framework was used to devise research questions in each category. The systematic reviews were performed for each research question. The Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach was used to assess outcomes of critical interest. The guideline panel consisting of expert members of different subspecialties, analyzed the evidence and made recommendations.ResultsThe guideline panel proposed 21 recommendations. There are five recommendations in category 1 to 3, two recommendations in category 4 and four recommendations in category 5.ConclusionIn pelvi-acetabular fractures there is strong evidence to suggest that thromboprophylaxis should be given. It should be initiated as early as possible after control of hemorrhage. The chemical prophylaxis is the preferred mode and LMWH is the preferred agent of choice. The mechanical methods can be used as an adjunct. The routine prophylactic use of IVC filters is not recommended. However, the use of retrievable IVC filters in high risk patients with established VTE in preoperative period can be considered. The use of newer directly acting oral anticoagulants is gaining importance.     

Guidelines for the prevention of venous thromboembolism in hospitalized patients with pelvi-acetabular trauma

BackgroundVenous thromboembolism is a dreaded complication leading to increased morbidity and mortality in patients having pelvi-acetabular fractures.ObjectivesThese evidence based guidelines aim to provide the decision making ability in the prevention of venous thromboembolism in patients with pelvi-acetabular trauma planned for operative or non operative treatment.MethodsThe patients were subclassified into 5 categories. The PICO framework was used to devise research questions in each category. The systematic reviews were performed for each research question. The Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach was used to assess outcomes of critical interest. The guideline panel consisting of expert members of different subspecialties, analyzed the evidence and made recommendations.ResultsThe guideline panel proposed 21 recommendations. There are five recommendations in category 1 to 3, two recommendations in category 4 and four recommendations in category 5.ConclusionIn pelvi-acetabular fractures there is strong evidence to suggest that thromboprophylaxis should be given. It should be initiated as early as possible after control of hemorrhage. The chemical prophylaxis is the preferred mode and LMWH is the preferred agent of choice. The mechanical methods can be used as an adjunct. The routine prophylactic use of IVC filters is not recommended. However, the use of retrievable IVC filters in high risk patients with established VTE in preoperative period can be considered. The use of newer directly acting oral anticoagulants is gaining importance.     

Tendon allograft for treatment of chronic Achilles tendon rupture: A systematic review

BackgroundTo summarize available evidence and determine if tendon allograft is an effective treatment for chronic Achilles tendon rupture.MethodsA search was performed in the PubMed, Web of Science, Embase and Cochrane Database from 1960 to April 2017 to identify relevant articles. Predefined inclusion and exclusion criteria were applied to identify all eligible articles.ResultsTotal 186 articles were identified through our systematic search. Of these, 9 publications met the inclusion criteria. Five studies were case reports; three were case series; and one were expert opinion. Of a total 35 patients, 34 underwent Achilles tendon allograft repair and 1 peroneus brevis tendon allograft reconstruction. All patients experienced good clinical and functional results, but most reports used non-validated outcome measures.ConclusionsThe evidence suggests that tendon allograft offers favorable outcomes in patients with chronic Achilles tendon rupture. However, randomized controlled trials which use validated functional outcome measures are required to determine effectiveness of this intervention.Level of evidence: Level V, systematic review of Level IV and V studies.     

National consensus quality indicators to assess quality of care for active surveillance in low-risk prostate cancer: An evidence-informed,modified Delphi survey of Canadian urologists/radiation oncologists

IntroductionAlthough many low-risk prostate cancer (PCa) patients worldwide currently receive active surveillance (AS), adherence to clinical guidelines on AS and variations in care at the population level remain poorly understood. We sought to develop system-level quality indicators (QIs) and performance measures for benchmarking the quality of care during AS.MethodsConvenience sampling methods were used to identify an expert panel among practicing urologists and radiation oncologists across Canada. QI development involved two phases: 1) proposed QIs were identified through a literature search and published clinical guidelines on AS; and 2) indicators were selected through a modified Delphi process during which each panelist independently rated each indicator based on clinical importance. QI items were chosen as appropriate measures for quality of AS care if they met prespecified criteria (disagreement index <1 and median importance of ≥7 on a nine-point scale).ResultsAmong 42 invited expert panel members, the response rate was 45% (n=19). Expert panel members were well-represented by type of physician (84% urologists, 16% radiation oncologists) and practice setting (79% academic, 21% non-academic). The expert panel endorsed 20 of 27 potential indicators as appropriate for measuring quality of AS care.ConclusionsWe developed a set of QIs to measure AS care using published guidelines and clinical experts. Use of the indicators will be assessed for feasibility in healthcare databases. Reporting quality of care with these AS indicators may enhance adherence, reduce variation in care, and improve patient outcomes among low-risk PCa patients on AS.     

Prognosis and follow-up of psoriatic arthritis with peripheral joint involvement: Development of recommendations for clinical practice based on published evidence and expert opinion

ObjectivesTo develop recommendations about prognosis and follow-up of psoriatic arthritis (PsA) with peripheral joint involvement in everyday clinical practice.MethodsThe strategy was as following: (a) The choice of five questions, by the scientific committee according to the Delphi method, considered as a basis for the recommendations; (b) the Systematic Literature Research based on Medline, Cochrane and abstracts from the annual meetings of SFR, EULAR and ACR. An expert committee composed with 68 rheumatologists elaborated and validated the recommendations, specifying the strength and the degree of agreement for each of them.ResultsThe questions selected were: (1) How can articular and cutaneous disease activity of PsA be assessed in usual clinical practice? (2) Which parameters are predictive for functional, radiological and fatal outcome in PsA? (3) Which clinical and biological parameters are useful for the follow-up of PsA? At which frequency? (4) Which X-rays are useful for the follow-up of PsA? At which frequency? (5) How can the response to treatments be assessed in PsA? The literature search identified 1181 abstracts and 123 articles were included and analyzed. Seven recommendations, whose strength ranged from B to D, were drafted and validated by a final vote of the expert committee.ConclusionSeven recommendations about follow-up of patients with PsA for daily practice were developed. They can be expected to improve clinical practice uniformity and, in the longer term, to optimize the management of patients with PsA.     

Guía clínica de la Asociación Europea de Urología sobre el tratamiento quirúrgico de la incontinencia urinaria

ContextThe European Association of Urology (EAU) guidelines on urinary incontinence published in March 2012 have been rewritten based on an independent systematic review carried out by the EAU guidelines panel using a sustainable methodology.ObjectiveWe present a short version here of the full guidelines on the surgical treatment of patients with urinary incontinence, with the aim of dissemination to a wider audience.Evidence acquisitionEvidence appraisal included a pragmatic review of existing systematic reviews and independent new literature searches based on Population, Intervention, Comparator, Outcome (PICO) questions. The appraisal of papers was carried out by an international panel of experts, who also collaborated in a series of consensus discussions, to develop concise structured evidence summaries and action-based recommendations using a modified Oxford system.Evidence summaryThe full version of the guidance is available online (www.uroweb.org/guidelines/online-guidelines/). The guidance includes algorithms that refer the reader back to the supporting evidence and have greater accessibility in daily clinical practice. Two original meta-analyses were carried out specifically for these guidelines and are included in this report.ConclusionsThese new guidelines present an up-to-date summary of the available evidence, together with clear clinical algorithms and action-based recommendations based on the best available evidence. Where high-level evidence is lacking, they present a consensus of expert panel opinion.     

External Assessment of the GEMA2009 Recommendations by a Multidisciplinary Expert Panel on Asthma

ObjectivesTo assess the level of agreement on the GEMA 2009 clinical recommendations by a Spanish expert panel on asthma.Materials and methodsThe study was divided into four stages: 1) establishment of a 9 member scientific committee (GEMA authors) for selection of GEMA recommendations to use in the survey; 2) formation of a panel of 74 professionals with expertise in this field (pulmonologists, allergists, family doctors, ear, nose and throat and paediatric specialists); 3) Delphi survey in two rounds, sent by mail, with intermediate processing of opinions and a report to the panel members; and 4) analysis and discussion of results for the Scientific Committee.ResultsSeventy four participants completed the two rounds of survey. During the first round, a consensus was reached in 49 out of 56 questions analysed. Following discussion by the panel, the consensus was increased to a total of 53 items in the survey. With respect to the remaining questions, Insufficient consensus was obtained on the rest of the questions, due to differing views between sub-specialists, or lack of criteria by most of the experts.ConclusionsThe external analysis by asthma experts from different specialities showed a high level of professional agreement with the GEMA 2009 recommendations in Spain (96.5 %). The disagreement shown in three recommendations reflect the lack of a high level evidence. These issues represent areas of interest for future research.     

Interobserver variance and patient heterogeneity influencing the treatment of grade I spondylolisthesis

BACKGROUND CONTEXTDespite well done randomized clinical trials, the role of fusion as an adjunct to decompression for the treatment of patients with degenerative spondylolisthesis remains controversial. There is substantial variation in the use of fusion as well as the techniques used for fusion for a population of patients all described by a single ICD10 code.PURPOSEWe sought to investigate the source of the variation in the perceived role of fusion by looking at surgeon as well as patient-specific factors.STUDY DESIGNProspective cohort study examining the variability of recommendations from an expert panel of surgeons-based imaging and clinical vignettes.PATIENT SAMPLEPatients with degenerative spondylolisthesis and stenosis.OUTCOME MEASURESA six-category treatment schema based on level of invasiveness of proposed surgeries with one through three representing nonfusion strategies and categories four through six representing fusion strategies.METHODSThe authors are conducting the ongoing spinal laminectomy vs instrumented pedicle screw II study in which patients with grade one degenerative spondylolisthesis and stenosis are randomized to two groups: a review group in which patients are treated as per recommendations of an expert panel and a nonreview group in which patients are treated as per the referring surgeon's preference. In the former (review group), clinical vignettes and radiographic studies were evaluated by an expert panel of spine surgeons. The panel then provided these recommendations to the referring surgeon. We investigated the underlying variability by looking both at the number of similar or different recommendations received by an individual patient (surgeon-related variability) as well as the number of similar or different recommendations offered by individual surgeons across the population of patients (patient heterogeneity). Agreement between surgeons for fusion vs nonfusion (Categories 1–3 vs 4–6) was calculated using a Kappa value from a mixed effects logistic regression model. We looked at Kappa for agreement and weighted Kappa for association of ratings on the ordinal 1 to 6 scale with a mixed effects linear regression model. Additionally, we analyzed the summary of data between patients after averaging the rater scores within patients. Similarly, we summarized the data between surgeons after averaging their scores over the patients that each surgeon reviewed.RESULTSOne hundred and fourteen patients received 1,463 treatment recommendations. On average, fusion was recommended 58.5% of the time. Overall agreement was low, and perfect agreement on the need for fusion was seen in only 24 (21.1%) of patients. Kappa statistic for agreement on fusion was 0.378 (95% confidence interval 0.324–0.432). The average score across surgeons was 4.2 (0.6) with a range of 3 to 5.3. The most common single recommendation was for fusion with interbody fusion (40.8%) and the lowest was for decompression with noninstrumented fusion (0.5%).CONCLUSIONSWe demonstrated variability in surgical approach when individual patients were evaluated by a panel of surgeons indicating that even "expert" surgeons disagree with each other regarding the need for fusion in individual patients. We were also able to demonstrate that individual patients received consistent recommendations that were very different from those received by other individuals evaluated by the same surgeons. This indicates that there is patient-related heterogeneity driving variability independent of surgeon factors.