Doug Altman, medical statistician par excellence: What can radiologists learn from his legacy?

This narrative review describes our experience of working with Doug Altman, the most highly cited medical statistician in the world. Doug was particularly interested in diagnostics, and imaging studies in particular. We describe how his insights helped improve our own radiological research studies and we provide advice for other researchers hoping to improve their own research practice.

Contemporary imaging of rectus diastasis and the abdominal wall.

Diastasis of the rectus abdominis muscles (rectus diastasis, RD) is common, particularly in postpartum women. Although imaging is not always mandatory for assessment, several cross-sectional imaging techniques, in particular ultrasound (US), computed tomography (CT) and magnetic resonance imaging (MRI) can depict the abdominal wall in exquisite detail. They permit simultaneous assessment of the degree and craniocaudal extent of RD, evaluation for co-existent hernia and subjective judgement of muscle quality. Increasingly, dynamic imaging techniques show both static anatomy and muscle movement and function. In this review, we highlight the imaging findings of RD, associated hernia, and potential mimics.

Meeting the new joint British Society of Gastrointestinal and Abdominal Radiology and Royal College of Radiologists CT colonography standards: a 6-year experience.

AIM: To audit the performance of computed tomography colonography (CTC) at St Mark's Hospital against the joint British Society of Gastrointestinal and Abdominal Radiology (BSGAR) and Royal College of Radiologists (RCR) standards. MATERIALS AND METHODS: A retrospective audit of all CTC studies between January 2012 to December 2017 was performed against the BSGAR/RCR standards along with additional data outwith the guidelines. Evidence was obtained from a central database, radiology information systems (RISs), picture archiving and communication systems (PACSs), and electronic patient records (EPRs). RESULTS: Over the 6 years, 13,143 CTCs were performed and 12,996 (99%) were adequate or better. Of the cases 1,867 had a >6 mm polyp or cancer reported (polyp identification rate [PIR] 14%) and the positive predictive value (PPV) was 93% (1,148/1,240). Median radiation dose was 458 mGy·cm, mean additional acquisition rate was 19% (2,505/13,143), subsequent endoscopy rate was 9% (1,222/13,143) and mean interpretation time for a negative study was 34.6 minutes. Nine perforations occurred (perforation rate of 0.068%) and one was symptomatic (symptomatic perforation rate of 0.008%). For suspected cancers, the same-day endoscopy rate was 27% (96/360) and same-day staging rate was 76% (272/360). Post-imaging colorectal cancer rates (PICRC) was 3.06 per 100 cancers detected and 0.23 per 1,000 CTCs. The service was always rated "good" or higher by patients. CONCLUSION: This audit shows the CTC service at St Mark's Hospital to be safe and of sufficiently high quality to meet the BSGAR/RCR standards with most outcomes equal to or above the aspirational target. Areas for service and individual reader improvement were also identified.

Identifying predictors of ventral hernia recurrence: systematic review and meta-analysis.

BACKGROUND: Ventra hernias are increasing in prevalence and many recur despite attempted repair. To date, much of the literature is underpowered and divergent. As a result there is limited high quality evidence to inform surgeons succinctly which perioperative variables influence postoperative recurrence. This systematic review aimed to identify predictors of ventral hernia recurrence. METHODS: PubMed was searched for studies reporting prognostic data of ventral hernia recurrence between 1 January 1995 and 1 January 2018. Extracted data described hernia type (primary/incisional), definitions of recurrence, methods used to detect recurrence, duration of follow-up, and co-morbidity. Data were extracted for all potential predictors, estimates and thresholds described. Random-effects meta-analysis was used. Bias was assessed with a modified PROBAST (Prediction model Risk Of Bias ASsessment Tool). RESULTS: Screening of 18 214 abstracts yielded 274 individual studies for inclusion. Hernia recurrence was defined in 66 studies (24.1 per cent), using 41 different unstandardized definitions. Three patient variables (female sex, age 65 years or less, and BMI greater than 25, 30, 35 or 40 kg/m2), five patient co-morbidities (smoking, diabetes, chronic obstructive pulmonary disease, ASA grade III-IV, steroid use), two hernia-related variables (incisional/primary, recurrent/primary), six intraoperative variables (biological mesh, bridged repair, open versus laparoscopic surgery, suture versus mesh repair, onlay/retrorectus, intraperitoneal/retrorectus), and six postoperative variables (any complication, surgical-site occurrence, wound infection, seroma, haematoma, wound dehiscence) were identified as significant prognostic factors for hernia recurrence. CONCLUSION: This study summarized the current evidence base for predicting ventral hernia recurrence. Results should inform best practice and future research.

European guidelines on achalasia: United European Gastroenterology and European Society of Neurogastroenterology and Motility recommendations.

INTRODUCTION: Achalasia is a primary motor disorder of the oesophagus characterised by absence of peristalsis and insufficient lower oesophageal sphincter relaxation. With new advances and developments in achalasia management, there is an increasing demand for comprehensive evidence-based guidelines to assist clinicians in achalasia patient care. METHODS: Guidelines were established by a working group of representatives from United European Gastroenterology, European Society of Neurogastroenterology and Motility, European Society of Gastrointestinal and Abdominal Radiology and the European Association of Endoscopic Surgery in accordance with the Appraisal of Guidelines for Research and Evaluation II instrument. A systematic review of the literature was performed, and the certainty of the evidence was assessed using the Grading of Recommendations Assessment, Development and Evaluation methodology. Recommendations were voted upon using a nominal group technique. RESULTS: These guidelines focus on the definition of achalasia, treatment aims, diagnostic tests, medical, endoscopic and surgical therapy, management of treatment failure, follow-up and oesophageal cancer risk. CONCLUSION: These multidisciplinary guidelines provide a comprehensive evidence-based framework with recommendations on the diagnosis, treatment and follow-up of adult achalasia patients.

Do radiological research articles apply the term "pilot study" correctly? Systematic review.

AIM: To determine what proportion of radiological studies used the term "pilot" correctly. MATERIAL AND METHODS: Indexed studies describing themselves as a "pilot" in their title were identified from four indexed radiological journals. The aim was to identify 20 consecutive, eligible studies from each journal, as this sample size was deemed sufficient to be representative as to how this methodological description was employed by authors of radiological articles. Data were extracted relating to study design and data presented. The review was reported according to PRISMA guidelines. RESULTS: The search string used identified 658 records across the four targeted journals. Ultimately, 78 reviews describing 5,572 patients were selected for systematic review. Median sample size was just 20 patients. No individual study qualified as a genuine pilot study when assessed against the a priori criteria. In reality, the large majority (66 studies, 84.6%) were framed as studies of diagnostic test accuracy. A significant proportion (21 studies, 26.9%) was retrospective, and the overwhelming majority were conducted in single centres (76 centres, 94.7%). Most (55 studies, 70.5%) stated no rationale for their sample size, and no study presented a formal power calculation. CONCLUSION: Radiological "pilot" studies are mostly underpowered studies of diagnostic test accuracy. In order to have scientific credibility, authors, reviewers, and editors of radiological journals are encouraged to familiarise themselves with different methodological study designs and their precise implications.

Automated versus subjective assessment of spatial and temporal MRI small bowel motility in Crohn's disease.

AIM: To investigate whether subjective radiologist grading of motility on magnetic resonance enterography (MRE) is as effective as software quantification, and to determine the combination of motility metrics with the strongest association with symptom severity. MATERIALS AND METHODS: One hundred and five Crohn's disease patients (52 male, 53 female, 16-68 years old, mean age 34 years old) recruited from two sites underwent MRE, including a 20 second breath-hold cine motility sequence. Each subject completed a Harvey-Bradshaw Index (HBI) symptom questionnaire. Five features within normally appearing bowel were scored visually by two experienced radiologists, and then quantified using automated analysis software, including (1) mean motility, (2) spatial motility variation, (3) temporal motility variation, (4) area of motile bowel, (5) intestinal distension. Multivariable linear regression derived the combination of features with the highest association with HBI score. RESULTS: The best automated metric combination was temporal variation (p<0.05) plus area of motile bowel (p<0.05), achieving an R2 adjusted value of 0.036. Spatial variation was also associated with symptoms (p<0.05, R2 adjusted = 0.034); however, when visually assessed by radiologists, none of the features had a significant relationship with the HBI score. CONCLUSION: Software quantified temporal and spatial variability in bowel motility are associated with abdominal symptoms in Crohn's disease. Subjective radiologist assessment of bowel motility is insufficient to detect aberrant motility. Automated analysis of motility patterns holds promise as an objective biomarker for aberrant physiology underlying symptoms in enteric disorders.

A systematic methodological review of non-randomised interventional studies of elective ventral hernia repair: clear definitions and a standardised minimum dataset are needed.

BACKGROUND: Ventral hernias (VHs) often recur after surgical repair and subsequent attempts at repair are especially challenging. Rigorous research to reduce recurrence is required but such studies must be well-designed and report representative and comprehensive outcomes. OBJECTIVE: We aimed to assesses methodological quality of non-randomised interventional studies of VH repair by systematic review. METHODS: We searched the indexed literature for non-randomised studies of interventions for VH repair, January 1995 to December 2017 inclusive. Each prospective study was coupled with a corresponding retrospective study using pre-specified criteria to provide matched, comparable groups. We applied a bespoke methodological tool for hernia trials by combining relevant items from existing published tools. Study introduction and rationale, design, participant inclusion criteria, reported outcomes, and statistical methods were assessed. RESULTS: Fifty studies (17,608 patients) were identified: 25 prospective and 25 retrospective. Overall, prospective studies scored marginally higher than retrospective studies for methodological quality, median score 17 (IQR: 14-18) versus 15 (IQR 12-18), respectively. For the sub-categories investigated, prospective studies achieved higher median scores for their, 'introduction', 'study design' and 'participants'. Surprisingly, no study stated that a protocol had been written in advance. Only 18 (36%) studies defined a primary outcome, and only 2 studies (4%) described a power calculation. No study referenced a standardised definition for VH recurrence and detection methods for recurrence varied widely. Methodological quality did not improve with publication year or increasing journal impact factor. CONCLUSION: Currently, non-randomised interventional studies of VH repair are methodologically poor. Clear outcome definitions and a standardised minimum dataset are needed.

Diagnostic pathways in Crohn's disease.

The management of Crohn's disease (CD) is shifting from a stepwise, incremental approach based on symptom control to more aggressive early combined immunosuppression in an attempt to induce remission more rapidly and avoid long-term bowel damage. Accurately defining disease activity is a major challenge, as there is often a disconnect between symptomatology and underlying disease status. The role of imaging in CD has evolved such that it now plays a central role establishing the initial diagnosis, characterising disease phenotype, activity assessment, disease surveillance, and assessing response to therapy. Furthermore, the "treat-to-target" approach is being investigated in CD, with resolution of transmural inflammation on cross-sectional imaging being the treatment goal. In this review, we summarise the principal imaging techniques available to the radiologist, the key findings, and provide some guidance on the preferred imaging option in the diagnostic pathway. We consider the relative merits and drawbacks of each imaging technique before offering a brief discussion of some current developments and research avenues in CD imaging. We discuss how imaging may be useful in a "treat-to-target" approach. Finally, we highlight some practical considerations around service configuration and delivery to optimise imaging in CD in an accurate, cost-effective manner.

What Exactly is Meant by "Loss of Domain" for Ventral Hernia? Systematic Review of Definitions.

Large ventral hernias are a significant surgical challenge. "Loss of domain" (LOD) expresses the relationship between hernia and abdominal volume, and is used to predict operative difficulty and success. This systematic review assessed whether different definitions of LOD are used in the literature. The PubMed database was searched for articles reporting large hernia repairs that explicitly described LOD. Two reviewers screened citations and extracted data from selected articles, focusing on the definitions used for LOD, study demographics, study design, and reporting surgical specialty. One hundred and seven articles were identified, 93 full-texts examined, and 77 were included in the systematic review. Sixty-seven articles were from the primary literature, and 10 articles were from the secondary literature. Twenty-eight articles (36%) gave a written definition for loss of domain. These varied and divided into six broad groupings; four described the loss of the right of domain, six described abdominal strap muscle contraction, five described the "second abdomen", five describing large irreducible hernias. Six gave miscellaneous definitions. Two articles gave multiple definitions. Twenty articles (26%) gave volumetric definitions; eight used the Tanaka method [hernia sac volume (HSV)/abdominal cavity volume] and five used the Sabbagh method [(HSV)/total peritoneal volume]. The definitions used for loss of domain were not dependent on the reporting specialty. Our systematic review revealed that multiple definitions of loss of domain are being used. These vary and are not interchangeable. Expert consensus on this matter is necessary to standardise this important concept for hernia surgeons.

A systematic methodological review of reported perioperative variables, postoperative outcomes and hernia recurrence from randomised controlled trials of elective ventral hernia repair: clear definitions and standardised datasets are needed.

BACKGROUND: This systematic review assesses the perioperative variables and post-operative outcomes reported by randomised controlled trials (RCTs) of VH repair. This review focuses particularly on definitions of hernia recurrence and techniques used for detection. OBJECTIVE: Our aim is to identify and quantify the inconsistencies in perioperative variable and postoperative outcome reporting, so as to justify future development of clear definitions of hernia recurrence and a standardised dataset of such variables. METHODS: The PubMed database was searched for elective VH repair RCTs reported January 1995 to March 2016 inclusive. Three independent reviewers performed article screening, and two reviewers independently extracted data. Hernia recurrence, recurrence rate, timing and definitions of recurrence, and techniques used to detect recurrence were extracted. We also assessed reported post-operative complications, standardised operative outcomes, patient reported outcomes, pre-operative CT scan hernia dimensions, intra-operative variables, patient co-morbidity, and hernia morphology. RESULTS: 31 RCTs (3367 patients) were identified. Only 6 (19.3%) defined hernia recurrence and methods to detect recurrence were inconsistent. Sixty-four different clinical outcomes were reported across the RCTs, with wound infection (30 trials, 96.7%), hernia recurrence (30, 96.7%), seroma (29, 93.5%), length of hospital stay (22, 71%) and haematoma (21, 67.7%) reported most frequently. Fourteen (45%), 11 (35%) and 0 trials reported CT measurements of hernia defect area, width and loss of domain, respectively. No trial graded hernias using generally accepted scales. CONCLUSION: VH RCTs report peri- and post-operative variables inconsistently, and with poor definitions. A standardised minimum dataset, including definitions of recurrence, is required.

Diffusion-weighted imaging for evaluating inflammatory activity in Crohn's disease: comparison with histopathology, conventional MRI activity scores, and faecal calprotectin.

PURPOSE: To evaluate whether the extent of enteric diffusion-weighted imaging (DWI) signal abnormality reflects inflammatory burden in Crohn's disease (CD), and to compare qualitative and quantitative grading. METHODS: 69 CD patients (35 male, age 16-78) undergoing MR enterography with DWI (MRE-D) and the same-day faecal calprotectin (cohort 1) were supplemented by 29 patients (19 male, age 16-70) undergoing MRE-D and terminal ileal biopsy (cohort 2). Global (cohort 1) and terminal ileal (cohort 2) DWI signal was graded (0 to 3) by 2 radiologists and segmental apparent diffusion coefficient (ADC) calculated. Data were compared to calprotectin and a validated MRI activity score [MEGS] (cohort 1), and a histopathological activity score (eAIS) (cohort 2) using nonparametric testing and rank correlation. RESULTS: Patients with normal (grades 0 and 1) DWI signal had lower calprotectin and MEGS than those with abnormal signal (grades 2 and 3) (160 vs. 492 µg/l, p = 0.0004, and 3.3 vs. 21, p < 0.0001), respectively. Calprotectin was lower if abnormal DWI affected <10 cm of small bowel compared to diffuse small and large bowel abnormality (236 vs. 571 µg, p = 0.009). The sensitivity and specificity for active disease (calprotectin > 120 µg/l) were 83% and 52%, respectively. There was a negative correlation between ileal MEGS and ADC (r = -0.41, p = 0.017). There was no significant difference in eAIS between qualitative DWI scores (p = 0.42). Mean ADC was not different in those with and without histological inflammation (2077 vs. 1622 × 10-6mm2/s, p = 0.10) CONCLUSIONS: Qualitative grading of DWI signal has utility in defining the burden of CD activity. Quantitative ADC measurements have poor discriminatory ability for segmental disease activity.

Comparative quantitative assessment of global small bowel motility using magnetic resonance imaging in chronic intestinal pseudo-obstruction and healthy controls.

BACKGROUND: Chronic intestinal pseudo-obstruction (CIPO) is characterized by dilatation of the bowel lumen and abnormal motility. In this study, we aimed to quantify small bowel dysmotility in CIPO using a validated pan-intestinal motility assessment technique based on motion capture magnetic resonance imaging (MRI) compared to normal controls. In addition, we explored if motility responses of CIPO patients to neostigmine challenge differed from healthy volunteers. METHODS: Twenty healthy volunteers (mean age 28, range 22-48) and 11 CIPO patients (mean age 47, range 19-90) underwent MRI enterography to capture global small bowel motility. Eleven controls and seven CIPO patients further underwent a randomized placebo-controlled crossover study of either intravenous neostigmine (0.5 mg) or saline with motility MRI repeated at a mean of 3 weeks. Motility was quantified in regions of interest placed to encompass the whole small bowel volume using a validated, postprocessing technique to give a global motility index in arbitrary units (AU). Baseline and stimulated motility was compared using Wilcoxon rank-sum paired T-tests. KEY RESULTS: Baseline global small bowel motility was significantly lower in CIPO patients compared to controls (mean 0.25 AU vs 0.35 AU, p < 0.001). Motility in both groups increased significantly after neostigmine (0.06 AU increase, p = 0.016 in CIPO and 0.06 AU increase, p = 0.002 in controls). Three patients with scleroderma had a reduced response to neostigmine. CONCLUSIONS & INFERENCES: Global small bowel motility in CIPO patients is significantly lower than controls and response to the pro-kinetic agent neostigmine may differ according to disease phenotype. Software-quantified bowel motility using cine MRI has potential as a future tool to investigate enteric dysmotility.

Effect of faecal occult blood positivity on detection rates and positive predictive value of CT colonography when screening for colorectal neoplasia.

AIM: To determine the detection rates and positive predictive value (PPV) of computed tomography (CT) colonography (CTC) according to the magnitude of faecal occult blood test (FOBt) positivity. MATERIALS AND METHODS: Anonymised data from individuals undergoing CTC after a positive FOBt in the English Bowel Cancer Screening Programme were analysed. The detection of colorectal cancer (CRC), advanced neoplasia, and ≥ 6 mm polyps were stratified by the number of positive FOBt windows. The PPV was calculated by reference to subsequent endoscopy results. The influence of the FOBt result on detection rates was estimated with multilevel logistic regression. PPV, CRC stage, and location were compared across groups according to FOBt positivity. RESULTS: Four thousand, six hundred and one individuals were included (mean = 66.7 years, 54.2% men). Detection rates of CRC and advanced neoplasia increased with greater numbers of positive FOBt windows (odds ratio [OR] for CRC = 1.41; 95% confidence interval [CI]: 1.31-1.52; OR for advanced neoplasia = 1.17; 95%CI: 1.12-1.23; both p < 0.0001). The PPV was significantly greater at higher FOBt levels (p = 0.020). The number of positive FOBt windows had no significant effect on stage (p = 0.30) or location (p = 0.20) of confirmed CRC. CONCLUSIONS: The magnitude of FOBt positivity influences the PPV and detection rates when screening for colorectal neoplasia. CTC may be particularly useful for FOBt patients with few positive test windows.