Rejection of Fecal Immunochemical Tests Within the Lower Gastrointestinal Diagnostic Pathway: A Cohort Study.

INTRODUCTION/OBJECTIVES: The fecal immunochemical test (FIT) helps triage primary care patients at risk of colorectal cancer (CRC). Improving FIT returns has received recent attention, however uncertainty exists regarding the accurate completion of samples provided for laboratory analysis. This study aims to identify the rejection rate of returned FIT samples and determine rejection causes. METHODS: FIT samples from symptomatic patients within South Yorkshire, Bassetlaw, and North Derbyshire are processed at a central laboratory. Tests requests are made from 225 GP practices, which serve an estimated 2 million population. This study describes a retrospective review of FIT samples received in the central laboratory between 01/09/19 and 31/12/22. Locally held data was interrogated in March 2023 to determine the number of FIT samples received and rejected during the study period. Documented reasons for rejection were explored to identify common themes. RESULTS: Total FIT specimens received during the study period was 126 422. Of these, 5190 (4.1%) were rejected. Monthly rejection rates fell from 17.4% in September 2019 to 1.3% in December 2022 (P < .001). Sampling errors were the most frequent cause for FIT rejection (2151/5190), with other causes including: expired specimen; no sample collection date/ time, no request form, incomplete patient information and illegible handwriting. CONCLUSIONS: This is the first study exploring FIT rejection rates in symptomatic primary care patients, which shows improvements in rejection rates over time. Targeted interventions could improve rejection rates further, thereby reducing NHS resource use and costs and diagnostic delays.

Fecal Immunochemical Testing in Patients With Low-Risk Symptoms of Colorectal Cancer: A Diagnostic Accuracy Study.

BACKGROUND: The fecal immunochemical test (FIT) is recommended for triaging primary care patients in England with low-risk symptoms of colorectal cancer (CRC). The evidence underpinning recommendations by the National Institute for Health and Care Excellence had limitations, with a paucity of primary care evidence. This study examines the diagnostic accuracy of FIT in a defined low-risk symptom primary care population. PATIENTS AND METHODS: Consecutive symptomatic adult patients referred for a FIT between October and December 2019 were included. Patients were derived from 225 primary care practices in England. Serious colorectal diseases (CRC, high-risk polyps, and inflammatory bowel disease [IBD]) were identified through patient follow-up over 18 months, using both primary and secondary healthcare records. Performance characteristics of FIT are reported according to differing thresholds, including the currently recommended threshold of ≥10 µg hemoglobin per gram of feces (µg/g). RESULTS: A total of 3,506 patients were included in the final analysis. Of these, 708 had a positive FIT result (≥10 µg/g). The prevalence of CRC was 1.3%. FIT positivity declined from 20.2% to 5.8% and 4.5% at cutoffs of 10, 80, and 120 µg/g, respectively. The sensitivity of FIT at ≥10 µg/g to detect CRC was 91.1% (95% CI, 77.9%-97.1%); its specificity was 80.7% (95% CI, 79.3%-82.0%); the positive predictive value (PPV) was 5.8% (95% CI, 4.2%-7.8%); and the negative predictive value (NPV) was 99.9% (95% CI, 99.6%-99.95%). The area under the receiver operating characteristic curve was 0.93 (0.91-0.96). PPV and specificity increased, whereas sensitivity and NPV decreased when serious colorectal diseases (CRC, high-risk polyps, and IBD) were combined. Age, sex, socioeconomic deprivation, and anemia did not significantly influence FIT sensitivity on subgroup analysis. CONCLUSIONS: Utilization of FIT at a threshold ≥10 µg/g can safely triage patients with low-risk symptoms in primary care, with negative results effectively ruling out CRC.

Prioritisation of lower gastrointestinal endoscopy during the COVID-19 pandemic: outcomes of a novel triage pathway.

Objective: The 2-week-wait (2ww) referral pathway is used in England to fast-track patients with suspected colorectal cancer (CRC). A two-stage triage pathway was used to prioritise lower gastrointestinal (LGI) endoscopy for suspected CRC during the COVID-19 pandemic. Method: All patients referred for an LGI endoscopy via a 2ww referral pathway between March 2020 and July 2020 were assessed. The first stage triaged patients to high, standard or low risk of CRC based on symptoms and faecal immunochemical test (FIT), and offered CT scans to those at high risk. The second stage, endoscopy prioritisation (EP), incorporated the CT results, FIT and symptoms to triage into four groups, EP1-EP4; with EP1 being the most urgent and EP4 the least. The primary outcome measure was CRC detection. Results: 514 patients were included. The risk of CRC was triaged as high in 190/514 patients (37%), standard in 274/514 patients (53%) and low in 50/514 (10%) patients. 422/514 patients (82%) underwent endoscopy with triage to EP1 in 52/422 (12%), EP2 in 105/422 (25%), EP3 in 210/422 (50%) and EP4 in 55/422 (13%). CRC was detected in 23 patients (5.4%). CRC was significantly more frequent in the EP1 group (23.1%, relative risk (RR)=16.2) and EP2 group (6.7%, RR=4.7) compared with EP3 group (1.4%). All CRC lesions were identified by CT imaging when performed prior to LGI endoscopy. Conclusion: This triage pathway designated 83% of patients with CRC to either EP1 or EP2. During a period of limited endoscopy provision, this pathway effectively prioritises endoscopy for those at greatest risk of CRC.

Diagnostic Yield of Colonoscopy in Patients With Symptoms Compatible With Rome IV Functional Bowel Disorders.

BACKGROUND & AIMS: There is little data on the diagnostic yield of colonoscopy in patients with symptoms compatible with functional bowel disorders (FBDs). Previous studies have only focused on diagnostic outcomes of colonoscopy in those with suspected irritable bowel syndrome using historic Rome I-III criteria, whilst having partially assessed for alarm features and shown markedly conflicting results. There is also no colonoscopy outcome data for other FBDs, such as functional constipation or functional diarrhea. Using the contemporaneous Rome IV criteria we determined the diagnostic yield of colonoscopy in patients with symptoms compatible with a FBD, stratified diligently according to the presence or absence of alarm features. METHODS: Basic demographics, alarm features, and bowel symptoms using the Rome IV diagnostic questionnaire were collected prospectively from adults attending out-patient colonoscopy in 2019. Endoscopists were blinded to the questionnaire data. Organic disease was defined as the presence of inflammatory bowel disease, colorectal cancer, or microscopic colitis. RESULTS: 646 patients fulfilled symptom-based criteria for the following Rome IV FBDs: IBS (56%), functional diarrhea (27%) and functional constipation (17%). Almost all had alarm features (98%). The combined prevalence of organic disease was 12%, being lowest for functional constipation and IBS-constipation (∼6% each), followed by IBS-mixed (∼9%), and highest amongst functional diarrhea and IBS-diarrhea (∼17% each); p = .005. The increased prevalence of organic disease in diarrheal versus constipation disorders was accounted for by microscopic colitis (5.7% vs. 0%, p < .001) but not inflammatory bowel disease (7.2% vs. 4.0%, p = .2) or colorectal cancer (4.2% vs. 2.3%, p = .2). However, 1-in-4 chronic diarrhea patients - conceivably at risk for microscopic colitis - did not have colonic biopsies taken. Finally, only 11 of 646 (2%) patients were without alarm features, in whom colonoscopy was normal. CONCLUSIONS: Most patients with symptoms of FBDs who are referred for colonoscopy have alarm features. The presence of organic disease is significantly higher in diarrheal versus constipation disorders, with microscopic colitis largely accounting for the difference whilst also being a missed diagnostic opportunity. In those patients without alarm features, the diagnostic yield of colonoscopy was nil.

Increased psychological distress and somatization in patients with irritable bowel syndrome compared with functional diarrhea or functional constipation, based on Rome IV criteria.

BACKGROUND: The Rome IV criteria for disorders of gut-brain interaction define irritable bowel syndrome (IBS) as a functional bowel disorder associated with frequent abdominal pain of at least 1 day per week. In contrast, functional diarrhea (FD) and functional constipation (FC) are relatively painless. We compared differences in mood and somatization between Rome IV IBS and FC/FD. METHODS: A total of 567 patients with Rome IV defined IBS or FD/FC completed a baseline questionnaire on demographics, abdominal pain frequency, mood (hospital anxiety and depression scale, HADS), and somatization (patient health questionnaire, PHQ-12). The primary analysis compared differences in mood and somatization between IBS and FC/FD, and the relative influence of abdominal pain frequency on these extra-intestinal symptoms. The secondary analysis evaluated differences across individual IBS subtypes, and also between FC and FD. KEY RESULTS: Patients with IBS-in comparison to those with FC/FD-had significantly higher mean PHQ-12 somatization scores (9.1 vs. 5.4), more somatic symptoms (6.0 vs. 4.3), abnormally high somatization levels (16% vs. 3%), higher HADS score (15.0 vs. 11.7), and clinically abnormal levels of anxiety (38% vs. 20%) and depression (17% vs. 10%). Increasing abdominal pain frequency correlated positively with PHQ-12, number of somatic symptoms, and HADS; p < 0.001. No differences in mood and somatization scores were seen between individual IBS subtypes, and nor between FC and FD. CONCLUSION & INFERENCES: Based on the Rome IV criteria, IBS is associated with increased levels of psychological distress and somatization compared with FD or FC. Patients reporting frequent abdominal pain should be comprehensively screened for psychosomatic disorders, with psychological therapies considered early in the disease course.

To PEG or not to PEG that is the question.

Nutrition support involves the use of oral supplements, enteral tube feeding or parenteral nutrition. These interventions are considered when oral intake alone fails to meet nutritional requirements. Special diets and oral supplements are usually the first approach to managing malnutrition; however, their role becomes limited when oral intake is restricted or if swallowing is unsafe. Enteral tube feeding or parenteral nutrition are alternative means of providing nutrition support for this select group of patients. Percutaneous endoscopic gastrostomy (PEG) feeding was introduced into clinical practice in 1980. It describes a feeding tube placed directly into the stomach under endoscopic guidance. It is an established means of providing enteral nutrition to those who have functionally normal gastrointestinal tracts, but who cannot meet their nutritional requirements due to inadequate oral intake. The intervention is usually reserved when nutritional intake is likely to be inadequate for more than 4-6 weeks. Although the benefits of PEG have been shown for a select group of patients, there currently exists concerns about the increasing frequency of this intervention, and also uncertainty about the long-term benefits for certain patients. The 2004 UK National Confidential Enquiry into Patient Outcome and Death report emphasised this concern, with almost a fifth of PEG being undertaken for futile indications that negatively influenced morbidity and mortality. The present review paper discusses the indications for, controversies surrounding and complications of gastrostomy feeding and provides practical advice on optimising patient selection for this intervention.

High prevalence of primary bile acid diarrhoea in patients with functional diarrhoea and irritable bowel syndrome-diarrhoea, based on Rome III and Rome IV criteria.

BACKGROUND: A high prevalence of primary bile acid diarrhoea (BAD) has been reported for Rome III defined irritable bowel syndrome (IBS)-diarrhoea and functional diarrhoea. We determined whether this still applies under the contemporaneous Rome IV criteria, given that the latter characterises IBS-diarrhoea as having more frequent abdominal pain compared with previous iterations, whilst no longer recognising abdominal discomfort. METHODS: Patients referred for a 75SeHCAT test completed a baseline questionnaire comprising, i) demographic data, ii) risk factors for BAD (inflammatory bowel disease, bowel resection, cholecystectomy, microscopic colitis, celiac disease, abdominal-pelvic radiotherapy), iii) the Rome III and IV bowel disorder questionnaire, and iv) mood and somatisation scores. A diagnosis of BAD constituted a 75SeHCAT of ≤15%, with moderate to severe disease being defined as ≤10% and ≤5%, respectively. FINDINGS: Of 300 patients with complete dataset, 184 had no risk factors for BAD and fulfilled criteria for either IBS-diarrhoea or functional diarrhoea. The prevalence of primary BAD was 38% (n = 70/184), with almost half having moderate (n = 16) to severe (n = 17) disease. Using the Rome III criteria, the prevalence of primary BAD was 36% in IBS-diarrhoea (n = 63/173) and 64% (n = 7/11) in functional diarrhoea; p = 0.11. Using the Rome IV criteria, the prevalence of primary BAD was 38% (n = 53/139) in IBS-diarrhoea and 38% (n = 17/45) in functional diarrhoea; p = 0.97. Patients with primary BAD experienced more frequent loose stools (p = 0.01) and had a higher body mass index (p<0.0001) compared to those without BAD, but otherwise no significant differences were seen in age, gender, mood, somatisation, or abdominal pain. The presence of primary BAD in patients classified as overweight or obese was approximately 40% and 60%, respectively. INTERPRETATION: Over a third of patients with Rome IV IBS-diarrhoea or functional diarrhoea have primary BAD, similar to Rome III. We therefore recommend that, in secondary care settings, generic testing for primary BAD should be considered in patients presenting with chronic diarrhoea of presumed functional origin regardless of concomitant abdominal pain. Centres that lack tests for primary BAD, and who empirically treat instead, may consider targeting patients who are overweight or obese.

Is Peer Support in Group Clinics as Effective as Traditional Individual Appointments? The First Study in Patients With Celiac Disease.

INTRODUCTION: Celiac disease (CD) is common, affecting approximately 1% of the population. The cornerstone of management is a gluten-free diet, with dietetic advice being the key to aiding implementation. The aim of the study was to assess group clinics in comparison with traditional individual appointments. METHODS: Patients with a new diagnosis of CD, confirmed histologically, were prospectively recruited over 18 months in Sheffield, United Kingdom. Patients received either a group clinic or traditional one-to-one appointment, led by a dietitian. Quality-of-life questionnaires were completed at baseline, as well as biochemical parameters being recorded. Patients were followed up at 3 months, where adherence scores were assessed as well as biochemical parameters and quality of life questionnaires being completed. RESULTS: Sixty patients with CD were prospectively recruited and received either an individual (n = 30) or group clinic (n = 30). A statistically significant reduction in tissue transglutaminase was noted following group clinics (mean 58.5, SD 43.4 U/mL vs mean 13.2, SD 5.7 U/mL, P < 0.01). No significant differences in baseline and follow-up biochemical parameters between one-to-one and group clinics were noted. At follow-up, there was no statistically significant difference between mean gluten-free diet adherence scores (mean 3.1, SD 0.4 vs mean 3.1, SD 0.7, P = 0.66) between one-to-one and group clinics. DISCUSSION: This first study assessing group clinics in CD demonstrates they are as effective as traditional one-to-one clinics, with the added benefits of peer support and greater efficiency, with an estimated 54% reduction of dietetic resources.

Use of small-bowel capsule endoscopy in cases of equivocal celiac disease.

BACKGROUND AND AIMS: Seronegative villous atrophy (SNVA), raised intraepithelial lymphocytes (IELs), and crypt hyperplasia on duodenal histology can be secondary to celiac disease (CD) or other causes such as medications or infections. Our aims were to assess the role of small-bowel capsule endoscopy (SBCE) in these patients and to ascertain whether findings on SBCE at diagnosis can predict disease outcome. METHODS: Patients (n = 177) with SNVA, IELs, ± crypt hyperplasia on duodenal histology were studied. These patients all had an equivocal diagnosis of CD. RESULTS: Overall, 56 patients (31.6%) had a positive SBCE. Thirty-three patients (58.9%) had disease affecting the proximal third of the small bowel (SB). The diagnostic yield of SBCE was 40.0% (22 patients), 51.4% (18 patients), 27.0% (10 patients), and 14.0% (7 patients) in patients with an unknown cause for SNVA (SNVA-UO), patients with SNVA who responded to a gluten-free diet (SNVA-CD), patients with a known cause for SNVA, and patients with railed IELs ± crypt hyperplasia, respectively. In SNVA-UO, SBCE at diagnosis was more likely to be positive in patients with persistent SNVA (10, 90.9%) and persistent SNVA with lymphoproliferative features (4, 80.4%) than patients with spontaneous resolution of SNVA (8, 20.5%) (P = .0001). All patients in the SNVA-CD group who eventually developed adverse events had a positive SBCE (P = .022). They also had more extensive SB disease than those without adverse events (50% vs 1% P = .002). More extensive SB disease on SBCE correlated with a higher SNVA-related mortality in patients with SNVA-UO and SNVA-CD (P = .019). Severity of histology did not correlate with mortality (P = .793). CONCLUSIONS: A positive SBCE at diagnosis predicts a worse outcome. More importantly, more extensive disease in these patients is associated with poor survival. Targeting patients with extensive disease at diagnosis with more aggressive therapy can help to improve prognosis.

In vitro trackable assembly of RNA-specific nucleocapsids of the respiratory syncytial virus.

The templates for transcription and replication by respiratory syncytial virus (RSV) polymerase are helical nucleocapsids (NCs), formed by viral RNAs that are encapsidated by the nucleoprotein (N). Proper NC assembly is vital for RSV polymerase to engage the RNA template for RNA synthesis. Previous studies of NCs or nucleocapsid-like particles (NCLPs) from RSV and other nonsegmented negative-sense RNA viruses have provided insights into the overall NC architecture. However, in these studies, the RNAs were either random cellular RNAs or average viral genomic RNAs. An in-depth mechanistic understanding of NCs has been hampered by lack of an in vitro assay that can track NC or NCLP assembly. Here we established a protocol to obtain RNA-free N protein (N0) and successfully demonstrated the utility of a new assay for tracking assembly of N with RNA oligonucleotides into NCLPs. We discovered that the efficiency of the NCLP (N-RNA) assembly depends on the length and sequence of the RNA incorporated into NCLPs. This work provides a framework to generate purified N0 and incorporate it with RNA into NCLPs in a controllable manner. We anticipate that our assay for in vitro trackable assembly of RSV-specific nucleocapsids may enable in-depth mechanistic analyses of this process.

Diagnostic yield of magnetically assisted capsule endoscopy versus gastroscopy in recurrent and refractory iron deficiency anemia.

BACKGROUND: Small-bowel capsule endoscopy is advocated and repeat upper gastrointestinal (GI) endoscopy should be considered for evaluation of recurrent or refractory iron deficiency anemia (IDA). A new device that allows magnetic steering of the capsule around the stomach (magnetically assisted capsule endoscopy [MACE]), followed by passive small-bowel examination might satisfy both requirements in a single procedure. METHODS: In this prospective cohort study, MACE and esophagogastroduodenoscopy (EGD) were performed in patients with recurrent or refractory IDA. Comparisons of total (upper GI and small bowel) and upper GI diagnostic yields, gastric mucosal visibility, and patient comfort scores were the primary end points. RESULTS: 49 patients were recruited (median age 64 years; 39 % male). Combined upper and small-bowel examination using the new capsule yielded more pathology than EGD alone (113 vs. 52; P < 0.001). In upper GI examination (proximal to the second part of the duodenum, D2), MACE identified more total lesions than EGD (88 vs. 52; P < 0.001). There was also a difference if only IDA-associated lesions (esophagitis, altered/fresh blood, angioectasia, ulcers, and villous atrophy) were included (20 vs. 10; P = 0.04). Pathology distal to D2 was identified in 17 patients (34.7 %). Median scores (0 - 10 for none - extreme) for pain (0 vs. 2), discomfort (0 vs. 3), and distress (0 vs. 4) were lower for MACE than for EGD (P < 0.001). CONCLUSION: Combined examination of the upper GI tract and small bowel using the MACE capsule detected more pathology than EGD alone in patients with recurrent or refractory IDA. MACE also had a higher diagnostic yield than EGD in the upper GI tract and was better tolerated by patients.

Sheffield Clinical Research Fellowship programme: a transferable model for UK gastroenterology.

Out of programme (OOP) opportunities are to be encouraged. This article gives an insightful view of the Sheffield Clinical Research Fellowship Programme. Unique trainee feedback is provided. The take home message is clear - trainees should grab OOP experiences with both hands! For consultants the logistics described are potentially transferrable to their own regions.

Clinical application of dietary therapies in irritable bowel syndrome.

BACKGROUND AND AIMS: Diet appears to play a pivotal role in symptom generation in Irritable Bowel Syndrome (IBS). First line dietary therapy for IBS has focused on advice concerning healthy eating and lifestyle management. Research recently has focused on the role of a diet low in fermentable oligo-, di-, and mono-saccharides and polyols (FODMAPs), gluten free (GFD) and wheat free (WFD) diets for the relief of symptoms in IBS. METHODS: A round table discussion with gastroenterologists and dietitians with a specialist interest in dietary therapies in IBS was held in Sheffield, United Kingdom in May 2017. Existing literature was reviewed. PubMed and EMBASE were searched with the MeSH terms irritable bowel syndrome/diet/diet therapy/gluten/low FODMAP in different combinations to identify relevant articles. A consensus on the application of these dietary therapies into day-to-day practice was developed. RESULTS: Fourteen randomized trials in IBS evaluating the low FODMAP diet (n studies = 9), GFD (n = 4) and WFD (n = 1) were included in this review. The total number of patients recruited from randomized trials reviewed was: n=580 low FODMAP diet (female, n=430), n=203 GFD (female, n=139), n=276 WFD (female, n=215). There was no significant difference in the gender of patients recruited for both the low FODMAP and GFD randomized studies (p=0.12). The response rate in the literature to a low FODMAP diet ranged between 50-76%, and to GFD ranged between 34-71%. Percentage of IBS patients identified as wheat sensitive was reported as 30% in the literature. CONCLUSION: There are no head-to-head trials to date utilizing the low FODMAP diet, GFD and WFD for dietary treatment of IBS and still a number of concerns for diets, including nutritional inadequacy and alteration of the gut microbiota. The consensus suggests that there is evidence for the use of the low FODMAP diet, GFD and WFD as dietary therapies for IBS; the decision-making process for using each individual therapy should be directed by a detailed history by the dietitian, involving the patient in the process.

Challenging current views on bile acid diarrhoea and malabsorption.

BACKGROUND: In 2012, the National Institute for Health and Care Excellence (NICE) assessed guidance (DG7) on the use of tauroselcholic (75selenium) acid (also known as SeHCAT) for the investigation of diarrhoea due to bile acid malabsorption (BAM) in patients with IBS-D and in patients with Crohn's disease who have not had an ileal resection. NICE concluded that tauroselcholic (75selenium) acid was recommended for use in research only. NICE will be reviewing the decision to update the guidance for tauroselcholic (75selenium) acid, for these populations, in March 2017. AIM: Our aim is to summarise advances in BAM, also known as bile acid diarrhoea (BAD), and encourage clinicians to re-evaluate their understanding of this disorder. APPROACH: We review the prevalence, diagnosis and treatment of BAD/BAM. We describe the new evidence available since the original NICE review in 2012, and discuss the economic issues associated with failure to diagnose or to treat BAD/BAM accurately. EVIDENCE UPDATE: There is new and compelling evidence available since DG7, which shows that tauroselcholic (75selenium) acid scanning is a powerful tool in the diagnosis of BAD/BAM. We summarise published prevalence data (approximately 1% prevalence in the UK, as suggested by clinical practice diagnosis rates), and highlight that the true prevalence of BAD/BAM could be far greater than this. CONCLUSION: We present evidence that challenges current opinion about this disorder, and we commend both clinicians and health technology assessment (HTA) agencies for being open to arguments and new evidence in any future HTAs.