Efficacy and accuracy of faecal sampling by a digital rectal examination for faecal immunochemical testing.

AIM: A digital rectal examination (DRE) during routine assessment for patients with abdominal symptoms provides an opportunity to obtain faeces from the glove for faecal immunochemical testing (FIT). Here, we compared sampling via DRE to the standard faecal sampling by patients. METHOD: Patients were recruited to a prospective observational cohort study between July 2019 and March 2020. Patients provided a sample for the FOB Gold Wide® which was compared to a further sample taken at clinic via DRE. Clinicians reported whether they obtained a 'good' sample filling all the grooves, a 'poor' sample filling some of the grooves or no faecal sample. Cohen's kappa was used to compare percentage agreement around a negative threshold of <10 µg haemoglobin/g of faeces. Sensitivity for serious bowel disease (SBD) was calculated. RESULTS: Of 596 patients who underwent attempted DRE sampling, there were 258 (43.3%) 'good' samples, 117 (19.6%) 'poor' samples and 221 (37.1%) with no sample to wipe in the grooves. Cohen's kappa dropped from 0.70 to 0.30 for the 'good' and 'poor' samples, respectively. Of those with DRE samples and definitive diagnostic outcomes, the sensitivity for SBD dropped significantly from 76.0% to 41.7% between 'good' and 'poor' samples, respectively (p = 0.041). CONCLUSIONS: A 'good' sample obtained by DRE provides comparable results to samples obtained by patients. This creates potential benefit in speed and ease of testing for patients. However, not all DRE sampling attempts are successful, and the clinician must be satisfied that enough faeces is obtained to wipe adequately into all grooves.

BMI and HbA1c are metabolic markers for pancreatic cancer: Matched case-control study using a UK primary care database.

BACKGROUND: Weight loss, hyperglycaemia and diabetes are known features of pancreatic cancer. We quantified the timing and the amount of changes in body mass index (BMI) and glycated haemoglobin (HbA1c), and their association with pancreatic cancer from five years before diagnosis. METHODS: A matched case-control study was undertaken within 590 primary care practices in England, United Kingdom. 8,777 patients diagnosed with pancreatic cancer (cases) between 1st January 2007 and 31st August 2020 were matched to 34,979 controls by age, gender and diabetes. Longitudinal trends in BMI and HbA1c were visualised. Odds ratios adjusted for demographic and lifestyle factors (aOR) and 95% confidence intervals (CI) were calculated with conditional logistic regression. Subgroup analyses were undertaken according to the diabetes status. RESULTS: Changes in BMI and HbA1c observed for cases on longitudinal plots started one and two years (respectively) before diagnosis. In the year before diagnosis, a 1 kg/m2 decrease in BMI between cases and controls was associated with aOR for pancreatic cancer of 1.05 (95% CI 1.05 to 1.06), and a 1 mmol/mol increase in HbA1c was associated with aOR of 1.06 (1.06 to 1.07). ORs remained statistically significant (p < 0.001) for 2 years before pancreatic cancer diagnosis for BMI and 3 years for HbA1c. Subgroup analysis revealed that the decrease in BMI was associated with a higher pancreatic cancer risk for people with diabetes than for people without (aORs 1.08, 1.06 to 1.09 versus 1.04, 1.03 to 1.05), but the increase in HbA1c was associated with a higher risk for people without diabetes than for people with diabetes (aORs 1.09, 1.07 to 1.11 versus 1.04, 1.03 to 1.04). CONCLUSIONS: The statistically significant changes in weight and glycaemic control started three years before pancreatic cancer diagnosis but varied according to the diabetes status. The information from this study could be used to detect pancreatic cancer earlier than is currently achieved. However, regular BMI and HbA1c measurements are required to facilitate future research and implementation in clinical practice.

Cocoa flavanol consumption improves lower extremity endothelial function in healthy individuals and people with type 2 diabetes.

Background: diabetes and age are major risk factors for the development of lower extremity peripheral artery disease (PAD). Cocoa flavanol (CF) consumption is associated with lower risk for PAD and improves brachial artery (BA) endothelial function. Objectives: to assess if femoral artery (FA) endothelial function and dermal microcirculation are impaired in individuals with type 2 diabetes mellitus (T2DM) and evaluate the acute effect of CF consumption on FA endothelial function. Methods: in a randomised, controlled, double-blind, cross-over study, 22 individuals (n = 11 healthy, n = 11 T2DM) without cardiovascular disease were recruited. Participants received either 1350 mg CF or placebo capsules on 2 separate days in random order. Endothelial function was measured as flow-mediated dilation (FMD) using ultrasound of the common FA and the BA before and 2 hours after interventions. The cutaneous microvasculature was assessed using optical coherence tomography angiography. Results: baseline FA-FMD and BA-FMD were significantly lower in T2DM (FA: 3.2 ± 1.1% [SD], BA: 4.8 ± 0.8%) compared to healthy (FA: 5.5 ± 0.7%, BA: 6.0 ± 0.8%); each p < 0.001. Whereas in healthy individuals FA-FMD did not significantly differ from BA-FMD (p = 0.144), FA-FMD was significantly lower than BA-FMD in T2DM (p = 0.003) indicating pronounced and additional endothelial dysfunction of lower limb arteries (FA-FMD/BA-FMD: 94 ± 14% [healthy] vs. 68 ± 22% [T2DM], p = 0.007). The baseline FA blood flow rate (0.42 ± 0.23 vs. 0.73 ± 0.35 l min-1, p = 0.037) and microvascular dilation in response to occlusion in hands and feet were significantly lower in T2DM subjects than in healthy ones. CF increased both FA- and BA-FMD at 2 hours, compared to placebo, in both healthy and T2DM subgroups (FA-FMD effect: 2.9 ± 1.4%, BA-FMD effect 3.0 ± 3.5%, each pintervention< 0.001). In parallel, baseline FA blood flow and microvascular diameter significantly increased in feet (3.5 ± 3.5 µm, pintervention< 0.001) but not hands. Systolic blood pressure and pulse wave velocity significantly decreased after CF in both subgroups (-7.2 ± 9.6 mmHg, pintervention = 0.004; -1.3 ± 1.3 m s-1, pintervention = 0.002). Conclusions: individuals with T2DM exhibit decreased endothelial function that is more pronounced in the femoral than in the brachial artery. CFs increase endothelial function not only in the BA but also the FA both in healthy individuals and in those with T2DM who are at increased risk of developing lower extremity PAD and foot ulcers.

Comparison of the QuikRead go® point-of-care faecal immunochemical test for haemoglobin with the FOB Gold Wide® laboratory analyser to diagnose colorectal cancer in symptomatic patients.

OBJECTIVES: Faecal immunochemical testing for haemoglobin (FIT) is used to triage patients for colonic investigations. Point-of-care (POC) FIT devices on the market have limited data for their diagnostic accuracy for colorectal cancer (CRC). Here, a POC FIT device is compared with a laboratory-based FIT system using patient collected samples from the urgent referral pathway for suspected CRC. METHODS: A prospective, observational cohort study. Patients collected two samples from the same stool. These were measured by POC QuikRead go® (Aidian Oy, Espoo, Finland) and laboratory-based FOB Gold Wide® (Sentinel Diagnostics, Italy). Faecal haemoglobin <10 µg haemoglobin/g of faeces was considered as negative. At this threshold, comparisons between the two systems were made by calculating percentage agreement and Cohen's kappa coefficient. Proportion of negative results were compared with Chi squared testing. Sensitivities for CRC were calculated. RESULTS: A total of 629 included patients provided paired samples for FIT to compare the QuikRead go® and FOB Gold Wide®. The agreement around the negative threshold was 83.0% and Cohen's kappa coefficient was 0.54. The QuikRead go® reported 440/629 (70.0% of samples) as negative compared to 523/629 (83.1%) for the FOB Gold Wide®, this difference was significant (p-value<0.001). Sensitivities for CRC detection by the QuikRead go® and FOB Gold Wide® were 92.9% (95% confidence interval (CI): 68.5-98.7%) and 100% (CI: 78.5-100%) respectively. CONCLUSIONS: Both systems were accurate in their ability to detect CRC. Whilst good agreement around the negative threshold was identified, more patients would be triaged to further colonic investigation if using the QuikRead go®.

Diagnostic accuracy of point of care faecal immunochemical testing using a portable high-speed quantitative analyser for diagnosis in 2-week wait patients.

AIM: Laboratory-based faecal immunochemical testing (FIT) is the gold standard for detecting the presence of blood in the stool. The aim was to perform a diagnostic accuracy study to confirm if a point of care (POC) analyser for FIT could be safely used as an adjunct in the triage and management of 2-week wait (TWW) colorectal patients. METHODS: The Point of Care Faecal Immunochemical Testing (POC FIT) prospective observational cohort study was designed for TWW patients at a regional referral centre. Between July 2019 and March 2020, patients were invited to perform and bring a FIT sample to clinic. FIT was completed within the clinic appointment using a POC quantitative analyser that has a 2-min processing time (QuikRead go®). Patients and clinicians were blinded to results within the clinic appointment. The results were compared with subsequent diagnostic outcomes. Faecal haemoglobin of <10 µg haemoglobin/g of faeces was considered a negative result. Sensitivities for colorectal cancer (CRC) and combined serious bowel disease (SBD) were calculated using this pre-determined cut-off. RESULTS: A total of 553 patients were included for analytical comparison with diagnostic outcomes. There were 14 (2.5%) patients with CRC and 52 (9.4%) with SBD. The sensitivities for CRC and SBD were 92.9% (95% CI 68.5%-98.7%) and 76.9% (95% CI 63.9%-86.3%) respectively. 379 (68.5%) patients had a negative FIT result (negative predictive value for CRC was 99.7%). CONCLUSIONS: This POC FIT device is a useful adjunct to better manage TWW patients. The high observed sensitivity for CRC offers opportunities, within a single consultation, for improved triage and rationalization of investigation for those with bowel symptoms.

Adoption of faecal immunochemical testing for 2-week-wait colorectal patients during the COVID-19 pandemic: an observational cohort study reporting a new service at a regional centre.

AIM: The COVID-19 pandemic has resulted in the near-complete loss of routine endoscopy services. We describe a major reorganization of service at a regional referral centre (Royal Surrey NHS Foundation Trust) to manage the crisis. Faecal immunochemical testing (FIT) was implemented for triage to make optimum use of limited diagnostic resources. Consultations were switched from face-to-face to telephone. Our aim was to evaluate the impact FIT had on resource allocation and patient diagnoses in the first 3 months of use. METHOD: All colorectal 2-week-wait patient referrals were posted a pack requesting FIT and notification of telephone consultation. A prepaid envelope was included for return of the samples. At consultation, FIT was incorporated with the presenting symptoms to guide the choice of investigation and triage urgency. FIT ≥10 µg/g was interpreted as positive. Outcome data were collected prospectively and compared with retrospective audit data from prepandemic levels across 3 months. RESULTS: From 26 March 2020 to 2 July 381 patients were referred who were invited to provide FIT samples and underwent telephone consultations. Three hundred and fifty eight FIT samples were returned (94%). Onward referral for colonoscopy reduced from 62% to 34% (P < 0.001). There were 14 colorectal cancers (CRC) (3.7%) diagnosed, which was not statistically different from the prepandemic level of 3.9% (P = 0.995). Twelve of the 14 patients with a CRC diagnosis had provided samples; all 12 had FIT ≥10 µg/g and were offered fast-track investigations. CONCLUSIONS: The incorporation of FIT optimized the allocation of limited resources to triage those who required urgent colonic investigation for detecting CRC.

3D laparoscopy does not reduce operative duration or errors in day-case laparoscopic cholecystectomy: a randomised controlled trial.

BACKGROUND: Contemporary 3D platforms have overcome past deficiencies. Available trainee and laboratory studies suggest stereoscopic imaging improves performance but there is little clinical data or studies assessing specialists. We aimed to determine whether stereoscopic (3D) laparoscopic systems reduce operative time and number of intraoperative errors during specialist-performed laparoscopic cholecystectomy (LC). METHODS: A parallel arm (1:1) randomised controlled trial comparing 2D and 3D passive-polarised laparoscopic systems in day-case LC using was performed. Eleven consultant surgeons that had each performed > 200 LC (including > 10 3D LC) participated. Cases were video recorded and a four-point difficulty grade applied. The primary outcome was overall operative time. Subtask time and the number of intraoperative consequential errors as identified by two blinded assessors using a hierarchical task analysis and the observational clinical human reliability analysis technique formed secondary endpoints. RESULTS: 112 patients were randomised. There was no difference in operative time between 2D and 3D LC (23:14 min (± 10:52) vs. 20:17 (± 9:10), absolute difference - 14.6%, p = 0.148) although 3D surgery was significantly quicker in difficulty grade 3 and 4 cases (30:23 min (± 9:24), vs. 18:02 (± 7:56), p < 0.001). No differences in overall error count was seen (total 47, median 1, range 0-4 vs. 45, 1, 0-3, p = 0.62) although there were significantly fewer 3D gallbladder perforations (15 vs. 6, p = 0.034). CONCLUSION: 3D laparoscopy did not reduce overall operative time or error frequency in laparoscopic cholecystectomies performed by specialist surgeons. 3D reduced Calot's dissection time and operative time in complex cases as well as the incidence of iatrogenic gallbladder perforation (NCT01930344).

The use of GLP-1 receptor agonists in hospitalised patients: An untapped potential.

In the outpatient setting, glucagon-like peptide-1 (GLP-1) receptor agonists have proved to be highly efficacious drugs that provide glycaemic control with a low risk of hypoglycaemia. These characteristics make GLP-1 receptor agonists attractive agents to treat dysglycaemia in perioperative or high-dependency hospital settings, where glycaemic variability and hyperglycaemia are associated with poor prognosis. GLP-1 also has a direct action on the myocardium and vasculature-which may be advantageous in the immediate aftermath of a vascular insult. This is a narrative review of the work in this area. The aim was to determine the populations of hospitalised patients being evaluated and the clinical and mechanistic end-points tested, with the institution of GLP-1 therapy in hospital. We searched the PubMed, Embase, and Google scholar databases, combining the term "glucagon-like peptide 1" OR "GLP-1" OR "incretin" OR "liraglutide" OR "exenatide" OR "lixisenatide" OR "dulaglutide" OR "albiglutide" AND "inpatient" OR "hospital" OR "perioperative" OR "postoperative" OR "surgery" OR "myocardial infarction" OR "stroke" OR "cerebrovascular disease" OR "transient ischaemic attack" OR "ICU" OR "critical care" OR "critical illness" OR "CCU" OR "coronary care unit." Pilot studies were reported in the fields of acute stroke, cardiac resuscitation, coronary care, and perioperative care that showed advantages for GLP-1 therapy, with normalisation of glucose, lower glucose variability, and lower risk of hypoglycaemia. Animal and human studies have reported improvements in myocardial performance when given acutely after vascular insult or surgery, but these have yet to be translated into randomised clinical trials.

Lixisenatide Reduces Chylomicron Triacylglycerol by Increased Clearance.

Context: Glucagon-like peptide-1 (GLP-1) agonists control postprandial glucose and lipid excursion in type 2 diabetes; however, the mechanisms are unclear. Objective: To determine the mechanisms of postprandial lipid and glucose control with lixisenatide (GLP-1 analog) in type 2 diabetes. Design: Randomized, double-blind, cross-over study. Setting: Centre for Diabetes, Endocrinology, and Research, Royal Surrey County Hospital, Guildford, United Kingdom. Patients: Eight obese men with type 2 diabetes [age, 57.3 ± 1.9 years; body mass index, 30.3 ± 1.0 kg/m2; glycosylated hemoglobin, 66.5 ± 2.6 mmol/mol (8.2% ± 0.3%)]. Interventions: Two metabolic studies, 4 weeks after lixisenatide or placebo, with cross-over and repetition of studies. Main Outcome Measures: Study one: very-low-density lipoprotein (VLDL) and chylomicron (CM) triacylglycerol (TAG) kinetics were measured with an IV bolus of [2H5]glycerol in a 12-hour study, with hourly feeding. Oral [13C]triolein, in a single meal, labeled enterally derived TAG. Study two: glucose kinetics were measured with [U-13C]glucose in a mixed-meal (plus acetaminophen to measure gastric emptying) and variable IV [6,6-2H2]glucose infusion. Results: Study one: CM-TAG (but not VLDL-TAG) pool-size was lower with lixisenatide (P = 0.046). Lixisenatide reduced CM [13C]oleate area under the curve (AUC)60-480min concentration (P = 0.048) and increased CM-TAG clearance, with no effect on CM-TAG production rate. Study two: postprandial glucose and insulin AUC0-240min were reduced with lixisenatide (P = 0.0051; P < 0.05). Total glucose production (P = 0.015), rate of glucose appearance from the meal (P = 0.0098), and acetaminophen AUC0-360min (P = 0.006) were lower with lixisenatide than with placebo. Conclusions: Lixisenatide reduced [13C]oleate concentrations, derived from a single meal in CM-TAG and glucose rate of appearance from the meal through delayed gastric emptying. However, day-long CM production, measured with repeated meal feeding, was not reduced by lixisenatide and decreased CM-TAG concentration resulted from increased CM-TAG clearance.