Long-term effectiveness and persistence rate of ustekinumab dose intensification in a South East Asian inflammatory bowel disease center.

BACKGROUND AND AIMS: Ustekinumab (UST) is an effective biologic for treatment of inflammatory bowel disease (IBD). However, some patients treated with UST have suboptimal clinical response with standard dosing. The aims of this study were to determine the effectiveness of UST dose intensification (DI), identify factors associated with DI, cumulative incidence of DI and persistence of UST among treated patients. METHODS: Clinical data of patients with Crohn's disease (CD) and ulcerative colitis (UC) who received UST from September 2017 to October 2022 in Singapore General Hospital were collected. Primary outcome was defined as achieving corticosteroid-free clinical remission, biochemical remission, endoscopic healing and/or transmural healing (CD). Statistical analysis was performed to identify factors, which are predictive of UST DI and effectiveness of UST DI. RESULTS: Forty-two patients (34 CD and 8 UC) underwent UST DI to either 6-weekly (n = 19, 45.2%) or 4-weekly (n = 23, 35.9%) and the median time to intensification was 31.1 weeks (17.8-65.7). Presence of perianal disease in CD (HR 4.9; 1.47-16.4) was associated with DI. After DI, 16 (38%) patients achieved primary outcome by week 52. The overall drug persistence rates at 1 year and 2 years were 75.7% (95% CI 62.9-84.6) and 63.5% (95% CI 49.9-74.3), respectively. CONCLUSION: Two third of IBD patients underwent DI while on UST treatment and the median time to DI was about 6 months after induction. CD patients with perianal disease is more likely to undergo DI. More than one third of dose-intensified patients achieved remission by week 52.

Diet and cancer of the esophagus and stomach.

PURPOSE OF REVIEW: Dietary factors have been linked to cancers. This review focuses on several nutrients, which have strong evidence showing increase in cancer risks in the esophagus and stomach. RECENT FINDINGS: Obesity is an important risk factor in upper gastrointestinal cancers. High sugar content in food and sugary drinks are the main drivers of obesity. Proinflammatory diet is another dietary factor, which is increasingly recognized as being associated with esophageal and gastric cancer. SUMMARY: Cancer has been predicted to be the leading cause of death in this century. Cancers of the esophagus and stomach are the six and third most common cause of death worldwide. Although Helicobacter pylori infection is a known cause of gastric cancer, obesity is a leading contributor to esophageal adenocarcinoma. Epidemiological data have shown that dietary factors are associated with the two cancers. Observational, case control, animal and recent large cohort studies have identified associations between dietary factors and upper gastrointestinal cancer. Data are also emerging from studies, which look at dietary patterns, such as reduction in the Dietary Inflammatory Index, as well as adherence to a modified Mediterranean diet, and its association with the incidence of esophageal and gastric cancer.

Mindfulness-based cognitive therapy in functional dyspepsia: A pilot randomized trial.

BACKGROUND AND AIM: Patients with functional dyspepsia (FD) often have concomitant anxiety and depression. Mindfulness-based cognitive therapy (MBCT) combines the principles of cognitive behavioral therapy and mindfulness. It is a group-based therapy and has been shown to be efficacious in functional gastrointestinal disorders. There are no randomized controlled trials (RCTs) evaluating MBCT in FD. We aimed to evaluate feasibility and efficacy of MBCT in FD management. METHODS: We performed a mixed-method single-center pilot randomized trial of 28 patients fulfilling ROME-III criteria for FD. Fifteen patients were randomized to an 8-week MBCT program while 13 underwent treatment-as-usual (TAU). Patients completed questionnaires at baseline and at week 8. Two focus-groups were conducted. Feasibility of recruitment, acceptability of randomization, procedures and intervention, handout compliance and feasibility of quantitative measures were assessed. The primary outcome was subjective-clinical-assessment of FD symptoms (SCA-FD). Secondary outcome measures included Short-form Nepean Dyspepsia Index (SF-NDI), subjective-clinical-assessment of general health (SCA-GH), EuroQoL-Visual Analog Scale (EuroQoL-VAS), and Depression, Anxiety and Stress Scale-21 Items (DASS-21). RESULTS: Twelve of 15 patients in the MBCT group completed the program. There was a trend towards symptom improvement, with 90% in the MBCT group reporting improvement in SCA-FD compared with 45% in TAU(P = 0.063). Patients who underwent MBCT reported greater improvement in SF-NDI (mean change: -8.8 (SD: 7.5) vs -0.7 (7.2), P = 0.018) and DASS-21 (-19.8 (29.5) vs -5.5 (6.6) P = 0.13) compared with TAU. There was no difference in SCA-GH and EuroQoL-VAS. Based on SCA-FD improvement, the eventual RCT will require 50 patients (25 in each group). CONCLUSIONS: Mindfulness-based cognitive therapy is likely efficacious for FD, and it would be feasible to conduct a RCT.

Colonic stenting in acute malignant large bowel obstruction: audit of efficacy and safety in a Singapore tertiary referral centre.

Introduction: Acute malignant large bowel obstruction (MBO) occurs in 8%-15% of colorectal cancer patients. Self-expandable metal stents (SEMS) have progressed from a palliative modality to use as bridge to surgery (BTS). We aimed to assess the safety and efficacy of SEMS for MBO in our institution. Methods: The data of patients undergoing SEMS insertion for MBO were reviewed. Technical success was defined as successful SEMS deployment across tumour without complications. Clinical success was defined as colonic decompression without requiring further surgical intervention. Rates of complications, median time to surgery, types of surgery and rates of recurrence were studied. Results: Seventy-nine patients underwent emergent SEMS placement from September 2013 to February 2020. Their mean age was 68.8 ± 13.8 years and 43 (54%) patients were male. Mean tumour length was 4.2 cm ± 2.2 cm; 89.9% of malignant strictures were located distal to the splenic flexure. Technical and clinical success was 94.9% and 98.7%, respectively. Perforation occurred in 5.1% of patients, with none having stent migration or bleeding. Fifty (63.3%) patients underwent SEMS insertion as BTS. Median time to surgery was 20 (range 6-57) days. Most (82%) patients underwent minimally invasive surgery. Primary anastomosis rate was 98%. Thirty-nine patients had follow-up beyond 1-year posttreatment (median 34 months). Local recurrence and distant metastasis were observed in 4 (10.3%) and 5 (12.8%) patients, respectively. Conclusion: Insertion of SEMS for acute MBO has high success rates and a good safety profile. Most patients in this audit underwent minimally invasive surgery and primary anastomosis after successful BTS.

Ulcerative colitis: STRIDE-ing beyond symptoms with new standards.

The landscape of ulcerative colitis has changed in the last two decades. Advancements in pharmacotherapeutics have heralded the introduction of new treatment options, with many agents in development. Better clinical outcomes are seen with tighter disease control, made possible with greater understanding of inflammatory pathways and their blockade with drugs. There has been a resultant shift in treatment targets, beyond symptoms to endoscopic and histological healing. Controlling the burden of disease activity also lowers the risk of developing colorectal cancer. Colorectal cancer screening now requires the use of dye-based agents and high definition colonoscopy to improve detection of colonic neoplasms.

Severe Symptomatic Hypophosphataemia as a Complication of Parenteral Iron Replacement.

Parental iron replacement is given to patients with severe iron deficiency or intolerance to oral iron. Hypophosphataemia has been reported to occur as a complication of parental iron replacement, and is postulated to be related to the carbohydrate moieties used in the parenteral preparations. Hypophosphataemia is under-diagnosed as symptoms such as fatigue, muscle weakness and poor effort tolerance mimic anaemia. Severe hypophosphataemia (<0.32 mmol/l) can result in significant complications such as confusion, rhabdomyolysis and arrhythmias. We report a patient with recurrent admissions for non-specific symptoms attributed to iron deficiency anaemia who received multiple doses of parenteral ferric carboxymaltose (FCM). He was found to have severe hypophosphataemia, with further evaluation showing increased renal phosphate wasting and elevated serum levels of fibroblast-growth-factor 23 (FGF23). FCM was stopped and he was given high-dose oral iron supplementation, with no further episodes of hypophosphataemia. LEARNING POINTS: The carbohydrate moieties used in parenteral iron preparations are different, and may have a dose-dependent relationship with the development of hypophosphataemia.The mechanism by which hypophosphataemia occurs after parenteral iron replacement is related to increased serum levels of FGF23, which increases renal phosphate wasting.The serum phosphate levels of patients receiving parenteral iron replacement (especially ferric carboxymaltose or iron polymaltose) should be routinely monitored for hypophosphataemia, which is an under-diagnosed complication.

Impact of enhanced personal protective equipment on colonoscopy performance during the COVID-19 pandemic.

Background and study aims Using personal protective equipment (PPE) can reduce risk of disease transmission. During the COVID-19 pandemic, enhanced PPE (EPPE) is recommended when performing endoscopy. We aimed to evaluate the impact of EPPE on colonoscopy performance when compared to standard PPE (SPPE). Patients and methods A review of electronic medical records and endoscopy reports of consecutive patients who underwent colonoscopy during two similar one-month time periods (in 2019 and during the COVID-19 pandemic in 2020) was performed. SPPE was used in 2019 and EPPE was used in 2020. Patient clinical data and procedure-related information were captured and analyzed. The primary outcomes were time to cecum (TTC) and total procedure time. Secondary outcomes were adenoma detection rate (ADR), polyp detection rate (PDR) and cecal intubation rate (CIR). Statistical analysis was performed using STATA v16.1. Results Two hundred and forty-seven colonoscopy procedures were analyzed. Baseline demographics and indications for colonoscopy of patients in both groups were similar. There were no significant differences in median TTC (10.0 vs 10.0 min, P  = 0.524) or total procedure time (22.5 vs 23.0 min, P  = 0.946) between colonoscopy performed in SPPE and EPPE. The ADR, PDR and CIR were also similar. Conclusion Our findings suggest that use of EPPE does not affect colonoscopy performance.

Systems 1 and 2 thinking processes and cognitive reflection testing in medical students.

BACKGROUND: Diagnostic decision-making is made through a combination of Systems 1 (intuition or pattern-recognition) and Systems 2 (analytic) thinking. The purpose of this study was to use the Cognitive Reflection Test (CRT) to evaluate and compare the level of Systems 1 and 2 thinking among medical students in pre-clinical and clinical programs. METHODS: The CRT is a three-question test designed to measure the ability of respondents to activate metacognitive processes and switch to System 2 (analytic) thinking where System 1 (intuitive) thinking would lead them astray. Each CRT question has a correct analytical (System 2) answer and an incorrect intuitive (System 1) answer. A group of medical students in Years 2 & 3 (pre-clinical) and Years 4 (in clinical practice) of a 5-year medical degree were studied. RESULTS: Ten percent (13/128) of students had the intuitive answers to the three questions (suggesting they generally relied on System 1 thinking) while almost half (44%) answered all three correctly (indicating full analytical, System 2 thinking). Only 3-13% had incorrect answers (i.e. that were neither the analytical nor the intuitive responses). Non-native English speaking students (n = 11) had a lower mean number of correct answers compared to native English speakers (n = 117: 1.0 s 2.12 respectfully: p < 0.01). As students progressed through questions 1 to 3, the percentage of correct System 2 answers increased and the percentage of intuitive answers decreased in both the pre-clinical and clinical students. CONCLUSIONS: Up to half of the medical students demonstrated full or partial reliance on System 1 (intuitive) thinking in response to these analytical questions. While their CRT performance has no claims to make as to their future expertise as clinicians, the test may be used in helping students to understand the importance of awareness and regulation of their thinking processes in clinical practice.