Clinical utility of thiopurine metabolite monitoring in inflammatory bowel disease and its impact on healthcare utilization in Singapore.

Background and Aim: Thiopurines are recommended for maintenance of steroid-free remission (SFR) in inflammatory bowel disease (IBD). Thiopurine metabolite monitoring (MM) is increasingly used in the West but remains novel in Singapore, with limited information on its therapeutic and economic benefits. Hence, this study aims to investigate MM's clinical utility and its impact on healthcare resource utilization in Singaporean IBD patients. Methods: A retrospective observational study was conducted at Singapore General Hospital outpatient IBD Centre. Patients with IBD, baseline MM during 2014-2017, and weight-based thiopurine doses for ≥4 weeks were followed up for 1 year. Actions were taken to optimize therapy, and metabolite levels before and after the first action were documented. Outcomes assessed included SFR, no therapy escalation or surgery, healthcare resource utilization, and direct healthcare costs. Results: Ninety IBD patients (50 Crohn's disease, 40 ulcerative colitis) were included. Among them, 40% had baseline metabolite levels within therapeutic range, 31.1% sub-therapeutic, 21.1% supra-therapeutic, and 7.8% shunters. Repeated MM with subsequent dose optimization helped 67.2% of patients achieve therapeutic levels after 1 year. Overall, 87.8% of patients achieved SFR and 90% had no therapy escalation or surgery. Despite greater outpatient visits and laboratory investigations with MM, the median total healthcare costs at 1 year only increased marginally (S$6407.66 [shunters] vs S$5215.20 [supra-therapeutic] vs S$4970.80 [sub-therapeutic] vs S$4370.48 [control (within therapeutic range)], P = 0.592). Conclusion: MM guided timely therapy escalation for non-responders, identification of non-adherence, and reversal of shunting. Therefore, it is a useful clinical tool to optimize thiopurines without significantly increasing healthcare costs.

A quality improvement project reduces time spent at an inflammatory bowel disease infusion center with accelerated infliximab infusion protocol.

Background and Aim: Patients with inflammatory bowel disease (IBD) requiring infliximab frequently spend hours to attend treatment. Through quality improvement (QI) methodology, we aimed to shorten the time spent in the biologics infusion center using the accelerated infusion protocol and describe patient outcomes, safety, and associated cost savings. Methods: From September 2018 through December 2019, eligible IBD patients receiving infliximab were recruited. We implemented interventions including the accelerated infusion protocol, and modifying collection location of infliximab. Statistical process control charts were created. Patients' clinical outcome and cost savings data were analyzed using descriptive statistics and Pearson's chi-square. Results: During the study period, a total of 60 patients with IBD receiving infliximab were recruited. A total of 315 infusions were administered-152 were under accelerated infusion protocol and 163 under standard protocol. The mean infliximab infusion time was reduced by 47%, from 2.4 h (142 ± 14 min) to 1.2 h (75 ± 10 min) (142 min vs 75 min, P < 0.001), with total time spent in the infusion center reduced by 52%, from 3.6 h (214 ± 25 min) to 1.7 h (102 ± 14 min) (214 vs 106 min, P < 0.001). Three mild infusion-related reactions (3/152 = 1.97%) were recorded. Estimated cost savings over the 16-month project period was SGD $6721.4 (nursing) and SGD $23 560 (patients). A high level of satisfaction (4.84 out of 5) with the protocol was reported. Conclusion: Our QI project shortened the infliximab infusion time and total time spent in the infusion center, without compromising patient safety. Estimated cost savings were substantial. The protocol helps reduce work productivity loss.

Vaccinations and inflammatory bowel disease - a systematic review.

INTRODUCTION: Patients with inflammatory bowel disease(IBD) are at risk of infections, many of which are preventable with vaccinations. We performed a systematic review on various aspects of vaccination in IBD. METHODS: We searched PubMed, and EMBASE databases, through 31 January 2021. Primary outcomes included vaccination rates, predictors of vaccination, reasons of vaccination hesitancy and acceptance, and outcomes of intervention. Findings were presented with medians, ranges, and narrative synthesis. RESULTS: We included 33 observational studies comprising 146,918 patients and 681 physicians. The median vaccination rates of influenza, pneumococcal pneumonia, and hepatitis B vaccines were 42%(IQR, 28%-61.5%), 20%(IQR, 9%-38.5%), and 48%(IQR, 29%-53%), respectively. Uses of immunosuppressant, older age and physician recommendations have positive influence on vaccination rate. Lack of vaccine-related knowledge and awareness of need for vaccination are main reasons of vaccine hesitancy among patients and physicians. There was disagreement between gastroenterologists and primary-care physicians on whose responsibility to offer vaccination. Education was the sole intervention identified, with variable success. CONCLUSION: This systematic review demonstrates that the vaccination rates of IBD patients, similar to other chronic diseases, are suboptimal. Lack of vaccine-related knowledge and awareness of the need for vaccination are main reasons of vaccine hesitancy amongst patients and physicians. Education, though effective, was the only available intervention identified. Gastroenterologist could take the lead in educating, and initiating vaccination among IBD patients.

Health-related quality of life of patients with inflammatory bowel disease in Singapore.

BACKGROUND/AIMS: Inflammatory bowel disease (IBD) is associated with considerable impairment of patients' health-related quality of life (HRQoL). Knowledge of factors that significantly affect IBD patients' HRQoL can contribute to better patient care. However, the HRQoL of IBD patients in non-Western countries are limited. Hence, we assessed the HRQoL of Singaporean IBD patients and identified its determinants. METHODS: A prospective, cross-sectional study was conducted at Singapore General Hospital outpatient IBD Centre. The HRQoL of IBD patients was assessed using the short IBD questionnaire (SIBDQ), Short Form-36 physical and mental component summary (SF-36 PCS/MCS) and EuroQol 5-dimensions 3-levels (EQ-5D-3L) and visual analogue scale (VAS). Independent samples t-test was used to compare HRQoL between Crohn's disease (CD) and ulcerative colitis (UC). Determinants of HRQoL were identified through multiple linear regression. RESULTS: A total of 195 IBD patients (103 UC, 92 CD) with a mean disease duration of 11.2 years were included. There was no significant difference in HRQoL between patients with UC and CD. Factors that significantly worsened HRQoL were presence of active disease (b=-6.293 [SIBDQ], -9.409 [PCS], -9.743 [MCS], -7.254 [VAS]), corticosteroids use (b=-7.392 [SIBDQ], -10.390 [PCS], -8.827 [MCS]), poor medication adherence (b=-4.049 [SIBDQ], -1.320 [MCS], -8.961 [VAS]), presence of extraintestinal manifestations (b=-13.381 [PCS]), comorbidities (b=-4.531 [PCS]), non-employment (b=-9.738 [MCS], -0.104 [EQ-5D-3L]) and public housing (b=-8.070 [PCS], -9.207 [VAS]). CONCLUSIONS: The HRQoL is impaired in this Asian cohort of IBD. The magnitude of HRQoL impairment was similar in UC and CD. Clinical characteristics were better determinants of patients' HRQoL than socio-demographic factors. Recognizing the factors that impact patients' HRQoL would improve the holistic management of IBD patients.

Multicenter phase II study of sequential radioembolization-sorafenib therapy for inoperable hepatocellular carcinoma.

BACKGROUND: The safety and tolerability of sequential radioembolization-sorafenib therapy is unknown. An open-label, single arm, investigator-initiated Phase II study (NCT0071279) was conducted at four Asia-Pacific centers to evaluate the safety and efficacy of sequential radioembolization-sorafenib in patients with hepatocellular carcinoma (HCC) not amenable to curative therapies. METHODS: Sorafenib (400 mg twice-daily) was initiated 14 days post-radioembolization with yttrium-90 (90Y) resin microspheres given as a single procedure. The primary endpoints were safety and tolerability and best overall response rate (ORR) using RECIST v1.0.Secondary endpoints included: disease control rate (complete [CR] plus partial responses [PR] and stable disease [SD]) and overall survival (OS). RESULTS: Twenty-nine patients with Barcelona Clinic Liver Cancer (BCLC) stage B (38%) or C (62%) HCC received a median of 3.0 GBq (interquartile range, 1.0) 90Y-microspheres followed by sorafenib (median dose/day, 600.0 mg; median duration, 4.1 months). Twenty eight patients experienced ≥1 toxicity; 15 (52%) grade ≥3. Best ORR was 25%, including 2 (7%) CR and 5 (18%) PR, and 15 (54%) SD. Disease control was 100% and 65% in BCLC stage B and C, respectively. Two patients (7%) had sufficient response to enable radical therapy. Median survivals for BCLC stage B and C were 20.3 and 8.6 months, respectively. CONCLUSIONS: This study shows the potential efficacy and manageable toxicity of sequential radioembolization-sorafenib. TRIAL REGISTRATION: ClinicalTrials.gov NCT00712790.

A questionnaire survey of patient experience with the Rheumatology Monitoring Clinic in Singapore.

AIM: The concept of a pharmacist/advanced practice nurse (APN)-led Rheumatology Monitoring Clinic (RMC) is a novel service in Singapore; we therefore conducted a questionnaire survey of patient experience. METHODS: Patients attending the RMC were provided with a set of questionnaires. As a substudy, a separate questionnaire was given to the rheumatologists and therapists conducting the RMC. RESULTS: Of the 105 patients surveyed, a total of 97 (92.4%) patients were satisfied/strongly satisfied with the overall service, and none were dissatisfied; 96% felt that the pharmacists/APNs provided clear, detailed information about their disease and medication, while 92% of patients were confident they knew what side-effects were possible. Ninety-two percent and 93% of patients were more likely to adhere to treatment, and were willing to come back for follow-up at the RMC, respectively. There was no difference in patient satisfaction in the average Likert summed scores, between the pharmacists and APNs. Age, gender, ethnicity and underlying disease did not exert any influence on the responses. All the rheumatologists surveyed were satisfied with the patients' management and the professionalism of the therapists. They opined that the RMC freed up time for them to see more complex cases. All the pharmacists/APNs concurred that the referrals were appropriately selected. CONCLUSIONS: We established the acceptability of a non-physician-led clinic in our local setting and highlighted the usefulness of having a routine clinic for monitoring medication toxicity and patient education. The RMC received positive feedback from patients, rheumatologists and allied health therapists, with a high degree of satisfaction among the respondents.

Feasibility, cost-effectiveness and patients' acceptance of point-of-care INR testing in a hospital-based anticoagulation clinic.

Point-of-care (POC) coagulometers are increasingly used by patients for self-monitoring of oral vitamin K antagonists therapy. We studied the feasibility of introducing POC international normalised ratio (INR) testing in place of standard laboratory assays in a hospital-based anticoagulation clinic with 250 active patients. The CoaguChek XS system was first validated in 253 INR samples and found to have a correlation of r = 0.945 with standard assays. Variations increased with INR readings above 3.5 and this was chosen as the cutoff for acceptance of POC INR results. POC testing was done for 1,332 clinic visits during the subsequent 6-month study. Rate of rejections of INR over 3.5 was 4.3% (95% CI 3.3-5.5%). POC testing reduced clinic visit duration by 35 min (p < 0.001, 95% CI 25-45) without cost increments to patients or the laboratory. Among 232 respondents surveyed, 87.5% (95% CI 82.5-91.5%) preferred POC INR monitoring. Rates of thrombosis and major bleeding complications were 1.2% (95% CI 0.2-3.5%) and 0.4% (95% CI 0.01-2.2%), respectively. In conclusion, provided mechanisms are in place to address increased variations of INR at higher ranges, POC testing can be successfully implemented in busy hospital-based anticoagulation clinics.