6-Thioguanine nucleotide levels are associated with infliximab but not adalimumab levels in inflammatory bowel disease patients on combination therapy.

BACKGROUND: Thiopurine co-therapy with anti-tumour necrosis factor-alpha (anti-TNFα) agents is associated with higher anti-TNFα drug levels and reduced immunogenicity in inflammatory bowel disease (IBD). AIMS: We aimed to evaluate the association between 6-thioguanine nucleotide (6-TGN) and anti-TNFα levels and the optimal 6-TGN threshold level associated with higher anti-TNFα levels in combination therapy. METHODS: We performed a retrospective cross-sectional multicentre study of patients with IBD on combination anti-TNFα and thiopurine maintenance therapy between January 2015 and August 2021. Primary outcomes were infliximab and adalimumab levels. Secondary outcomes were antibodies to infliximab (ATI) or adalimumab (ATA). Univariable and multivariable linear regression were performed to identify variables associated with anti-TNFα levels. Receiver operator characteristic curves were used to define the optimal 6-TGN cut-off levels associated with therapeutic anti-TNFα levels. RESULTS: The study included 743 paired 6-TGN and anti-TNFα levels (640 infliximab and 103 adalimumab). 6-TGN levels were associated with infliximab levels, but not adalimumab levels, on univariable and multivariable regression. The optimal 6-TGN cut-off associated with therapeutic infliximab levels (≥5 mcg/mL) was 261 pmol/8 × 108 red blood cell (RBC) (area under the curve (AUC) = 0.57) for standard infliximab dosing and 227.5 pmol/8 × 108 RBC (AUC = 0.58) for escalated dosing. For therapeutic adalimumab levels (≥7.5 mcg/mL), the 6-TGN cut-off was 218.5 pmol/8 × 108 RBC (AUC = 0.59) for standard adalimumab dosing and 237.5 pmol/8 × 108 RBC (AUC = 0.63) for escalated dosing. CONCLUSION: 6-TGN levels were weakly associated with infliximab but not adalimumab levels in combination therapy. 6-TGN levels in the lower end of the therapeutic range (230-260 pmol/8 × 108 RBC) may be adequate to maintain higher infliximab levels, particularly with escalated infliximab dosing.

The impact of COVID-19 restrictions on the delivery of occupational therapy: How technology use affected practice during COVID-19 among occupational therapists in British Columbia.

INTRODUCTION: COVID-19 activity restrictions altered clinical practice around the world. Anecdotal evidence observed by the Canadian Association of Occupational Therapists - British Columbia (CAOT-BC) suggested a rapid adjustment to virtual care technologies occurred among occupational therapists in the initial restrictions. The purpose of the study was to determine the scope of how COVID-19 restrictions impacted the use of technology to provide client care in British Columbia. It will inform the future provision of occupational therapy in the developing technological landscape related to heath care provision. METHODS: This descriptive cross-sectional survey was completed using Qualtrics, an online survey tool. Registered occupational therapists received the survey via email invitations. The data were analysed using descriptive statistics in IBM SPSS Software. RESULTS: Of 342 participants, 98.4% reported increased technology use to support practice with the advent of COVID-19 restrictions. Those with some technology experience prior to COVID-19 reported higher intent to continue using technology following COVID-19 restrictions. Overall, occupational therapists were confident in their perceived abilities to use technology in their practice. Occupational therapist-related, client-related, and practice area considerations occurred with the rapid uptake of technology. Some components of practice were perceived to be improved and others impaired with the use of technology. CONCLUSION: Occupational therapists substantially increased their use of technology to enable ongoing client care during the Covid-19 restrictions. Implications for improvements and reduction of limitations in care delivery are substantial, given the intent to continue using technology going forward. These implications can be further explored to understand how the advances in occupational therapists' ability to use technology may impact rural or remote care, which practice areas may be most amenable technology use, and how policies and funding can facilitate effective and appropriate use of technology to support clinical care in public and private settings.

Barriers to medication adherence in a rural-urban dual economy: a multi-stakeholder qualitative study.

BACKGROUND: One of the most cost-effective treatments for secondary prevention of stroke and other non-communicable diseases is a long-term medication regimen. However, the complexities of medication adherence extend far beyond individual behavior change, particularly in low- and middle-income countries. The purpose of this study was to examine stakeholder perspectives on barriers to medication adherence for stroke patients in Beijing, China, identifying opportunities to improve care and policy in resource-constrained settings. METHODS: We conducted a qualitative, phenomenological analysis of data obtained from 36 individuals. Participants were patients; caregivers; healthcare providers; and representatives from industry and government, purposively selected to synthesize multiple perspectives on medication management and adherence for stroke secondary prevention in Beijing, China. Data was analyzed by thematic analysis across iterative coding cycles. RESULTS: Four major themes characterized barriers on medication adherence, across stakeholders and geographies: limitations driven by individual patient knowledge / attitudes; lack of patient-provider interaction time; lack of coordination across the stratified health system; and lack of affordability driven by high overall costs and limited insurance policies. CONCLUSIONS: These barriers to medication management and adherence suggest opportunities for policy reform and local practice changes, particularly for multi-tiered health systems. Findings from this study in Beijing, China could be explored for applicability in other low- and middle-income countries with urban centers serving large geographic regions.

Patient-reported Outcome Measures in Ileoanal Pouch Surgery: a Systematic Review.

OBJECTIVE: To summarise frequency, type, and heterogeneity of patient-reported outcomes measures [PROMs] in papers reporting on outcomes after ileal pouch anal anastomosis [IPAA]. BACKGROUND: Prevalence of ulcerative colitis [UC] has risen in Western countries, and one in three patients requires surgery. IPAA is a frequently performed procedure for UC, and a lack of standardisation is manifest in reporting outcomes for inflammatory bowel disease [IBD] despite the clear need for inclusion of PROMs as primary outcomes in IBD trials. METHODS: Scopus, Pubmed, and Web of Science databases were searched from January 2010 to January 2023 for studies investigating outcomes in IPAA surgery. The primary outcome was the proportion of studies reporting outcomes for IPAA surgery for UC, which included PROMs. RESULTS: The search identified a total of 8028 studies which, after de-duplication and exclusion, were reduced to 79 articles assessing outcomes after IPAA surgery. In all 44 [55.7%] reported PROMs, with 23 including validated questionnaires and 21 papers using authors' questions, 22 different PROMs were identified, with bowel function as the most investigated item. The majority of studies [67/79, 85%] were retrospective, only 14/79 [18%] were prospective papers and only two were [2.5%] randomised, controlled trials. CONCLUSIONS: Only half of the papers reviewed used PROMs. The main reported item is bowel function and urogenital, social, and psychological functions are the most neglected. There is lack of standardisation for use of PROMs in IPAA. Complexity of UC and of outcomes after IPAA demands a change in clinical practice and follow-up, given how crucial PROMs are, compared with their non-routine use.

Outcomes of a Comprehensive Specialist Inflammatory Bowel Disease Nursing Service.

BACKGROUND: Inflammatory bowel disease (IBD) is best managed by a multidisciplinary team within a dedicated IBD service. IBD nurses play an important role within this team. We aimed to evaluate the contribution of our comprehensive outpatient IBD nursing service on patient outcomes, quality of care, and healthcare costs. METHODS: We performed a retrospective review of all IBD nurse encounters with patients over a 12-month period from October 2020 to September 2021 at a tertiary IBD referral center. Each nurse encounter was classified with respect to its clinical context, activities, and outcomes. Descriptive statistics were used to characterize these encounters and an economic analysis was performed to estimate the cost savings to the hospital. RESULTS: A total of 2537 nurse encounters occurred with 682 patients; 41% of encounters were nurse-initiated contacts with patients and 34% were patient-initiated contacts with the nurse helpline (26% via email, 8% via telephone). Most encounters involved clinical assessments (66%), providing education, counseling or updates (47%), and reviewing investigation results (38%). A gastroenterologist was consulted for advice in 35% of contacts. An estimated 29 emergency department visits, 1925 outpatient clinic visits, and 137 general practitioner visits were avoided. After deducting costs incurred, a net estimated annual saving of up to AUD $570 838 was achieved. Nurses commonly facilitated faster access to investigations (29%), education provision (28%), delivery of biologic services (25%), and medication changes (19%). CONCLUSIONS: A comprehensive IBD nursing service is associated with improved patient outcomes and quality of care, and reduced healthcare costs. This study supports the expanding role of IBD nurses in a modern multidisciplinary IBD service and the need for greater funding and integration of IBD nurses into IBD services.

Prevalence of NUDT15 Genetic Variants and Incidence of Thiopurine-induced Leukopenia in Inflammatory Bowel Disease: A Systematic Review and Meta-analysis.

BACKGROUND AND AIMS: Nudix hydrolase 15 [NUDT15] genetic variants confer an increased risk of thiopurine-induced leukopenia [TIL]; however, their global prevalence in inflammatory bowel disease [IBD] patients is unknown. We aimed to evaluate the global prevalence of NUDT15 variants in IBD patients and incidence of TIL in these patients. METHODS: Six databases were searched from inception until July 2022. Studies reporting the frequency of any NUDT15 variant and/or frequency of leukopenia in adult IBD patients with these variants were included. A random effects model was performed to estimate the pooled prevalence of variants, incidence of early [≤8 weeks] and late [>8 weeks] leukopenia, and relative risk of developing leukopenia. RESULTS: Twenty studies comprising 5232 patients were included. The pooled prevalence of the *1/*3 c.415C > T C/T diplotype was 13% (95% confidence interval [CI]: 10-18%), *3/*3 c.415C > T T/T diplotype was 2% [95% CI: 1-2%], *1/*5 c.52G > A G/A diplotype was 2% [95% CI: 1-3%], and *1/*6 c.36_37insGGAGTC ins/- diplotype was 7% [95% CI: 4-12%]. The pooled prevalence of *1/*3 was high in Japanese [20%, 95% CI: 16-24%] and Chinese patients [18%, 95% CI: 12-27%]. The incidence of early leukopenia was 20% [95% CI: 16-26%] in *1/*3 patients, 99% [95% CI: 7-100%] in *3/*3 patients, and 49% [95% CI: 29-69%] in *1/*6 patients. The incidence of late leukopenia was 36% [95% CI: 26-49%] in *1/*3 patients. CONCLUSIONS: NUDT15 variants are common and strongly predict TIL in IBD patients. Pre-treatment NUDT15 genotyping should be considered particularly in Asian populations, to guide thiopurine dosing and prevent myelotoxicity.

Interventions to Improve Adherence to Preventive Care in Inflammatory Bowel Disease: A Systematic Review.

BACKGROUND: Preventive health measures reduce treatment and disease-related complications including infections, osteoporosis, and malignancies in patients with inflammatory bowel disease (IBD). Although guidelines and quality measures for IBD care highlight the importance of preventive care, their uptake remains variable. This systematic review evaluates interventions aimed at improving the rates of provision and uptake of preventive health measures, including vaccinations, bone density assessment, skin cancer screening, cervical cancer screening, and smoking cessation counseling. METHODS: We searched PubMed, MEDLINE, EMBASE, and CENTRAL for full text articles published until March 2021. Studies were included if they evaluated interventions to improve the provision or uptake of 1 or more preventive health measures in adult IBD patients and if they reported pre- and postintervention outcomes. RESULTS: In all, 4655 studies were screened, and a total of 17 studies were included, including 1 randomized controlled trial, 1 cluster-controlled trial, and 15 prospective interventional studies. A variety of interventions were effective in improving the rates of adherence to preventive health measures. The most common interventions targeted gastroenterologists, including education, electronic medical records tools, and audit feedback. Other interventions targeted patients, such as education, questionnaires, and offering vaccine administration at clinic visits. Few interventions involved IBD nurses or primary care physicians. CONCLUSIONS: A range of interventions-targeted at gastroenterologists, patients, or both-were effective in improving the provision and uptake of preventive care. Future studies should involve randomized controlled trials evaluating multifaceted interventions that target barriers to adherence and involve IBD nurses and primary care physicians.