The MiniMed 780G automated insulin delivery system adapts to substantial changes in daily routine: Lessons from real world users during Ramadan.

AIM: To report on the effectiveness and safety of the MiniMed 780G automated insulin delivery system in real-world users during the month of Ramadan. MATERIALS AND METHODS: CareLink Personal data were extracted from MiniMed 780G system users from the Gulf region. Users were included if they had ≥10 days of sensor glucose data during the month of Ramadan 2022 as well as in the month before and after. For the main analysis, continuous glucose monitoring endpoints were aggregated per month and were reported by time of day (daytime: 05.31-18.00 h, and night-time). Additional analyses were performed to study the pace at which the algorithm adapts. RESULTS: Glycaemic control was well kept in the 449 included users (mean sensor glucose = 152.6 ± 18.7 mg/dl, glucose management indicator = 7.0 ± 0.4%, time in range = 70.7 ± 11.0%, time below 70 mg/dl = 2.3 ± 2.3%). Albeit some metrics differed from the month before (p < .0001 for all), absolute differences were very small and considered clinically irrelevant. During Ramadan, there was no increased risk of hypoglycaemia during daytime (time below 70 mg/dl = 2.3 ± 2.4%), time in range was highest during daytime (80.0 ± 10.7%, night: 60.4 ± 15.3%), while time above 180 mg/dl was highest during night-time (37.3 ± 16.3%, day: 17.7 ± 10.7%). The algorithm adapted immediately upon lifestyle change. CONCLUSION: The MiniMed 780G automated insulin delivery system is effective, safe and fast in adapting to the substantial changes that occur in the lifestyle of people with type 1 diabetes during Ramadan.

The significance of coefficient of variation as a measure of hypoglycaemia risk and glycaemic control in real world users of the automated insulin delivery MiniMed 780G system.

AIM: Use of the MiniMed 780G system (MM780G) can result in a reduction in mean and standard deviation (SD) of sensor glucose (SG) values. We assessed the significance of the coefficient of variation (CV) as a measure of hypoglycaemia risk and glycaemic control. MATERIALS AND METHODS: Data from 10 404 MM780G users were analysed using multivariable logistic regression to assess the contribution of CV to (a) hypoglycaemia risk, measured as not reaching target <1% for time below range (TBR), and (b) achieving targets of time-in-range (TIR) >70% and glucose management indicator <7%. CV was compared with SD and low blood glucose index. To assess the relevance of CV <36% as a therapeutic threshold, we identified the CV cut-off point that optimally discriminated users at risk of hypoglycaemia. RESULTS: The contribution of CV was the smallest in terms of risk of hypoglycaemia (vs. low blood glucose index and SD) and TIR and glucose management indicator targets (vs. SD). In all cases the models with SD showed the best fit. A CV <43.4% (95% CI: 42.9-43.9) was the optimal cut-off point with a correct classification rate of 87.2% (vs. 72.9% for CV <36%). CONCLUSION: For MM780G users, CV is a poor marker for hypoglycaemia risk and glycaemic control. We recommend using, for the former, TBR and whether the TBR target is met (and not using CV <36% as a therapeutic threshold for hypoglycaemia); for the latter, TIR, time above range, whether targets are met and a discrete description of mean SG and SD of SG values.

Twelve-month results of the ADAPT randomized controlled trial: Reproducibility and sustainability of advanced hybrid closed-loop therapy outcomes versus conventional therapy in adults with type 1 diabetes.

AIMS: To reassess the 6-month efficacy and to assess the 12-month sustained efficacy of the MiniMed™ 780G advanced hybrid closed-loop automated insulin delivery (AID) system compared to multiple daily injections plus intermittently scanned glucose monitoring (MDI+isCGM) in people with type 1 diabetes not meeting glucose targets. METHODS: The ADAPT study was a prospective, multicentre, open-label, randomized control trial in people with type 1 diabetes, with a glycated haemoglobin (HbA1c) concentration of at least 8.0% (64 mmol/mol), on MDI+isCGM therapy. After a 6-month study phase, participants randomized at baseline to MDI+isCGM switched to AID (SWITCH) while the others continued AID therapy (SUSTAIN) for an additional 6 months. The primary endpoint of this continuation phase was the within-group change in mean HbA1c between 6 and 12 months, with superiority in the SWITCH group and noninferiority in the SUSTAIN group (ClinicalTrials.gov: NCT04235504). RESULTS: A total of 39 SWITCH and 36 SUSTAIN participants entered the continuation phase. In the SWITCH group, HbA1c was significantly decreased by -1.4% (95% confidence interval [CI] -1.7% to -1.1%; P < 0.001) from a mean ± SD of 8.9% ± 0.8% (73.9 ± 8.6 mmol/mol) at 6 months to 7.5% ± 0.6% (58.5 ± 6.9 mmol/mol) at 12 months. Mean HbA1c increased by 0.1% (95% CI -0.05% to +0.25%), from 7.3% ± 0.6% (56.5 ± 6.7 mmol/mol) to 7.4% ± 0.8% (57.7 ± 9.1 mmol/mol) in the SUSTAIN group, meeting noninferiority criteria. Three severe hypoglycaemia events occurred in two SWITCH participants during the continuation phase. CONCLUSION: ADAPT study phase glycaemic improvements were reproduced and sustained in the continuation phase, supporting the early adoption of AID therapy in people with type 1 diabetes not meeting glucose targets on MDI therapy.

Real-world performance of the MiniMed 780G advanced hybrid closed loop system in Latin America: Substantial improvement in glycaemic control with each technology iteration of the MiniMed automated insulin delivery system.

AIM: We studied real-world performance of MiniMed (MM) 780G system users from Argentina, Brazil, Colombia and Chile (geographical analysis), and the effect of each technology iteration of the MM system on glycaemic control (technology iteration analysis). MATERIALS AND METHODS: CareLink data from August 2020 to September 2022 were extracted. Endpoints included continuous glucose monitoring metrics. For the geographical analysis, aggregated endpoints for MM780G system users were calculated. For the technology iteration analysis, MM780G system user outcomes were compared with outcomes when the same individuals were still using the MM640G or MM670G system. RESULTS: On average, 1025 MM780G system users from the geographical analysis were followed for 136 (SD 135) days, spent 91.5 (14.3)% in advanced hybrid closed loop, showed a glucose management indicator (GMI) of 6.7 (0.3)%, a time in range between 70 and 180 mg/dl (TIR) of 76.5 (9.0)%, and a time below range 70 mg/dl (TBR) of 2.7 (2.1)%. The percentage of users reaching targets of GMI <7%, TIR >70% and TBR <4% was 80.8%, 78.1% and 80.1%, respectively. The technology iteration analysis on users transitioning from MM640G to MM780G system (N = 381) showed 0.4% decrease in GMI (7.1% to 6.7%, p < .0001), 10.7% increase in TIR (65.9% to 76.6%, p < .0001), while TBR remained. The percentage of insulin delivered automatically increased as well (47.5%-57.7%, p < .0001). Users transitioning from MM670G system (N = 78) showed a similar but less pronounced pattern. CONCLUSIONS: Real-world Latin American MM780G users on average showed good glucose control, achieving international targets. Glycaemic control increased with every technology iteration of the MM system, providing more automation each time.

Ambient air quality as risk factor for microscopic colitis - A geographic information system (GIS) study.

BACKGROUND: Microscopic colitis (MC) is considered a multifactorial disease, strongly associated with smoking. However, little is known about the role of environmental factors such as ambient air pollution in MC pathophysiology. There is an overlap in components of cigarette smoke and ambient air pollution. Therefore, the aim of this study was to explore an independent association between ambient air quality and MC. METHODS: A case-control study was performed. MC cases in South Limburg, the Netherlands, diagnosed between 2000 and 2012, were retrieved from the national pathology registry and matched to non-MC controls from the same area based on age (±2 years) and gender. A stable residential address for ≥3 years was required. Residential land use, proximity to major road, and concentrations of air pollution compounds, were determined using a Geographic Information System (GIS). Univariate and multivariable regression analyses were corrected for age, gender and smoking status. RESULTS: In total, 345 MC cases (78.6% female) and 583 matched controls (77.2% female) were included. In the univariate analyses, the percentage of urban green within a 500 m buffer and residential proximity to the nearest highway were associated with MC (both p < 0.10). On the multivariable level only a higher age at diagnosis (OR 1.02, 95%-CI 1.01-1.04) and current smoking at index date (OR 4.30; 95%-CI 3.01-6.14) were significantly associated with MC. CONCLUSION: Based on the current findings, ambient air quality does not seem to be an important risk factor for MC, in contrast to the well-known risk factors age and current smoking.

Corticosteroid Sparing in Inflammatory Bowel Disease is More Often Achieved in the Immunomodulator and Biological Era-Results from the Dutch Population-Based IBDSL Cohort.

OBJECTIVES: Corticosteroid-free remission is an emerging treatment goal in the management of inflammatory bowel disease (IBD). In the population-based Inflammatory Bowel Disease South Limburg cohort, we studied temporal changes in corticosteroid use and assessed the corticosteroid-sparing effects of immunomodulators and biologicals in real life. METHODS: In total, 2,823 newly diagnosed patients with Crohn's disease (CD) or ulcerative colitis (UC) were included. Corticosteroid exposure and cumulative days of use were compared between patients diagnosed in 1991-1998 (CD: n=316, UC: n=539), 1999-2005 (CD: n=387, UC: n=527), and 2006-2011 (CD: n=459, UC: n=595). Second, the corticosteroid-sparing effects of immunomodulators and biologicals were assessed. RESULTS: Over time, the corticosteroid exposure rate was stable (54.0% in CD and 31.4% in UC), even as the cumulative corticosteroid use in the first disease year (CD: 83 days (interquartile range (IQR) 35-189), UC: 62 days (IQR 0-137)). On the long-term, a gradual decrease in cumulative corticosteroid use was seen in CD (era '91-'98: 366 days (IQR 107-841), era '06-'11: 120 days (IQR 72-211), P<0.01), whereas in UC an initial decrease was observed (era '91-'98: 184 days (IQR 86-443), era '99-'05: 166 days (IQR 74-281), P=0.03), and stabilization thereafter. Immunomodulator and biological users had a lower risk of requiring corticosteroids than matched controls in CD only (33.6% vs. 49.9%, P<0.01, and 25.7% vs. 38.2%, P=0.04, respectively). CONCLUSIONS: In a real-world setting, more recently diagnosed IBD patients used lower amounts of corticosteroids as of the second year of disease. For CD, a significant association was found with the use of immunomodulators and biologicals. These conclusions support the increasing use of these treatment modalities.

Improvements in the Long-Term Outcome of Crohn's Disease Over the Past Two Decades and the Relation to Changes in Medical Management: Results from the Population-Based IBDSL Cohort.

OBJECTIVES: Medical treatment options and strategies for Crohn's disease (CD) have changed over the past decades. To assess its impact, we studied the evolution of the long-term disease outcome in the Dutch Inflammatory Bowel Disease South Limburg (IBDSL) cohort. METHODS: In total, 1,162 CD patients were included. Three eras were distinguished: 1991-1998 (n=316), 1999-2005 (n=387), and 2006-2011 (n=459), and patients were followed until 2014. Medication exposure and the rates of hospitalization, surgery, and phenotype progression were estimated using Kaplan-Meier survival analyses and compared between eras by multivariable Cox regression models. Second, propensity score matching was used to assess the relation between medication use and the long-term outcome. RESULTS: Over time, the immunomodulator exposure rate increased from 30.6% in the era 1991-1998 to 70.8% in the era 2006-2011 at 5 years. Similar, biological exposure increased from 3.1% (era 1991-1998) to 41.2% (era 2006-2011). In parallel, the hospitalization rate attenuated from 65.9% to 44.2% and the surgery rate from 42.9% to 17.4% at 5 years, respectively (both P<0.01). Progression to a complicated phenotype has not changed over time (21.2% in the era 1991-1998 vs. 21.3% in the era 2006-2011, P=0.93). Immunomodulator users had a similar risk of hospitalization, surgery, or phenotype progression as propensity score-matched nonusers (P>0.05 for all analyses). Similar results were found for biological users (P>0.05 for all analyses). CONCLUSIONS: Between 1991 and 2014, the hospitalization and surgery rates decreased, whereas progression to complicated disease is still common in CD. These improvements were not significantly related to the use of immunomodulators and biologicals.

High Percentage of IBD Patients with Indefinite Fecal Calprotectin Levels: Additional Value of a Combination Score.

BACKGROUND AND AIM: Monitoring mucosal inflammation in inflammatory bowel disease (IBD) is of major importance to prevent complications and improve long-term disease outcome. The correlation of clinical activity indices with endoscopic disease activity is, however, moderate. Fecal calprotectin (FC) is a better predictor of mucosal inflammation, but values between 100 and 250 µg/g are difficult to interpret in clinical practice. We aimed to evaluate the occurrence of indefinite FC levels in a real-life IBD cohort and study the additional value of a combination of biochemical markers and clinical activity indices. METHODS: In total, 148 Crohn's disease (CD) and 80 ulcerative colitis (UC) patients visiting the outpatient clinic were enrolled. FC, clinical disease activity scored by the Harvey-Bradshaw index or Simple Clinical Colitis Activity Index, and C-reactive protein (CRP) were assessed. In a subset of patients, endoscopic activity was scored by the simple endoscopic score-Crohn's disease and Mayo endoscopic subscore. Clinical activity index, CRP, and FC were integrated in a combination score and compared with endoscopy. RESULTS: Indefinite FC values were present in 24% of CD and 15% of UC. In the cohort of patients with endoscopy scores available, the combination score predicted endoscopic disease activity in CD with a sensitivity of 83% and specificity of 69% [positive predictive value (PPV) 58%, negative predictive value (NPV) 89%]. In UC, this was 88 and 75% (PPV 93%, NPV 60%). CONCLUSIONS: A combination of FC with clinical activity indices or CRP may aid in classifying patients with indefinite disease activity according to FC alone.

Inflammatory bowel disease, cancer and medication: Cancer risk in the Dutch population-based IBDSL cohort.

The management of inflammatory bowel disease (IBD) has changed since the mid-1990s (e.g., use of thiopurines/anti-TNFα agents, improved surveillance programs), possibly affecting cancer risk. To establish current cancer risk in IBD, updates are warranted from cohorts covering this time span, and detailed enough to study associations with phenotype and medication. We studied intestinal-, extra-intestinal- and overall cancer risk in the Dutch population-based IBDSL cohort. In total, 1,157 Crohn's disease (CD) and 1,644 ulcerative colitis (UC) patients were diagnosed between 1991 and 2011, and followed until 2013. Standardized incidence ratios (SIRs) were calculated for CD and UC separately, as well as for gender-, phenotype-, disease duration-, diagnosis era- and medication groups. We found an increased risk for colorectal cancer in CD patients with colon involvement (SIR 2.97; 95% CI 1.08-6.46), but not in the total CD or UC population. In addition, CD patients were at increased risk for hematologic- (2.41; 1.04-4.76), overall skin- (1.55; 1.06-2.19), skin squamous cell- (SCC; 3.83; 1.83-7.04) and overall cancer (1.28; 1.01-1.60), whereas UC patients had no increased risk for extra-intestinal- and overall cancer. Finally, in a medication analysis on CD and UC together, long-term immunosuppression exposure (>12 months) was associated with an increased risk for hematologic cancer, non-Hodgkin lymphoma, SCC and overall cancer, and this increase was mainly attributed to thiopurines. IBD patients with long-term immunosuppression exposure can be considered as having a higher cancer risk, and our data support the advice in recent IBD guidelines to consider skin cancer screening in these patients.

Time in Tight Glucose Range in Type 1 Diabetes: Predictive Factors and Achievable Targets in Real-World Users of the MiniMed 780G System.

OBJECTIVE: We studied time in tight range (TITR) (70-140 mg/dL) in real-world users of the MiniMed 780G system (MM780G). RESEARCH DESIGN AND METHODS: CareLink Personal data were extracted (August 2020 to December 2022) to examine TITR and its relationship with time in range (TIR; 70-180 mg/dL), factors predicting higher TITR, and which TITR target is a reasonable treatment goal. RESULTS: The 13,461 users (3,762 age ≤15 years and 9,699 age >15 years) showed an average TITR of 48.9% in those age ≤15 years and 48.8% in the older group (vs. TIR 71.2% and 73.9%, respectively). Consistent use of a glucose target (GT) of 100 mg/dL and active insulin time (AIT) of 2 h were the most relevant factors predicting higher TITR (P < 0.0001). In users consistently applying these optimal settings, TITR was 56.7% in those age ≤15 years and 57.0% in the older group, and the relative impact of these settings on TITR was 60% and 86% greater than that on TIR, respectively. TITRs of ∼45% (age ≤15 years 46.3% and older group 45.4%), ∼50% (50.7% and 50.7%) and ∼55% (56.4% and 58.0%) were best associated with glucose management indicators <7.0%, <6.8%, and <6.5%, respectively. TITRs of >45%, >50%, and >55% were achieved in 91%, 74%, and 55% of those age ≤15 years and 93%, 81%, and 57% of older group users, respectively, at optimal settings. CONCLUSIONS: This study demonstrates that 1) mean TIR is high with a high mean TITR in MM780G users (>48%), 2) consistent use of optimal GT/AIT improves TITR (>56%), 3) the impact of these settings on TITR is larger than on TIR, and 4) a TITR target >50% is our suggested treatment goal.

Future of Time-in-Range Goals in the Era of Advanced Hybrid Closed-Loop Automated Insulin Delivery Systems.

The concept of maintaining blood glucose levels within the 70-180 mg/dL range, known as time-in-range, has raised questions regarding its representation of true physiological euglycemia. Some have speculated that focusing on the time spent within the 70-140 mg/dL range, introduced as time in tight range (TITR) through the International Consensus statement, could serve as a more precise metric for assessing normoglycemia in individuals with type 1 diabetes. This article delves into the current status of TITR as an emerging marker and explores how advanced hybrid closed-loop systems may offer a promising avenue for achieving this higher level of glycemic control.

Celebrating the Data from 100,000 Real-World Users of the MiniMed™ 780G System in Europe, Middle East, and Africa Collected Over 3 Years: From Data to Clinical Evidence.

Introduction: The present report celebrates the benchmarking of 100,000 MiniMed™ 780G system users in Europe, Middle East, and Africa (EMEA) and summarizes the major insights into the usability and outcomes of this system. Methods: Carelink Personal data (August 2020-August 2023) of users living in EMEA were analyzed. Continuous glucose monitoring-based endpoints were aggregated for (1) the full cohort and (2) a 12-month longitudinal cohort. Subanalyses were done for users on optimal settings (those spending ≥95% of time with glucose target of 100 mg/dL, and ≥95% of time with active insulin time of 2 h), for self-reported age groups (≤15 and ≥56 years) and for various countries/regions. Results: Data from 101,629 users (34 countries) were analyzed. Mean time in range (TIR) was 72.3%, glucose management indicator (GMI) was 7%, time below 70 mg/dL (TBR70) was 2.0% and time below 54 mg/dL (TBR54) was 0.4%. In terms of international targets, 59.6% of users achieved a GMI <7%, 62.5% a TIR >70%, 88.4% a TBR70 < 4%, and 90.0% a TBR54 < 1%. Data improved impressively in optimal setting users (TIR = 78.8%, and users reaching TIR >70% = 86.3%) while safety remained (TBR70 = 2.2% and TBR54 = 0.4%). Data showed consistency across self-reported age groups and geographies. In the longitudinal cohort, TIR reached 75.5% in the first month and remained 73.3% or higher over the 12-month period. Conclusion: Over 100,000 users of the MiniMed™ 780G system have demonstrated consistency in achieving target control of glycemia.

Simplified Meal Announcement Versus Precise Carbohydrate Counting in Adolescents With Type 1 Diabetes Using the MiniMed 780G Advanced Hybrid Closed Loop System: A Randomized Controlled Trial Comparing Glucose Control.

OBJECTIVE: We aimed to compare glucose control in adolescents with type 1 diabetes (T1D) using the MiniMed 780G system who used simplified meal announcement with those who used precise carbohydrate counting. RESEARCH DESIGN AND METHODS: This randomized controlled trial included 34 participants (age 12-18 years) with T1D who were on multiple daily injections or insulin pump and were scheduled to start using the MiniMed 780G system at Sidra Medicine in Qatar. After a 7-day run-in period, participants were randomly assigned to the fix group (simplified meal announcement by preset of three personalized fixed carbohydrate amounts) or the flex group (precise carbohydrate counting) and followed for 12 weeks. Between-group difference in time in range (TIR) was the primary end point. Secondary end points included HbA1c and other glycometrics. RESULTS: During the 12-week study phase, TIR was 73.5 ± 6.7% in the fix and 80.3 ± 7.4% in the flex group, with a between-group difference of 6.8% in favor of flex (P = 0.043). Time >250 mg/dL was better in the flex group (P = 0.012), whereas HbA1c (P = 0.168), time below range (P = 0.283), and time between 180 and 250 mg/dL (P = 0.114) did not differ. CONCLUSIONS: Adolescents using the MiniMed 780G system with a preset of three personalized fixed carbohydrate amounts can reach international targets of glycemic control. Therefore, it may be a valuable alternative to precise carbohydrate counting in users who are challenged by precise carbohydrate counting. Because carbohydrate counting further improves outcomes, these skills remain important for MiniMed 780G users.

Advanced Hybrid Closed Loop in Adult Population With Type 1 Diabetes: A Substudy From the ADAPT Randomized Controlled Trial in Users of Real-Time Continuous Glucose Monitoring.

BACKGROUND: This analysis reports the findings from a predefined exploratory cohort (cohort B) from the ADAPT (ADvanced Hybrid Closed Loop Study in Adult Population with Type 1 Diabetes) study. Adults with type 1 diabetes (T1D) with suboptimal glucose control were randomly allocated to an advanced hybrid closed-loop (AHCL) system or multiple daily injections of insulin (MDI) plus real-time continuous glucose monitoring (RT-CGM). METHODS: In this prospective, multicenter, exploratory, open-label, randomized controlled trial, 13 participants using MDI + RT-CGM and with HbA1c ≥8.0% were randomized to switch to AHCL (n = 8) or continue with MDI + RT-CGM (n = 5) for six months. Prespecified endpoints included the between-group difference in mean change from baseline in HbA1c, CGM-derived measures of glycemic control, and safety. RESULTS: The mean HbA1c level decreased by 1.70 percentage points in the AHCL group versus a 0.60 percentage point decrease in the MDI + RT-CGM group, with a model-based treatment effect of -1.08 percentage points (95% confidence interval [CI] = -2.17 to 0.00 percentage points; P = .0508) in favor of AHCL. The percentage of time spent with sensor glucose levels between 70 and 180 mg/dL in the study phase was 73.6% in the AHCL group and 46.4% in the MDI + RT-CGM group; model-based between-group difference of 28.8 percentage points (95% CI = 12.3 to 45.3 percentage points; P = .0035). No diabetic ketoacidosis or severe hypoglycemia occurred in either group. CONCLUSIONS: In people with T1D with HbA1c ≥8.0%, the use of AHCL resulted in improved glycemic control relative to MDI + RT-CGM. The scale of improvement suggests that AHCL should be considered as an option for people not achieving good glycemic control on MDI + RT-CGM.

Disease Activity Patterns of Crohn's Disease in the First Ten Years After Diagnosis in the Population-based IBD South Limburg Cohort.

BACKGROUND AND AIMS: Real-life data on long-term disease activity in Crohn's disease [CD] are scarce. Most studies describe disease course by using proxies, such as drug exposure, need for surgery or hospitalisations, and disease progression. We aimed to describe disease course by long-term disease activity and to identify distinctive disease activity patterns in the population-based IBD South Limburg cohort [IBDSL]. METHODS: All CD patients in IBDSL with ≥10 years follow-up [n = 432] were included. Disease activity was defined for each yearly quarter by mucosal inflammation on endoscopy or imaging, hospitalisation, surgery, or treatment adjustment for increased symptoms. Six distinct disease activity clusters were defined. Subsequently, the associations between clinical characteristics and the patterns were assessed using multivariable logistic regression models. RESULTS: On average, patients experienced 5.44 (standard deviation [SD] 3.96) quarters of disease activity during the first 10 years after diagnosis. Notably, 28.2% of the patients were classified to a quiescent pattern [≤2 active quarters in 10 years], and 89.8% of those never received immunomodulators nor biologics. Surgery at diagnosis (odds ratio [OR] 2.99; 95% confidence interval [CI] 1.07-8.34) and higher age [OR 1.03; 95% CI 1.01-1.06] were positively associated with the quiescent pattern, whereas inverse associations were observed for ileocolonic location [OR 0.44; 95% CI 0.19-1.00], smoking [OR 0.43; 95% CI 0.24-0.76] and need for steroids <6 months [OR 0.24; 95% CI 0.11-0.52]. CONCLUSIONS: Considering long-term disease activity, 28.2% of CD patients were classified to a quiescent cluster. Given the complex risk-benefit balance of immunosuppressive drugs, our findings underline the importance of identifying better predictive markers to prevent both over-treatment and under-treatment.

Laryngeal Carcinoma in Patients With Inflammatory Bowel Disease: Clinical Outcomes and Risk Factors.

BACKGROUND: Inflammatory bowel disease (IBD) patients are at increased risk for developing extra-intestinal malignancies, mainly due to immunosuppressive medication. The risk of developing head and neck cancer in immunosuppressed transplant patients is increased. The relation between IBD patients and laryngeal cancer (LC) remains unclear. We aimed (1) to identify risk factors in IBD patients for LC development and (2) to compare clinical characteristics, outcome, and survival of LC in IBD patients with the general population. METHODS: All IBD patients with LC (1993-2011) were retrospectively identified using the Dutch Pathology Database. We performed 2 case-control studies: (1) to identify risk factors, we compared patients with IBD and LC (cases) with the general IBD population; (2) to analyze LC survival, we compared cases with controls from the general LC population. RESULTS: We included 55 cases, 1800 IBD controls, and 2018 LC controls. Cases were more frequently male compared with IBD controls (P < 0.001). For ulcerative colitis (UC), cases were older at IBD diagnosis (P < 0.001). Crohn's disease (CD) cases were more frequently tobacco users (P < 0.001) and more often had stricturing (P = 0.006) and penetrating (P = 0.008) disease. We found no survival difference. Immunosuppressive medication had no impact on survival. CONCLUSIONS: Male sex was a risk factor for LC in IBD patients. Older age at IBD diagnosis was a risk factor for UC to develop LC. Tobacco use and stricturing and penetrating disease were risk factors for LC development in CD patients. Inflammatory bowel disease was not associated with impaired survival of LC. Immunosuppressive medication had no influence on survival.

Development and Validation of a Patient-reported Score to Screen for Mucosal Inflammation in Inflammatory Bowel Disease.

BACKGROUND AND AIMS: Patient-reported outcome measures [PROMs] assessing inflammatory bowel disease [IBD] activity are of interest for monitoring in clinical practice, telemedicine systems, or trials. Different PROMs for follow-up of disease activity are available; however, none was developed with endoscopy as gold standard. The objective of this study was to develop and validate a PROM to predict endoscopic disease activity, following the recommendations of the Food and Drug Administration. METHODS: During development, 178 IBD patients undergoing a colonoscopy were asked to fill out 13 clinical questions derived from the literature. During endoscopy, inflammation was assessed with the simplified endoscopic score for Crohn's disease [CD] and the Mayo endoscopic subscore for ulcerative colitis [UC]. Based on correlation with endoscopic inflammation, questions were reduced to a total of six for CD and five for UC. The newly developed Monitor IBD At Home questionnaire [MIAH] was validated in an independent cohort of 135 CD and 131 UC patients. Additionally, diagnostic accuracy of the MIAH combined with a calprotectin home test [CHT] was assessed. RESULTS: The MIAH-CD includes questions on rectal bleeding, mucus, stool frequency, urgency, fatigue, and patient-reported disease activity. The MIAH-UC contains items on rectal bleeding, stool frequency, urgency, abdominal pain, and patient-reported disease activity. Both questionnaires showed to be valid, reliable, and responsive to changes. The MIAH and CHT combined had a sensitivity, specificity, negative predictive value [NPV], and positive predicitive value [PPV] of 96.7%, 66.7%, 94.7%, and 76.3% for CD and of 88.2%, 81.4%, 95.6%, and 60.0% for UC, respectively, compared with endoscopy. CONCLUSIONS: The MIAH is the first PROM developed to predict endoscopic inflammation in IBD patients. A combination of this questionnaire and a CHT shows excellent diagnostic accuracy to screen for patients who need further assessment of disease activity, and can be used in daily practice, telemedicine systems, and trials.

Incidence and Classification of Postcolonoscopy Colorectal Cancers in Inflammatory Bowel Disease: A Dutch Population-Based Cohort Study.

BACKGROUND AND AIMS: Patients with inflammatory bowel disease [IBD] colitis are at increased risk for colorectal cancer [CRC]. We examined the proportion and most likely aetiology of potentially preventable postcolonoscopy CRCs [PCCRCs] in a population-based cohort. Furthermore, adherence to IBD surveillance guidelines was evaluated in both PCCRCs and the remainder of prevalent CRCs. METHODS: All IBD patients diagnosed from 1991 to 2011 in the South Limburg region of The Netherlands [i.e. IBDSL cohort] were included. CRC cases were cross-checked with the Dutch pathology database and cancer registry. PCCRCs were defined as cancers diagnosed within 6-60 months after a colonoscopy and were classified as attributable to 'inappropriate surveillance interval', 'inadequate bowel examination', 'incomplete resection', 'missed lesion' or 'newly developed cancer'. RESULTS: Twenty CRC cases were identified during 25,931 patient years of follow-up in 2,801 patients. The proportion of PCCRCs was 45.0%. Of these, 55.6% could be considered a 'missed lesion', while other possible aetiologies occurred only once. Considering both PCCRCs [n=9] and prevalent CRCs [n=11], ten were detected after publication of the surveillance guideline, but only three patients were enrolled. Moreover, 6 CRCs [30.0%] were detected before the recommended start of surveillance. CONCLUSIONS: In the IBDSL cohort, 45.0% of all CRCs were considered to be PCCRCs, mainly classified as missed lesions. Additionally, a large proportion of CRCs in our cohort were observed before a surveillance endoscopy was performed. Therefore, stringent adherence to IBD surveillance guidelines, improving endoscopy techniques and adjusting the surveillance program may lead to a decrease in CRC incidence.