Quality of Surveillance Impacts the Colitis-Associated Advanced Neoplasia Risk: A Multicenter Case-Control Study.

BACKGROUND AND AIMS: Although colorectal cancer (CRC) surveillance is embedded in clinical inflammatory bowel disease (IBD) practice, a subset of patients still develops advanced neoplasia (AN) (high-grade dysplasia [HGD] and/or CRC). We aimed to assess the impact of surveillance quality on AN risk in IBD. METHODS: In this multicenter case-control study, we searched the Dutch nationwide pathology databank to identify IBD cases with AN and controls with indefinite or low-grade dysplasia. The surveillance colonoscopy preceding the index lesion (first indefinite for dysplasia [IND]/low-grade dysplasia [LGD] or AN) was used to assess the impact of surveillance quality. We assessed intervals, bowel preparation, cecal intubation, and absence of inflammation as primary quality indicators. In addition, we assessed chromoendoscopy, endoscopist expertise, hospital setting, and biopsy strategy. Associations of quality indicators with AN risk were determined with multivariable logistic regression analyses with Firth's correction. RESULTS: We included 137 cases and 138 controls. Delayed intervals (58.2% vs 39.6%) and active inflammation (65.3% vs 41.8%) were frequently present in cases and controls and were associated with AN (delayed interval: adjusted odds ratio [aOR], 2.00; 95% confidence interval [CI], 1.07-3.81; P = .03; active inflammation: aOR, 2.46; 95% CI, 1.33-4.61; P < .01). Surveillance compliant with primary quality indicators was associated with a reduced AN risk (aOR, 0.43; 95% CI, 0.22-0.91; P = .03), similar to chromoendoscopy (OR, 0.11; 95% CI, 0.01-0.89; P = .01). Other indicators were not significantly associated with AN. CONCLUSIONS: Surveillance compliant with primary quality indicators is associated with a reduced colitis-associated AN risk. Delayed surveillance intervals and active inflammation were associated with an increased AN risk. This underlines the importance of procedural quality, including endoscopic remission to optimize the effectiveness of endoscopic surveillance.

Increased Colorectal Neoplasia Risk in Patients with Inflammatory Bowel Disease and Serrated Polyps with Dysplasia.

BACKGROUND: The impact of serrated polyps on the advanced colorectal neoplasia (CRN) risk in inflammatory bowel disease (IBD) patients is unknown. Serrated polyps are histologically categorized as hyperplastic polyps (HPs), sessile serrated lesions (SSLs), and traditional serrated adenomas (TSAs). AIMS: We aimed (1) to characterize the serrated polyps in IBD patients, (2) to identify factors associated with the presence of serrated polyps in IBD, and (3) to assess the CRN risk in IBD patients with serrated polyps. METHODS: We established a retrospective cohort of IBD patients with and without colonic serrated polyps. Cox-regression analysis with time-dependent variables was used to compare advanced CRN risk in IBD patients with and without serrated polyps. RESULTS: Of the 621 enrolled IBD patients, 198 had a serrated polyp (92 HPs, 88 SSLs without dysplasia, 13 SSLs with dysplasia, and 5 TSAs). Independent factors associated with serrated polyps were ulcerative colitis (UC) (odds ratio (OR) 1.77, 95% confidence interval (CI) 1.19-2.62, p = 0.005), male gender (OR 1.63, 95% CI 1.11-2.40, p = 0.013), and older age (per year increase, OR 1.06, 95%CI 1.05-1.08, p < 0.001). TSAs and SSLs with dysplasia were risk factors for subsequent advanced CRN (HR 13.51, 95% CI 3.11-58.68, p < 0.001), while HPs (HR 1.98, 95% CI 0.46-8.60, p = 0.36) and SSLs without dysplasia (HR 0.87, 95% CI 0.11-6.88, p-0.89) did not impact the subsequent advanced CRN risk. CONCLUSIONS: UC, male gender and older age were associated with the presence of serrated polyps. The majority of serrated polyps (91%) were HPs and SSL without dysplasia and did not affect the CRC risk. However TSAs and SSLs with dysplasia, representing a small subgroup of serrated polyps (9%), were associated with subsequent advanced CRN.

Toward the Integration of Technology-Based Interventions in the Care Pathway for People with Dementia: A Cross-National Study.

BACKGROUND: The integration of technology-based interventions into health and care provision in our aging society is still a challenge especially in the care pathway for people with dementia. OBJECTIVE: The study aims to: (1) identify which socio-demographic characteristics are independently associated with the use of the embodied conversational agent among subjects with dementia, (2) uncover patient cluster profiles based on these characteristics, and (3) discuss technology-based interventions challenges. METHODS: A virtual agent was used for four weeks by 55 persons with dementia living in their home environment. RESULTS: Participants evaluated the agent as easy-to-use and quickly learnable. They felt confident while using the system and expressed the willingness to use it frequently. Moreover, 21/55 of the patients perceived the virtual agent as a friend and assistant who they could feel close to and who would remind them of important things. CONCLUSIONS: Technology-based interventions require a significant effort, such as personalized features and patient-centered care pathways, to be effective. Therefore, this study enriches the open discussion on how such virtual agents must be evidence-based related and designed by multidisciplinary teams, following patient-centered care as well as user-centered design approaches.

Usability and Acceptance of the Embodied Conversational Agent Anne by People With Dementia and Their Caregivers: Exploratory Study in Home Environment Settings.

BACKGROUND: Information and communication technologies are tools that are able to support cognitive functions, monitor health and movements, provide reminders to maintain residual memory abilities, and promote social support, especially among patients with dementia. Among these technologies, embodied conversational agents (ECAs) are seen as screen-based entities designed to stimulate human face-to-face conversation skills, allowing for natural human-machine interaction. Unfortunately, the evidence that such agents deliver care benefits in supporting people affected by dementia and their caregivers has not yet been well studied. Therefore, research in this area is essential for the entire scientific community. OBJECTIVE: This study aims to evaluate the usability and acceptability of the virtual agent Anne by people living with dementia. The study is also designed to assess the ability of target users to use the system independently and receive valuable information from it. METHODS: We conducted a 4-week trial that involved 20 older adults living with dementia and 14 family caregivers in home environment settings in Italy. This study used a mixed methods approach, balancing quantitative and qualitative instruments to gather data from users. Telemetry data were also collected. RESULTS: Older users were particularly engaged in providing significant responses and participating in system improvements. Some of them clearly discussed how technical problems related to speech recognition had a negative impact on the intention to use, adaptiveness, usefulness, and trust. Moreover, the usability of the system achieved an encouraging score, and half of the sample recognized a role of the agent Anne. This study confirms that the quality of automatic speech recognition and synthesis is still a technical issue and has room for improvement, whereas the touch screen modality is almost stable and positively used by patients with dementia. CONCLUSIONS: This study demonstrated the ability of target users to use the system independently in their home environment; overall, the involved participants shared good engagement with the system, approaching the virtual agents as a companion able to support memory and enjoyment needs. Therefore, this research provides data that sustain the use of ECAs as future eHealth systems that are able to address the basic and higher-level needs of people living with dementia. This specific field of research is novel and poorly discussed in the scientific community. This could be because of its novelty, yet there is an urgent need to strengthen data, research, and innovation to accelerate the implementation of ECAs as a future method to offer nonpharmacological support to community-dwelling people with dementia.

Prognostic Factors for Advanced Colorectal Neoplasia in Inflammatory Bowel Disease: Systematic Review and Meta-analysis.

BACKGROUND AND AIMS: Patients with inflammatory bowel disease (IBD) have an increased risk of colorectal cancer (CRC). We performed a systematic review and meta-analysis to identify all prognostic factors for advanced colorectal neoplasia (aCRN, high-grade dysplasia, or CRC) in patients with IBD. METHODS: A systematic literature search was conducted according to the Meta-analysis Of Observational Studies in Epidemiology (MOOSE) guidelines. Risk of bias was assessed using the Quality in Prognostic Studies tool. Random-effects models were created separately for odds and hazard ratios, different study designs, and univariable or multivariable data. The evidence for all prognostic factors was categorized as "weak", "moderate", or "strong", based on estimate of effect sizes, heterogeneity, and risk of bias. RESULTS: A total of 164 studies were included, allowing pooled analysis of 31 potential prognostic factors. In the univariable analysis, the evidence for extensive disease was classified as strong while evidence for low-grade dysplasia, strictures, primary sclerosing cholangitis, post-inflammatory polyps, family history of CRC, and ulcerative colitis versus Crohn's disease was considered moderate. Evidence for any dysplasia, colon segment resection, aneuploidy, male sex, and age was classified as weak. In addition, histologic inflammation was identified as a risk factor in multivariable analysis (weak evidence). The evidence for the protective factors colonoscopic surveillance, 5-Aminosalicylic Acid, thiopurines, and smoking was moderate in univariable analysis. Multivariable analysis provided weak evidence for statin use. CONCLUSIONS: In this systematic review and meta-analysis, we identified 13 risk factors and 5 protective factors for aCRN in IBD patients, based on univariable and/or multivariable pooled analyses. These findings might lay the groundwork for an improved CRC risk stratification-based surveillance in IBD.

Cross-cultural translation and validation of the IBD-control questionnaire in The Netherlands: a patient-reported outcome measure in inflammatory bowel disease.

BACKGROUND: There is a need for easy-to-use patient-reported outcome measures (PROMS) in inflammatory bowel disease (IBD) practice. The 'IBD-control' is a short IBD-specific questionnaire capturing disease control from the patient's perspective. The International Consortium for Health Outcomes Measurement (ICHOM) recommends the use of the IBD-control even though it has only been validated in the United Kingdom. We aimed to cross-culturally translate and validate the IBD-control in the Netherlands using IBDREAM, a prospective multicentre IBD registry. METHODS: Lack of ambiguity and acceptability were verified in a pilot patient group (n = 5) after forward-backward translation of the IBD-control. Prospective validation involved completion of the IBD-control, Short Form-36, short IBDQ and disease activity measurement by Physician Global Assessment (PGA) and Simple Clinical Colitis Activity Index or Harvey-Bradshaw Index. Test-retest (2-week repeat) was used for measuring reliability. RESULTS: Questionnaires were completed by 998 IBD patients (674 Crohn's disease, 324 ulcerative colitis). Internal consistency (Cronbach's alpha) was 0.82 for the sub-group of 8 questions (IBD-control-8-sub-score). Mean completion time was 105 s. Construct validity analyses demonstrated moderate-to-strong correlations of the IBD-control-8-subscore and the other instruments (0.49-0.81). Test-retest reliability for stable patients was high (intraclass correlation coefficient 0.95). The IBD-control-8-subscore showed good discriminant ability between the PGA categories (ANOVA, p<.001). Sensitivity to change analyses showed large effect sizes of 0.81-1.87 for the IBD-control-8 subscore. CONCLUSIONS: These results support the IBD-control as a rapid, reliable, valid and sensitive instrument for measuring disease control from an IBD patient's perspective in the Netherlands.

Increased risk of high-grade dysplasia and colorectal cancer in inflammatory bowel disease patients with recurrent low-grade dysplasia.

BACKGROUND AND AIMS: The impact of recurrent low-grade dysplasia (LGD) on the risk of advanced neoplasia (high-grade dysplasia and colorectal cancer) in inflammatory bowel disease (IBD) patients is unknown. In addition, it is unclear how a neoplasia-free period after index LGD impacts this risk. We aimed to determine whether recurrent LGD is a risk factor for advanced neoplasia development and to evaluate the impact of a neoplasia-free time period after initial LGD diagnosis on the advanced neoplasia risk. METHODS: This is a nationwide cohort study using data from the Dutch National Pathology Registry to identify all IBD patients with LGD and ≥1 follow-up colonoscopy between 1991 and 2010 in the Netherlands. Follow-up data were collected until January 2016. We compared the cumulative advanced neoplasia incidence between patients with and without recurrent LGD at first follow-up colonoscopy using log-rank analysis. We subsequently studied the impact of a neoplasia-free period after initial LGD on the advanced neoplasia incidence. RESULTS: We identified 4284 IBD patients with colonic LGD with a median follow-up of 6.4 years. Recurrent LGD was a risk factor for advanced neoplasia (hazard ratio, 1.66; 95% confidence interval, 1.22-2.25; P = .001). A neoplasia-free period of at least 3 years after LGD protected against advanced neoplasia. CONCLUSIONS: Recurrent LGD at follow-up colonoscopy after initial LGD was a risk factor for advanced neoplasia. A neoplasia-free period of at least 3 years after initial LGD was associated with a reduced subsequent risk of advanced neoplasia.

No Increased Risk of Colorectal Neoplasia in Patients With Inflammatory Bowel Disease and Postinflammatory Polyps.

BACKGROUND: Patients with inflammatory bowel disease (IBD) who have postinflammatory polyps (PIPs) may have an increased risk of developing colorectal neoplasia. Current guidelines recommend an intensified surveillance strategy in these patients, although the evidence for this recommendation is conflicting. The aim of our study was to assess whether IBD patients with PIPs are at increased risk of colorectal neoplasia. METHODS: We established a retrospective cohort in a tertiary IBD center with IBD patients undergoing colorectal cancer (CRC) surveillance in the current era. We compared cumulative incidences of colorectal neoplasia since IBD diagnosis between patients with and without PIPs and corrected for confounders. Second, we compared the risk of receiving a colectomy. RESULTS: In our cohort with >22 years of median follow-up, 154 of 519 patients had PIPs. PIPs were associated with extensive disease (odds ratio [OR], 2.76; 95% confidence interval [CI], 1.61-4.42; P < 0.001) and with more severe inflammation at colonoscopy (OR, 3.54; 95% CI, 2.28-5.50; P < 0.001). After correction for confounders, the presence of PIPs was not associated with development of colorectal neoplasia (hazard ratio [HR], 1.28; 95% CI, 0.85-1.93; P = 0.24) or with development of advanced neoplasia (HR, 1.38; 95% CI, 0.52-3.68; P = 0.52). There was a higher risk of colectomy in patients with PIPs (HR, 3.41; 95% CI, 1.55-7.54; P = 0.002). CONCLUSION: In this cohort, PIPs were associated with disease extent, inflammation, and higher rates of colectomy. However, the presence of PIPs was not associated with the development of neoplasia. These findings suggest that patients with PIPs may not need an intensified surveillance strategy.

Long-term Risk of Advanced Neoplasia After Colonic Low-grade Dysplasia in Patients With Inflammatory Bowel Disease: A Nationwide Cohort Study.

BACKGROUND AND AIMS: The long-term risk of high-grade dysplasia [HGD] and colorectal cancer [CRC] following low-grade dysplasia [LGD] in inflammatory bowel disease [IBD] patients is relatively unknown. We aimed to determine the long-term cumulative incidence of advanced neoplasia [HGD and/or CRC], and to identify risk factors for advanced neoplasia in a nationwide IBD cohort with a history of LGD. METHODS: This is a nationwide cohort study using data from the Dutch National Pathology Registry [PALGA] to identify all IBD patients with LGD between 1991 and 2010 in the Netherlands. Follow-up data were collected until January 2016. We determined the cumulative incidence of advanced neoplasia and identified risk factors via multivariable Cox regression analysis. RESULTS: We identified 4284 patients with colonic LGD with a median follow-up of 6.4 years after initial LGD diagnosis. The cumulative incidence of subsequent advanced neoplasia was 3.6, 8.5, 14.4 and 21.7%, after 1, 5, 10 and 15 years, respectively. The median time to develop advanced neoplasia after LGD was 3.6 years. Older age [≥ 55 years] at moment of LGD (hazard ratio [HR] 1.73, 95% confidence interval [CI] 1.44-2.06), male sex [HR 1.33, 95% CI 1.10-1.60], and follow-up at an academic [vs non-academic] medical centre [HR 1.37, 95% CI 1.07-1.76] were independent risk factors for advanced neoplasia following LGD. CONCLUSIONS: In a large nationwide cohort with long-term follow-up of IBD patients with LGD, the cumulative incidence of advanced neoplasia was 21.7% after 15 years. Older age at LGD [≥55 years], male sex and follow-up by a tertiary IBD referral centre were independent risk factors for advanced neoplasia development after initial LGD.

A randomized cross-over study on the blood pressure lowering effect of the combined passive head-up and -down movement with Device-Guided slow breathing.

Purpose: Baroreflex emerges as a therapeutic target of hypertension. We investigated blood pressure (BP) lowering effect of the combined passive head-up and -down movement with device-guided slow breathing in untreated mild hypertension or high-normal BP. Methods: In a randomized, cross-over trial, untreated subjects with an ambulatory systolic/diastolic BP of 125-140/80-90 mmHg and a clinic BP of 130-150/80-90 mmHg were randomized to intervention treatment with head movement and slow breathing or sham control, and then crossed over. Both treatments consisted of 1-week preparation, 2-week treatment, and 1-week recovery. During the 2-week treatment, subjects were treated for a session of 20 min/day. BP, pulse rate and respiration were measured before and after each treatment session. Ambulatory BP monitoring was performed at baseline and the end of the 2-week treatments' period, and home BP monitoring in the morning and evening for the whole 8-week follow-up period. Results: 14 subjects completed the study. The intervention treatment, compared to control, reduced respiration rate by -2.1 breaths/min (95% CI -2.9 to -1.2, p = .0001), but not clinic BP and pulse rate (p ≥ .67). The intervention treatment, compared to control, significantly reduced nighttime systolic/diastolic blood pressure by -5.63/-3.82 mm Hg (p ≤ .01) but not 24-h or daytime ambulatory blood pressure (p ≥ .69). Home BP decreased with the intervention treatment, but the between-treatment difference was not statistically significant (p ≥ .27). Conclusions: The combined head movement with slow breathing did not influence 24-h BP, but reduced nighttime BP in untreated mild hypertension or high-normal BP.

Consecutive negative findings on colonoscopy during surveillance predict a low risk of advanced neoplasia in patients with inflammatory bowel disease with long-standing colitis: results of a 15-year multicentre, multinational cohort study.

OBJECTIVES: Surveillance colonoscopy is thought to prevent colorectal cancer (CRC) in patients with long-standing colonic IBD, but data regarding the frequency of surveillance and the findings thereof are lacking. Our aim was to determine whether consecutive negative surveillance colonoscopies adequately predict low neoplastic risk. DESIGN: A multicentre, multinational database of patients with long-standing IBD colitis without high-risk features and undergoing regular CRC surveillance was constructed. A 'negative' surveillance colonoscopy was predefined as a technically adequate procedure having no postinflammatory polyps, no strictures, no endoscopic disease activity and no evidence of neoplasia; a 'positive' colonoscopy was a technically adequate procedure that included at least one of these criteria. The primary endpoint was advanced colorectal neoplasia (aCRN), defined as high-grade dysplasia or CRC. RESULTS: Of 775 patients with long-standing IBD colitis, 44% (n=340) had >1 negative colonoscopy. Patients with consecutive negative surveillance colonoscopies were compared with those who had at least one positive colonoscopy. Both groups had similar demographics, disease-related characteristics, number of surveillance colonoscopies and time intervals between colonoscopies. No aCRN occurred in those with consecutive negative surveillance, compared with an incidence rate of 0.29 to 0.76/100 patient-years (P=0.02) in those having >1 positive colonoscopy on follow-up of 6.1 (P25-P75: 4.6-8.2) years after the index procedure. CONCLUSION: Within this large surveillance cohort of patients with colonic IBD and no additional high-risk features, having two consecutive negative colonoscopies predicted a very low risk of aCRN occurrence on follow-up. Our findings suggest that longer surveillance intervals in this selected population may be safe.

Severity in polycystic liver disease is associated with aetiology and female gender: Results of the International PLD Registry.

BACKGROUND & AIMS: Polycystic liver disease (PLD) occurs in two genetic disorders, autosomal-dominant polycystic kidney disease (ADPKD) and autosomal-dominant polycystic liver disease (ADPLD). The aim of this study is to compare disease severity between ADPKD and ADPLD by determining the association between diagnosis and height-adjusted total liver volume (hTLV). METHODS: We performed a cross-sectional analysis with hTLV as endpoint. Patients were identified from the International PLD Registry (>10 liver cysts) and included in our analysis when PLD diagnosis was made prior to September 2017, hTLV was available before volume-reducing therapy (measured on computed tomography or magnetic resonance imaging) and when patients were tertiary referred. Data from the registry were retrieved for age, diagnosis (ADPKD or ADPLD), gender, height and hTLV. RESULTS: A total of 360 patients (ADPKD n = 241; ADPLD n = 119) met our inclusion criteria. Female ADPKD patients had larger hTLV compared with ADPLD (P = 0.008). In a multivariate regression analysis, ADPKD and lower age at index CT were independently associated with larger hTLV in females, whereas in males a higher age was associated with larger hTLV. Young females (≤51 years) had larger liver volumes compared with older females (>51 years) in ADPKD. CONCLUSION: Aetiology is presented as a new risk factor associated with PLD severity. Young females with ADPKD represent a subgroup of PLD patients with the most severe phenotype expressed in hTLV.

Short article: Recommendations on rectal surveillance for colorectal cancer after subtotal colectomy in patients with inflammatory bowel disease.

Approximately 30% of patients with ulcerative colitis require a colectomy during their disease course. This substantially reduces colorectal cancer risk, although it is still possible to develop colorectal neoplasia in the remaining rectum. Although clear and well-accepted surveillance guidelines exist for patients with inflammatory bowel disease with an intact colon, specific surveillance recommendations following colectomy are less clear. Here, we aim to summarize the prevalence, incidence, and risk factors for developing colorectal cancer in patients with inflammatory bowel disease who underwent subtotal colectomy with a permanent end ileostomy and rectal stump, or with ileorectal anastomosis. Subsequently, gained insights are integrated into a proposed endoscopic surveillance strategy of the residual rectum.