JointAI: Joint Analysis and Imputation of Incomplete Data in R

Missing data occur in many types of studies and typically complicate the analysis. Multiple imputation, either using joint modelling or the more flexible fully conditional specification approach, are popular and work well in standard settings. In settings involving non-linear associations or interactions, however, incompatibility of the imputation model with the analysis model is an issue often resulting in bias. Similarly, complex outcomes such as longitudinal or survival outcomes cannot be adequately handled by standard implementations. In this paper, we introduce the R package JointAI, which utilizes the Bayesian framework to perform simultaneous analysis and imputation in regression models with incomplete covariates. Using a fully Bayesian joint modelling approach it overcomes the issue of uncongeniality while retaining the attractive flexibility of fully conditional specification multiple imputation by specifying the joint distribution of analysis and imputation models as a sequence of univariate models that can be adapted to the type of variable. JointAI provides functions for Bayesian inference with generalized linear and generalized linear mixed models and extensions thereof as well as survival models and joint models for longitudinal and survival data, that take arguments analogous to corresponding well known functions for the analysis of complete data from base R and other packages. Usage and features of JointAI are described and illustrated using various examples and the theoretical background is outlined.Comment: imputation, Bayesian, missing covariates, non-linear, interaction, multi-level, survival, joint model R, JAG

Exploring the relation of active surveillance schedules and prostate cancer mortality

Background: Active surveillance (AS), where treatment is deferred until cancer progression is detected by a biopsy, is acknowledged as a way to reduce overtreatment in prostate cancer. However, a consensus on the frequency of taking biopsies while in AS is lacking. In former studies to optimize biopsy schedules, the delay in progression detection was taken as an evaluation indicator and believed to be associated with the long-term outcome, prostate cancer mortality. Nevertheless, this relation was never investigated in empirical data. Here, we use simulated data from a microsimulation model to fill this knowledge gap. Methods: In this study, the established MIcrosimulation SCreening Analysis model was extended with functionality to simulate the AS procedures. The biopsy sensitivity in the model was calibrated on the Canary Prostate Cancer Active Surveillance Study (PASS) data, and four (tri-yearly, bi-yearly, PASS, and yearly) AS programs were simulated. The relation between detection delay and prostate cancer mortality was investigated by Cox models. Results: The biopsy sensitivity of progression detection was found to be 50%. The Cox models show a positive relation between a longer detection delay and a higher risk of prostate cancer death. A 2-year delay resulted in a prostate cancer death risk of 2.46%–2.69% 5 years after progression detection and a 10-year risk of 5.75%–5.91%. A 4-year delay led to an approximately 8% greater 5-year risk and an approximately 25% greater 10-year risk. Conclusion: The detection delay is confirmed as a surrogate for prostate cancer mortality. A cut-off for a “safe” detection delay could not be identified.</p

Child-Patient Perspective on Results after Correction of Sagittal Synostosis and the Difference between Child-Patient and Parent's Perspectives

Objective: This study assesses the level of child-patient satisfaction with the surgical result after scaphocephaly correction and the difference between child-patient and parents' perspectives. Methods: A questionnaire was sent out to children between 6 and 18 years old with isolated sagittal synostosis, who had undergone either a frontobiparietal remodeling or extended strip craniotomy, and separately to their parents. Results: The questionnaire was completed by 96 patients, 81.2% of the patients considered their head to be similar or slightly different from others. Despite the majority being satisfied with the outcome, 33% would change the shape of their head if they could. Patients who underwent extended strip craniotomy wanted to change the back of their head more often (P = 0.002), whereas patients who underwent frontobiparietal remodeling wanted to change their forehead (P = 0.005). The patients' own perspective on head shape was independent of the cephalic index (CI). However, patients with a relatively narrow CI received more remarks from others about their heads (P = 0.038). Parent and child agreement was 49.7% on average. Differences between child-patients and parents were found in reporting adaptive behavior. Conclusion: The majority of patients were satisfied with the outcome of their intervention. The child's perspective seems to be a valuable addition to evaluate sagittal synostosis surgery as it is independent of the CI and differentiates between different surgical techniques. In addition, the patient's perspective is comparable to the parent's perspective, but gives more details on adaptive behavior.</p

Child-Patient Perspective on Results after Correction of Sagittal Synostosis and the Difference between Child-Patient and Parent's Perspectives

Objective: This study assesses the level of child-patient satisfaction with the surgical result after scaphocephaly correction and the difference between child-patient and parents' perspectives. Methods: A questionnaire was sent out to children between 6 and 18 years old with isolated sagittal synostosis, who had undergone either a frontobiparietal remodeling or extended strip craniotomy, and separately to their parents. Results: The questionnaire was completed by 96 patients, 81.2% of the patients considered their head to be similar or slightly different from others. Despite the majority being satisfied with the outcome, 33% would change the shape of their head if they could. Patients who underwent extended strip craniotomy wanted to change the back of their head more often (P = 0.002), whereas patients who underwent frontobiparietal remodeling wanted to change their forehead (P = 0.005). The patients' own perspective on head shape was independent of the cephalic index (CI). However, patients with a relatively narrow CI received more remarks from others about their heads (P = 0.038). Parent and child agreement was 49.7% on average. Differences between child-patients and parents were found in reporting adaptive behavior. Conclusion: The majority of patients were satisfied with the outcome of their intervention. The child's perspective seems to be a valuable addition to evaluate sagittal synostosis surgery as it is independent of the CI and differentiates between different surgical techniques. In addition, the patient's perspective is comparable to the parent's perspective, but gives more details on adaptive behavior.</p

A digital intake tool to avert outpatient visits in a FIT-based colorectal cancer screening population:study protocol of a multicentre, prospective non-randomized trial - the DIT-trial

Background: Currently all participants of the Dutch colorectal cancer (CRC) screening program with a positive faecal immunochemical test (FIT) are seen at the outpatient clinic to assess their health status, receive information on colonoscopy and CRC risk, and provide informed consent. However, for many patients this information could probably also safely be exchanged in an online setting, in order to reduce the burden for patients, healthcare system, and environment. In this study we will evaluate if a face-to-face pre-colonoscopy consultation can be replaced by a Digital Intake Tool (DIT) in a CRC screening population. Methods: This is a prospective multicentre single-arm, non-randomized study with a non-inferiority design. The DIT will triage a total of 1000 participants and inform them about CRC risk, colonoscopy, sedation, and provide bowel preparation instructions. Participants identified as high-risk (i.e., red-triaged) will be contacted by phone or scheduled for an appointment at the outpatient clinic. The primary outcome measure will be adequate bowel preparation rate, defined as the proportion of participants with a Boston Bowel Preparation (BBPS) score ≥ 6. To compare our primary outcome, we will use colonoscopy data from 1000 FIT positive participants who visited the outpatient clinic for pre-colonoscopy consultation. Secondary outcomes will include participation rate, colonoscopy adherence rate, patient experience in terms of satisfaction and anxiety, knowledge transfer, number of outpatient visits that can be averted by the DIT, and cost-effectiveness of the tool. Ethical approval was obtained from the Medical Ethical Committee of the Erasmus Medical Center (MEC-2021-0098). Discussion: This study aims to assess if a face-to-face pre-colonoscopy consultation can be replaced by an eHealth assessment and education tool in a FIT-based CRC screening program. In case favourable results are established, the intervention evaluated in this study could significantly impact CRC screening programs, benefiting both patients and healthcare systems on a (inter)national scale. Additionally, it would enable more personalized care as the DIT can be easily customized and made feasible in other languages, thereby enhancing healthcare accessibility. Trial registration: Dutch Trial Register: NL9315 , date of registration: March 8th, 2021.</p

Impact of the Coronavirus Disease Pandemic on Health-Related Quality of Life of Patients with Inflammatory Bowel Disease

BACKGROUND: To learn from the crisis caused by the coronavirus disease (COVID-19) pandemic and be prepared for future pandemics, it is important to investigate the impact of this period on the wellbeing of patients with inflammatory bowel disease (IBD). AIMS: To describe the health-related quality of life (HRQoL) and disease control of IBD patients during the first wave of the COVID-19 pandemic in The Netherlands. METHODS: Between March 17 and July 1, 2020, patients aged 18 years and older with IBD from the Erasmus MC (Rotterdam, The Netherlands) were invited to complete online questionnaires at week 0, 2, 6 and 12. The Inflammatory Bowel Disease Questionnaire (IBDQ), the Inflammatory Bowel Disease Control-8 (IBD-control-8) and the numeric rating scale on fatigue were used. The evolution of the different outcomes over time was measured using mixed models. RESULTS: Of 1151 invited patients, 851 patients (67% CD and 33% UC or IBD-U) participated in the study (response rate 74%). No relevant changes in total scores were found over time for the IBDQ (effect estimate 0.006, 95% CI [− 0.003 to 0.015]) and IBD-control-8 (effect estimate 0.004, 95% CI [0.998–1.011]). There was a slight, increasing trend in fatigue scores over time (effect estimate 0.011, 95% CI [0.004, 0.019]). CONCLUSIONS: This first lock down due to the COVID-19 pandemic in The Netherlands did not impact on the HRQoL and disease control of patients with IBD. Up to date information may have contributed to a stable HRQoL in IBD patients even in an extreme period with restrictions and insecurities. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s10620-021-07118-8

Decreasing Trends in Intestinal Resection and Re-Resection in Crohn's Disease: A Nationwide Cohort Study

OBJECTIVE: To assess time trends in intestinal resection and re-resection in Crohn's disease (CD) patients. SUMMARY OF BACKGROUND DATA: CD treatment has changed considerably over the past decades. The effect of these advances on the necessity of intestinal resections and the risk of re-resection is unclear. METHODS: In this nationwide cohort study, adult CD patients with ileocolonic, small bowel, colon, or rectum resections between 1991 and 2015 were included. Data were retrieved from the Dutch nationwide network and registry of histopathology and cytopathology (PALGA). Time trends were analyzed with a broken stick model and Cox proportional hazard model with smoothing splines. RESULTS: The identified cohort comprised 8172 CD patients (3293/4879 male/female) in whom 10,315 intestinal resections were performed. The annual intestinal resection rate decreased nonlinearly from 22.7/100,000 CD patients (1991) to 2.5/100,000 (2015). A significantly steeper decrease was observed before 1999 (slope -1.56) as compared to subsequent years (slope -0.41) (P < 0.001). Analogous trends were observed for ileocolonic, small bowel, and colon resections. Overall cumulative risk of re-resection was 10.9% at 5 years, 18.6% at 10 years, and 28.3% at 20 years after intestinal resection. The hazard for intestinal re-resection showed a nonlinear decreasing trend, with hazard ratio 0.39 (95% confidence interval 0.36-0.44) in 2000 and hazard ratio 0.25 (95% confidence interval 0.18-0.34) in 2015 as compared to 1991. CONCLUSION: Over the past 25 years, intestinal resection rate has decreased significantly for ileocolonic, small bowel, and colonic CD. In addition, current postoperative CD patients are at 75% lower risk of intestinal re-resection

Adherence to a plant-based, high-fibre dietary pattern is related to regression of non-alcoholic fatty liver disease in an elderly population

Dietary lifestyle intervention is key in treating non-alcoholic fatty liver disease (NAFLD). We aimed to examine the longitudinal relation between well-established dietary patterns as well as population-specific dietary patterns and NAFLD. Participants from two subsequent visits of the Rotterdam Study were included. All underwent serial abdominal ultrasonography (median follow-up: 4.4 years) and filled in a food frequency questionnaire. Secondary causes of steatosis were excluded. Dietary data from 389 items were collapsed into 28 food groups and a posteriori dietary patterns were identified using factor analysis. Additionally, we scored three a priori dietary patterns (Mediterranean Diet Score, Dutch Dietary Guidelines and WHO-score). Logistic mixed regression models were used to examine the relation between dietary patterns and NAFLD. Analyses were adjusted for demographic, lifestyle and metabolic factors. We included 963 participants of whom 343 had NAFLD. Follow-up data was available in 737 participants. Incident NAFLD was 5% and regressed NAFLD was 30%. We identified five a posteriori dietary patterns (cumulative explained variation [R2] = 20%). The patterns were characterised as: vegetable and fish, red meat and alcohol, traditional, salty snacks and sauces, high fat dairy & refined grains pattern. Adherence to the traditional pattern (i.e. high intake of vegetable oils/stanols, margarines/butters, potatoes, whole grains and sweets/desserts) was associated with regression of NAFLD per SD increase in Z-score (0.40, 95% CI 0.15–1.00). Adherence to the three a priori patterns all showed regression of NAFLD, but only the WHO-score showed a distinct association (0.73, 95% CI 0.53–1.00). Hence, in this large elderly population, adherence to a plant-based, high-fibre and low-fat diet was related to regression of NAFLD

Increased Prevalence of Autoimmune Gastritis in Patients with a Gastric Precancerous Lesion

Background: Autoimmune gastritis (AIG), characterized with the presence of anti-parietal-cell antibodies (APCA), is a risk factor for gastric cancer. However, AIG may go underdiagnosed, especially in the case of H. pylori infection and the presence of gastric precancerous lesions (GPL), due to the ambiguous pathology and delayed symptom onset. Aim: Investigate the prevalence and characteristics of AIG in GPL patients. Methods:Prevalence of AIG was determined with the presence of APCA in patients with GPL (n = 256) and the control group (n = 70). Pathological characteristics and levels of gastrin 17 (G17), pepsinogen (PG) I and II and anti-Helicobacter pylori IgG were assessed in GPL cases, and the severity of intestinal metaplasia and gastric atrophy was scored by expert pathologists. Results: APCA positivity was observed in 18% of cases vs. 7% of controls (p = 0.033). Only 3/256 patients were previously diagnosed with AIG. The presence of APCA was associated with corpus-limited and extended GPL. A receiver operating curve analysis demonstrated that the G17 and PGI/II ratio could identify APCA-positive patients within GPL cases (AUC: 0.884). Conclusions: The prevalence of AIG is higher in patients with GPL but goes undiagnosed. Using G17 and PG I/II as diagnostic markers can help to identify patients with AIG and improve surveillance programs for patients with GPL.</p

Effect of novel endoscope cleaning brush on duodenoscope contamination

Background and aims:Current duodenoscope reprocessing protocols are insufficient to prevent contamination and require adaptations to prevent endoscopy-associated infections (EAI). This study aimed to investigate the effect of a new endoscope cleaning brush on the contamination rate of ready-to-use duodenoscopes. Methods:This retrospective before-and-after intervention study collected duodenoscope surveillance culture results from March 2018 to June 2022. Contamination was defined as ≥1 colony-forming units of gastrointestinal or oral microorganisms (MGO). In December 2020, an endoscope cleaning brush with a sweeper design was introduced as the intervention in the manual cleaning of duodenoscopes. A logistic mixed effects model was used to study the effects of the intervention. Results:Data were collected from 176 culture sets before the new brush's introduction and 81 culture sets after. Pre-introduction, culture sets positive with MGO comprised 45.5% (95% CI: 38.3%-52.8%, 80/176), decreasing to 17.3% (95% CI: 10.6%-26.9%, 14/81) after implementing the new brush. Compared to the former brush, duodenoscopes cleaned with the new brush had lower odds of contamination with MGO (aOR=0.25, 95% CI: 0.11-0.58, p=0.001).Conclusions:Use of the new brush in manual cleaning reduced contamination with MGO and is expected to prevent EAIs. These findings should be confirmed in future prospective randomized studies.</p