Belgian Study Research Articles

Integration of Chronic Care in a Fragmented Healthcare System Comment on "Integration or Fragmentation of Health Care? Examining Policies and Politics in a Belgian Case Study".

The authors of "Integration or Fragmentation of Health Care? Examining Policies and Politics in a Belgian Case Study" present a fresh perspective on the inertia of integrated care (IC) implementation. They conclude that the decisive power in Belgium is fragmented and undermines efforts towards IC. As researchers in integrated heart failure (HF) care and active primary healthcare professionals, we comment on the three policy initiatives evaluated by Martens et al from a bottom-up perspective. A Learning Healthcare Network (LHCN) was established September 2019 to overcome fragmentation, the lack of evaluation and capacity loss each time a pilot project ends. This commentary wishes to illustrate that a LHCN can be a powerful meso-level mechanism to engage in alignment work and to overcome macro-level barriers that are often difficult to change and not supportive of IC.

Integration of Healthcare in Belgium: Insufficient, but There Is Hope Comment on "Integration or Fragmentation of Health Care? Examining Policies and Politics in a Belgian Case Study".

The maturity of integrated care in Belgium is rather low. The reasons are the country's complex organization, a lack of leadership and finances, an abundance of pilot projects, very long implementation and change processes, a healthcare system driven by providers and different cultures of action. However, new projects and ongoing research can help overcome these barriers. The primary care zones in Flanders, the National Hospital Plan and the Federal Plan to support mental health in particular are luxating opportunities. Well planned research is urgently needed to confirm the hope these projects arouse.

Clinical and microbiological evaluation of temocillin for bloodstream infections with Enterobacterales: a Belgian single-centre retrospective study

BackgroundExpanding the use of temocillin could be an important weapon in the fight against antimicrobial resistance. However, EUCAST defined clinical breakpoints for a limited number of species and only for urinary tract infections (UTI), including urosepsis but excluding severe sepsis and septic shock. Moreover, a dosage of 2 g q8h is advised in most cases.ObjectivesEvaluation of temocillin use for the treatment of bacteraemia, correlating clinical and microbiological outcomes with infection site, infection severity, temocillin dosage, Enterobacterales species and MIC.Patients and methodsAll adult patients with blood cultures positive for temocillin-susceptible Enterobacterales and treated with temocillin for ≥72 h from June 2018 until June 2021 were considered for inclusion. The primary outcome was clinical success, defined as resolution of infection signs, no relapse of the same infection and no antibiotic switch due to insufficient clinical improvement. The secondary outcome was microbiological success.ResultsIn total, 182 episodes were included [140 UTI versus 42 non-UTI, 171 Escherichia coli, Klebsiella species (except Klebsiella aerogenes) and Proteus mirabilis (EKPs) versus 11 non-EKPs]. Clinical and microbiological failure were low (8% and 3%, respectively). No difference in outcome was observed for dosages of 2 g q12h versus 2 g q8h, either for EKP versus non-EKP isolates or MIC values ≤8 versus 16 mg/L. Considering only bacteraemia episodes of UTI origin, using the 16 mg/L breakpoint, there was no difference in success rate between regimens of 2 g q12h and 2 g q8h.ConclusionsTemocillin 2 g q12h can be successfully used for the treatment of systemic UTI. Prospective studies are needed to assess outcomes and evaluate non-inferiority compared with other broad-spectrum antibiotics in non-UTI infections, including bacteraemia.

Back to Work After Bariatric Surgery? A Belgian Population Study.

Aside from an impact on health, obesity is also associated with higher social and economic costs such as impaired productivity, increased work absenteeism, and higher rates of unemployment. The aim of this study was to assess the effect of bariatric surgery on employment status in a large nationwide database, using data from all patients that underwent bariatric surgery in Belgium. This is a retrospective analysis of all Belgian patients that underwent bariatric surgery between 2014 and 2015. The work status of these patients was examined yearly: 4years before and 3years after surgery. Increased employment after surgery was defined (1) as a reduction in days of unemployment and incapacity and (2) as the resumption of work among the unemployed. In total, 16,276 patients were included. The number of working people rose from 49.7% before to 61.2% 3years after bariatric surgery, i.e., an increase of 11.5% between pre- and post-surgery. The largest improvement in reduction in unemployment was found in individuals who were absent from work for more than 9months, namely, a reduction from 13.4 to 7.2%. In the population of unemployed patients, 20.9% became employed after bariatric surgery. We found an increase in employment rate and a decrease in work incapacity and unemployment after bariatric surgery. Higher rates of employment after bariatric surgery may also contribute to an increased cost-effectiveness of bariatric surgery. It would be interesting to research possible targeting strategies to increase the employment rate even more after bariatric surgery.

Policy by Pilot? Learning From Demonstration Projects for Integrated Care Comment on "Integration or Fragmentation of Health Care? Examining Policies and Politics in a Belgian Case Study".

Analysis of policy implementation for chronic disease in Belgium highlights the difficulties of launching experiments for integrated care in a health system with fragmented governance. It also entreats us to consider the inherent challenges of piloting integrated care for chronic disease. Sociomedical characteristics of chronic disease -political, social, and economic aspects of improving outcomes - pose distinct problems for pilot projects, particularly because addressing health inequity requires collaboration across health and social sectors and a long-term, life-course perspective on health. Drawing on recent US experience with demonstration projects for health service delivery reform and on chronic disease research, I discuss constraints of and lessons from pilot projects. The policy learning from pilots lies beyond their technical evaluative yield. Pilot projects can evince political and social challenges to achieving integrated chronic disease care, and can illuminate overlooked perspectives, such as those of community-based organizations (CBOs), thereby potentially extending the terms of policy debate.

General practitioner contacts, hospitalizations, and nursing home transfers in older patients up to three years after new cancer diagnosis: Results from a large data linkage cohort study.

12041 Background: Long-term outcomes after cancer diagnosis in older persons are largely unexplored because of limited follow-up in clinical studies. By linking clinical data with population-based data, studying long-term outcomes in large cohorts becomes feasible. The current study aims to explore long-term outcomes in the care trajectory of older patients with cancer and to assess their association with baseline geriatric screening and assessment (GS/GA) results. Methods: A large cohort study of older patients with a new cancer diagnosis was set up by linking clinical, cancer registry and administrative health data based on a unique patient identifier. Clinical data were derived from a previously performed prospective multicentric Belgian study (2009-2015). Patients aged ≥ 70 years were screened with G8 followed by GA in case of an abnormal result (≤14/17). Tumor characteristics and vital status were derived from cancer registry data and long-term outcomes (general practitioner (GP) contacts, hospitalizations and nursing home transfers) from administrative health data. In patients that survived at least 3 months since inclusion, outcomes were assessed from the day after inclusion until 3 years after. Event rates were calculated using person-time at risk to allow for varying follow-up time. Patients were censored 3 months before death to exclude influence of end-of-life care. Results: After data linkage, 6,391 older patients with a new cancer diagnosis were available for this analysis. The median age was 77 (range: 70–100) and 59.8% was female. Diagnoses included solid (92.8%) and hematologic malignancies (7.2%). In the patients with a solid tumor, breast, colorectal and lung cancer were the most common and 20.1% of patients had stage IV. 64.3% of patients had an abnormal baseline G8 score. During the 3 year follow-up, 2,602 (40.7%) of the included patients died. In these 3 years, 5,985 (95.2%) patients had at least one contact with a GP and 4,634 (72.5%) had at least one new hospital admission (event rates in Table 1). Of the 3,724 patients living independently at inclusion and still alive after 3 years, 281 (7.5%) had been transferred to a nursing home and of those, 240 (85.4%) patients had an abnormal baseline G8 score. Conclusions: Older patients with an abnormal baseline G8 score have more GP contacts, hospital admissions and nursing home transfers in the 3 years following a new cancer diagnosis compared to patients with normal baseline G8 score. Baseline G8 could help identify patients at risk for higher long-term healthcare utilization.[Table: see text]

Biological site suitability for exposed self-regulating cultivation of blue mussel (Mytilus edulis): A Belgian case study

Several reasons, from stakeholder conflicts to water quality issues, are pushing bivalve cultivation to less accessible, exposed, and offshore waters. Because sheltered areas are absent along the Belgian coastline, the possibility to culture mussels with self-regulated systems in exposed conditions has been explored by various research projects. Farmers consider offshore environments unsuitable on the assumption that spat densities are low, and growth is insufficient for commercialization.This study evaluates the potential for self-regulated mussel cultivation in an exposed North Sea environment based on data collected from several research projects that evaluated the biological and technical feasibility of commercial longline cultivation in Belgium. The cultivation methods were variable, but always relied on wild spat that was grown to market size. No husbandry practices such as seed harvesting, thinning, grading, or socking were performed. This cultivation technique, also called self-regulating cultivation, reduces operational costs when extreme weather and exposed conditions limit handling.A 3D hydro-dynamic larvae dispersal model (LDM) was used to simulate the spatial variability in arrivals and the timing of the arrival peak. In addition, a locally validated metabolic model (DEB) for the blue mussel (M. edulis) was forced with 10 year optimized remote sensing observations (Copernicus, Sentinel-3/OLCI) to predict industry-relevant information such as site suitability, inter-annual growth variability, and cultivation time.This study concludes that exposed mussel cultivation near the Belgian east coast is characterised by fast growth. Mussels grown in this area will reach a marketable size (6 cm) after 12–15 months of cultivation, which is just in time for the peak consumption season (July-August). Moving offshore prolongs the cultivation cycles to 17–25 months, but provides more stable growth conditions with less inter-annual variability. When considering a cultivation period of 12 months, the mussels originating from offshore cultivation are comparable in size to the smaller Dutch “Smitse” and French "Bouchots".

Satisfied unlike me? How the perceived difference with close network contacts prevents radical and protest voting

Fitting with a common scheme across European democracies, the last election in Belgium led radical (left and right) parties to increase their vote share. One of the key drivers of the radical vote is political dissatisfaction (Droste 2011). Yet, the latter does not always translate into radical or protest voting behaviors. Using the 2019s RepResent Belgian Elections Study, we show the moderating effect of close social contacts in this relationship. For dissatisfied voters who believe that most contacts are similarly discontent, the probability to vote for radical parties (or, if not, to adopt other protest behaviors) is reinforced. However, the odds decrease the more they perceive their contacts different from themselves, i.e., as politically satisfied voters. Then, they become more likely to avoid protest/radical choices and to vote for institutionalized parties. Overall, our study yields findings showing that voting behaviors should be studied by considering also the voters’ social networks, which seem to exert a role in defining the acceptability of voting choices. What matters is not only how one perceives politics but also how one believes his close contacts perceive politics too.

Lipid-lowering therapy and risk-based LDL-C goal attainment in Belgium: DA VINCI observational study

Background Cardiovascular disease (CVD) is one of the leading causes of death in Belgium. Current strategies for the prevention and management of CVD focus on reducing low-density lipoprotein cholesterol (LDL-C) levels. This analysis assessed whether LDL-C goals, recommended by the European Society of Cardiology (ESC)/European Atherosclerosis Society (EAS) guidelines, were being achieved in a Belgian study population. Methods The cross-sectional, observational, DA VINCI study enrolled patients prescribed lipid-lowering therapy (LLT) between 21 June 2017 and 20 November 2018. Data for patients from Belgium were extracted for this country-specific analysis. Primary endpoint was the proportion of patients who achieved 2016 ESC/EAS risk-based LDL-C goals; attainment of 2019 risk-based LDL-C goals was evaluated post hoc. Results Of 497 enrolled patients, 41% were female and mean age was 68 years. Among subjects with an LDL-C measurement on stabilised LLT, moderate-intensity statin monotherapy was the most prescribed LLT regimen (59%). Overall, 63% of patients achieved their risk-based LDL-C goals according to the 2016 ESC/EAS guidelines. Among patients with established ASCVD, risk-based LDL-C goal attainment was higher in patients with peripheral arterial disease (53%) than patients with coronary (37%) and cerebrovascular disease (42%). According to the updated 2019 ESC/EAS guidelines, less than half (41%) of patients achieved their risk-based LDL-C goal. The proportion of primary and secondary prevention patients who achieved 2019 risk-based LDL-C goals was 59% and 18%, respectively. Conclusion These findings reveal a large gap between the LDL-C goals advocated by the ESC/EAS and the levels achieved in routine clinical practice in Belgium.

Neonatologists' Resuscitation Decisions at Birth for Extremely Premature Infants. A Belgian Qualitative Study.

ObjectiveDeciding whether initiating or withholding resuscitation at birth for extremely preterm infants (EPIs) can be difficult due to uncertainty on outcomes. Clinical uncertainty generates ethical uncertainty. Thus, physicians’ attitudes and perspectives on resuscitation of EPIs might influence resuscitation decisions. We aimed at understanding how neonatologists make clinical-ethical decisions for EPI resuscitation and how they perceive these decisions.MethodsWe performed a qualitative study using a constructivist account of grounded theory. Face-to-face, semi-structured in-depth interviews with neonatologists comprised data collection. For data analysis, we used the Qualitative Analysis Guide of Leuven.ResultsWe interviewed 20 neonatologists working in 10 hospitals in Belgium. Participants’ decision-making can be described as consensus-based, gestational age-based, contextualized, progressive, and shared. All participants agreed on the importance of using the consensus expressed in guidelines as a guidance for the decision-making, i.e., consensus-based. Consequently, all 20 participants use GA thresholds indicated in the guidelines, i.e., GA-based. However, they use these thresholds differently in their decisions. Few participants rigidly follow established thresholds. The vast majority reported using additional contextual factors as birthweight or parents’ wishes in the decision-making, rather than only the EPIs’ GA, i.e., contextualized. All participants agreed on the importance of involving the parents in the decision-making, i.e., shared, and indeed parents’ wishes were among the most valued factors considered in the decision-making. However, the extent to which parents were involved in the decision-making depended on the infant’s GA. Participants described a gray zone in which parents’ were viewed as the main decision-makers due to the high clinical uncertainty. This mean that participants tend to follow parents’ request even when they disagree with it. Outside the gray zone, physicians were viewed as the main decision-makers. This mean that, although parents’ wishes were still considered, counseling was more directive and the final decision was made by the physician.ConclusionAlthough an EPI’s GA remains the main factor guiding neonatologists’ resuscitation decisions, other factors are seriously considered in the decision-making process. All neonatologist participants agreed on the importance of involving parents in the decision-making. However, they involve parents differently depending on the EPI’s GA.

Belgium's Healthcare System: The Way Forward to Address the Challenges of the 21st Century Comment on "Integration or Fragmentation of Health Care? Examining Policies and Politics in a Belgian Case Study".

In this paper we have tried, starting from the results of an analysis of the functioning of integrated care in the Belgian Health System by Martens et al, to design a strategy that could contribute to better addressing the challenges of the 21st century in Belgium. We proposed health system changes at the macro-, meso- and micro-level. We focused on health policy development and organization of care, emphasizing the importance of a shift from a hospital-centric towards a primary care based approach. Special attention was paid to the need for institutional reforms, in order to facilitate the further development of interprofessional integrated care, that focuses on the achievement of the life-goals of a person.

Overcoming Political Fragmentation: The Potential of Meso-Level Mechanisms Comment on "Integration or Fragmentation of Health Care? Examining Policies and Politics in a Belgian Case Study".

Martens and colleagues' paper "Integration or Fragmentation of Health Care? Examining Policies and Politics in a Belgian Case Study," offers an in-depth examination of integrated care policy efforts in Belgium. A key finding in this case study was that political fragmentation proved too great an obstacle for integration efforts. In this commentary, I draw on the organizational behaviour and integrated care literatures to suggest how meso-level mechanisms related to sensemaking, distributive leadership, and evaluation could help overcome policy (or macro) level challenges like those experienced in Belgium. The commentary also suggests we need to consider and address both the process and normative challenges in these transformation efforts.

Real-World Estimation of First- and Second-Line Treatments for Diffuse Large B-Cell Lymphoma Using Health Insurance Data: A Belgian Population-Based Study.

We determined first- and second-line regimens, including hematopoietic stem cell transplantations, in all diffuse large B cell lymphoma (DLBCL) patients aged ≥20 yr (n = 1,888), registered at the Belgian Cancer Registry (2013–2015). Treatments were inferred from reimbursed drugs, and procedures registered in national health insurance databases. This real-world population-based study allows to assess patients usually excluded from clinical trials such as those with comorbidities, other malignancies (12%), and advanced age (28% are ≥80 yr old). Our data show that the majority of older patients are still started on first-line regimens with curative intent and a substantial proportion of them benefit from this approach. First-line treatments included full R-CHOP (44%), “incomplete” (R-)CHOP (18%), other anthracycline (14%), non-anthracycline (9%), only radiotherapy (3%), and no chemo-/radiotherapy (13%), with significant variation between age groups. The 5-year overall survival (OS) of all patients was 56% with a clear influence of age (78% [20–59 yr] versus 16% [≥85 yr]) and of the type of first-line treatments: full R-CHOP (72%), other anthracycline (58%), “incomplete” (R-)CHOP (47%), non-anthracycline (30%), only radiotherapy (30%), and no chemo-/radiotherapy (9%). Second-line therapy, presumed for refractory (7%) or relapsed disease (9%), was initiated in 252 patients (16%) and was predominantly (71%) platinum-based. The 5-year OS after second-line treatment without autologous stem cell transplantation (ASCT) was generally poor (11% in ≥70 yr versus 17% in <70 yr). An ASCT was performed in 5% of treated patients (n = 82). The 5-year OS after first- or second-line ASCT was similar (69% versus 66%). After adjustment, multivariable OS analyses indicated a significant hazard ratio (HR) for, among others, age (HR 1.81 to 5.95 for increasing age), performance status (PS) (HR 4.56 for PS >1 within 3 months from incidence), subsequent malignancies (HR 2.50), prior malignancies (HR 1.34), respiratory and diabetic comorbidity (HR 1.41 and 1.24), gender (HR 1.25 for males), and first-line treatment with full R-CHOP (HR 0.41) or other anthracycline-containing regimens (HR 0.72). Despite inherent limitations, patterns of care in DLBCL could be determined using an innovative approach based on Belgian health insurance data.

Sexual Activity and Physical Tenderness in Older Adults: Prevalence and Associated Characteristics From a Belgian Study

Despite the World Health Organization calling for sexuality to be recognized as an aspect of well-being, no studies have explored sexual activity and physical tenderness in older adults aged ≥ 75 years in Belgium or those aged ≥ 85 years worldwide. To assess the prevalence and predictors of sexual activity and physical tenderness in a sample of older adults. Using data from a Belgian cross-sectional study on sexual violence (UN-MENAMAIS), information on sexual activity, physical tenderness, and associated characteristics was collected during structured face-to-face interviews with older adults living in the community, assisted living facilities, or nursing homes. Cluster random probability sampling with a random route-finding approach was used to select the participants. Current sexual activity and physical tenderness in the previous 12 months, sociodemographic characteristics, chronological age, subjective age, number of sexual partners, sexual satisfaction, attitudes toward sexuality in later life, quality of life, and lifetime sexual victimisation. Among the 511 participants included, 50.3% were in a relationship, mainly living with their partner; 31.3% indicated they were sexually active; and 47.3% of sexually inactive participants reported having experienced forms of physical tenderness in the previous 12 months. Sexual activity was associated with the presence of a partner, satisfaction with sexual life, permissive attitudes regarding sexuality in later life, a younger age, and a lack of disability. Physical tenderness was associated with the presence of a partner, community residency, and permissive attitudes regarding sexuality in later life. Raising awareness among the general population, healthcare professionals, and older adults about sexuality in later life could contribute to ending this taboo and should therefore be a priority for society. Our study fills a gap in the literature regarding sexual activity and physical tenderness in older adults aged ≥ 70 years, including respondents aged up to 99 years. Additionally, we explored different forms of sexual expression beyond intercourse, and face-to-face interviews contributed to the quality of the collected data. The main limitation of this study was the sample size, although the findings were similar to recent statistical indicators in Belgium. One in 3 older adults aged ≥ 70 years living in Belgium are sexually active. These findings provide an opportunity to inform the general public and older adults about later life sexuality and to educate healthcare professionals about aging sexuality to increase discussions and avoid assumptions of asexuality in later life.

Disease mapping method comparing the spatial distribution of a disease with a control disease.

Small-area methods are being used in spatial epidemiology to understand the effect of location on health and detect areas where the risk of a disease is significantly elevated. Disease mapping models relate the observed number of cases to an expected number of cases per area. Expected numbers are often calculated by internal standardization, which requires both accurate population numbers and disease rates per gender and/or age group. However, confidentiality issues or the absence of high-quality information about the characteristics of a population-at-risk can hamper those calculations. Based on methods in point process analysis for situations without accurate population data, we propose the use of a case-control approach in the context of lattice data, in which an unrelated, spatially unstructured disease is used as a control disease. We correct for the uncertainty in the estimation of the expected values, which arises by using the control-disease's observed number of cases as a representation of a fraction of the total population. We apply our methods to a Belgian study of mesothelioma risk, where pancreatic cancer serves as the control disease. The analysis results are in close agreement with those coming from traditional disease mapping models based on internally standardized expected counts. The simulation study results confirm our findings for different spatial structures. We show that the proposed method can adequately address the problem of inaccurate or unavailable population data in disease mappinganalysis.

P496 Efficacy and safety of ustekinumab for chronic antibiotic refractory pouchitis: A Belgian open-label multicentre pilot study

Abstract Background Up to 10% of ulcerative colitis patients who undergo a proctocolectomy with ileal pouch-anal anastomosis, will develop chronic antibiotic refractory pouchitis (CARP). As there is a large unmet need in the management of these patients, we evaluated the efficacy and safety of induction therapy with ustekinumab (UST) for this indication. Methods We performed a prospective, Belgian, multicentre, open-label study of patients with CARP. Patients received a weight-range-based infusion of UST at baseline (6mg/kg) and one subcutaneous injection of 90mg UST at week 8. The first 4 weeks, ciprofloxacin 500mg BID was added as bridging therapy, but need of antibiotics thereafter was regarded as treatment failure. Patients underwent pouchoscopy at baseline and week 16, with assessment of the modified pouchitis disease activity index (mPDAI). The primary endpoint was the proportion of patients achieving clinically relevant steroid-free remission (mPDAI &amp;lt;5 and reduction by ≥2 points from baseline) at week 16. Secondary endpoints at week 16 were the proportion of patients achieving response (reduction of mPDAI by ≥2 points from baseline), change in symptomatic and endoscopic mPDAI subscore, and change in C-reactive protein (CRP) and faecal calprotectin levels compared to baseline. Descriptive statistics and paired nonparametric tests (Wilcoxon signed-rank) of changes from baseline were performed. Results We report the first 18 patients (56% male, median age 41.5 years, median time after surgery 11.2 years) who reached the primary endpoint assessment. Eleven (61.1%) patients had previously been treated with biologics (anti-TNF, n=8; vedolizumab, n=6; tofacitinib, n=1) for CARP (table 1). At week 16, clinically relevant steroid-free remission was reached in 27.8% and response in 50.0% of patients. A significant decrease in total mPDAI (8.0 (7.0–8.3) vs. 6.5 (3.8–9.0), p=0.04) and clinical subscore (3.0 (2.0–4.0) vs. 2.0 (1.0–3.3), p=0.04) but not endoscopic subscore (5.0 (4.0–6.0) vs. 4.0 (3.0–6.0), p=0.1) was observed at week 16 (figure 1). Faecal calprotectin (288.0 (154.8–634.8) vs. 145 (88.3–749.3) mg/kg, p=0.47) and CRP (4.8 (1.9–7.2) vs. 3.9 (1.9–8.9) mg/L, p=0.63) levels did however not decrease significantly (figure 2). Three serious adverse events (hospitalization for subobstruction, worsening pouchitis and choledocholithiasis) were recorded, but were not considered related to UST. Conclusion In this open-label pilot study in patients with CARP, induction therapy with UST showed a clinical effect in half of the patients, but was not associated with endoscopic improvement or changes in inflammatory biomarkers. Placebo-controlled studies are needed for further positioning UST in the treatment algorithm of CARP.

P576 Real-world effectiveness and safety of risankizumab in patients with moderate-to-severe multi-refractory Crohn’s disease: a Belgian multi-centric cohort study

Abstract Background In recent phase 3 trials, risankizumab (RZB), a humanised monoclonal IgG1 antibody targeting the interleukin 23 p19 subunit, proved to be superior to placebo in inducing and maintaining clinical remission and endoscopic response in patients with moderate-to-severe Crohn’s disease. In this study, we aimed to evaluate the effectiveness and safety of RZB in a real-world cohort of multi-refractory CD patients. Methods Adult CD patients from six Belgian IBD centres who initiated RZB prior to May 2021 as part of a medical need program were prospectively followed. Patients with an ostomy were excluded for the main analyses. The primary endpoint was steroid-free clinical remission at week 24 (average daily liquid stool frequency [SF] ≤2.8 and average abdominal pain [AP] score ≤1, both not worse than baseline). Secondary endpoints included clinical response, endoscopic remission, endoscopic response, biological remission, biological response, need for CD-related hospitalisation or surgery, and serious adverse events (definitions in Figure 1). Given that a follow-up endoscopy has not yet been performed in some patients, results are shown for both “all patients” (with non-responder imputation) and “as observed”. Results A total of 27 patients started RZB of whom 19 patients were eligible for this study with a minimal follow-up of 24 weeks (Table 1). Eight patients were excluded as they had an ostomy at time of RZB initiation. Eighteen patients (95%) had been exposed to more than 3 biologicals and 13 (68%) previously underwent a CD-related intestinal resection. By week 24, 7/19 (37%) and 7/19 (37%) patients achieved steroid-free clinical remission and endoscopic response, respectively (Figure 1). In the “as observed” analyses, these rates were 7/18 (39%) and 7/9 (78%), respectively (Figure 2). Five patients used concomitant steroids at baseline and were all able to stop it after a median of 10 weeks. Eventually, three patients had to be hospitalized for bowel resection (2 with placement of an ostomy) after a median of 24 weeks, two of them required earlier an emergent hospitalization due to flares of abdominal pain and bloody diarrhea. None of the patients experienced serious infections or intolerance. Based on physician global assessment, three out of eight patients with an ostomy did achieve clinical remission, and two other achieved clinical response. Endoscopic follow-up data were available in six patients, and three of them experienced endoscopic response. Conclusion In this real-world, multi-refractory cohort, clinical remission and endoscopic response were both observed by week 24 in more than one third of CD patients initiating RZB. RZB was well tolerated with no safety issues.

WGS- versus ORF5-Based Typing of PRRSV: A Belgian Case Study.

Porcine reproductive and respiratory syndrome virus (PRRSV) is the causative agent of one of the most widespread and economically devastating diseases in the swine industry. Typing circulating PRRSV strains by means of sequencing is crucial for developing adequate control strategies. Most genetic studies only target the highly variable open reading frame (ORF) 5, for which an extensive database is available. In this study, we performed whole-genome sequencing (WGS) on a collection of 124 PRRSV-1 positive serum samples that were collected over a 5-year period (2015–2019) in Belgium. Our results show that (nearly) complete PRRSV genomes can be obtained directly from serum samples with a high success rate. Analysis of the coding regions confirmed the exceptionally high genetic diversity, even among Belgian PRRSV-1 strains. To gain more insight into the added value of WGS, we performed phylogenetic cluster analyses on separate ORF datasets as well as on a single, concatenated dataset (CDS) containing all ORFs. A comparison between the CDS and ORF clustering schemes revealed numerous discrepancies. To explain these differences, we performed a large-scale recombination analysis, which allowed us to identify a large number of potential recombination events that were scattered across the genome. As PRRSV does not contain typical recombination hot-spots, typing PRRSV strains based on a single ORF is not recommended. Although the typing accuracy can be improved by including multiple regions, our results show that the full genetic diversity among PRRSV strains can only be captured by analysing (nearly) complete genomes. Finally, we also identified several vaccine-derived recombinant strains, which once more raises the question of the safety of these vaccines.

Diagnostic performance of automated MRI volumetry by icobrain DM for Alzheimer's disease in a clinical setting: A REMEMBER study

AbstractBackgroundMagnetic resonance imaging (MRI) has become important in the diagnostic work‐up of neurodegenerative diseases. icobrain dm, a CE‐labeled and FDA‐cleared automatic tool for brain volumetry using clinical MRI scans, has shown great potential in differentiating cognitively healthy controls (HC) from Alzheimer’s disease (AD) dementia (ADD) patients in selected research cohorts (Struyfs H, et al. (2020)).This study examined the diagnostic value of icobrain dm for AD in routine clinical practice, and compared it to FreeSurfer, one of the standard tools in neuroimaging research.MethodThe Belgian Dementia Council (BeDeCo) initiated a retrospective, multi‐center Belgian study (REMEMBER). Through automated volumetric analyses of whole brain, gray matter, cortical gray matter, frontal, parietal, occipital and temporal cortices, hippocampal volumes and lateral ventricles on real‐world clinical brain MRI T1w (n=820) images across the AD continuum, icobrain dm’s (v.4.4.0) ability to differentiate diagnostic groups in the AD continuum vs. HC was compared to FreeSurfer (v.6.0). Using icobrain dm’s automated volumetric output, we also investigated which combined brain volumes contributed most to establish an AD diagnosis and could differentiate between different stages of the disease.ResultThe final study population consisted of subjects from eight Belgian memory clinics, with HC (n=89), subjective cognitive decline (SCD, n=89), mild cognitive impairment (MCI, n=350), and ADD (n=250) (Table 1). icobrain dm outperformed FreeSurfer in processing time (15‐30 minutes vs. 9‐32 hours), robustness (0 failures vs. 67 failures due to complete abortion of analysis during topology corrections) and diagnostic performance (AUC, sensitivity and specificity) in univariate differentiation between HC and ADD patients (Figure 1, Table 2). Stepwise backward regression models showed improved diagnostic accuracy for pairwise group differentiations when combining multiple brain volumes computed by icobrain dm, with highest performance obtained for distinguishing HC from ADD patients (AUC=0.914; Specificity 83.0%; Sensitivity 86.3%) (Table 3).ConclusionAutomated volumetry has a diagnostic value for ADD diagnosis in routine clinical practice. Our findings indicate that icobrain dm’s automated volumetry can improve diagnostic certainty in a real‐world clinical setting with a significantly reduced processing time, robustness and diagnostic performance, as compared to FreeSurfer.

Impact of Maternal Pertussis Antibodies on the Infants' Cellular Immune Responses.

Maternal antibody interference of the infant's humoral immune responses raises some concern to the strategy of maternal Tdap (tetanus, diphtheria, acellular pertussis [aP]) vaccination. This study assessed the impact of maternal Tdap antibodies on the infant's pertussis-specific T lymphocyte responses following infant vaccination with an aP containing vaccine, in a term and preterm born cohort. Heparin samples (±0.5mL) were conveniently drawn from infants of a Belgian prospective cohort study (N = 79, NCT02511327), including Tdap vaccinated (Boostrix®) and nonvaccinated women (no Tdap vaccine in the last 5 years) that delivered at term or prematurely. Sampling was performed before and 1 month after primary (8-12-16 weeks) and booster vaccination (13 or 15 months) with DTaP-IPV-HB-PRP~T vaccine (Hexyon®). Pertussis toxin (PT)-specific CD3+, CD3+ CD4+ and CD3+ CD8+ lymphoblasts and their cytokine secretions were measured using a flow cytometric assay on whole blood (FASCIA) and multiplex technology (Meso Scale Discovery), respectively. In total, 57% of all infants were considered PT-specific CD3+ CD4+ lymphoblasts responders after primary and booster vaccination, whereas 17% were CD3+ CD8+ lymphoblast responders. Interferon (IFN)-γ, interleukin (IL)-13, IL-17A, and IL-5 cytokine secretions after primary and booster vaccination were indicative of a mixed T helper (Th) 1/Th2/Th17 cell profile. Lymphoblast and cytokine levels were comparable between term and preterm infants. Nonresponders for IL-13 after booster vaccination had higher maternal PT immunoglobulin G (IgG) levels at birth when compared to responders. Term and preterm born infants are capable of inducing Th1, Th2, and Th17 responses after aP vaccination, yet maternal vaccination modulate these responses. Evaluation of this effect in larger trials is needed.