Clinical course of suspected familial and sporadic idiopathic pulmonary fibrosis: Data from the PROOF-Next registry.

BACKGROUND AND OBJECTIVE: Real-life data on suspected familial fibrosis, defined as the occurrence of the disease in a patient younger than 50 and/or having at least one relative affected by pulmonary fibrosis remain scarce. METHODS: The Belgian and Luxembourg IPF registry (PROOF-Next) is a multicentric prospective longitudinal and observational study set in Belgium and Luxembourg. We compared characteristics and clinical course of patients with suspected familial pulmonary fibrosis (FPF) and sporadic IPF. RESULTS: We included 618 patients in the analysis, of whom 76 (12%) fulfilled criteria for FPF. They were significantly younger than sIPF (median age (range) 65 (43-87), vs. 72 (51-98), p = 0.0001). Male gender proportion and smoking status did not differ between groups, but the number of pack-year among current and former smokers was lower in FPF (20 vs. 25, p = 0.02). Besides, 87% of FPF and 76% of sIPF were treated with antifibrotic (p = 0.047). Baseline pulmonary function tests were similar in both groups, as well as median time before progression and transplant-free survival. Finally, genetic testing, performed in a minority, led to the identification of 10 telomerase-related gene variants. CONCLUSION: Although younger and exposed to less tobacco, patients with FPF show an equally aggressive progression as observed in sporadic IPF patients. These results warrant early referral of FPF patients to expert centres for optimal management.

Explaining the formation of a plateau in rotavirus vaccine impact on rotavirus hospitalisations in Belgium.

BACKGROUND: Observational data on the reduction in hospitalisations after rotavirus vaccine introduction in Belgium suggest that vaccine impact plateaued at an unexpectedly high residual hospitalisation rate. The objective of this analysis was to identify factors that influence real-world vaccine impact. METHODS: Data were collected on hospitalisations in children aged ≤ 5 years with rotavirus disease from 11 hospitals since 2005 (the RotaBIS study). The universal rotavirus vaccination campaign started late in 2006. A mathematical model simulated rotavirus hospitalisations in different age groups using vaccine efficacy and herd effect, influenced by vaccine coverage, vaccine waning, and secondary infection sources. The model used optimisation analysis to fit the simulated curve to the observed data, applying Solver add-in software. It also simulated an 'ideal' vaccine introduction maximising hospitalisation reduction (maximum coverage, maximum herd effect, no waning), and compared this with the best-fit simulated curve. Modifying model input values identified factors with the largest impact on hospitalisations. RESULTS: Compared with the 'ideal' simulation, observed data showed a slower decline in hospitalisations and levelled off after three years at a higher residual hospitalisation rate. The slower initial decline was explained by the herd effect in unvaccinated children. The higher residual hospitalisation rate was explained by starting the vaccine programme in November, near the rotavirus seasonal peak. This resulted in low accumulated vaccine coverage during the first rotavirus disease peak season, with the consequential appearance of secondary infection sources. This in turn reduced the herd effect, resulting in a diminished net impact. CONCLUSIONS: Our results indicate that countries wishing to maximise the impact of rotavirus vaccination should start vaccinating well ahead of the rotavirus seasonal disease peak. This maximises herd effect during the first year leading to rapid and high reduction in hospitalisations. Secondary infection sources explain the observed data in Belgium better than vaccine waning.

Infections and hospital bed-days among aging adults: A five-year retrospective study in a Belgian general hospital.

Background: Infectious disease in aging adults (≥61 years) often occurs in combination with other health conditions leading to long hospital stays. Detailed studies on infection in aging adults investigating this problem are sparse. Aim: To quantify the effect of primary and secondary diagnosed infections on hospitalization bed-days among aging adult patients. Design: Retrospective patient-file study. Setting: Ziekenhuis Netwerk Antwerpen (ZNA) Hospital, a 1,858-bed general hospital in Belgium, with 364 beds allocated to geriatric patients. Data source: Database of hospitalized adult patients aged ≥61 years. Methods: All adult patients aged ≥61 years hospitalized on two wards, Geriatrics and Pulmonology, from 2010 to 2014 were included. Primary diagnosed infections were defined as infections known at entry to be treated first. Secondary diagnosed infections included infections known at entry but treated in parallel to primary non-infectious causes of entry, infections unknown at entry, and hospital-acquired (nosocomial) infections. Data were analyzed by patient age, gender, year, ward type, bed-days of hospitalization, infection rates, and seasonality. Results: There were 3,306 primary diagnosed infections (18%) and 14,758 secondary infections (82%) identified in the two wards combined (54.7% of all hospital stays at those 2 wards). Secondary diagnosed infections accounted for a significantly higher proportion of hospitalizations in both wards (+40% for Geriatric ward; +20% for Pulmonology ward; p < 0.001) and were associated with a significantly longer average hospital stay (+4 days for Geriatric ward; +5 days for Pulmonology ward; p < 0.001). Nosocomial infections (12% for Geriatric ward; 7% for Pulmonology ward) were associated with particularly high bed-days of hospitalization, at approximately +15 days and +12 days on Geriatric and Pulmonology wards, respectively. Both wards showed marked seasonality for respiratory infections with winter peaks. Conclusion: Real-world data showed that secondary diagnosed infections in aging adults imposed a high burden on hospital care along with longer hospital stays. This hampered bed availability during peak seasons.

Complete pathological response to neoadjuvant treatment is associated with better survival outcomes in patients with soft tissue sarcoma: Results of a retrospective multicenter study.

BACKGROUND: Locally advanced soft tissue sarcoma (STS) management may include neoadjuvant or adjuvant treatment by radiotherapy (RT), chemotherapy (CT) or chemoradiotherapy (CRT) followed by wide surgical excision. While pathological complete response (pCR) to preoperative treatment is prognostic for survival in osteosarcomas, its significance for STS is unclear. We aimed to evaluate the prognostic significance of pCR to pre-operative treatment on 3-year disease-free survival (3y-DFS) in STS patients. METHODS: This is an observational, retrospective, international, study of adult patients with primary non-metastatic STS of the extremities and trunk wall, any grade, diagnosed between 2008 and 2012, treated with at least neoadjuvant treatment and surgical resection and observed for a minimum of 3 years after diagnosis. The primary objective was to evaluate the effect of pCR. (≤5% viable tumor cells or ≥95% necrosis/fibrosis) on 3y-DFS. Effect on local recurrence-free survival (LRFS), distant recurrence-free survival (MFS) overall survival (OS) at 3 years was also analyzed. Statistical univariate analysis utilized chi-square independence test and odds ratio confidence interval (CI) estimate, multivariate analysis was performed using LASSO. RESULTS: A total of 330 patients (median age 56 years old, range:19-95) treated by preoperative RT (67%), CT (15%) or CRT (18%) followed by surgery were included. pCR was achieved in 74/330 (22%) of patients, of which 56/74 (76%) had received RT. 3-yr DFS was observed in 76% of patients with pCR vs 61% without pCR (p < 0.001). Multivariate analysis showed that pCR is statistically associated with better MFS (95% CI, 1.054-3.417; p = 0.033), LRFS (95% CI, 1.226-5.916; p = 0.014), DFS (95% CI, 1.165-4.040; p = 0.015) and OS at 3 years (95% CI, 1.072-5.210; p = 0.033). CONCLUSIONS: In a wide, heterogeneous STS population we showed that pCR to preoperative treatment is prognostic for survival.

Lessons Learned from Long-Term Assessment of Rotavirus Vaccination in a High-Income Country: The Case of the Rotavirus Vaccine Belgium Impact Study (RotaBIS).

INTRODUCTION: The rotavirus (RV) vaccine Belgium Impact Study (RotaBIS) evaluated the vaccine effect on RV-related hospital care in children up to 5 years old over a period of 13 years. Different forces were identified that influence the reduction in hospital care. Our analysis aims to report on the current RotaBIS dataset and explore through model simulation whether, how, and when the results could have been improved. METHODS: As performed in previous assessments, this analysis evaluated RV-related events per year, per age group, RV nosocomial infections, hospitalization duration, and herd effect. It subsequently identified results that were surprising or unexpected. To know whether those data could have been improved through specific interventions, we developed a model with the forces acting on the disease transmission and the vaccine effect on RV-related hospital care. Scenario analysis of the forces should explain the current findings and identify ways to optimize the results. RESULTS: The RotaBIS data show that annual RV-related hospital cases (n = 1345 pre-vaccination) dropped by 70% (95% confidence interval [CI] 66-74%) by year 5 (n = 395) after vaccine introduction, and by 84% (95% CI 79-89%) by year 10 (n = 217). The herd effect during the first year was limited to 14% extra gain. During the last 5 years, small disease increases were seen biennially. The simulation model indicates that higher vaccine coverage of the major transmitters during the peak season of the first year of vaccination could have reduced RV-related hospital care by nearly 90% at 5 and 10 years after vaccine introduction owing to a higher herd effect. The smaller peaks observed in recent years would have been dramatically reduced. CONCLUSION: The current RotaBIS data show a maintained reduction, around 76%, in RV hospitalization cases. Simulations show that these results could have been improved to an important extent with a more optimal initiation of the vaccination program. TRIAL REGISTRATION: ClinicalTrials.gov identifier, NCT01563146 and NCT01563159.

Retrospective chart review of hospitalizations and costs associated with the treatment of adults with Philadelphia-negative B-cell relapsed or refractory acute lymphoblastic leukemia in Belgium.

OBJECTIVES: To quantify hospitalizations and costs among adults with Philadelphia-negative relapsed or refractory (R/R) B-cell acute lymphoblastic leukemia (ALL) who received current salvage chemotherapies in Belgium. METHODS: A retrospective chart review identified patients aged ≥18 years and hospitalized between 2005 and 2015 for Ph-negative R/R B-cell ALL. Data were collected from the index date (first diagnosis of R/R ALL) until death or loss to follow-up. The salvage chemotherapy period was defined as the first chemotherapy hospitalization after the index date to the earliest of death, loss to follow-up, last chemotherapy dose plus 30 days, or initiation of hematological stem cell transplantation (HSCT). The primary endpoint was the percent of time in the hospital during the salvage chemotherapy period. Hospitalization costs were reported from the public health care payer perspective. RESULTS: Nineteen patients were included, with median age of 37 years. The average proportion of time patients spent in the hospital during the salvage chemotherapy period was 50.5%. From the index date to death, patients received a mean of 1.8 lines of chemotherapy, most commonly hyper-CVAD (31%). There was a mean of 5.5 inpatient hospitalizations and 40.1 outpatient visits with 40.8 outpatient lab tests. Mean costs per patient were €79,973 for hospitalization (excluding HSCT), €26,337 for HSCT, €21,007 for chemotherapy drugs, and €6,341 for outpatient management, resulting in a total cost from the payer's perspective of €133,965 per patient. CONCLUSION: Adults with Ph-negative R/R ALL spend half the time receiving salvage chemotherapy in the hospital. Their treatment is associated with large reimbursement costs in Belgium.

Medium- to Long-Term Impact of Rotavirus Vaccination on Hospital Care in Belgium: A 7-Year Follow-Up of the Rotavirus Belgium Impact Study (RotaBIS).

INTRODUCTION: Rotavirus (RV) vaccination was introduced in Belgium in 2006. With the high uptake it had (>85%), a sharp decline in hospitalizations was observed during the first years after vaccine introduction. The objective of this study was to investigate whether this decline was maintained and to simulate projections. METHODS: The Rotavirus Belgium Impact Study allowed an analysis of the RV vaccine impact amongst children in 11 hospitals in Belgium over a 9-year period (2005-2013) with 2 years pre- and 7 years post-vaccine introduction. Results were compared by year and by subsequent birth cohort aging up to 5 years. The two different analysis methods helped dismantling the different (direct and indirect) effects of vaccine protection to simulate future hospitalization trends. RESULTS: During the whole observation period, 40,552 RV detection tests were performed of which 5832 were positive (14.4%). After RV vaccine introduction, a significant reduction in number of tests performed (-38%) was combined with a dramatic drop in numbers of positive tests (-76.6%). The decreases were spectacular during the first two years of vaccine introduction; after that period, the decrease flattened. Cross-sectional comparison with cohort data showed that the initial drop was heavily influenced by the herd effect of the vaccine. Cohort analysis demonstrated a low rate of residual disease over time, suggesting another infection source other than the child population. CONCLUSION: The residual disease will be maintained in the community when a same vaccination strategy is continued over time, starting vaccination of children only at 6 weeks' time. FUNDING: GlaxoSmithKline Biologicals SA. TRIAL REGISTRATION: ClinicalTrials.gov identifier, NCT01563146.

The Sustained Rotavirus Vaccination Impact on Nosocomial Infection, Duration of Hospital Stay, and Age: The RotaBIS Study (2005-2012).

INTRODUCTION: The benefits of rotavirus (RV) vaccination in developed countries have focused on reductions in mortality, hospitalization and medical visits, and herd protection. We investigated other aspects related to RV-induced nosocomial infection, duration of hospital stay, age shift, and sustained vaccine impact (VI) over time. METHOD: RotaBIS (Rotavirus Belgian Impact Study; ClinicalTrials.gov identifier, NCT01563146) annually collects retrospective data on hospitalization linked to RV testing in children up to 5 years old from 11 pediatric wards located all over Belgium. Data from 2005 to 2012 have been split in pre- (2005-2006) and post-vaccination (2007-2012) period. Information was collected on age, gender, RV test result, nosocomial infection caused by RV and duration of hospital stay. RESULTS: Over the 6-year period after the introduction of the RV vaccine, an 85% reduction in nosocomial infections was observed (221 in 2005 to 33 in 2012, p < 0.001). A significant reduction of almost 2 days in average duration of hospital stay per event was observed overall (7.62 days in 2005 to 5.77 days in 2012, p < 0.001). The difference is mainly explained by the higher reduction in number of nosocomial infections. A pronounced age shift (+24%, p < 0.01) of RV nosocomial infection to infants ≤2 months old was observed, increasing with length of post-vaccination period. VI was maintained over the follow-up (±79% VI per birth cohort). A decrease was seen depending on age, 85% (95% CI 76-91%) in the youngest to 63% (95% CI 22-92%) in the oldest age group. CONCLUSION: The higher reduction in nosocomial infection may affect the overall average duration of hospital stay for RV infection. No change in VI by birth cohort, but a reduction by age group was observed. These findings could be important for decision-makers considering the introduction of universal mass RV vaccination programs. TRIAL REGISTRATION: ClinicalTrials.gov identifier, NCT01563146. FUNDING: GlaxoSmithKline Biologicals SA (Rixensart, Belgium).

Multidisciplinary outpatient rehabilitation following cardiac revascularization or valve surgery: patient-related factors for uptake.

BACKGROUND: There are concerns in Europe regarding the service provision and accessibility of multidisciplinary cardiac rehabilitation (MDCR) in general, and particularly in ambulatory settings. This paper analyses the utilization of outpatient MDCR and its determinants after cardiac revascularization or valve surgery in Belgium. METHODS: Claims rehabilitation data for all patients discharged in 2007 after a percutaneous cardiac intervention or cardiac surgery were available from the Belgian Common Sickness Funds Agency. Logistic regressions were performed to identify patients demographic and socioeconomic characteristics associated with the uptake of outpatient MDCR during the year following the hospital discharge. RESULTS: A total of 29,021 patients were included. During the hospitalization for the cardiac procedure, 44% were offered inpatient MDCR. After discharge, only 15.6% followed at least one session of outpatient MDCR. The chance of attending outpatient MDCR was lower for female, disabled, and older patients, as well as unemployed patients. The absence of an authorized MDCR centre in the neighbourhood of the patient's residence decreased the chance of attending outpatient MDCR, while living in a neighbourhood with a high education and income level increased this probability. CONCLUSION: These results confirm the low rates of MDCR attendance found in a previous study performed by the European Association of Cardiovascular Prevention and Rehabilitation. The study shows specific patient groups that should be targeted in priority, i.e. women, elderly, unemployed patients, disabled persons, and patients with a low socioeconomic status.

Reduction in pediatric rotavirus-related hospitalizations after universal rotavirus vaccination in Belgium.

BACKGROUND: This study investigated the effect of pediatric vaccination against rotavirus on the number of rotavirus-related hospitalizations of children in Belgium. METHODS: This retrospective database study was conducted at 12 pediatric hospitals in Belgium (546 pediatric beds, 30.6% of Belgian total). Children ≤ 5 years attending hospital for any reason were eligible if they had a rotavirus stool test at one of the study centers. The number of rotavirus-positive stool tests and hospitalizations for acute gastroenteritis (AGE) were compared for prevaccination (June 2004-May 2006) and postvaccination (June 2007-May 2009) study periods. RESULTS: The number of rotavirus-positive stool tests in children who were ≤ 5 years of age decreased from an average of 881 in the prevaccination period to 368 in the first year postvaccination period and 199 in the second. In children 2 to 24 months of age, the percentage reductions were 65% (95% confidence interval [CI]: 62%, 69%) and 80% (95% CI: 77%, 83%) in the first and second years after vaccination, respectively, compared with prevaccination. In children <2 months, the reductions were 50% (95% CI: 36%, 64%) and 64% (95% CI: 49%, 76%), respectively, and in children >24 months the corresponding values were 20% (95% CI: 14%, 28%) and 64% (95% CI: 56%, 72%). The number of AGE-driven hospital admissions and hospitalization days for AGE declined by 33% and 36%, respectively, from prevaccination to the second year postvaccination in children ≤ 2 years of age. CONCLUSIONS: Pediatric rotavirus vaccination in Belgium significantly reduced rotavirus-related hospitalizations in the first and second years after introduction.

Cost-effectiveness analysis of aprepitant in the prevention of chemotherapy-induced nausea and vomiting in Belgium.

OBJECTIVES: Chemotherapy-induced nausea and vomiting (CINV) remains a major adverse effect of cancer chemotherapy which may increase morbidity, reduce quality of life and threaten the success of cancer therapy. Aprepitant is effective in preventing CINV, achieving higher complete response (no emesis and no rescue therapy) compared to standard prevention, in patients receiving either highly (HEC) or moderately emetogenic chemotherapy (MEC; absolute reduction = 11 and 13%, respectively). We assessed the cost effectiveness of aprepitant-based vs standard prevention in these indications in Belgium. MATERIALS AND METHODS: A decision analytical model was developed in MS Excel (Fig. 1). To estimate resource use, two approaches were used. The first is based on the preventive regimens applied in randomized controlled trials comparing aprepitant-based CINV prevention (for HEC: aprepitant days 1-3, ondansetron 32 mg i.v. day 1, oral placebo twice daily days 2-4, oral dexamethasone days 1-4; for MEC: aprepitant days 1-3, ondansetron 16 mg p.o. day 1, placebo on days 2-3, oral dexamethasone day 1), vs a standard regimen (for HEC: oral placebo days 1-3, ondansetron 32 mg i.v. day 1 and 16 mg p.o. days 2-4, oral dexamethasone days 1-4; for MEC: oral placebo, ondansetron 16 mg p.o. days 1-3, dexamethasone day 1) The second analysis is based on current real-world resource use in the Belgian setting in the prevention of CINV using a longitudinal Hospital Database. CINV-specific utility values were used to calculate quality-adjusted life years (QALYs). Drug costs were obtained from official reimbursement listings. Treatment costs for CINV were obtained from a German study and adapted to Belgium. RESULTS: The aprepitant-based regimen is associated with 0.003 and 0.014 more QALYs in HEC and MEC, respectively and with per patient savings of 66.84 (trial based) and 74.62 (real-life based) for HEC and 17.95 (trial based) and 21.70 (real-life based) for MEC. Hence, aprepitant is both more effective and less expensive (=dominant). One-way sensitivity analyses were performed on treatment cost of emesis, the clinical benefit of aprepitant and the cost of ondansetron and showed that the results were robust on the first two parameters but sensitive on the decrease in cost of ondansetron for the moderately emetogenic chemotherapy regimens. CONCLUSIONS: In both approaches, the aprepitant-based strategy is more effective and less expensive compared to standard care.