Epidemiology, Outcomes, and Complement Gene Variants in Secondary Thrombotic Microangiopathies.

BACKGROUND: The identification of complement defects as major drivers of primary atypical hemolytic uremic syndrome (HUS) has transformed the landscape of thrombotic microangiopathies (TMAs), leading to the development of targeted therapies and better patient outcomes. By contrast, little is known about the presentation, genetics, and outcomes of TMA associated with specific diseases or conditions, also referred to as secondary TMA. METHODS: In this study, we assessed the relative incidence, clinical and genetic spectra, and long-term outcomes of secondary TMA versus other TMAs in consecutive patients hospitalized with a first episode of TMA from 2009 to 2019 at two European reference centers. RESULTS: During the study period, 336 patients were hospitalized with a first episode of TMA. Etiologies included atypical HUS in 49 patients (15%), thrombotic thrombocytopenic purpura (TTP) in 29 (9%), shigatoxin-associated HUS in 70 (21%), and secondary TMA in 188 (56%). The main causes of secondary TMA were hematopoietic stem-cell transplantation ( n =56, 30%), solid-organ transplantation ( n =44, 23%), and malignant hypertension ( n =25, 13%). Rare variants in complement genes were identified in 32 of 49 patients (65%) with atypical HUS and eight of 64 patients (13%) with secondary TMA; pathogenic or likely pathogenic variants were found in 24 of 49 (49%) and two of 64 (3%) of them, respectively ( P < 0.001). After a median follow-up of 1157 days, death or kidney failure occurred in 14 (29%), eight (28%), five (7%), and 121 (64%) patients with atypical HUS, TTP, shigatoxin-associated HUS, and secondary TMA, respectively. Unadjusted and adjusted Cox regressions showed that patients with secondary TMA had the highest risk of death or kidney failure (unadjusted hazard ratio [HR], 3.35; 95% confidence interval [CI], 1.85 to 6.07; P < 0.001; adjusted HR, 4.11; 95% CI, 2.00 to 8.46; P < 0.001; considering atypical HUS as reference). CONCLUSIONS: Secondary TMAs represent the main cause of TMA and are independently associated with a high risk of death and progression to kidney failure.

Non-COVID-19 In-Hospital Admission in a Large Academic Center in Belgium During the First Two Waves of the COVID-19 Pandemic.

BACKGROUND: Preliminary reports described a reduction in non-COVID admissions during the first wave of the pandemic including some of critical diseases such as cancer, myocardial and cerebral infarction. OBJECTIVE: The aim of our study was to evaluate the impact of the COVID-19 pandemic on non-COVID in-hospital admissions in a large academic center in Belgium. MATERIALS AND METHODS: We performed a retrospective study of non-COVID-19 in-hospital admissions during the first two waves of the COVID-19 pandemic. The average number of admissions per week in 2020 has been compared to that of the same period in 2019 and 2018. Comparisons were made first for all admissions, then by disease groups, using the classification of APRDRG, and then by diagnoses using ICD-10-CM classification. RESULTS: Overall in-hospital admissions were reduced by around 39% and 29% during the first and the second waves of the COVID-19 pandemic respectively compared to 2018 and 2019. No significant difference was found between the average number of admissions in the early-COVID and the pre-COVID baseline period during the two waves. The average number of admissions was significantly reduced in the peak-COVID period compared to the baseline (first wave: 332 versus 763 admissions/week, p<0.01, -57%; second wave: 496 versus 788 admissions/week, p<0.01, -37%), as well as in the late-COVID period compared to the baseline (first wave: 412 versus 763 admissions/week, p<0.01, -46%; second wave: 470 versus 788 admissions/week, p<0.01, -40%). Cancer, myocardial and cerebral infarction admissions were not statistically reduced during the the two waves of COVID pandemic compared to the pre-COVID period. CONCLUSION: Our study shows that non-COVID in-hospital admissions rates were substantially reduced during the first two waves of COVID-19 pandemic. In our study, cancer, myocardial and cerebral infarction admissions were not statistically reduced, which was not in accordance to what was described in the literature.

Comorbidity in head and neck cancer: Is it associated with therapeutic delay, post-treatment mortality and survival in a population-based study?

OBJECTIVES: This study aims to investigate the relationship between comorbidities and therapeutic delay, post-treatment mortality, overall and relative survival in patients diagnosed with squamous cell carcinoma of the head and neck (HNSCC). PATIENTS AND METHODS: 9245 patients with a single HNSCC diagnosed between 2009 and 2014 were identified in the Belgian Cancer Registry. The Charlson Comorbidity Index (CCI) was calculated for 8812 patients (95.3%), distinguishing patients having none (0), mild (1-2), moderate (3-4) or severe comorbidity (>4). The relationship between CCI and therapeutic delay was evaluated using the Spearman correlation. Post-treatment mortality was modelled with logistic regression, using death within 30 days as the event. The association between comorbidity and survival was assessed using Cox proportional hazard models. RESULTS: Among 8812 patients with a known CCI, 39.2% had at least one comorbidity. Therapeutic delay increased from 31 to 36 days when the CCI worsened from 0 to 4 (rho = 0.087). After case-mix adjustment, higher baseline comorbidity was associated with increased post-surgery mortality (mild, OR 3.52 [95% CI 1.91-6.49]; severe, OR 18.71 [95% CI 6.85-51.12]) and post-radiotherapy mortality (mild, OR 2.23 [95% CI 1.56-3.19]; severe, OR 9.33 [95% CI 4.83-18.01]) and with reduced overall survival (mild, HR 1.39, [95% CI 1.31-1.48]; severe, HR 2.41 [95% CI 2.00-2.90]). That was also the case for relative survival in unadjusted analyses (mild, EHR 1.77 [95% CI 1.64-1.92]; severe, EHR = 4.15 [95% CI 3.43-5.02]). CONCLUSION: Comorbidity is significantly related to therapeutic delay, post-treatment mortality, 5-year overall and relative survival in HNSCC patients. Therapeutic decision support tools should optimally integrate comorbidity.

Variability in elective day-surgery rates between Belgian hospitals - Analyses of administrative data explained by surgical experts.

BACKGROUND: In the last decades, day surgery has steadily and significantly grown in many countries, yet the increase has been uneven. There are large variations in day-surgery activity between countries, but also within countries between hospitals and surgeons. This paper explores the variability in day-care activity for elective surgical procedures between Belgian hospitals. MATERIALS AND METHODS: The administrative hospital data of all patients formally admitted in a Belgian hospital for inpatient or day-care surgery between 2011 and 2013 were analysed and summarized in graphs. During 11 expert meetings with ad-hoc surgical expert groups the variability in day-surgery share between hospitals was discussed in depth. RESULTS: The variability in day-care share between Belgian hospitals is considerable. For 37 out of 486 elective surgical procedures, the variability ranged between 0 and 100%. High national day-care rates do not preclude room for improvement for certain hospitals as for the majority of these procedures there are "low performers". According to the consulted clinical experts, the high variability in day-care share may for the greater part be explained by medical team related factors, customs and traditions, the lack of clinical guidelines, financial factors, organisational factors and patient related factors. CONCLUSION: If a further expansion of day surgery is envisaged in Belgium the factors that contribute to the current variability in day-surgery rates between hospitals should be addressed. In addition, a feedback system in which hospitals and health care providers have the figures on their percentage of procedures carried out in day surgery compared to other hospitals and care providers (benchmarking) and the monitoring of a number of quality indicators (e.g. unplanned readmission, unplanned inpatient stay, emergency department visit) should be installed.

Terminal patients in Belgian nursing homes: a cost analysis.

Policy makers and health care payers are concerned about the costs of treating terminal patients. This study was done to measure the costs of treating terminal patients during the final month of life in a sample of Belgian nursing homes from the health care payer perspective. Also, this study compares the costs of palliative care with those of usual care. This multicenter, retrospective cohort study enrolled terminal patients from a representative sample of nursing homes. Health care costs included fixed nursing home costs, medical fees, pharmacy charges, other charges, and eventual hospitalization costs. Data sources consisted of accountancy and invoice data. The analysis calculated costs per patient during the final month of life at 2007/2008 prices. Nineteen nursing homes participated in the study, generating a total of 181 patients. Total mean nursing home costs amounted to 3,243 € per patient during the final month of life. Total mean nursing home costs per patient of 3,822 € for patients receiving usual care were higher than costs of 2,456 € for patients receiving palliative care (p = 0.068). Higher costs of usual care were driven by higher hospitalization costs (p < 0.001). This study suggests that palliative care models in nursing homes need to be supported because such care models appear to be less expensive than usual care and because such care models are likely to better reflect the needs of terminal patients.

Positron-emission computed tomography in cyst infection diagnosis in patients with autosomal dominant polycystic kidney disease.

BACKGROUND: Cyst infection remains a challenging issue in patients with autosomal dominant polycystic kidney disease (ADPKD). In most patients, conventional imaging techniques are inconclusive. Isolated observations suggest that (18)fluorodeoxyglucose (¹8FDG) positron-emission computed tomography (PET/CT) might help detect cyst infection in ADPKD patients. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Comparative assessment of administrative databases from January 2005 to December 2009 identified 27 PET/CT scans performed in 24 ADPKD patients for suspicion of abdominal infection. Cyst infection was definite if confirmed by cyst fluid analysis. Cyst infection was probable if all four of the following criteria were met: temperature of >38°C for >3 days, loin or liver tenderness, C-reactive protein plasma level of >5 mg/dl, and no CT evidence for intracystic bleeding. Episodes with only two or three criteria were grouped as "fever of unknown origin". RESULTS: Thirteen infectious events in 11 patients met all criteria for kidney (n = 3) or liver (n = 10) cyst infection. CT was contributive in only one patient, whereas PET/CT proved cyst infection in 11 patients (84.6%). In addition, 14 episodes of "fever of unknown origin" in 13 patients were recorded. PET/CT identified the source of infection in nine patients (64.3%), including 2 renal cyst infections. Conversely, PET/CT showed no abnormal ¹8FDG uptake in 5 patients, including 2 intracystic bleeding. The median delay between the onset of symptoms and PET/CT procedure was 9 days. CONCLUSIONS: This retrospective series underscores the usefulness of PET/CT to confirm and locate cyst infection and identify alternative sources of abdominal infection in ADPKD patients.

Palliative inpatients in general hospitals: a one day observational study in Belgium.

BACKGROUND: Hospital care plays a major role at the end-of-life. But little is known about the overall size and characteristics of the palliative inpatient population. The aim of our study was to analyse these aspects. METHODS: We conducted a one-day observational study in 14 randomly selected Belgian hospitals. Patients who met the definition of palliative patients were identified as palliative. Then, information about their socio-demographic characteristics, diagnoses, prognosis, and care plan were recorded and analysed. RESULTS: There were 2639 in-patients on the day of the study; 9.4% of them were identified as "palliative". The mean age of the group was 72 years. The primary diagnosis was cancer in 51% of patients and the estimated life expectancy was shorter than 3 months in 33% of patients and longer than 1 year in 28% of patients. The professional caregivers expected for most of the patients (73%), that the treatment would improve patient comfort rather than prolong life. Antibiotics, transfusions, treatments specific to the pathology, and artificial nutrition were administered in 90%, 78%, 57% and 50% of the patients, respectively, but were generally given with a view to controlling the symptoms. CONCLUSIONS: This analysis presents a first national estimate of the palliative inpatient population. Our results confirm that hospitals play a major role at the end-of-life, with one out of ten inpatients identified as a "palliative" patient. These data also demonstrate the complexity of the palliative population and the substantial diversity of care that they can require.

Costs of terminal patients who receive palliative care or usual care in different hospital wards.

BACKGROUND: In addition to the effectiveness of hospital care models for terminal patients, policy makers and health care payers are concerned about their costs. This study aims to measure the hospital costs of treating terminal patients in Belgium from the health care payer perspective. Also, this study compares the costs of palliative and usual care in different types of hospital wards. METHODS: A multicenter, retrospective cohort study compared costs of palliative care with usual care in acute hospital wards and with care in palliative care units. The study enrolled terminal patients from a representative sample of hospitals. Health care costs included fixed hospital costs and charges relating to medical fees, pharmacy and other charges. Data sources consisted of hospital accountancy data and invoice data. RESULTS: Six hospitals participated in the study, generating a total of 146 patients. The findings showed that palliative care in a palliative care unit was more expensive than palliative care in an acute ward due to higher staffing levels in palliative care units. Palliative care in an acute ward is cheaper than usual care in an acute ward. CONCLUSIONS: This study suggests that palliative care models in acute wards need to be supported because such care models appear to be less expensive than usual care and because such care models are likely to better reflect the needs of terminal patients. This finding emphasizes the importance of the timely recognition of the need for palliative care in terminal patients treated in acute wards.

Comparing the quality of care across Belgian hospitals from medical basic datasets: the case of thromboembolism prophylaxis after major orthopaedic surgery.

RATIONALE, AIMS AND OBJECTIVES: In the current context, the assessment of the quality of care in daily clinical practice becomes essential. The aim of this study was to use medical basic datasets associated with information on pharmacological treatments to assess the quality of care of a prophylaxis treatment after major orthopaedic surgery and to compare hospitals' clinical practices. METHODS: The study was performed in 20 Belgian hospitals. Patients who underwent total hip replacement (THR), total knee replacement (TKR), or hip fracture surgery (HFS) were selected retrospectively from the hospitals' 2002 and 2003 administrative databases (n = 14,991). Quality indicators assessed were incidence of venous thromboembolism, major bleeding and death. Prophylaxis analysed were enoxaparin, nadroparin and fondaparinux. RESULTS: Venous thromboembolism and major bleeding events were rare (1.9% and 1.1% respectively). Patients who underwent HFS were at greater risk of having pulmonary embolism [OR = 2.01; confidence interval (CI) = 1.38-2.92; P = 0.0002], major bleeding (OR = 4.00; CI = 2.93-5.46; P < 0.0001) or death from any cause (OR = 8.86; CI = 6.85-11.45; P < 0.0001) than patients who underwent THR or TKR. Multivariate analyses showed that the hospital variable had a significant impact on the probability to have adverse events and that patients who received enoxaparin were at greater risk of death than patients who received nadroparin (OR(enoxaparin vs fraxiparin) = 1.59; 95% CI = 1.04-2.44; P = 0.033). CONCLUSION: Results indicate that differences in thromboembolism prophylaxis practices among hospitals have a significant impact on adverse events. This reinforces the need to develop data-processing tools that enable better monitoring of quality of care.

Cost-effectiveness analysis of FDG PET-CT in the management of pulmonary metastases from malignant melanoma.

OBJECTIVES: Most guidelines consider FDG PET-CT to detect occult extra-pulmonary disease prior to lung metastasectomy. A cost-effectiveness analysis, using a Markov model over a 10 year period, was performed to compare two different surveillance programs, either PET-CT or whole-body CT, in patients with suspected pulmonary metastasised melanoma. METHODS: Data from published studies provided probabilities for the model. Complication and care costs were obtained from standardised administrative databases from 19 hospitals identified by DRG codes (reported in 2009 Euros). For the cost calculation of PET-CT we performed a microcosting analysis. All costs and benefits were yearly discounted at respectively 3% and 1.5%. Outcomes included life-months gained (LMG) and the number of futile surgeries avoided. Cost-effectiveness ratios were in Euros per LMG. Univariate and probabilistic sensitivity analyses addressed uncertainty in all model parameters. RESULTS: The PET-CT strategy provided 86.29 LMG (95% CI: 81.50-90.88 LMG) at a discounted cost of euro3,974 (95% CI: euro1,339-12,303), while the conventional strategy provided 86.08 LMG (95% CI: 81.37-90.68 LMG) at a discounted cost of euro5,022 (95% CI: euro1,378-16,018). This PET-CT strategy resulted in a net saving of euro1,048 with a gain of 0.2 LMG. Based on PET-CT findings, 20% of futile surgeries could be avoided. CONCLUSION: Integrating PET-CT in the management of patients with high risk MM appears to be less costly and more accurate by avoiding futile thoracotomies in one of five patients as well as by providing a small survival benefit at 10 years.

Assessing the quality of pharmacological treatments from administrative databases: the case of low-molecular-weight heparin after major orthopaedic surgery.

RATIONALE, AIMS AND OBJECTIVES: 'Real world data' are needed to assess the quality of pharmacological treatments in clinical practice. The aim of this study was to determine whether administrative databases can be used to assess the quality of prophylaxis with low-molecular-weight heparin after major orthopaedic surgery. METHODS: The study was performed in a Belgian university hospital. Patients undergoing total hip replacement (THR), total knee replacement (TKR) or hip fracture surgery (HFS) were selected retrospectively from the hospital's 2002 and 2003 administrative databases. Readmissions during the same year as the procedure were also analysed. Three quality indicators were assessed: incidence of venous thromboembolism (VTE), major bleeding and death; adherence to guidelines; and the costs of care. RESULTS: Although 70% of data were collected from administrative databases, patients' records also had to be examined. During the period studied, VTE and major bleeding events were rare. Patients undergoing HFS were at greater risk of having a pulmonary embolism [Exact odds ratio (OR)=3.78; 95% confidence interval (CI)=1.13-16.22; P=0.03] or of death from any cause (Exact OR=2.15; 95% CI=1.52-infinity; P<0.01) than patients undergoing THR or TKR. The hospital's prophylaxis protocol was not always followed. Half the patients received higher prophylaxis doses than recommended and 11% received lower doses but no impact on adverse events was demonstrated. CONCLUSION: Results show that administrative databases contain enough information to measure the frequency of adverse events but complementary data on patient weight and on non-reimbursed drugs must be extracted from the patients' records to evaluate adherence to guidelines. Our findings stress the need for better integration of information systems.

Prevalence and determinants of coronary and aortic calcifications assessed by chest CT in renal transplant recipients.

BACKGROUND: Coronary artery calcifications independently predict cardiovascular events (CVE) in the general population. We assessed the prevalence and determinants of coronary (CAC) and thoracic aorta (AoC) calcifications in renal transplant recipients (RTR). METHODS: Consecutive RTR living in Belgium, with an isolated kidney graft functioning for more than 1 year, were asked to participate. They underwent a 16-slice spiral computerized tomography in order to measure calcium mass. Demographic, clinical, biochemical and urinary parameters were recorded. RESULTS: We included 281 patients. CAC and AoC were detected in 81 and 85%, with geometric means (SD) of 52.2 (4.9) and 99.3 (8.2) mg, respectively. By multiple linear regression, independent predictors of both types of calcifications included older age, longer time on dialysis, a history of CVE, of multiple transplantations and of smoking. Other determinants of CAC were male gender, current statin use and history of parathyroidectomy, and other determinants of AoC included higher pulse pressure, shorter time under mycophenolate mofetil and current use of anti-vitamin-K. CONCLUSION: The prevalence of both CAC and AoC is substantial in RTR. We delineate independent determinants either common to both CAC and AoC or specific to one, and known as classic or chronic kidney disease related risk factors.