Context Fibrous dysplasia/McCune-Albright syndrome (FD/MAS) is a rare genetic disorder. Incidence and prevalence are not well-studied. Epidemiological research is complicated by the rarity of FD... Show moreContext Fibrous dysplasia/McCune-Albright syndrome (FD/MAS) is a rare genetic disorder. Incidence and prevalence are not well-studied. Epidemiological research is complicated by the rarity of FD/MAS, absence of registries, heterogeneous presentation, and possibly asymptomatic phenotype. FD/MAS may present with FGF23-mediated hypophosphatemia, of which the epidemiology is also unclear.Objective Evaluate incidence and prevalence of FD/MAS and FD/MAS-related hypophosphatemia.Methods This cohort study based on the nationwide Danish National Patient Registry from 1995-2018, included patients identified by ICD-10 codes M85.0 (monostotic FD [MFD]) and Q78.1 (polyostotic FD [PFD]/MAS). Incidence rates and prevalence were calculated and stratified by sex, age, calendar period, and diagnosis code. Cases were screened for FD-associated hypophosphatemia by diagnosis code E.83 (disorder of mineral metabolism) and dispatched vitamin D analogues.Results A total of 408 patients were identified, 269 with MFD (66%), 139 with PFD/MAS (34%), comparable between sexes. Incidence of FD/MAS demonstrated increasing secular trend with a rate of 3.6 per 1 000 000 person-years (95% CI: 2.9, 4.5) in 2015-2018. Incidence peaked between age 11 and 20. Prevalence of FD/MAS increased over time to 61.0 (95% CI: 54.6, 67.4) per 1 000 000 persons in 2018. The incidence rate of MFD was 1.5-fold that of PFD/MAS in the first decade, rising to 2.5-fold in the last decade. No FD/MAS cases were registered with diagnosis code or treatment for hypophosphatemia.Conclusion FD/MAS is rare, diagnosis peaks during adolescence without sex predominance, and MFD is most prevalent. Hypophosphatemia may be underdiagnosed and undertreated, or it may be underregistered, comparing this study to literature. Show less
Bizzarri, D.; Reinders, M.J.T.; Beekman, M.; Slagboom, P.E.; Akker, E.B. van den; BbmriNl 2023
H-1-NMR metabolomics data is increasingly used to track health and disease. Nightingale Health, a major supplier of H-1-NMR metabolomics, has recently updated the quantification strategy to further... Show moreH-1-NMR metabolomics data is increasingly used to track health and disease. Nightingale Health, a major supplier of H-1-NMR metabolomics, has recently updated the quantification strategy to further align with clinical standards. Such updates, however, might influence backward replicability, particularly affecting studies with repeated measures. Using data from BBMRI-NL consortium (similar to 28,000 samples from 28 cohorts), we compared Nightingale data, originally released in 2014 and 2016, with a re-quantified version released in 2020, of which both versions were based on the same NMR spectra. Apart from two discontinued and twenty-three new analytes, we generally observe a high concordance between quantification versions with 73 out of 222 (33%) analytes showing a mean rho > 0.9 across all cohorts. Conversely, five analytes consistently showed lower Spearman's correlations (rho < 0.7) between versions, namely acetoacetate, LDL-L, saturated fatty acids, S-HDL-C, and sphingomyelins. Furthermore, previously trained multi-analyte scores, such as MetaboAge or MetaboHealth, might be particularly sensitive to platform changes. Whereas MetaboHealth replicated well, the MetaboAge score had to be retrained due to use of discontinued analytes. Notably, both scores in the re-quantified data recapitulated mortality associations observed previously. Concluding, we urge caution in utilizing different platform versions to avoid mixing analytes, having different units, or simply being discontinued. Show less
Beek, P.E. van; Rijken, M.; Broeders, L.; Horst, H.J. ter; Koopman-Esseboom, C.; Kort, E. de; ... ; Andriessen, P. 2023
Objective After lowering the Dutch threshold for active treatment from 25 to 24 completed weeks' gestation, survival to discharge increased by 10% in extremely preterm live born infants. Now that... Show moreObjective After lowering the Dutch threshold for active treatment from 25 to 24 completed weeks' gestation, survival to discharge increased by 10% in extremely preterm live born infants. Now that this guideline has been implemented, an accurate description of neurodevelopmental outcome at school age is needed.Design Population-based cohort study.Setting All neonatal intensive care units in the Netherlands.Patients All infants born between 24(0/7) and 26(6/7 )weeks' gestation who were 5.5 years' corrected age (CA) in 2018-2020 were included.Main outcome measures Main outcome measure was neurodevelopmental outcome at 5.5 years. Neurodevelopmental outcome was a composite outcome defined as none, mild or moderate-to-severe impairment (further defined as neurodevelopmental impairment (NDI)), using corrected cognitive score (Wechsler Preschool and Primary Scale of Intelligence Scale-III-NL), neurological examination and neurosensory function. Additionally, motor score (Movement Assessment Battery for Children-2-NL) was assessed. All assessments were done as part of the nationwide, standardised follow-up programme.Results In the 3-year period, a total of 632 infants survived to 5.5 years' CA. Data were available for 484 infants (77%). At 5.5 years' CA, most cognitive and motor (sub)scales were significantly lower compared with the normative mean. Overall, 46% had no impairment, 36% had mild impairment and 18% had NDI. NDI-free survival was 30%, 49% and 67% in live born children at 24, 25 and 26 weeks' gestation, respectively (p<0.001).Conclusions After lowering the threshold for supporting active treatment from 25 to 24 completed weeks' gestation, a considerable proportion of the surviving extremely preterm children did not have any impairment at 5.5 years' CA. Show less
Background: Elevated levels of coagulation factors (F) II (FII), FV, FVII, FIX, FX, and FXI have often been related with coronary heart disease, ischemic stroke, and venous thrombosis (VT). However... Show moreBackground: Elevated levels of coagulation factors (F) II (FII), FV, FVII, FIX, FX, and FXI have often been related with coronary heart disease, ischemic stroke, and venous thrombosis (VT). However, there are few studies on their associations with all-cause mortality. Objective: We explored whether elevated levels of FII, FV, FVII, FIX, FX, and FXI are associated with an increased risk of death in patients who had VT and in individuals from the general population.Methods: We followed 1919 patients with previous VT and 2800 age-and sex -matched community controls in whom coagulation factor levels were measured. A high coagulation factor was defined as the >90th percentile of normal in the controls. Cox regression analyses were adjusted for age and sex and for being a patient with VT or being a control subject.Results: The median age at time of enrolment was 48 years for both patients and controls, and slightly more women than men were followed. Over a median follow-up of 6.1 years for patients and 5.0 years for controls, there were 79 and 60 deaths in patient and controls respectively. There was no association of FII, FV, FVII, FIX, FX, and FXI with all-cause mortality in patients or in control individuals.Conclusions: Elevated levels of FII, FV, FVII, FIX, FX, and FXI levels may not be associated with an increased risk of all-cause mortality. Only for cardiac death, an association with high FX and FXI was found, which confirms the findings of previous studies, but numbers were small. Show less
Schuurman, M.S.; Lemmens, V.E.P.P.; Portielje, J.E.A.; Aa, M.A. van der; Visser, O.; Dinmohamed, A.G. 2023
Adults aged =80 years (the oldest-old) comprise the fastest growing age group in Western populations. Yet little is known about their cancer burden. In this nation-wide study, we assessed their... Show moreAdults aged =80 years (the oldest-old) comprise the fastest growing age group in Western populations. Yet little is known about their cancer burden. In this nation-wide study, we assessed their trends in incidence, treatment and survival over a 30-year period, and predicted their future cancer incidence. All 2 468 695 incident cancer cases during 1990 to 2019 were selected from the Netherlands Cancer Registry, of whom 386 611 were diagnosed in the oldest-old (16%). The incidence of the oldest-old was predicted until 2032. Net and overall survival (OS) were calculated. Patients were divided into four age groups (<80, 80-84, 85-89 and =90 years). The incidence of the oldest-old doubled between 1990 and 2019 and is expected to grow annually with 5% up to 2032. In virtually all cancers the share of oldest-old patients grew, but declined for prostate cancer (25% in 1990-1994 vs 13% in 2015-2019). The proportion of undetermined disease stage increased with age in most cancers. The application of systemic therapy increased, albeit less pronounced in the oldest-old than their younger counterparts (1990 vs 2019: 12%-34%, 3%-15%, 2%-7% and 1%-3% in <80, 80-84, 85-89 and =90 years old). Five-year OS of the oldest-old patients increased by 7 percentage points (to 26%) between 1990 to 1994 and 2015 to 2019 compared to 19 percentage points (to 63%) in <80 years old. The oldest-old cancer patients are a rapidly growing group who benefitted less from improvements in cancer treatment than younger patients, reflecting the multiple challenges faced in the care of the oldest-old. Show less
Beukel, M.D. van den; Stoelinga, A.E.C.; Meer, A.J. van der; Meulen, S. van der; Zhang, L.; Tushuizen, M.E.; ... ; Trouw, L.A. 2023
Background(Auto)immune mediated and cholestatic liver disease (AILD) includes autoimmune hepatitis (AIH), primary biliary cholangitis (PBC) and primary sclerosing cholangitis (PSC). Especially AIH... Show moreBackground(Auto)immune mediated and cholestatic liver disease (AILD) includes autoimmune hepatitis (AIH), primary biliary cholangitis (PBC) and primary sclerosing cholangitis (PSC). Especially AIH is characterized by the presence of autoantibodies and elevated serum immunoglobulins. In rheumatoid arthritis, autoantibodies against post-translational modifications (PTMs) such as citrullination (Cit) and carbamylation (CarP) are used as diagnostic and prognostic markers, respectively. We studied the presence of six anti-PTM antibodies in patients with the three AILDs and non-AILD. MethodsAntibodies against six PTMs (malondialdehyde-acetaldehyde adducts (MAA), advanced glycation end-products (AGE), CarP, acetylation (AL), Cit, and nitration (NT)) were tested in sera of patients with AILD (n = 106), non-AILD (n = 101) and compared with healthy controls (HC) (n = 100). Levels and positivity were correlated with clinical and biochemical features in a well-defined cohort of untreated AIH patients. ResultsAnti-PTM antibodies were more often detectable in sera from AILD patients compared with HCs (anti-MAA: 67.9% vs. 2.0%, anti-AGE: 36.8% vs. 4.0%, anti-CarP: 47.2% vs. 5.0% and anti-AL: 18.9% vs. 5.0%). In untreated AIH, time to complete biochemical response (CBR) was associated with anti-MAA, anti-AGE, anti-CarP and anti-AL antibodies. Significantly more patients with at least three anti-PTM antibodies attained CBR at 12 months of treatment (13 vs. 3 p = 0.01). ConclusionAnti-PTM antibodies are frequently present in AILD. The presence of anti-MAA, anti-AGE and anti-CarP antibodies correlates with the presence of AIH within this cohort. In AIH, harboring at least three anti-PTM antibody responses is positively associated with CBR. Determination of anti-PTM antibodies in liver disease may have diagnostic and prognostic value. Show less
This narrative review addresses the definition of acute-on-chronic liver failure, a condition associated with high short-term mortality in patients with chronic liver disease and/or cirrhosis. We... Show moreThis narrative review addresses the definition of acute-on-chronic liver failure, a condition associated with high short-term mortality in patients with chronic liver disease and/or cirrhosis. We provide two major points of view: the East and the West perspective. Both definitions vary regarding the underlying patient population and organ failure(s) definition. Nevertheless, all the definitions have their clinical utility: from the core concept of having the "liver" as a conditio sine qua non, the syndrome cannot exist (Asian Pacific Association for the Study of the Liver); a data-driven, robust definition (European Association for the Study of the Liver); a bedside tool that can quickly identify patients at high risk of dying (North American Consortium for the Study of End-stage Liver Disease [NACSELD]). In each section, we provide the overall definitions, the criteria of organ failure(s), and some epidemiological data illustrating how these apply in each area of the world. Show less
Background: Studies exploring the possible protective effect of coffee and tea consumption on dementia have shown inconsistent results so far. We aimed to investigate whether consumption of tea and... Show moreBackground: Studies exploring the possible protective effect of coffee and tea consumption on dementia have shown inconsistent results so far. We aimed to investigate whether consumption of tea and different types of coffee at midlife are associated with dementia later in life and whether sex or ApoE4 influence such association. Methods: We included 7381 participants from the Norwegian HUNT Study. Self-reported questionnaires assessed daily consumption of coffee and tea at baseline. After 22 years, individuals 70 years or older were screened for cognitive impairment. Results: General coffee consumption and tea consumption was not associated with dementia risk. Compared to daily consumption of 0–1 cups of coffee, daily consumption of ≥8 cups of boiled coffee was associated with increased dementia risk in women (OR: 1.83, 95% CI: 1.10–3.04, p-value for trend = 0.03) and daily consumption of 4–5 cups of other types of coffee was associated with a decrease in dementia risk in men (OR: 0.48, 95% CI: 0.32–0.72, p-value for trend = 0.05). Furthermore, the association between boiled coffee and increased dementia risk was only found in ApoE4 non-carriers. Differences by sex or ApoE4 carrier status were not supported by strong statistical evidence for interaction. Tea consumption was not associated with dementia risk. Conclusion: type of coffee may play a role in the direction of the association between coffee-drinking habits and dementia later in life. Show less
ObjectiveOwing to the paucity of data, this study aimed to investigate sex differences in clinical features and prognosis of patients with cardiac sarcoidosis (CS). MethodsThis study was a... Show moreObjectiveOwing to the paucity of data, this study aimed to investigate sex differences in clinical features and prognosis of patients with cardiac sarcoidosis (CS). MethodsThis study was a secondary analysis of the ILLUstration of the Management and prognosIs of JapaNese PATiEnts with Cardiac Sarcoidosis registry-a retrospective multicentre registry that enrolled patients with CS between 2001 and 2017. The primary outcome was potentially fatal ventricular arrhythmia events (pFVAEs)-a composite of sudden cardiac death, sustained ventricular tachycardia lasting >30 s, ventricular fibrillation or the requirement for implantable cardioverter defibrillator therapy. ResultsOf the 512 participants (mean age +/- SD 61.6 +/- 11.4 years), 329 (64.2%) were females. Both sexes had peak ages of 60-64 years at diagnosis. Male patients were younger and had a higher prevalence of coronary artery disease and lower left ventricular ejection fraction than female patients. During a median follow-up of 3 years (IQR 1.6-5.6), pFVAEs were observed in 99 patients, with males having a significantly higher risk than females (p=0.002). This association was retained even after adjustment for other risk factors for pFVAEs, including left ventricular ejection fraction (adjusted HR 1.80; 95% CI 1.08 to 3.01, p=0.025). ConclusionApproximately two-thirds of patients with CS were females, with a peak age of approximately 60 years at clinical diagnosis in both sexes; male patients were younger than female patients. Male patients had a significantly higher risk of pFVAEs than female patients. Show less
Trinks-Roerdink, E.M.; Geersing, G.J.; Hemels, M.E.W.; Gelder, I.C. van; Klok, F.A.; Smeden, M. van; ... ; Doorn, S. van 2023
Objective Patients with cancer are at increased bleeding risk, and anticoagulants increase this risk even more. Yet, validated bleeding risk models for prediction of bleeding risk in patients with... Show moreObjective Patients with cancer are at increased bleeding risk, and anticoagulants increase this risk even more. Yet, validated bleeding risk models for prediction of bleeding risk in patients with cancer are lacking. The aim of this study is to predict bleeding risk in anticoagulated patients with cancer.Methods We performed a study using the routine healthcare database of the Julius General Practitioners’ Network. Five bleeding risk models were selected for external validation. Patients with a new cancer episode during anticoagulant treatment or those initiating anticoagulation during active cancer were included. The outcome was the composite of major bleeding and clinically relevant non-major (CRNM) bleeding. Next, we internally validated an updated bleeding risk model accounting for the competing risk of death.Results The validation cohort consisted of 1304 patients with cancer, mean age 74.0±10.9 years, 52.2% males. In total 215 (16.5%) patients developed a first major or CRNM bleeding during a mean follow-up of 1.5 years (incidence rate; 11.0 per 100 person-years (95% CI 9.6 to 12.5)). The c-statistics of all selected bleeding risk models were low, around 0.56. Internal validation of an updated model accounting for death as competing risk showed a slightly improved c-statistic of 0.61 (95% CI 0.54 to 0.70). On updating, only age and a history of bleeding appeared to contribute to the prediction of bleeding risk.Conclusions Existing bleeding risk models cannot accurately differentiate bleeding risk between patients. Future studies may use our updated model as a starting point for further development of bleeding risk models in patients with cancer. Show less
Lay Summary Our study compared the incidence of dialysis, the most common treatment modality for kidney failure, in the Netherlands with 11 other European countries/regions between 2001 and 2019.... Show moreLay Summary Our study compared the incidence of dialysis, the most common treatment modality for kidney failure, in the Netherlands with 11 other European countries/regions between 2001 and 2019. We observed a decline in the dialysis incidence in the last decade, most marked among patients aged >= 65 years. Similar trends were found in Austria, Denmark, England/Wales, Finland, Scotland, and Sweden. Although the number of kidney transplantations increased significantly, this can only explain a minor part of the observed decrease in the dialysis incidence among these older patients. An increase in the number of patients choosing to forego dialysis (i.e. conservative care) or improvement of preventive care for cardiovascular- or kidney disease, are likely explanations. Our study stresses the need for registration of patients with earlier stages of chronic kidney disease and patients that choose conservative care. This would allow for better assessment of healthcare utilization and outcomes in these patient groups.Introduction After decades of increasing dialysis incidence, we observed a decreasing trend in the Netherlands in the last decade. We compared this trend with trends in other European countries. Materials and Methods Aggregated data for calendar years 2001-2019 from the Dutch registries of kidney replacement therapy patients and the European Renal Association Registry were used. Dialysis incidence in the Netherlands was compared with that in 11 other European countries/regions using three age groups: 20-64, 65-74, and >= 75 years, taking into account pre-emptive kidney transplantation (PKT) incidence. Time trends were assessed as annual percentage change (APC) with 95% confidence intervals (CI) using joinpoint regression analysis. Results Between 2001 and 2019 the Dutch dialysis incidence decreased slightly among patients aged 20-64 years (APC -0.9, 95% CI -1.4; -0.5). For patients 65-74 and >= 75 years old, a peak was seen in 2004 and 2009, respectively. Afterwards, the decrease was most marked in patients aged >= 75 years: APC -3.2 (-4.1; -2.3) versus APC -1.8 (-2.2; -1.3) for patients 65-74 years old. PKT incidence increased significantly during the study period but remained limited compared to the observed decrease in dialysis incidence, especially among older patients. Large differences in dialysis incidence were observed among European countries/regions. A decreasing dialysis incidence among older patients was also seen in Austria, Denmark, England/Wales, Finland, Scotland, and Sweden. Conclusions The Dutch dialysis incidence decreased most profoundly among older patients. This was also observed in several other European countries/regions. Although PKT incidence increased, it can only explain a minor part of the decrease in dialysis incidence. Show less
BackgroundPreterm infants commonly receive red blood cell (RBC), platelet and fresh frozen plasma (FFP) transfusions. The aim of this Neonatal Transfusion Network survey was to describe current... Show moreBackgroundPreterm infants commonly receive red blood cell (RBC), platelet and fresh frozen plasma (FFP) transfusions. The aim of this Neonatal Transfusion Network survey was to describe current transfusion practices in Europe and to compare our findings to three recent randomised controlled trials to understand how clinical practice relates to the trial data. MethodsFrom October to December 2020, we performed an online survey among 597 neonatal intensive care units (NICUs) caring for infants with a gestational age (GA) of ResultsResponses from 343 NICUs (response rate: 57%) are presented and showed substantial variation in clinical practice. For RBC transfusions, 70% of NICUs transfused at thresholds above the restrictive thresholds tested in the recent trials and 22% below the restrictive thresholds. For platelet transfusions, 57% of NICUs transfused at platelet count thresholds above 25x10(9)/L in non-bleeding infants of GA of <28 weeks, while the 25x10(9)/L threshold was associated with a lower risk of harm in a recent trial. FFP transfusions were administered for coagulopathy without active bleeding in 39% and for hypotension in 25% of NICUs. Transfusion volume, duration and rate varied by factors up to several folds between NICUs. ConclusionsTransfusion thresholds and aspects of administration vary widely across European NICUs. In general, transfusion thresholds used tend to be more liberal compared with data from recent trials supporting the use of more restrictive thresholds. Further research is needed to identify the barriers and enablers to incorporation of recent trial findings into neonatal transfusion practice. Show less
The medical research literature is abundant with regression analyses that include multiple covariates, so-called multivariable regression models. Despite their common application, the... Show moreThe medical research literature is abundant with regression analyses that include multiple covariates, so-called multivariable regression models. Despite their common application, the interpretation of their results is not always clear or claimed interpretations are not justified. To outline the distinctions between different interpretations, we describe several possible research objectives for which a multivariable regression analysis might be an appropriate way of analyzing the data. In addition, we describe caveats in the interpretation of results of multivariable regression analysis. Show less
Objectives: While Livestock-associated methicillin-resistant Staphylococcus aureus (LA-MRSA), defined as CC398, is a well-known pathogen among those working with livestock, there are indications... Show moreObjectives: While Livestock-associated methicillin-resistant Staphylococcus aureus (LA-MRSA), defined as CC398, is a well-known pathogen among those working with livestock, there are indications that LA-MRSA prevalence among the general population is increasing. However, the clinical impact in urban areas remains unknown. The aim of this study was to assess the genetic epidemiology and clinical characteristics of LA-MRSA in an urban area with a limited livestock population. Methods: In this retrospective study, we evaluated LA-MRSA strains that were collected between 2014 and 2018 from patients who received clinical care in a single urban area in Netherlands. Patient files were assessed for livestock exposure data, clinical findings, and contact tracing information. Next-generation sequencing (NGS) analysis in combination with wgMLST was conducted to assess genetic diversity and relatedness and to detect virulence and resistance genes. Results: LA-MRSA strains were cultured from 81 patients, comprising 12% of all the MRSA strains found in seven study laboratories between 2014 and 2018. No livestock link was found in 76% of patients (n = 61), and 28% of patients (n = 23) had an infection, mostly of the skin or soft tissue. Contact tracing had been initiated in 14 cases, leading to the identification of two hospital transmissions: a cluster of 9 cases and one of 2 cases. NGS data were available for 91% (n = 75) of the patients. wgMLST confirmed the clusters detected via contact tracing (n = 2) and identified 5 additional clusters without a known epidemiological link. Relevant resistance and virulence findings included the PVL virulence gene (3 isolates) and tetracycline resistance (79 isolates). Conclusion: LA-MRSA may cause a relevant burden of disease in urban areas. Surprisingly, most infections in the present study occurred in the absence of a livestock link, suggesting inter-human transmission. These findings and the presence of PVL and other immune evasive complex virulence genes warrant future surveillance and preventative measures. Show less
Objectives: While Livestock-associated methicillin-resistant Staphylococcus aureus (LA-MRSA), defined as CC398, is a well-known pathogen among those working with livestock, there are indications... Show moreObjectives: While Livestock-associated methicillin-resistant Staphylococcus aureus (LA-MRSA), defined as CC398, is a well-known pathogen among those working with livestock, there are indications that LA-MRSA prevalence among the general population is increasing. However, the clinical impact in urban areas remains unknown. The aim of this study was to assess the genetic epidemiology and clinical characteristics of LA-MRSA in an urban area with a limited livestock population.Methods: In this retrospective study, we evaluated LA-MRSA strains that were collected between 2014 and 2018 from patients who received clinical care in a single urban area in Netherlands. Patient files were assessed for livestock exposure data, clinical findings, and contact tracing information. Next-generation sequencing (NGS) analysis in combination with wgMLST was conducted to assess genetic diversity and relatedness and to detect virulence and resistance genes.Results: LA-MRSA strains were cultured from 81 patients, comprising 12% of all the MRSA strains found in seven study laboratories between 2014 and 2018. No livestock link was found in 76% of patients (n = 61), and 28% of patients (n = 23) had an infection, mostly of the skin or soft tissue. Contact tracing had been initiated in 14 cases, leading to the identification of two hospital transmissions: a cluster of 9 cases and one of 2 cases. NGS data were available for 91% (n = 75) of the patients. wgMLST confirmed the clusters detected via contact tracing (n = 2) and identified 5 additional clusters without a known epidemiological link. Relevant resistance and virulence findings included the PVL virulence gene (3 isolates) and tetracycline resistance (79 isolates).Conclusion: LA-MRSA may cause a relevant burden of disease in urban areas. Surprisingly, most infections in the present study occurred in the absence of a livestock link, suggesting inter-human transmission. These findings and the presence of PVL and other immune evasive complex virulence genes warrant future surveillance and preventative measures. Show less
Background Large clinical trials on drugs for hospitalized coronavirus disease 2019 (COVID-19) patients have shown significant effects on mortality. There may be a discrepancy with the observed... Show moreBackground Large clinical trials on drugs for hospitalized coronavirus disease 2019 (COVID-19) patients have shown significant effects on mortality. There may be a discrepancy with the observed real-world effect. We describe the clinical characteristics and outcomes of hospitalized COVID-19 patients in the Netherlands during 4 pandemic waves and analyze the association of the newly introduced treatments with mortality, intensive care unit (ICU) admission, and discharge alive. Methods We conducted a nationwide retrospective analysis of hospitalized COVID-19 patients between February 27, 2020, and December 31, 2021. Patients were categorized into waves and into treatment groups (hydroxychloroquine, remdesivir, neutralizing severe acute respiratory syndrome coronavirus 2 monoclonal antibodies, corticosteroids, and interleukin [IL]-6 antagonists). Four types of Cox regression analyses were used: unadjusted, adjusted, propensity matched, and propensity weighted. Results Among 5643 patients from 11 hospitals, we observed a changing epidemiology during 4 pandemic waves, with a decrease in median age (67-64 years; P < .001), in in-hospital mortality on the ward (21%-15%; P < .001), and a trend in the ICU (24%-16%; P = .148). In ward patients, hydroxychloroquine was associated with increased mortality (1.54; 95% CI, 1.22-1.96), and remdesivir was associated with a higher rate of discharge alive within 29 days (1.16; 95% CI, 1.03-1.31). Corticosteroids were associated with a decrease in mortality (0.82; 95% CI, 0.69-0.96); the results of IL-6 antagonists were inconclusive. In patients directly admitted to the ICU, hydroxychloroquine, corticosteroids, and IL-6 antagonists were not associated with decreased mortality. Conclusions Both remdesivir and corticosteroids were associated with better outcomes in ward patients with COVID-19. Continuous evaluation of real-world treatment effects is needed. Show less
Buonsenso, D.; Perramon, A.; Catala, M.; Torres, J.P.; Camacho-Moreno, G.; Rojas-Solano, M.; ... ; COPEDI-CAT Res Grp 2022
Background: SARS-CoV-2 variations as well as immune protection after previous infections and/or vaccination may have altered the incidence of multisystemic inflammatory syndrome in children (MIS-C)... Show moreBackground: SARS-CoV-2 variations as well as immune protection after previous infections and/or vaccination may have altered the incidence of multisystemic inflammatory syndrome in children (MIS-C). We aimed to report an international time-series analysis of the incidence of MIS-C to determine if there was a shift in the regions or countries included into the study. Methods: This is a multicenter, international, cross-sectional study. We collected the MIS-C incidence from the participant regions and countries for the period July 2020 to November 2021. We assessed the ratio between MIS-C cases and COVID-19 pediatric cases in children <18 years diagnosed 4 weeks earlier (average time for the temporal association observed in this disease) for the study period. We performed a binomial regression analysis for 8 participating sites [Bogota (Colombia), Chile, Costa Rica, Lazio (Italy), Mexico DF, Panama, The Netherlands and Catalonia (Spain)]. Results: We included 904 cases of MIS-C, among a reference population of 17,906,432 children. We estimated a global significant decrease trend ratio in MIS-C cases/COVID-19 diagnosed cases in the previous month (P < 0.001). When analyzing separately each of the sites, Chile and The Netherlands maintained a significant decrease trend (P < 0.001), but this ratio was not statistically significant for the rest of sites. Conclusions: To our knowledge, this is the first international study describing a global reduction in the trend of the MIS-C incidence during the pandemic. COVID-19 vaccination and other factors possibly linked to the virus itself and/or community transmission may have played a role in preventing new MIS-C cases. Show less
Mac Donald-Ottevanger, M.S.; Prins, M.; Dissel, J. van; Rier, N.; Reimerink, J.; Zijlmans, W.C.W.R.; ... ; Boyd, A. 2022
Background Hepatitis A virus (HAV) and hepatitis E virus (HEV) have enteric modes of transmission and are common causes of acute hepatitis in low- and middle-income countries. HEV is also... Show moreBackground Hepatitis A virus (HAV) and hepatitis E virus (HEV) have enteric modes of transmission and are common causes of acute hepatitis in low- and middle-income countries. HEV is also characterised as a zoonotic infection and is prevalent in high-income countries. Data on HAV and HEV prevalence in Suriname, a middle-income country in South America, are scarce. Methods Serum samples of 944 and 949 randomly selected patients attending the Emergency Department at the Academic Hospital of Paramaribo, the capital of Suriname, were analysed for anti-HAV antibodies (anti-HAV) and anti-HEV antibodies (anti-HEV), respectively. Determinants of anti-HAV and anti-HEV positive serology were evaluated using multivariable logistic regression. Results Anti-HAV prevalence was 58.3% (95% CI 55.4 to 61.4%) and higher prevalence was independently associated with belonging to the Tribal or Indigenous population and older age. Anti-HEV prevalence was 3.7% (95% CI 2.6 to 5.0%) and higher prevalence was associated with Tribal and Creole ethnicity and older age. Conclusions In Suriname, exposure to HAV is consistent with a very low endemic country and exposure to HEV was rare. Both viruses were more prevalent in specific ethnic groups. As anti-HAVantibodies were less frequently found in younger individuals, they could be susceptible to potential HAV outbreaks and might require HAV vaccination. Show less