Objective
Systemic juvenile idiopathic arthritis (JIA) is a multifactorial autoinflammatory disease with a historically poor prognosis. With current treatment regimens, approximately half of patients ...still experience active disease after 1 year of therapy. This study was undertaken to evaluate a treat‐to‐target approach using recombinant interleukin‐1 receptor antagonist (rIL‐1Ra; anakinra) as first‐line monotherapy to achieve early inactive disease and prevent damage.
Methods
In this single‐center, prospective study, patients with new‐onset systemic JIA with an unsatisfactory response to nonsteroidal antiinflammatory drugs received rIL‐1Ra monotherapy according to a treat‐to‐target strategy. Patients with an incomplete response to 2 mg/kg rIL‐1Ra subsequently received 4 mg/kg rIL‐1Ra or additional prednisolone, or switched to alternative therapy. For patients in whom inactive disease was achieved, rIL‐1Ra was tapered after 3 months and subsequently stopped.
Results
Forty‐two patients, including 12 who had no arthritis at disease onset, were followed up for a median of 5.8 years. The median time to achieve inactive disease was 33 days. At 1 year, 76% had inactive disease, and 52% had inactive disease while not receiving medication. High neutrophil counts at baseline and a complete response after 1 month of rIL‐1Ra were highly associated with inactive disease at 1 year. After 5 years of follow‐up, 96% of the patients included had inactive disease, and 75% had inactive disease while not receiving medication. Articular or extraarticular damage was reported in <5%, and only 33% of the patients received glucocorticoids. Treatment with rIL‐1Ra was equally effective in systemic JIA patients without arthritis at disease onset.
Conclusion
Treatment to target, starting with first‐line, short‐course monotherapy with rIL‐1Ra, is a highly efficacious strategy to induce and sustain inactive disease and to prevent disease‐ and glucocorticoid‐related damage in systemic JIA.
To evaluate the prognostic value of the coefficient of variance of axial light loss of monocytes (cv-ALL of monocytes) for adverse clinical outcomes in patients suspected of infection in the ...emergency department (ED). We performed an observational, retrospective monocenter study including all medical patients greater than or equal to18 years admitted to the ED between September 2016 and June 2019 with suspected infection. Adverse clinical outcomes included 30-day mortality and ICU/MCU admission <3 days after presentation. We determined the additional value of monocyte cv-ALL and compared to frequently used clinical prediction scores (SIRS, qSOFA, MEWS). Next, we developed a clinical model with routinely available parameters at the ED, including cv-ALL of monocytes. A total of 3526 of patients were included. The OR for cv-ALL of monocytes alone was 2.21 (1.98-2.47) for 30-day mortality and 2.07 (1.86-2.29) for ICU/MCU admission <3 days after ED presentation. When cv-ALL of monocytes was combined with a clinical score, the prognostic accuracy increased significantly for all tested scores (SIRS, qSOFA, MEWS). The maximum AUC for a model with routinely available parameters at the ED was 0.81 to predict 30-day mortality and 0.81 for ICU/MCU admission. Cv-ALL of monocytes is a readily available biomarker that is useful as prognostic marker to predict 30-day mortality. Furthermore, it can be used to improve routine prediction of adverse clinical outcomes at the ED.
Summary
Objective
The annual prevalence of antiepileptic drug (AED) prescribing reported in the literature differs considerably among European countries due to use of different type of data sources, ...time periods, population distribution, and methodologic differences. This study aimed to measure prevalence of AED prescribing across seven European routine health care databases in Spain, Denmark, The Netherlands, the United Kingdom, and Germany using a standardized methodology and to investigate sources of variation.
Methods
Analyses on the annual prevalence of AEDs were stratified by sex, age, and AED. Overall prevalences were standardized to the European 2008 reference population.
Results
Prevalence of any AED varied from 88 per 10,000 persons (The Netherlands) to 144 per 10,000 in Spain and Denmark in 2001. In all databases, prevalence increased linearly: from 6% in Denmark to 15% in Spain each year since 2001. This increase could be attributed entirely to an increase in “new,” recently marketed AEDs while prevalence of AEDs that have been available since the mid‐1990s, hardly changed. AED use increased with age for both female and male patients up to the ages of 80 to 89 years old and tended to be somewhat higher in female than in male patients between the ages of 40 and 70. No differences between databases in the number of AEDs used simultaneously by a patient were found.
Significance
We showed that during the study period of 2001–2009, AED prescribing increased in five European Union (EU) countries and that this increase was due entirely to the newer AEDs marketed since the 1990s. Using a standardized methodology, we showed consistent trends across databases and countries over time. Differences in age and sex distribution explained only part of the variation between countries. Therefore, remaining variation in AED use must originate from other differences in national health care systems.
A PowerPoint slide summarizing this article is available for download in the Supporting Information section here.
Non‐Hodgkin orbital lymphoma (NHOL) and idiopathic orbital inflammation (IOI) are common orbital conditions with largely unknown pathophysiology that can be difficult to diagnose. In this study we ...aim to identify serum miRNAs associated with NHOL and IOI. We performed OpenArray® miRNA profiling in 33 patients and controls. Differentially expressed miRNAs were technically validated across technology platforms and replicated in an additional cohort of 32 patients and controls. We identified and independently validated a serum miRNA profile of NHOL that was remarkably similar to IOI and characterized by an increased expression of a cluster of eight miRNAs. Pathway enrichment analysis indicated that the miRNA‐cluster is associated with immune‐mediated pathways, which we supported by demonstrating the elevated expression of this cluster in serum of patients with other inflammatory conditions. The cluster contained miR‐148a, a key driver of B‐cell tolerance, and miR‐365 that correlated with serum IgG and IgM concentrations. In addition, miR‐29a and miR‐223 were associated with blood lymphocyte and neutrophil populations, respectively. NHOL and IOI are characterized by an abnormal serum miRNA‐cluster associated with immune pathway activation and linked to B cell and neutrophil dysfunction.
MicroRNA profiling in non‐Hodgkin orbital lymphoma and idiopathic orbital inflammation identified and independently replicated the increased expression of a pan‐inflammatory cluster of microRNAs accompanied by B cell and neutrophil dysfunction.
Suspected penicillin allergy (Pen-A) is often not verified or excluded by diagnostic testing.
To assess the prevalence and impact of Pen-A registration in a Dutch University Medical Center.
In a ...prospective matched cohort study, all admitted patients (July 2013-July 2014) who underwent a pharmacotherapeutic interview were selected. Patients with a registered Pen-A were matched on age, sex, and department of admission with up to 3 patients without a registered Pen-A. Relative risks (RRs) of receiving a reserve antibiotic, death during hospitalization, and rehospitalization were compared in the 2 cohorts. The number and type of antibiotics prescribed during admission and duration of hospitalization were compared.
Of 17,959 patients, 1010 (5.6%) patients (66.7% women; median age, 55 years) had a Pen-A registration. These patients had a higher risk of receiving reserve antibiotics (RR, 1.38; 95% CI, 1.22-1.56) and of being rehospitalized within 12 weeks (RR, 1.28; 95% CI, 1.10-1.49). A significantly larger proportion of Pen-A registered patients received reserve antibiotics such as tetracyclines (1.8% vs 0.8%), macrolides/lincosamides/streptogramins (12.5% vs 4.9%), and quinolones (7.9% vs 4.3%) or received 2 or more types of antibiotics during hospitalization (21.7% vs 16.9%).
Prevalence of Pen-A registration in hospitalized patients is high, has high impact on antibiotic prescribing, and is associated with a higher risk of readmission. Verification of the Pen-A in hospitalized patients might restrict the use of reserve antibiotics and improve patient outcome.
The overwhelming amount, production speed, multidimensionality, and potential value of data currently available-often simplified and referred to as big data -exceed the limits of understanding of the ...human brain. At the same time, developments in data analytics and computational power provide the opportunity to obtain new insights and transfer data-provided added value to clinical practice in real time. What is the role of the health care professional in collaboration with the data scientist in the changing landscape of modern care? We discuss how health care professionals should provide expert knowledge in each of the stages of clinical decision support design: data level, algorithm level, and decision support level. Including various ethical considerations, we advocate for health care professionals to responsibly initiate and guide interprofessional teams, including patients, and embrace novel analytic technologies to translate big data into patient benefit driven by human(e) values.
Background
Severe postpartum hemorrhage (SPPH) is the leading cause of maternal mortality and morbidity worldwide. Platelet anomalies frequently occur during pregnancy. However, their role in the ...etiology of SPPH is largely unknown.
Objective
To study the relation between platelet parameters and SPPH.
Methods
This retrospective single‐center cohort included deliveries between 2009 and 2017. SPPH was defined as ≥1000 ml blood loss within 24 h after delivery. Platelet parameters were measured within 72 h before delivery. Multiple imputation was performed for missing data. Odds ratios were adjusted (aORs) for maternal age, multiple gestation, macrosomia, induction of labor, preeclampsia, and hemolysis, elevated liver enzymes, and low platelets syndrome.
Results
A total of 23 205 deliveries were included. Of the 2402 (10.4%) women with thrombocytopenia (<150 × 109/L), 10.3% developed SPPH, compared with 7.6% of women with a normal platelet count (aOR: 1.34, 95% CI: 1.14–1.59). Women with a platelet count of <50 × 109/L were most at risk (aOR of 2.24 1.01–4.94) compared with the reference group with normal platelet counts; the aOR was 1.22 (0.77–1.93) for the 50–99 × 109/L platelet count group and 1.31 (1.10–1.56) for the 100–149 × 109/L platelet count group. Plateletcrit was associated with SPPH (aOR 1.15 1.08–1.21 per 0.05% decrease), and, although rarely present, a platelet distribution width (PDW) ≥23% (n = 22) also increased the odds of SPPH (aOR 6.05 2.29–16.20).
Conclusion
Different degrees of thrombocytopenia were independently associated with the occurrence of SPPH. Despite their relation to SPPH, plateletcrit and a PDW of ≥23% have limited additional value in addition to platelet count.
The purpose of this study was to assess the impact of age and sex on the reporting of cough and angioedema related to renin–angiotensin system (RAS) inhibitors. A case/noncase study was performed in ...VigiBase. Two case groups were identified, reports of cough and reports of angioedema, and noncases were all reports of all other adverse events. Logistic regression analysis was used to assess the association between reporting of cough and angioedema with each class of RAS inhibitors stratified by age/sex and to control for confounding. The reporting of cough with angiotensin‐converting enzyme (ACE) inhibitors was significantly higher in women than in men adjusted reporting odds ratio (ROR): 44.0, 95% CI (43.2–44.8) for women vs. 29.2, 95% CI (28.5–29.9) for men. There was no difference in reporting of cough linked to angiotensin receptor blockers (ARBs) and aliskiren between men and women. In contrast, the reporting of angioedema with ACE inhibitors and ARBs was significantly higher in men than in women, but for aliskiren, women had a significantly higher ROR than men adjusted ROR: 5.20, 95% CI (4.18–6.46) for women vs. 3.04, 95% CI (2.30–4.02) for men. The reporting of cough with ACE inhibitors was increased with age until reaching a plateau at middle adulthood (40–59 years) and the reporting of angioedema with ACE inhibitors was increased with age until elderly (60–79 years). Age had only a slight effect on the reporting of cough and angioedema with ARBs and aliskiren. Both age and sex have substantial effects on the reporting of cough and angioedema with RAS inhibitors and in particular ACE inhibitors. Further study is needed to determine whether these differences mainly express different adverse drug reaction risks in subgroups or also can be explained by factors influencing reporting.
The predictive value of traditional risk factors for vascular events in patients with manifest vascular disease is limited, underscoring the need for novel biomarkers to improve risk stratification. ...Since hematological parameters are routinely assessed in clinical practice, they are readily available candidates.
We used data from 3,922 vascular patients, who participated in the Second Manifestations of ARTerial Disease (SMART) study. We first investigated associations between recurrent vascular events and 22 hematological parameters, obtained from the Utrecht Patient Oriented Database (UPOD), and then assessed whether parameters associated with outcome improved risk prediction.
After adjustment for all SMART risk score (SRS) variables, lymphocyte %, neutrophil count, neutrophil % and red cell distribution width (RDW) were significantly associated with vascular events. When individually added to the SRS, lymphocyte % improved prediction of recurrent vascular events with a continuous net reclassification improvement (cNRI) of 17.4% 95% CI: 2.1, 32.1% and an increase in c-statistic of 0.011 0.000, 0.022. The combination of lymphocyte % and neutrophil count resulted in a cNRI of 22.2% 3.2, 33.4% and improved c-statistic by 0.011 95% CI: 0.000, 0.022. Lymphocyte % and RDW yielded a cNRI of 18.7% 3.3, 31.9% and improved c-statistic by 0.016 0.004, 0.028. However, the addition of hematological parameters only modestly increased risk estimates for patients with an event during follow-up.
Several hematological parameters were independently associated with recurrent vascular events. Lymphocyte % alone and in combination with other parameters enhanced discrimination and reclassification. However, the incremental value for patients with a recurrent event was limited.
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