41 results on '"Ten Berg MJ"'
Search Results
2. PGI21 BURDEN OF ILLNESS OF IBS PATIENTS IN THE NETHERLANDS
- Author
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Ten Berg, MJ, primary, Goettsch, WG, additional, Van den Boom, G, additional, Smout, AJPM, additional, and Herings, RMC, additional
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- 2005
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3. PGI12 HEALTH-RELATED QUALITY OF LIFE AND PATIENT SELFPERCEIVED HEALTH STATUS IN IBS
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Ten Berg, MJ, primary, Goettsch, WG, additional, Van den Boom, G, additional, Smout, AJPM, additional, and Herings, RMC, additional
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- 2004
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4. Thrombocytopenia in adult cancer patients receiving cytotoxic chemotherapy: results from a retrospective hospital-based cohort study.
- Author
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Ten Berg MJ, van den Bemt PM, Shantakumar S, Bennett D, Voest EE, Huisman A, van Solinge WW, Egberts TC, Ten Berg, Maarten J, van den Bemt, Patricia M L A, Shantakumar, Sumitra, Bennett, Dimitri, Voest, Emile E, Huisman, Albert, van Solinge, Wouter W, and Egberts, Toine C G
- Abstract
Background: Data on the frequency and relative risk (RR) of chemotherapy-induced thrombocytopenia (CIT) in patients with solid tumours receiving chemotherapy in clinical practice are limited.Objective: The aim of the study was to estimate the frequency and RR of thrombocytopenia in adult patients with solid tumours receiving chemotherapy treatment.Methods: For this retrospective, hospital-based study, adult patients with solid tumours who received chemotherapy at the University Medical Center Utrecht in the period 2004-6 were identified from the Utrecht Patient Oriented Database. We examined the frequency of (i) overall thrombocytopenia (defined as platelet count <100 × 109/L) with or without other cytopenias; (ii) isolated thrombocytopenia (i.e. without other cytopenias); and (iii) the frequency and RR of overall thrombocytopenia and isolated thrombocytopenia associated with different cytotoxic agents.Results: A total of 614 patients receiving one of 37 different chemotherapy regimens was included. Overall thrombocytopenia frequency was 21.8% and isolated thrombocytopenia frequency was 6.2%. The highest frequencies of thrombocytopenia were observed in patients receiving carboplatin monotherapy (81.8%) and combination therapies that included carboplatin (58.2%), gemcitabine (64.4%) or paclitaxel (59.3%). The highest RRs of thrombocytopenia, compared with cisplatin-based therapy, were observed for combination therapies of carboplatin/gemcitabine (RR 10.1; 95% CI 5.5, 18.5) and carboplatin/paclitaxel/etoposide (RR 11.8; 95% CI 6.7, 20.8). In 54% of cases, the thrombocytopenia was of grade 2-4, which are considered to be the most clinically relevant grades. The highest frequencies of isolated thrombocytopenia were found with combination therapies that included oxaliplatin (28.6%) or gemcitabine (28.9%).Conclusions: The results suggest that CIT is a relevant problem in clinical practice. Further research is necessary to investigate the clinical consequences of thrombocytopenia. The observed frequencies of thrombocytopenia were lower than those observed in older studies, but comparable with that observed in a recent US-based study. The observed increased risks for possible immune-mediated thrombocytopenia associated with exposure to oxaliplatin and gemcitabine contribute to the suspicion that these drugs can cause immune-mediated thrombocytopenia, and warrant further investigation. For clinicians, the mechanism has important consequences because in immune-mediated thrombocytopenia the drug must be avoided, while in dose-dependent thrombocytopenia a dose reduction may be sufficient. [ABSTRACT FROM AUTHOR]- Published
- 2011
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5. Compliance with platelet count monitoring recommendations and management of possible heparin-induced thrombocytopenia in hospitalized patients receiving low-molecular-weight heparin.
- Author
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ten Berg MJ, van den Bemt PM, Huisman A, Schobben AF, Egberts TC, and van Solinge WW
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- 2009
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6. Platelet measurements versus discharge diagnoses for identification of patients with potential drug-induced thrombocytopenia: a cross-sectional study in the Netherlands.
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Ten Berg MJ, van Solinge WW, van den Bemt PM, Huisman A, Schobben AF, Egberts TC, ten Berg, Maarten J, van Solinge, Wouter W, van den Bemt, Patricia M L A, Huisman, Albert, Schobben, Alfred F A M, and Egberts, Toine C G
- Abstract
Background: In pharmacoepidemiological studies on the risk of drug-induced blood dyscrasias, including drug-induced thrombocytopenia (DIT), hospital discharge diagnoses have been used to identify potential cases. One of the possible limitations of discharge diagnoses is that due to incomplete registration not all potential cases are identified, which may limit statistical power. Clinical laboratory data have been suggested as a data type that is potentially more sensitive for identifying potential cases of adverse drug reactions than discharge diagnoses.Objective: To compare the number of patients with potential DIT that could be identified by using platelet measurements with the number of patients with potential DIT that could be identified by using discharge diagnoses for thrombocytopenia within a population of hospitalized patients.Methods: The study population of this cross-sectional study comprised all patients admitted to the University Medical Center Utrecht in 2004 and 2005, as captured within the Utrecht Patient Oriented Database (UPOD). The ratio of the number of patients with potential DIT based on platelet measurements (>or=1 platelet count below 100x10(9)/L without alternative diagnoses for DIT) to the number of patients with potential DIT based on discharge diagnoses for thrombocytopenia (International Classification of Diseases, 9th Revision, Clinical Modification [ICD-9-CM] codes 287.3-287.5 without alternative diagnoses for DIT) was determined.Results: Within the study period there were 56,411 hospitalizations. 2817 patients (5.0%) had >or=1 platelet count below 100x10(9)/L. In 96.3% of these patients, alternative diagnoses for DIT were present, resulting in 103 (0.2%) patients with potential DIT based on platelet measurements. There were 74 patients (0.1%) with a discharge diagnosis for thrombocytopenia. In 81.1% of these patients, alternative diagnoses for DIT were present, resulting in 14 (0.02%) patients with potential DIT based on discharge diagnoses. This resulted in a ratio of the number of patients with potential DIT based on platelet measurements to the number of patients with potential DIT based on discharge diagnoses for thrombocytopenia of seven.Conclusion: This study showed that the use of platelet measurements is a more sensitive approach to the identification of patients with potential DIT than the use of discharge diagnoses for thrombocytopenia. [ABSTRACT FROM AUTHOR]- Published
- 2009
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7. Quality of life of patients with irritable bowel syndrome is low compared to others with chronic diseases.
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Ten Berg MJ, Goettsch WG, van den Boom G, Smout AJP, Herings RMC, ten Berg, Maarten J, Goettsch, Wim G, van den Boom, Guido, Smout, André J P M, and Herings, Ron M C
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- 2006
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8. Prevention of severe infectious complications after colorectal surgery
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Mulder, Tessa, Kluijtmans, Jan, Bonten, Marc, ten Berg, MJ, and University Utrecht
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Colorectal surgery ,Infection prevention ,Surgical site infection - Abstract
In the Netherlands, one in ten patients who undergo colorectal surgery develops a wound infection. These infections have important consequences: they cause pain, extend the length of hospital stay and increase the risk of another surgical intervention. Despite preventative measures, the risk of infection remains high. This thesis aimed to improve infection control for colorectal surgery using two approaches. First, we investigated if we could enhance the efficiency of infection surveillance. We found that 98.5% of infections were detected by an algorithm that uses information from the medical records. Consequently, the time spent on detecting infections was strongly reduced. Secondly, we studied if infections could be prevented with preventative oral antibiotics that are taken before surgery, also called oral antibiotic prophylaxis (OAP). We first studied the impact of OAP in one hospital were OAP was implemented and found that OAP reduced severe wound infections by 42%. We also investigated if OAP is safe by analyzing the blood of patients who took OAP. The antibiotics are thought not to be absorbed by the gut, which strongly lowers the risk of pharmacological side effects. We did not find any traces of antibiotics in the blood, which confirmed our hypothesis. Consequently, we conducted a placebo-controlled trial in six Dutch hospitals to confirm the efficacy of OAP and to thoroughly study the risk of side effects. The trial was prematurely ended as other studies provided evidence for beneficial effect of OAP and it was no longer considered ethical to treat patients with a placebo.
- Published
- 2019
9. Added diagnostic value of routinely measured hematology variables in diagnosing immune checkpoint inhibitor mediated toxicity in the emergency department.
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Niemantsverdriet MSA, Vrijsen BEL, Visser 't Hooft T, Suijkerbuijk KPM, van Solinge WW, Ten Berg MJ, and Haitjema S
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- Humans, Emergency Service, Hospital, Retrospective Studies, Immune Checkpoint Inhibitors adverse effects, Hematology
- Abstract
Background: Immune checkpoint inhibitors (ICI) show remarkable results in cancer treatment, but at the cost of immune-related adverse events (irAE). irAE can be difficult to differentiate from infections or tumor progression, thereby challenging treatment, especially in the emergency department (ED) where time and clinical information are limited. As infections are traceable in blood, we were interested in the added diagnostic value of routinely measured hematological blood cell characteristics in addition to standard diagnostic practice in the ED to aid irAE assessment., Methods: Hematological variables routinely measured with our hematological analyzer (Abbott CELL-DYN Sapphire) were retrieved from Utrecht Patient Oriented Database (UPOD) for all patients treated with ICI who visited the ED between 2013 and 2020. To assess the added diagnostic value, we developed and compared two models; a base logistic regression model trained on the preliminary diagnosis at the ED, sex, and gender, and an extended model trained with lasso that also assessed the hematology variables., Results: A total of 413 ED visits were used in this analysis. The extended model showed an improvement in performance (area under the receiver operator characteristic curve) over the base model, 0.79 (95% CI 0.75-0.84), and 0.67 (95% CI 0.60-0.73), respectively. Two standard blood count variables (eosinophil granulocyte count and red blood cell count) and two advanced variables (coefficient of variance of neutrophil depolarization and red blood cell distribution width) were associated with irAE., Conclusion: Hematological variables are a valuable and inexpensive aid for irAE diagnosis in the ED. Further exploration of the predictive hematological variables could yield new insights into the pathophysiology underlying irAE and in distinguishing irAE from other inflammatory conditions., (© 2023 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)
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- 2023
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10. A Case of Yellow Airway Secretions and Oral Fluid.
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Zuidhof HR, van Schelt M, Roodhart JML, Ten Berg MJ, and Kemperman H
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- 2023
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11. Shorter laboratory turnaround time is associated with shorter emergency department length of stay: a retrospective cohort study.
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Vrijsen BEL, Haitjema S, Westerink J, Hulsbergen-Veelken CAR, van Solinge WW, and Ten Berg MJ
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- Humans, Length of Stay, Retrospective Studies, Hospitals, Teaching, Emergency Service, Hospital, Diagnostic Techniques and Procedures
- Abstract
Background: A longer emergency department length of stay (EDLOS) is associated with poor outcomes. Shortening EDLOS is difficult, due to its multifactorial nature. A potential way to improve EDLOS is through shorter turnaround times for diagnostic testing. This study aimed to investigate whether a shorter laboratory turnaround time (TAT) and time to testing (TTT) were associated with a shorter EDLOS., Methods: A retrospective cohort study was performed, including all visits to the emergency department (ED) of an academic teaching hospital from 2017 to 2020 during which a standardized panel of laboratory tests had been ordered. TTT was calculated as the time from arrival in the ED to the ordering of laboratory testing. TAT was calculated as the time from test ordering to the reporting of the results, and was divided into a clinical and a laboratory stage. The outcome was EDLOS in minutes. The effect of TTT and TAT on EDLOS was estimated through a linear regression model., Results: In total, 23,718 ED visits were included in the analysis. Median EDLOS was 199.0 minutes (interquartile range [IQR] 146.0-268.0). Median TTT was 7.0 minutes (IQR 2.0-12.0) and median TAT was 51.1 minutes (IQR 41.1-65.0). Both TTT and TAT were positively associated with EDLOS. The laboratory stage comprised a median of 69% (IQR 59-78%) of total TAT., Conclusion: Longer TTT and TAT are independently associated with longer EDLOS. As the laboratory stage predominantly determines TAT, it provides a promising target for interventions to reduce EDLOS and ED crowding., (© 2022. The Author(s).)
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- 2022
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12. A Wolf in Sheep's Clothing: Reuse of Routinely Obtained Laboratory Data in Research.
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Overmars LM, Niemantsverdriet MSA, Groenhof TKJ, De Groot MCH, Hulsbergen-Veelken CAR, Van Solinge WW, Musson REA, Ten Berg MJ, Hoefer IE, and Haitjema S
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- Humans, Electronic Health Records, Research Personnel, Delivery of Health Care, Laboratories, Decision Support Systems, Clinical
- Abstract
Electronic health records (EHRs) contain valuable data for reuse in science, quality evaluations, and clinical decision support. Because routinely obtained laboratory data are abundantly present, often numeric, generated by certified laboratories, and stored in a structured way, one may assume that they are immediately fit for (re)use in research. However, behind each test result lies an extensive context of choices and considerations, made by both humans and machines, that introduces hidden patterns in the data. If they are unaware, researchers reusing routine laboratory data may eventually draw incorrect conclusions. In this paper, after discussing health care system characteristics on both the macro and micro level, we introduce the reader to hidden aspects of generating structured routine laboratory data in 4 steps (ordering, preanalysis, analysis, and postanalysis) and explain how each of these steps may interfere with the reuse of routine laboratory data. As researchers reusing these data, we underline the importance of domain knowledge of the health care professional, laboratory specialist, data manager, and patient to turn routine laboratory data into meaningful data sets to help obtain relevant insights that create value for clinical care., (©L Malin Overmars, Michael S A Niemantsverdriet, T Katrien J Groenhof, Mark C H De Groot, Cornelia A R Hulsbergen-Veelken, Wouter W Van Solinge, Ruben E A Musson, Maarten J Ten Berg, Imo E Hoefer, Saskia Haitjema. Originally published in the Journal of Medical Internet Research (https://www.jmir.org), 18.11.2022.)
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- 2022
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13. Redundant laboratory testing on referral from general practice to the outpatient clinic: a post-hoc analysis.
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Vrijsen BE, Ten Berg MJ, van Solinge WW, and Westerink J
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Background: Inappropriately repeated laboratory testing is a commonly occurring problem. However, this has not been studied extensively in the outpatient clinic after referral by GPs., Aim: The aim of this study was to investigate how often laboratory tests ordered by the GP were repeated on referral to the outpatient clinic, and how many of the normal test results remained normal on repetition., Design & Setting: This is a post-hoc analysis of a study on laboratory testing strategies in patients newly referred to the outpatient clinic between April 2015 and April 2017., Method: All patients who had a referral letter including laboratory test results ordered by the GP were included. These results were compared with the laboratory test results ordered in the outpatient clinic., Results: Data were available for 295 patients, 191 of which had post-visit testing done. In this group, 56% of tests ordered by the GP were repeated. Tests with abnormal results were repeated more frequently than tests with normal results (65% versus 53%; P <0.001). A longer test interval was associated with slightly smaller odds of tests being repeated (odds ratio [OR] 0.97, 95% confidence interval [CI] = 0.95 to 0.99; P = 0.003). Of the tests with normal test results that were repeated, 90% remained normal. This was independent of testing interval or testing strategy., Conclusion: Laboratory tests ordered by the GP are commonly repeated on referral to the outpatient clinic. The number of test results remaining normal on repetition suggests a high level of redundancy in laboratory test repetition., (Copyright © 2021, The Authors.)
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- 2022
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14. The Impact of a Standardized Pre-visit Laboratory Testing Panel in the Internal Medicine Outpatient Clinic: a Controlled "On-Off" Trial.
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Vrijsen BEL, Ten Berg MJ, Naaktgeboren CA, Vis JY, Dijstelbloem HM, Westerink J, Dekker D, Hoefer IE, Haitjema S, Hulsbergen-Veelken CAR, van Solinge WW, and Kaasjager HAH
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- Humans, Referral and Consultation, Ambulatory Care Facilities
- Abstract
Background: In several settings, a shorter time to diagnosis has been shown to lead to improved clinical outcomes. The implementation of a rapid laboratory testing allows for a pre-visit testing in the outpatient clinic, meaning that test results are available during the first outpatient visit., Objective: To determine whether the pre-visit laboratory testing leads to a shorter time to diagnosis in the general internal medicine outpatient clinic., Design: An "on-off" trial, allocating subjects to one of two treatment arms in consecutive alternating blocks., Participants: All new referrals to the internal medicine outpatient clinic of a university hospital were included, excluding second opinions. A total of 595 patients were eligible; one person declined to participate, leaving data from 594 patients for analysis., Intervention: In the intervention group, patients had a standardized pre-visit laboratory testing before the first visit., Main Measures: The primary outcome was the time to diagnosis. Secondary outcomes were the correctness of the preliminary diagnosis on the first day, health care utilization, and patient and physician satisfaction., Key Results: There was no difference in time to diagnosis between the two groups (median 35 days vs 35 days; hazard ratio 1.03 [0.87-1.22]; p = .71). The pre-visit testing group had higher proportions of both correct preliminary diagnoses on day 1 (24% vs 14%; p = .003) and diagnostic workups being completed on day 1 (10% vs 3%; p < .001). The intervention group had more laboratory tests done (50.0 [interquartile range (IQR) 39.0-69.0] vs 43.0 [IQR 31.0-68.5]; p < .001). Otherwise, there were no differences between the groups., Conclusions: Pre-visit testing did not lead to a shorter overall time to diagnosis. However, a greater proportion of patients had a correct diagnosis on the first day. Further studies should focus on customizing pre-visit laboratory panels, to improve their efficacy., Trial Registration: NL5009., (© 2021. The Author(s).)
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- 2021
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15. Inappropriate laboratory testing in internal medicine inpatients: Prevalence, causes and interventions.
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Vrijsen BEL, Naaktgeboren CA, Vos LM, van Solinge WW, Kaasjager HAH, and Ten Berg MJ
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Background: To reduce overutilization of laboratory testing many interventions have been tried, but selecting the most effective intervention for a given setting is challenging. To be sustainable, interventions need to align with healthcare providers' needs and daily practices. This study aimed to assess the extent of overutilization and the perspectives of healthcare providers, which may be used to guide the choice of intervention., Methods: The extent of inappropriate laboratory testing in internal medicine inpatients was evaluated using a database. Surveys and focus groups were used to investigate healthcare providers' perceptions on its causes and solutions., Results: On average, patients had 5.7 laboratory orders done during the first week of admission, whereas guidelines advise performing laboratory testing no more than twice per week. Repeat testing of normal test results occurred in up to 85% of patients. The frequency of laboratory testing was underestimated by survey responders, even though the majority of responders (78%) thought that laboratory tests are ordered too frequently. Residents were considered to be most responsible for laboratory test ordering.The primary causes of overutilization discussed were personal factors, such as a lack of awareness and knowledge, as well as feelings of insecurity. Regarding possible solutions, residents generally recommended educational interventions, whereas specialists tended to favour technical solutions such as lockouts., Conclusion: Inappropriate laboratory testing is common in internal medicine. The most important causes are a lack of awareness and knowledge, especially in residents. The intervention most favoured by residents is education, suggesting educational interventions may be most applicable., Competing Interests: None of the authors have any actual or potential conflict of interest to disclose pertaining to this study., (© 2020 The Authors.)
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- 2020
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16. Unbound Fraction of Clozapine Significantly Decreases with Elevated Plasma Concentrations of the Inflammatory Acute-Phase Protein Alpha-1-Acid Glycoprotein.
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Man WH, Wilting I, Heerdink ER, Hugenholtz GWK, Bognár T, Ten Berg MJ, van Solinge WW, Egberts TACG, and van Maarseveen EM
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- Chromatography, Liquid methods, Clozapine metabolism, Humans, Netherlands epidemiology, Prospective Studies, Serotonin Antagonists metabolism, Tandem Mass Spectrometry methods, Clozapine blood, Inflammation metabolism, Orosomucoid metabolism, Serotonin Antagonists blood, alpha-Macroglobulins metabolism
- Abstract
Background: During inflammation, elevated total (unbound plus protein-bound) clozapine plasma concentrations have been observed. Elevated alpha-1-acid glycoprotein concentrations during inflammation are suggested to cause increased plasma clozapine-alpha-1-acid glycoprotein binding, resulting in elevated total clozapine plasma concentrations without significant changes in unbound concentrations. Here, we investigated the association between alpha-1-acid glycoprotein plasma concentrations and clozapine unbound fraction., Methods: First, 25 and 60 µL of alpha-1-acid glycoprotein solution (20 mg/mL) were added to plasma samples (n = 3) of clozapine users (spiking experiment). Second, the association between alpha-1-acid glycoprotein plasma concentration and clozapine unbound fraction was assessed in patient samples (patient study). Samples were determined by liquid chromatography-tandem mass spectrometry. Data were analyzed with a paired t test (spiking experiment) and an unpaired t test (patient study)., Results: The spiking experiment showed significantly lower mean unbound fractions following 25- and 60-µL alpha-1-acid glycoprotein spikes (relative reductions of 28.3%, p = 0.032 and 43.4%, p = 0.048). In the patient study, total clozapine plasma concentrations were 10% higher in elevated (n = 6) compared with normal alpha-1-acid glycoprotein (n = 20) samples [525 µg/L vs. 479 µg/L, mean difference = 47 µg/L (95% confidence interval -217 to 310), p = 0.72]. Elevated alpha-1-acid glycoprotein samples had a 26% lower mean unbound fraction compared with normal samples [1.22% vs. 1.65%, mean difference = -0.43% (95% confidence interval -0.816 to -0.0443), p = 0.03]., Conclusions: Both the spiking experiment and patient study showed a significant association between elevated alpha-1-acid glycoprotein plasma concentrations and a lower clozapine unbound fraction. Future studies should include clinical data to examine whether this association is clinically relevant, suggesting any clozapine dose adjustments.
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- 2019
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17. Association of a Multifaceted Intervention With Ordering of Unnecessary Laboratory Tests Among Caregivers in Internal Medicine Departments.
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Bindraban RS, van Beneden M, Kramer MHH, van Solinge WW, van de Ven PM, Naaktgeboren CA, Al-Dulaimy M, van der Wekken LC, Bandt YC, Stam F, Neppelenbroek SIM, Griffioen-Keijzer A, Castelijn DAR, Wevers BA, Boerman AW, van Wijnen M, Ten Berg MJ, and Nanayakkara PWB
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- Adult, Aged, Clinical Laboratory Techniques standards, Female, Hospital Departments standards, Humans, Internal Medicine standards, Length of Stay statistics & numerical data, Male, Middle Aged, Patient Readmission statistics & numerical data, Quality Improvement, Clinical Laboratory Techniques statistics & numerical data, Hospital Departments statistics & numerical data, Internal Medicine statistics & numerical data, Pneumonia therapy, Unnecessary Procedures statistics & numerical data
- Abstract
Importance: Inappropriate use of laboratory testing is a challenging problem. Estimated overuse rates of approximately 20% have been reported. Effective, sustainable solutions to stimulate optimal use are needed., Objective: To determine the association of a multifaceted intervention with laboratory test volume., Design, Setting, and Participants: A before-after quality improvement study was performed between August 1, 2016, and April 30, 2018, in the internal medicine departments of 4 teaching hospitals in the Netherlands. Data on laboratory order volumes from 19 comparable hospitals were used as controls. The participants were clinicians ordering laboratory tests., Interventions: The intervention included creating awareness through education and feedback, intensified supervision of residents, and changes in order entry systems. Interventions were performed by local project teams and guided by a central project team during a 6-month period. Sustainability was investigated during an 8-month follow-up period., Main Outcomes and Measures: The primary outcome was the change in slope for laboratory test volume. Secondary outcomes were change in slope for laboratory expenditure, order volumes and expenditure for other diagnostic procedures, and clinical outcomes. Data were collected on duration of hospital stay, rate of repeated outpatient visits, 30-day readmission rate, and rate of unexpected prolonged duration of hospital stay for patients admitted for pneumonia., Results: The numbers of internists and residents ordering tests in hospitals 1 to 4 were 16 and 30, 18 and 20, 13 and 17, and 21 and 60, respectively. Statistically significant changes in slope for laboratory test volume per patient contact were found at hospital 1 (change in slope, -1.55; 95% CI, -1.98 to -1.11; P < .001), hospital 3 (change in slope, -0.74; 95% CI, -1.42 to -0.07; P = .03), and hospital 4 (change in slope, -2.18; 95% CI, -3.27 to -1.08; P < .001). At hospital 2, the change in slope was not statistically significant (-0.34; 95% CI, -2.27 to 1.58; P = .73). Laboratory test volume per patient contact decreased by 11.4%, whereas the volume increased by 2.4% in 19 comparable hospitals. Statistically significant changes in slopes for laboratory costs and volumes and costs for other diagnostic procedures were also observed. Clinical outcomes were not associated with negative changes. Important facilitators were education, continuous attention for overuse, feedback, and residents' involvement. Important barriers were difficulties in data retrieval, difficulty in incorporation of principles in daily practice, and high resident turnover., Conclusions and Relevance: A set of interventions aimed at changing caregivers' mindset was associated with a reduction in the laboratory test volume in all departments, whereas the volume increased in comparable hospitals in the Netherlands. This study provides a framework for nationwide implementation of interventions to reduce unnecessary laboratory testing.
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- 2019
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18. Routine Blood Tests Do Not Predict Survival in Patients with Glioblastoma-Multivariable Analysis of 497 Patients.
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Maas SLN, Draaisma K, Snijders TJ, Senders JT, Berendsen S, Seute T, Schiffelers RM, van Solinge WW, Ten Berg MJ, Robe PA, and Broekman MLD
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- Adult, Aged, Aged, 80 and over, Blood Chemical Analysis mortality, Female, Hematologic Tests mortality, Humans, Male, Middle Aged, Prognosis, Retrospective Studies, Young Adult, Biomarkers blood, Brain Neoplasms blood, Brain Neoplasms mortality, Glioblastoma blood, Glioblastoma mortality
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Background: Multiple reports have attributed a prognostic value to routine blood tests results for patients with glioblastoma. However, these studies have reported conflicting results and have often had small sample sizes. We sought to validate the prognostic value of the described tests in an independent glioblastoma patient population., Methods: We performed a retrospective single-center multivariable analysis of 497 patients with glioblastoma who had postoperatively undergone radiotherapy and/or chemotherapy to identify the prognostic value for median overall survival of hemoglobin, white blood cell, monocyte, neutrophil, leukocyte, and platelet counts, neutrophil/lymphocyte ratio, C-reactive protein, erythrocyte sedimentation rate, activated partial thromboplastin time, prothrombin time, and lactate dehydrogenase. We also evaluated known prognostic factors for survival such as patient age, intervention type, IDH1 status, Karnofsky clinical performance status, and postoperative treatment modality., Results: In a multivariable model, after correcting for multiple testing bias, biopsy alone (hazard ratio, 0.35; 95% confidence interval, 0.26-0.49; false discovery rate-adjusted P < 0.001) and monotherapy after surgery (hazard ratio, 0.46; 95% confidence interval, 0.33-0.66; false discovery rate-adjusted P < 0.001) remained significantly associated with worse median overall survival. Patient age and Karnofsky performance status score ≥70 did not significantly influence survival in the multivariable model. No routine blood test included in the multivariable analysis was significantly associated with survival., Conclusions: In the present study, hemoglobin, white blood cell, monocyte, neutrophil, leukocyte, and platelet counts, neutrophil/lymphocyte ratio, C-reactive protein, erythrocyte sedimentation rate, activated partial thromboplastin time, prothrombin time, and lactate dehydrogenase levels did not independently predict for overall survival in patients with glioblastoma., (Copyright © 2019 Elsevier Inc. All rights reserved.)
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- 2019
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19. A Human(e) Factor in Clinical Decision Support Systems.
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Bezemer T, de Groot MC, Blasse E, Ten Berg MJ, Kappen TH, Bredenoord AL, van Solinge WW, Hoefer IE, and Haitjema S
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- Data Science, Humans, Decision Support Systems, Clinical standards
- Abstract
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., (©Tim Bezemer, Mark CH de Groot, Enja Blasse, Maarten J ten Berg, Teus H Kappen, Annelien L Bredenoord, Wouter W van Solinge, Imo E Hoefer, Saskia Haitjema. Originally published in the Journal of Medical Internet Research (http://www.jmir.org), 19.03.2019.)
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- 2019
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20. [Data-driven integrated diagnostics: the natural evolution of clinical chemistry?]
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van Solinge WW, Ten Berg MJ, and Haitjema S
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- Algorithms, Forecasting, Humans, Artificial Intelligence trends, Big Data, Chemistry, Clinical trends, Diagnostic Techniques and Procedures trends, Patient Care Team trends
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In the near future, making a correct medical diagnosis will be increasingly supported by artificial intelligence. The development of algorithms that integrate all data from an individual into the diagnostic process calls for a multidisciplinary approach that includes not only healthcare professionals and patients, but also data scientists. Because of the position of the clinical chemist in the current health care process, this medical specialist is naturally suited to initiate the development of self-learning diagnostic algorithms and to take the lead in the process to take big data to the next level and create value for health care.
- Published
- 2019
21. Improving home haemodialysis: Stability evaluation of routine clinical chemistry analytes in blood samples of haemodialysis patients.
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Nonkes LJP, van Gelder MK, Kemperman H, Abrahams AC, Boereboom FTJ, Ten Berg MJ, and Gerritsen KGF
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- Bicarbonates blood, Blood Glucose analysis, Blood Preservation, Calcium blood, Clinical Chemistry Tests methods, Hemodialysis, Home methods, Humans, Lactic Acid blood, Potassium blood, Blood Specimen Collection, Clinical Chemistry Tests standards, Hemodialysis, Home standards
- Abstract
Introduction: A growing number of dialysis patients is treated with home haemodialysis. Our current pre-analytical protocols require patients to centrifuge the blood sample and transfer the plasma into a new tube at home. This procedure is prone to errors and precludes accurate bicarbonate measurement, required for determining dialysate bicarbonate concentration and maintaining acid-base status. We therefore evaluated whether cooled overnight storage of gel separated plasma is an acceptable alternative., Materials and Methods: Venous blood of 34 haemodialysis patients was collected in 2 lithium heparin blood collection tubes with gel separator (LH PSTTM II, REF 367374; Becton Dickinson, New Jersey, USA). One tube was analysed directly for measurement of bicarbonate, potassium, calcium, phosphate, glucose, urea, lactate, aspartate aminotransferase (AST), and lactate dehydrogenase (LD); whereas the other was centrifuged and stored unopened at 4 °C and analysed 24 h later. To measure analyte stability after 24 h of storage, the mean difference was calculated and compared to the total allowable error (TEa) which was used as acceptance limit., Results: Potassium (Z = - 4.28, P < 0.001), phosphate (Z = - 3.26, P = 0.001), lactate (Z = - 5.11, P < 0.001) and AST (Z = - 2.71, P = 0.007) concentrations were higher, whereas glucose (Z = 4.00, P < 0.001) and LD (Z = 3.13, P = 0.002) showed a reduction. All mean differences were smaller than the TEa and thus not clinically relevant. Bicarbonate (Z = 0.69, P = 0.491), calcium (Z = - 0.23, P = 0.815) and urea (Z = 0.81, P =0.415) concentrations were stable., Conclusions: Our less complex, user-friendly pre-analytical procedure resulted in at least 24 h stability of analytes relevant for monitoring haemodialysis, including bicarbonate. This allows shipment and analysis the next day., Competing Interests: Potential conflict of interest: None declared.
- Published
- 2019
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22. Reducing Test Utilization in Hospital Settings: A Narrative Review.
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Bindraban RS, Ten Berg MJ, Naaktgeboren CA, Kramer MHH, Van Solinge WW, and Nanayakkara PWB
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- Databases, Factual, Reproducibility of Results, Diagnostic Tests, Routine statistics & numerical data, Laboratories, Hospital
- Abstract
Background: Studies addressing the appropriateness of laboratory testing have revealed approximately 20% overutilization. We conducted a narrative review to (1) describe current interventions aimed at reducing unnecessary laboratory testing, specifically in hospital settings, and (2) provide estimates of their efficacy in reducing test order volume and improving patient-related clinical outcomes., Methods: The PubMed, Embase, Scopus, Web of Science, and Canadian Agency for Drugs and Technologies in Health-Health Technology Assessment databases were searched for studies describing the effects of interventions aimed at reducing unnecessary laboratory tests. Data on test order volume and clinical outcomes were extracted by one reviewer, while uncertainties were discussed with two other reviewers. Because of the heterogeneity of interventions and outcomes, no meta-analysis was performed., Results: Eighty-four studies were included. Interventions were categorized into educational, (computerized) provider order entry [(C)POE], audit and feedback, or other interventions. Nearly all studies reported a reduction in test order volume. Only 15 assessed sustainability up to two years. Patient-related clinical outcomes were reported in 45 studies, two of which found negative effects., Conclusions: Interventions from all categories have the potential to reduce unnecessary laboratory testing, although long-term sustainability is questionable. Owing to the heterogeneity of the interventions studied, it is difficult to conclude which approach was most successful, and for which tests. Most studies had methodological limitations, such as the absence of a control arm. Therefore, well-designed, controlled trials using clearly described interventions and relevant clinical outcomes are needed., Competing Interests: No potential conflicts of interest relevant to this article were reported., (© The Korean Society for Laboratory Medicine.)
- Published
- 2018
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23. A Multicenter Before-After Study on Reducing Unnecessary Diagnostics by Changing the Attitude of Caregivers: Protocol for the RODEO Project.
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Bindraban RS, van Beneden MLH, Kramer MHH, van Solinge WW, Neppelenbroek SIM, van Wijnen M, Griffioen-Keijzer A, Al-Dulaimy M, Ten Berg MJ, and Nanayakkara PWB
- Abstract
Background: Appropriate use of diagnostic laboratory tests is challenging, and estimates of 20% for overutilization and 45% for underutilization have been reported. Introducing effective and sustainable solutions to stimulate optimal use of laboratory testing in clinical practice is a challenge. A recent pilot study from our group, focusing on increasing the awareness about appropriate laboratory testing with the aim of changing the mindset of health care workers, has shown promising results. In this project, we aim to extend this multistep intervention to the internal medicine departments of 4 large Dutch hospitals. We aim to reduce unnecessary laboratory testing by 5%., Objective: Our primary objective is to determine the effect of our intervention on diagnostic laboratory test order volume. Our secondary objectives are to determine the effect of our intervention on laboratory expenditure and order volumes, expenditures for other diagnostic modalities, and clinical patient outcomes. We will also analyze the barriers and facilitators for deimplementation of unnecessary laboratory testing., Methods: The main interventions of this before-after study will be an intensified supervision of residents by experienced physicians regarding test ordering, creating awareness through education and monthly feedback on ordering patterns, and changes in (computerized) order entry systems., Results: At the time of publication of this protocol, the project is in the phase of data collection. We expect to present data on reduction early in the fourth quarter of 2018., Conclusions: In this project, we aim to reduce the unnecessary diagnostic testing in the internal medicine departments of 4 teaching hospitals. Although the main interventions will be similar, each clinic is given the opportunity to focus on the specific facets of the interventions as deemed useful according to the local situation. If effective, the study provides a framework for a nationwide initiative for reducing inappropriate laboratory testing., Registered Report Identifier: RR1-10.2106/10473., (©Renuka S Bindraban, Marlou LH van Beneden, Mark HH Kramer, Wouter W van Solinge, Suzanne IM Neppelenbroek, Merel van Wijnen, Anita Griffioen-Keijzer, Muhammad Al-Dulaimy, Maarten J ten Berg, Prabath WB Nanayakkara. Originally published in JMIR Research Protocols (http://www.researchprotocols.org), 21.08.2018.)
- Published
- 2018
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24. Commonly available hematological biomarkers are associated with the extent of coronary calcifications.
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den Harder AM, de Jong PA, de Groot MCH, Wolterink JM, Budde RPJ, Iŝgum I, van Solinge WW, Ten Berg MJ, Lutgens E, Veldhuis WB, Haitjema S, Hoefer IE, and Leiner T
- Subjects
- Adult, Aged, Cell Nucleus Shape, Cell Size, Computed Tomography Angiography, Coronary Angiography methods, Coronary Artery Disease diagnostic imaging, Coronary Artery Disease pathology, Cross-Sectional Studies, Databases, Factual, Female, Humans, Male, Middle Aged, Netherlands, Severity of Illness Index, Vascular Calcification diagnosis, Vascular Calcification pathology, Coronary Artery Disease blood, Erythrocyte Indices, Lymphocytes pathology, Neutrophils pathology, Reticulocytes, Vascular Calcification blood
- Abstract
Background and Aims: We aimed to improve the understanding of potential associations between commonly available hematological biomarkers and the coronary artery calcification (CAC) score, which may help unravel the pathophysiology of coronary calcifications and subclinical coronary artery disease., Methods: A cross-sectional study was performed within the Utrecht Patient Oriented Database (UPOD). Patients with suspected or known coronary artery disease who underwent CT CAC scoring as well as standard hematology analysis that was part of routine clinical care (within 3 months of CT acquisition) were included. Complete hematology datasets were extracted from hematology analyzers. Linear regression adjusted for potential confounders was used to assess if hematological biomarkers were related to the CAC score., Results: In total, 1504 patients were included, of whom 43% (n = 647) had a CAC score of 0. Mean age (±SD) was 53 ± 13 years, and 34% of patients were women. Red blood cell distribution width (RDW, β = 0.20 [0.05-0.36], p=0.007), the fraction of immature reticulocytes (β = 0.97 [0.10-6.43], p=0.004), coefficient of variation of neutrophil lobularity (β = 0.13 [0.01-0.25], p=0.040) and mean lymphocyte cell size (β = 0.21 [0.08-0.34], p=0.001) were positively associated with the CAC score after adjustment for age, sex, body mass index (BMI), diabetes, glomerular filtration rate (GFR) and high-density lipoprotein (HDL)., Conclusions: This study confirms the known association of RDW with the CAC score, and presents the fraction of immature reticulocytes, coefficient of variation of neutrophil lobularity, and mean lymphocyte cell size as new markers associated with a higher CAC score., (Copyright © 2018 Elsevier B.V. All rights reserved.)
- Published
- 2018
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25. Evidence-Based Guidelines to Eliminate Repetitive Laboratory Testing?
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Bindraban RS, Ten Berg MJ, and Naaktgeboren CA
- Published
- 2018
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26. Exploring the value of routinely measured hematology parameters for identification of elderly patients at high risk of death at the Emergency Department.
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Bindraban RS, Ten Berg MJ, Haitjema S, Hoefer IE, de Regt M, Kramer M, van Solinge WW, Nanayakkara P, and Naaktgeboren CA
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- Aged, C-Reactive Protein, Diagnostic Tests, Routine, Humans, Prognosis, Risk Assessment, Emergency Service, Hospital, Hematology
- Abstract
Of the warning scores in use for recognition of high-risk patients at the Emergency Department (ED), few incorporate laboratory results. Although hematological characteristics have shown prognostic value in small studies, large studies in elderly ED populations are lacking. We studied the association between blood cell and platelet counts and characteristics as well as C-reactive protein (CRP) at ED presentation with mortality in non-multitrauma patients ≥ 65 years. Comparison between survivors and non-survivors showed small, significant differences with AUROCs ranging between 56.6% and 65.2% for 30-day mortality. Combining parameters yielded an evident improvement (AUROC of 70.4%). Efforts should be pursued to study the added value of hematological parameters on top of clinical data when assessing patient risk.
- Published
- 2018
27. Long-term sustainability of a multi-step intervention to reduce unnecessary diagnostic testing.
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Bindraban RS, van Beneden M, Ten Berg MJ, and Nanayakkara PWB
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- Humans, Program Evaluation, Unnecessary Procedures economics, Diagnostic Tests, Routine economics, Internal Medicine education, Practice Patterns, Physicians' economics, Unnecessary Procedures trends
- Published
- 2017
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28. Effect of Monocyte-to-Lymphocyte Ratio on Heart Failure Characteristics and Hospitalizations in a Coronary Angiography Cohort.
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Gijsberts CM, Ellenbroek GHJM, Ten Berg MJ, Huisman A, van Solinge WW, Lam CS, Asselbergs FW, den Ruijter HM, Pasterkamp G, Hoefer IE, and de Kleijn DP
- Subjects
- Aged, Biomarkers blood, C-Reactive Protein metabolism, Coronary Artery Disease complications, Coronary Artery Disease diagnosis, Echocardiography, Female, Follow-Up Studies, Heart Failure complications, Heart Failure diagnosis, Humans, Lymphocyte Count, Male, Middle Aged, Natriuretic Peptide, Brain blood, Odds Ratio, Prognosis, Risk Factors, Severity of Illness Index, Time Factors, Troponin I blood, Coronary Angiography methods, Coronary Artery Disease blood, Heart Failure blood, Hospitalization trends, Lymphocytes, Monocytes
- Abstract
Inflammation is a shared mechanism in coronary artery disease (CAD) and subsequent heart failure (HF), and circulating monocyte and lymphocyte counts predict CAD severity and outcomes. We investigated whether the monocyte-to-lymphocyte ratio (MLR) correlates with biomarkers of HF and extent of CAD, as well as future HF hospitalizations in patients undergoing coronary angiography. Therefore, we studied 1754 patients undergoing coronary angiography for stable CAD, unstable angina, or myocardial infarction. MLR was determined at blood draw before angiography and related cross-sectionally to HF biomarkers (ejection fraction, N-terminal pro-B-type natriuretic peptide [NTproBNP] levels) and CAD severity, as well as longitudinally with risk of HF hospitalizations during follow-up. In the entire cohort, median (interquartile range) MLR was 0.32 (0.24 to 0.43). High MLR was defined as the upper quartile and significantly associated with nonstable CAD (unstable angina; odds ratio [OR] 1.13, 95% confidence interval 1.06 to 1.21] or myocardial infarction [OR 1.10, 1.04 to 1.16]), more severe CAD (OR 1.39, 1.15 to 1.68), poorer ejection fraction (OR 1.63, 1.29 to 2.05), and higher NTproBNP levels (β 0.78, 0.59 to 0.96), all p <0.001. The associations with nonstable CAD and NTproBNP remained highly significant after covariate adjustment. Over a mean follow-up of 1.3 years, 46 HF hospitalizations occurred. A high MLR was significantly and independently predictive of HF hospitalizations during follow-up (hazard ratio 2.1 [1.1 to 4.1], p = 0.039) after adjustment for covariates and addition of MLR to the basic model significantly improved reclassification. In conclusion, MLR is strongly related to HF markers and predicts HF hospitalizations during follow-up in patients with CAD., (Copyright © 2017. Published by Elsevier Inc.)
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- 2017
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29. White blood cell count and new-onset atrial fibrillation after cardiac surgery.
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Jacob KA, Buijsrogge MP, Frencken JF, Ten Berg MJ, Suyker WJ, van Dijk D, and Dieleman JM
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- Adult, Aged, Analysis of Variance, Atrial Fibrillation blood, Atrial Fibrillation mortality, Biomarkers blood, Cardiac Surgical Procedures methods, Cohort Studies, Databases, Factual, Elective Surgical Procedures methods, Female, Follow-Up Studies, Hospital Mortality, Humans, Male, Middle Aged, Multivariate Analysis, Netherlands, Perioperative Care methods, Postoperative Complications blood, Postoperative Complications mortality, Postoperative Complications physiopathology, Prospective Studies, Risk Assessment, Survival Analysis, Atrial Fibrillation etiology, Cardiac Surgical Procedures adverse effects, Elective Surgical Procedures adverse effects, Leukocyte Count methods
- Abstract
Background: Postoperative new-onset atrial fibrillation (PNAF) is the most common complication following cardiac surgery. The inflammatory response, as a potential underlying mechanism, has been extensively studied. In small studies, the white blood cell count (WBC) has been shown to be the only consistent inflammatory marker associated with PNAF. This study aimed to determine the association between perioperative WBC response and PNAF in a larger study cohort., Methods: Patients ≥18years, undergoing elective cardiac surgery with a preoperative sinus rhythm were included. WBC was routinely measured preoperatively, and daily during the first four postoperative days. Main outcomes were the difference between peak postoperative WBC and neutrophil/lymphocyte ratio (N/L ratio) and preoperative WBC and N/L ratio (ΔWBC and ΔN/L ratio respectively). Development of PNAF was evaluated in all patients with continuous 12-lead ECG monitoring., Results: 657 patients were included and 277 (42%) developed PNAF. Univariable analyses showed a statistically significant relationship between ΔWBC (P=0.030) and ΔN/L ratio (P=0.002), and PNAF. In multivariable analysis no significant relationship was found between ΔWBC (OR: 1.14 per 1×10
9 /L increase; 95% CI: 0.65-2.03; P=0.645), ΔN/L ratio (OR: 1.65 per 1×109 /L increase; 95% CI: 0.94-2.90; P=0.089), and PNAF. Increasing age (OR: 1.08 per year; 95% CI: 1.01-1.16; P=0.022) and (additional) valve surgery (versus CABG) (OR: 4.96; 95% CI: 2.07-6.91; P≤0.001) were associated with PNAF., Conclusions: The perioperative WBC response and its components were not associated with the development of PNAF., (Copyright © 2016 Swiss Tropical and Public Health Institute. Published by Elsevier Ireland Ltd.. All rights reserved.)- Published
- 2017
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30. Routinely analyzed leukocyte characteristics improve prediction of mortality after coronary angiography.
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Gijsberts CM, Ellenbroek GH, Ten Berg MJ, Huisman A, van Solinge WW, Asselbergs FW, den Ruijter HM, Pasterkamp G, de Kleijn DP, and Hoefer IE
- Subjects
- Adult, Aged, Atherosclerosis blood, Cause of Death trends, Coronary Angiography adverse effects, Coronary Artery Disease blood, Female, Follow-Up Studies, Humans, Leukocyte Count, Male, Middle Aged, Netherlands epidemiology, Predictive Value of Tests, Retrospective Studies, Risk Factors, Survival Rate trends, Atherosclerosis diagnosis, Coronary Angiography mortality, Coronary Artery Disease diagnosis, Diagnostic Tests, Routine methods, Leukocytes pathology, Risk Assessment methods
- Abstract
Background: Inflammation and leukocyte infiltration are hallmarks of atherosclerosis. Clinically routine hematology analyzers mostly perform an entire differential blood count by default, irrespective of the requested parameter. We hypothesize that these normally unreported leukocyte characteristics associate with coronary artery disease (CAD) severity and can improve prediction of mortality in coronary angiography patients., Methods: We studied coronary angiography patients suspected of CAD (n = 1015) from the Utrecht Coronary Biobank cohort. Leukocyte characteristics were routinely assessed in blood drawn directly prior to angiography using an automated hematology analyzer and extracted from the Utrecht patient oriented database (UPOD) database. Patients were followed up for a median duration of 805 days, during which 65 patients died. We evaluated the association of leukocyte characteristics with synergy between PCI with taxus and cardiac surgery (SYNTAX) score as a measure of CAD severity, all-cause and cardiovascular mortality and major adverse cardiovascular events (MACEs). In order to determine the improvement of risk prediction, we calculated continuous net reclassification improvement (cNRI) and integrated discrimination improvement (IDI)., Results: Monocyte percentage showed strong independent predictive value for all-cause mortality (hazard ratio (HR) 1.44 (1.19-1.74), p < 0.001), and the monocyte-to-lymphocyte ratio performed best for cardiovascular mortality (HR 1.42 (1.11-1.81), p = 0.005). The cNRIs and IDIs of leukocyte characteristics for all-cause mortality confirmed the improvement in mortality risk prediction. No significantly predictive leukocyte characteristics were found for MACEs., Conclusion: Readily available yet unreported leukocyte characteristics from routine hematology analyzers significantly improved prediction of mortality in coronary angiography patients on top of clinical characteristics., (© The European Society of Cardiology 2015.)
- Published
- 2016
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31. Methodologies for evaluating strategies to reduce diagnostic error: report from the research summit at the 7th International Diagnostic Error in Medicine Conference.
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Bruce BB, El-Kareh R, Ely JW, Kanter MH, Rao G, Schiff GD, Ten Berg MJ, and McDonald KM
- Abstract
In this article we review current evidence on strategies to evaluate diagnostic error solutions, discuss the methodological challenges that exist in investigating the value of these strategies in patient care, and provide recommendations for methods that can be applied in investigating potential solutions to diagnostic errors. These recommendations were developed iteratively by the authors based upon initial discussions held during the Research Summit of the 7th Annual Diagnostic Error in Medicine Conference in September 2014. The recommendations include the following elements for designing studies of diagnostic research solutions: (1) Select direct and indirect outcomes measures of importance to patients, while also practical for the particular solution; (2) Develop a clearly-stated logic model for the solution to be tested; (3) Use rapid, iterative prototyping in the early phases of solution testing; (4) Use cluster-randomized clinical trials where feasible; (5) Avoid simple pre-post designs, in favor of stepped wedge and interrupted time series; (6) Leverage best practices for patient safety research and engage experts from relevant domains; and (7) Consider sources of bias and design studies and their analyses to minimize selection and information bias and control for confounding. Areas of diagnostic error mitigation research identified for further attention include: role of competing diagnoses, understanding the impacts of organizational culture, timing of diagnosis, and sequencing of research studies. Future research will likely require novel clinical, health services, and qualitative research methods to address the age-old problem of arriving at an accurate diagnosis.
- Published
- 2016
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32. Hematological Parameters Improve Prediction of Mortality and Secondary Adverse Events in Coronary Angiography Patients: A Longitudinal Cohort Study.
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Gijsberts CM, den Ruijter HM, de Kleijn DPV, Huisman A, Ten Berg MJ, van Wijk RHA, Asselbergs FW, Voskuil M, Pasterkamp G, van Solinge WW, and Hoefer IE
- Subjects
- Aged, Cardiovascular Agents therapeutic use, Cardiovascular Diseases drug therapy, Cardiovascular Diseases epidemiology, Coronary Artery Disease diagnostic imaging, Coronary Artery Disease epidemiology, Female, Hematologic Tests, Humans, Longitudinal Studies, Male, Middle Aged, Prognosis, Risk Factors, Severity of Illness Index, Coronary Angiography statistics & numerical data, Coronary Artery Disease blood, Coronary Artery Disease mortality
- Abstract
Prediction of primary cardiovascular events has been thoroughly investigated since the landmark Framingham risk score was introduced. However, prediction of secondary events after initial events of coronary artery disease (CAD) poses a new challenge. In a cohort of coronary angiography patients (n = 1760), we examined readily available hematological parameters from the UPOD (Utrecht Patient Oriented Database) and their addition to prediction of secondary cardiovascular events. Backward stepwise multivariable Cox regression analysis was used to test their ability to predict death and major adverse cardiovascular events (MACE). Continuous net reclassification improvement (cNRI) and integrated discrimination improvement (IDI) measures were calculated for the hematological parameters on top of traditional risk factors to assess prediction improvement. Panels of 3 to 8 hematological parameters significantly improved prediction of death and adverse events. The IDIs ranged from 0.02 to 0.07 (all P < 0.001) among outcome measures and the cNRIs from 0.11 to 0.40 (P < 0.001 in 5 of 6 outcome measures). In the hematological panels red cell distribution width (RDW) appeared most often. The multivariable adjusted hazard ratio of RDW per 1 standard deviation (SD) increase for MACE was 1.19 [1.08-1.32], P < 0.001. Routinely measured hematological parameters significantly improved prediction of mortality and adverse events in coronary angiography patients. Accurately indicating high-risk patients is of paramount importance in clinical decision-making.
- Published
- 2015
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33. Seasonal changes in gene expression represent cell-type composition in whole blood.
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De Jong S, Neeleman M, Luykx JJ, ten Berg MJ, Strengman E, Den Breeijen HH, Stijvers LC, Buizer-Voskamp JE, Bakker SC, Kahn RS, Horvath S, Van Solinge WW, and Ophoff RA
- Subjects
- Adult, Blood Proteins genetics, Female, Humans, Longitudinal Studies, Male, Periodicity, Reticulocyte Count, Seasons, Blood Proteins metabolism, Transcriptome physiology
- Abstract
Seasonal patterns in behavior and biological parameters are widespread. Here, we examined seasonal changes in whole blood gene expression profiles of 233 healthy subjects. Using weighted gene co-expression network analysis, we identified three co-expression modules showing circannual patterns. Enrichment analysis suggested that this signal stems primarily from red blood cells and blood platelets. Indeed, a large clinical database with 51 142 observations of blood cell counts over 3 years confirmed a corresponding seasonal pattern of counts of red blood cells, reticulocytes and platelets. We found no direct evidence that these changes are linked to genes known to be key players in regulating immune function or circadian rhythm. It is likely, however, that these seasonal changes in cell counts and gene expression profiles in whole blood represent biological and clinical relevant phenomena. Moreover, our findings highlight possible confounding factors relevant to the study of gene expression profiles in subjects collected at geographical locations with disparaging seasonality patterns.
- Published
- 2014
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34. Rituximab-induced thrombocytopenia: a cohort study.
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Giezen TJ, Mantel-Teeuwisse AK, ten Berg MJ, Straus SM, Leufkens HG, van Solinge WW, and Egberts TC
- Subjects
- Cohort Studies, Humans, Risk Factors, Rituximab, Antibodies, Monoclonal, Murine-Derived adverse effects, Thrombocytopenia chemically induced
- Abstract
The combined information of drug exposure and laboratory test results on an individual patient level obtained in daily clinical practice can add important information about the safety of a drug. Thrombocytopenia is a known adverse drug reaction of rituximab, which has already been identified during the preregistration trials, but knowledge on incidence and risk factors in clinical practice is limited. We, therefore, aimed to estimate the incidence and explore the risk factors for the development of rituximab-induced thrombocytopenia (a platelet count, <100 × 10(9) platelets/L) in clinical practice. Ninety patients were eligible for inclusion of which 27 developed thrombocytopenia (cumulative incidence, 30%) within 30 days after administration of rituximab and 18 patients developed grade 3/4 thrombocytopenia (cumulative incidence, 20%). Patients with and without thrombocytopenia were compared to explore risk factors. Patients with a relatively low platelet count (217 vs. 324 × 10(9) /L, P = 0.011) before administration of rituximab had a higher risk for the development of thrombocytopenia, and although not statistically significant, patients treated with rituximab within the oncology setting (OR, 4.7; 95% CI, 1.0-23.3), independent of concomitant use of cytostatics, as compared to the autoimmune diseases and patients with a high platelet distribution width (PDW) (16.1 vs. 15.8, P = 0.051). In conclusion, the incidence of rituximab-induced thrombocytopenia was higher than that identified during the clinical trials. Healthcare professionals should consider thrombocytopenia as a relevant reaction during treatment with rituximab. More frequent monitoring of the platelet count is especially advised in patients treated in the oncology indication and/or with a low platelet count and high PDW., (© 2012 John Wiley & Sons A/S.)
- Published
- 2012
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35. Discriminative value of platelet size indices for the identification of the mechanism of chemotherapy-induced thrombocytopenia.
- Author
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ten Berg MJ, Huisman A, van den Bemt PM, den Breeijen H, Egberts TC, and van Solinge WW
- Subjects
- Adult, Aged, Antineoplastic Agents adverse effects, Antineoplastic Agents pharmacology, Antineoplastic Agents therapeutic use, Female, Humans, Male, Middle Aged, Neoplasms drug therapy, Platelet Count, Retrospective Studies, Biomarkers, Pharmacological blood, Blood Platelets pathology, Cell Size drug effects, Drug-Related Side Effects and Adverse Reactions, Thrombocytopenia chemically induced, Thrombocytopenia pathology
- Abstract
Context: A biomarker for discriminating mechanisms of chemotherapy-induced thrombocytopenia (CIT) (i.e. increased platelet destruction and decreased platelet production) would be valuable in managing treatment., Objective: We explored the discriminating value of platelet size indices for this purpose in a population of adult oncology patients., Materials and Methods: Mean platelet volume (MPV) and platelet distribution width (PDW) were compared between patients with (i) thrombocytopenia possibly due to increased platelet destruction; (ii) thrombocytopenia possibly due to decreased platelet destruction; and (iii) no thrombocytopenia., Results and Conclusions: We obtained negative results, suggesting that these indices are not useful for discriminating different CIT mechanisms.
- Published
- 2011
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36. Identification of exacerbations in obstructive lung disease through biomarkers.
- Author
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Velthove KJ, Bracke M, Souverein PC, Schweizer RC, Ten Berg MJ, Leufkens HG, and van Solinge WW
- Subjects
- Adult, Aged, Asthma blood, Asthma diagnosis, Case-Control Studies, Disease Progression, Eosinophilia blood, Eosinophilia diagnosis, Female, Hospitalization, Humans, Leukocyte Count, Male, Middle Aged, Odds Ratio, Pulmonary Disease, Chronic Obstructive blood, Pulmonary Disease, Chronic Obstructive diagnosis, Severity of Illness Index, Asthma pathology, Eosinophils pathology, Neutrophils pathology, Pulmonary Disease, Chronic Obstructive pathology
- Abstract
Inflammation has been identified as an important factor for disease exacerbation in obstructive lung disease. In this study, we used neutrophil and eosinophil counts as biomarkers for exacerbation in obstructive lung disease. We conducted a case-control study within a cohort of patients frequenting an outpatient clinic of Respiratory Medicine using data from the Utrecht Patient Oriented Database (UPOD). Cases were patients with a hospital admission for obstructive lung disease in 2005. For each case, one control patient was sampled from the same study base. We identified 143 cases (118 patients with chronic obstructive pulmonary disease and 25 asthma patients) and 143 controls. Admission was associated with both neutrophilia (adjusted odds ratio (OR) 4.3; 95% confidence interval (CI) 2.2-8.5), and eosinophilia (adjusted OR 2.6; 95% CI 1.1-6.2). The association with eosinophilia was only seen in asthma patients. In conclusion, neutrophil and eosinophil counts seem to be useful biomarkers for identifying exacerbations in pharmacoepidemiological studies on obstructive lung disease.
- Published
- 2009
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37. Frequency and nature of drug-drug interactions in a Dutch university hospital.
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Zwart-van Rijkom JE, Uijtendaal EV, ten Berg MJ, van Solinge WW, and Egberts AC
- Subjects
- Adverse Drug Reaction Reporting Systems, Drug Prescriptions, Female, Humans, Male, Medication Errors prevention & control, Netherlands epidemiology, Practice Guidelines as Topic, Reminder Systems, Risk Management, Drug Interactions, Hospitalization statistics & numerical data, Medication Errors statistics & numerical data, Pharmaceutical Services standards, Practice Patterns, Physicians' standards
- Abstract
Aim: Drug-drug interactions (DDIs) may lead to often preventable adverse drug events and health damage. Especially within hospitals, this might be an important factor, as patients are severely ill and multiple medications may be prescribed simultaneously. The objective of this study was to measure the frequency and nature of DDI alerts in a Dutch university hospital., Methods: All patients hospitalized in the University Medical Centre Utrecht in 2006 who were prescribed at least one medication were included. The frequency of DDIs was calculated as: (i) the percentage of patients experiencing at least one DDI, and (ii) the percentage of prescriptions generating a DDI alert. Based on the national professional guideline, DDIs were classified into categories of potential clinical outcome, management advice, clinical relevance (A-F) and available evidence (0-4)., Results: Of the 21 277 admissions included, 5909 (27.8%) encountered at least one DDI. Overall, the prescribing physician received a DDI alert in 9.6% of all prescriptions. The most frequently occurring potential clinical consequence of the DDIs was an increased risk of side-effects such as increased bleeding risk (22.0%), hypotension (14.9%), nephrotoxicity (12.6%) and electrolyte disturbances (10.5%). Almost half (48.6%) of the DDIs could be managed by monitoring laboratory values., Conclusions: Computerized DDI alerts may be a useful tool to prevent adverse drug events within hospitals, but they may also result in 'alert fatigue'. The specificity of alerts could significantly improve by the use of more sophisticated clinical decision support systems taking into account, for example, laboratory values.
- Published
- 2009
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38. Changes in hematological parameters after switching treatment of HIV-infected patients from zidovudine to abacavir or tenofovir DF.
- Author
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Viergever RF, ten Berg MJ, van Solinge WW, Hoepelman AI, and Gisolf EH
- Subjects
- Adenine analogs & derivatives, Adenine therapeutic use, Adult, Aged, Analysis of Variance, Anemia blood, Anemia epidemiology, Dideoxynucleosides therapeutic use, Drug Combinations, Female, Hematologic Tests, Humans, Male, Middle Aged, Netherlands epidemiology, Organophosphonates therapeutic use, Tenofovir, Young Adult, Zidovudine adverse effects, Zidovudine therapeutic use, Anemia chemically induced, Anti-HIV Agents adverse effects, Anti-HIV Agents therapeutic use, HIV Infections blood, HIV Infections drug therapy
- Published
- 2009
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39. Linking laboratory and medication data: new opportunities for pharmacoepidemiological research.
- Author
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ten Berg MJ, Huisman A, van den Bemt PM, Schobben AF, Egberts AC, and van Solinge WW
- Subjects
- Hospital Information Systems, Humans, Clinical Laboratory Information Systems, Clinical Pharmacy Information Systems, Medical Record Linkage, Medical Records Systems, Computerized, Pharmacoepidemiology methods
- Abstract
Transfer of automated laboratory data collected during routine clinical care from the laboratory information system into a database format that enables linkage to other administrative (e.g., patient characteristics) or clinical (e.g., medication, diagnoses, procedures) data provides a valuable tool for clinical epidemiological research. It allows the investigation of biochemical characteristics of diseases, therapeutic effects and diagnostic and/or prognostic markers for disease with easy access and at relatively low cost. To this end, the Utrecht Patient Oriented Database (UPOD), an infrastructure of relational databases comprising data on patient characteristics, laboratory test results, medication orders, hospital discharge diagnoses and medical procedures for all patients treated at the University Medical Centre Utrecht since January 2004, was established. Current research within UPOD is focused on the innovative linkage of laboratory and medication data, which, for example, makes it possible to assess the quality of pharmacotherapy in clinical practice, to investigate interference between laboratory tests and drugs, to study the risk of adverse drug reactions, and to develop diagnostic and prognostic markers or algorithms for adverse drug reactions. Although recently established, we believe that UPOD broadens the opportunities for clinical pharmacoepidemiological research and can contribute to patient care from a laboratory perspective.
- Published
- 2007
- Full Text
- View/download PDF
40. Drug-induced thrombocytopenia: a population study.
- Author
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ten Berg MJ, Huisman A, Souverein PC, Schobben AF, Egberts AC, van Solinge WW, and van den Bemt PM
- Subjects
- Anti-Infective Agents adverse effects, Antirheumatic Agents adverse effects, Case-Control Studies, Female, Humans, Male, Medical Records Systems, Computerized, Middle Aged, Netherlands, Odds Ratio, Retrospective Studies, Risk Factors, Trimethoprim, Sulfamethoxazole Drug Combination adverse effects, beta-Lactams adverse effects, Drug-Related Side Effects and Adverse Reactions, Thrombocytopenia chemically induced
- Abstract
Background: Drug-induced immune thrombocytopenia, excluding heparin-induced thrombocytopenia, is a rare adverse drug reaction for which the evidence about frequency, relative risk and risk factors mainly originates from case reports and case studies. This study aims to quantify the risk for thrombocytopenia following exposure to drugs that are most often reported to cause thrombocytopenia in the general population., Methods: A retrospective, case-control study was conducted within the PHARMO record linkage system. Cases were defined as patients hospitalised for thrombocytopenia in the period 1 January 1990 to 31 December 2002. For each case, up to four controls were matched based on age, sex and geographical area. Exposure on the index date to anticonvulsants, beta-lactam antibacterials, cinchona alkaloids, disease modifying antirheumatic drugs (DMARDs), diuretics, NSAIDs, sulfonamide antibacterials and tuberculostatics was assessed and categorised into mutually exclusive groups of current, recent, past and non-use. The risk was quantified with multivariate conditional logistic regression analysis., Results: The study population comprised 705 cases and 2658 controls. Current use of beta-lactam antibacterials was associated with an increased risk for thrombocytopenia (adjusted odds ratio 7.4, 95% CI 1.8, 29.6). Increased risk estimates, although not significant, were found for current exposure to DMARDs and the sulfonamide antibacterial cotrimoxazole (trimethoprim/sulfamethoxazole). No increased risk was found for anticonvulsants, cinchona alkaloids, diuretics, NSAIDs or tuberculostatics., Conclusion: More evidence for an increased risk for thrombocytopenia in current use of beta-lactam antibacterials in the general population was provided. The expected increase in risk could not be confirmed for the other drugs investigated, which is possibly a result of the limited statistical power. Future studies including more patients and with laboratory data should confirm our findings before drawing definite conclusions.
- Published
- 2006
- Full Text
- View/download PDF
41. Meta-analysis of placebo rates in major depressive disorder trials.
- Author
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Stolk P, Ten Berg MJ, Hemels ME, and Einarson TR
- Subjects
- Chi-Square Distribution, Confidence Intervals, Humans, Placebo Effect, Statistics, Nonparametric, Antidepressive Agents therapeutic use, Depressive Disorder, Major drug therapy, Randomized Controlled Trials as Topic statistics & numerical data
- Abstract
Background: Placebo effects in major depressive disorder (MDD) have received much interest in the medical literature. However, few quantitative analyses have been done in homogeneous populations., Objective: To determine efficacy rates for placebo in patients with MDD; to quantify the correlation between efficacy and publication year, as well as between placebo and drug response rates., Design: Searching MEDLINE (1966-December 2000), EMBASE (1998-February 2001), HealthSTAR (1975-December 2000), and Cochrane (1980-December 2000) databases, randomized, placebo-controlled trials were retrieved including patients with MDD as defined by Diagnostic and Statistical Manual of Mental Disorders, 3rd and 4th editions criteria, Hamilton Rating Scale for Depression score >/=18 or Montgomery-Asberg Depression Rating Scale score >/=16, reporting successes as 50% decreases in scores after 6-8 weeks of treatment. Response rates were summarized using a random effects meta-analysis for per protocol (PP) and intent-to-treat (ITT) results., Results: We included 24 of 134 potential studies examining 4459 patients, 1786 on placebo and 2673 on an antidepressant. Placebo response rates were 45.5% (PP) and 26.9% (ITT). Correlations were significant between year and rates (PP rho 0.448, p = 0.042; ITT rho 0.557; p = 0.006), but not for active drugs. Placebo and drug rates were correlated (PP r 0.397, p = 0.020; ITT r 0.539; p = 0.002)., Conclusions: These placebo rates confirm those reported previously, but were from a homogeneous population. Although statistically significant, the correlation between drug and placebo rates was lower than others reported. During the study period, placebo rates increased linearly; active drugs did not. Correlations between placebo and drug response rates reflected moderate to strong effect sizes. We suggest that current methodology has been unsuccessful in achieving unbiased double-blind conditions not influenced by extra-trial factors, including time.
- Published
- 2003
- Full Text
- View/download PDF
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