Majanka H. Heijenbrok-Kal

Bivariate random effects meta-analysis of ROC curves.

Meta-analysis of receiver operating characteristic (ROC)-curve data is often done with fixed-effects models, which suffer many shortcomings. Some random-effects models have been proposed to execute a meta-analysis of ROC-curve data, but these models are not often used in practice. Straightforward modeling techniques for multivariate random-effects meta-analysis of ROC-curve data are needed. The 1st aim of this article is to present a practical method that addresses the drawbacks of the fixedeffects summary ROC (SROC) method of Littenberg and Moses. Sensitivities and specificities are analyzed simultaneously using a bivariate random-effects model. The 2nd aim is to show that other SROC curves can also be derived from the bivariate model through different characterizations of the estimated bivariate normal distribution. Thereby the authors show that the bivariate random-effects approach not only extends the SROC approach but also provides a unifying framework for other approaches. The authors bring the statistical meta-analysis of ROC-curve data back into a framework of relatively standard multivariate meta-analysis with random effects. The analyses were carried out using the software package SAS (Proc NLMIXED).

Optimal Electrocardiographic Pulsing Windows and Heart Rate : Effect on Image Quality and Radiation Exposure at Dual-Source Coronary CT Angiography

PURPOSE To determine the optimal width and timing of the electrocardiographic (ECG) pulsing window within the cardiac cycle in relation to heart rate (HR), image quality, and radiation exposure in patients who are suspected of having coronary artery disease. MATERIALS AND METHODS The institutional review board approved the study, and all patients gave informed consent. Dual-source computed tomography (CT) was performed in 301 patients (mean HR, 70.1 beats per minute +/- 13.3 [standard deviation]; range, 43-112 beats per minute) by using a wide ECG pulsing window (25%-70% of the R-R interval). Data sets were reconstructed in 5% steps from 20%-75% of R-R interval. Image quality was assessed by two observers on a per-segment level and was classified as good or impaired. High-quality data sets were those in which each segment was of good quality. The width and timing of the image reconstruction window was calculated. On the basis of these findings, an optimal HR-dependent ECG pulsing protocol was designed, and the potential dose-saving effect on effective dose (in millisieverts) was calculated. RESULTS At low HR (< or = 65 beats per minute), high-quality data sets were obtained during end diastole (ED); at high HR (> or = 80 beats per minute), they were obtained during end systole (ES); and at intermediate HR (66-79 beats per minute), they were obtained during both ES and ED. Optimal ECG pulsing windows for low, intermediate, and high HR were at 60%-76%, 30%-77%, and 31%-47% of the R-R interval, respectively, and with these levels, the effective dose was decreased at low HR from 18.7 to 6.8 mSv, at intermediate HR from 14.7 to 13.4 mSv, and at high HR from 11.3 to 4.2 mSv. CONCLUSION With optimal ECG pulsing, radiation exposure to patients, particularly those with low or high HR, can be reduced with preservation of image quality.

Uncertainty and Patient Heterogeneity in Medical Decision Models

Parameter uncertainty, patient heterogeneity, and stochastic uncertainty of outcomes are increasingly important concepts in medical decision models. The purpose of this study is to demonstrate the various methods to analyze uncertainty and patient heterogeneity in a decision model. The authors distinguish various purposes of medical decision modeling, serving various stakeholders. Differences and analogies between the analyses are pointed out, as well as practical issues. The analyses are demonstrated with an example comparing imaging tests for patients with chest pain. For complicated analyses step-by-step algorithms are provided. The focus is on Monte Carlo simulation and value of information analysis. Increasing model complexity is a major challenge for probabilistic sensitivity analysis and value of information analysis. The authors discuss nested analyses that are required in patient-level models, and in nonlinear models for analyses of partial value of information analysis.

A Prospective Study on Employment Outcome 3 Years After Moderate to Severe Traumatic Brain Injury

OBJECTIVES To evaluate the employment outcome in patients with moderate to severe traumatic brain injury (TBI) and to identify which patients are at risk of unemployment 3 years after injury. DESIGN Prospective cohort study. SETTING Patients with moderate and severe TBI discharged from the neurosurgery departments of 3 level 1 trauma centers in The Netherlands. PARTICIPANTS Patients aged 18 to 65 years (N=113; mean age ± SD, 33.2±13.1y; 73% men) who were hospitalized with moderate (26% of patients) to severe (74% of patients) TBI. INTERVENTIONS Not applicable. MAIN OUTCOME MEASURES The main outcome measure was employment status. Potential predictors included patient characteristics, injury severity factors, functional outcome measured at discharge from the acute hospital with the Glasgow Outcome Scale (GOS), Barthel Index (BI), and FIM, and cognitive functioning measured with the Functional Assessment Measure (FAM). RESULTS Ninety-four patients (83%) completed the 3-year follow-up. The employment rate dropped from 80% preinjury to 15% at 3 months postinjury and gradually increased to 55% after 3 years. The employment rate significantly increased from 3 months up to 1 year, but it did not change significantly from 1 to 3 years postinjury. Age, length of hospital stay, discharge to a nursing home (vs home), psychiatric symptoms, and BI, GOS, FIM, and FAM scores were found to be significant univariate determinants for employment status. By using multiple logistic regression analysis, the FAM score (adjusted odds ratio 1.1; P<.000) and psychiatric symptoms (adjusted odds ratio .08; P<.019) were selected as independent predictors for employment status. A FAM cutoff score of less than 65 to identify patients at risk of long-term unemployment had a good diagnostic value. CONCLUSIONS Patients with TBI with psychiatric symptoms and impaired cognitive functioning at hospital discharge are at the highest risk of long-term unemployment. These factors should be the focus of vocational rehabilitation.

Biologically effective dose in total-body irradiation and hematopoietic stem cell transplantation.

Background and Purpose:Total-body irradiation (TBI) is an important part of the conditioning regimen for hematopoietic stem cell transplantation (HSCT) in patients with hematologic malignancies. The results after treatment with various TBI regimens were compared, and dose-effect relationships for the endpoints relapse incidence, disease-free survival, treatment-related mortality, and overall survival were derived. The aim was to define requirements for an optimal treatment schedule with respect to leukemic cell kill and late normal-tissue morbidity.Material and Methods:A literature search was performed. Three randomized studies, four studies comparing results of two or three TBI regimens, and nine reports with results of one specific TBI regimen were identified. Biologically effective doses (BEDs) were calculated. The results of the randomized studies and the studies comparing results of two or three TBI regimens were pooled, and the pooled relative risk (RR) was calculated for the treatments with high BED values versus treatments with a low BED. BED-effect relationships were obtained.Results:RRs for the high BED treatments were significantly lower for relapse incidence, not significantly different for disease- free survival and treatment-related mortality, and significantly higher for overall survival. BED-effect relationships indicate a decrease in relapse incidence and treatment-related mortality and an increase in disease-free and overall survival with higher BED values.Conclusion:“More dose is better”, provided that a TBI setting is used limiting the BEDs of lungs, kidneys, and eye lenses.Hintergrund und Ziel:Die Ganzkörperbestrahlung ist eine wichtige Komponente bei der Konditionierung des Patienten vor einer hämatopoetischen Stammzelltransplantation bei hämatologischen Malignomen. Die Therapieergebnisse verschiedener Ganzkörperbestrahlungs-Regime wurden verglichen und Dosis-Wirkungs-Beziehungen für die Endpunkte Rückfallinzidenz, krankheitsfreies Überleben, behandlungsbezogene Letalität und Gesamtüberleben abgeleitet. Ziel war, die Bedingungen eines auf Elimination von Leukämiezellen und Spätschäden von Normalgewebe optimierten Behandlungsplans zu definieren.Material und Methoden:Es wurde eine Literaturrecherche durchgeführt. Drei randomisierte Studien, vier Studien zum Vergleich von zwei oder drei Ganzkörperbestrahlungs-Regimen und neun Berichte über Ergebnisse eines spezifischen Ganzkörperstrahlungs-Regimes wurden gefunden. Es wurden die biologisch effektiven Dosen (BEDs) berechnet. Die Ergebnisse der randomisierten und der Studien, die zwei oder drei Ganzkörperbestrahlungs-Regime miteinander verglichen, wurden zusammengefasst und das gepoolte relative Risiko (RR) berechnet für Behandlungen mit hohen BED-Werten im Vergleich mit Behandlungen mit niedriger BED. Man erhielt BED-Wirkungs-Beziehungen.Ergebnisse:Die RR-Werte für Behandlungsformen mit hoher BED waren signifikant niedriger für die Rückfallinzidenz, nicht signifikant unterschiedlich hinsichtlich des krankheitsfreien Überlebens und der behandlungsbezogenen Letalität und signifikant höher, bezogen auf Gesamtüberleben. Die BED-Wirkungs-Relationen zeigen eine Abnahme der Rückfallinzidenz und der behandlungsbezogenen Letalität und eine Zunahme von krankheitsfreiem Überleben und Gesamtüberleben bei höheren BED-Werten.Schlussfolgerung:„Mehr Bestrahlung ist besser“—eine Ganzkörperbestrahlung vorausgesetzt, die die BEDs an Lungen, Nieren und Linsen begrenzt.

The Efficacy and Timing of Melodic Intonation Therapy in Subacute Aphasia

Background. Little is known about the efficacy of language production treatment in subacute severe nonfluent aphasia. Although Melodic Intonation Therapy (MIT) is a language production treatment for this disorder, until now MIT effect studies have focused on chronic aphasia. Purpose. This study examines whether language production treatment with MIT is effective in subacute severe nonfluent aphasia. Methods. A multicenter, randomized controlled trial was conducted in a waiting-list control design: patients were randomly allocated to the experimental group (MIT) or the control group (control intervention followed by delayed MIT). In both groups, therapy started at 2 to 3 months poststroke and was given intensively (5 h/wk) during 6 weeks. In a second therapy period, the control group received 6 weeks of intensive MIT. The experimental group resumed their regular treatment. Assessment was done at baseline (T1), after the first intervention period (T2), and after the second intervention period (T3). Efficacy was evaluated at T2. The impact of delaying MIT on therapy outcome was also examined. Results. A total of 27 participants were included: n = 16 in the experimental group and n = 11 in the control group. A significant effect in favor of MIT on language repetition was observed for trained items, with mixed results for untrained items. After MIT there was a significant improvement in verbal communication but not after the control intervention. Finally, delaying MIT was related to less improvement in the repetition of trained material. Conclusions. In these patients with subacute severe nonfluent aphasia, language production treatment with MIT was effective. Earlier treatment may lead to greater improvement.

Memory complaints in chronic stroke patients are predicted by memory self-efficacy rather than memory capacity.

Background: Memory self-efficacy (MSE) is the belief about one’s mastery of memory functioning. In healthy elderly, memory complaints are related to MSE rather than to objectively measured memory capacity. MSE has scarcely been studied in patients that suffered a stroke. The aim of this study was twofold: (1) to examine whether memory capacity and MSE can predict the presence of memory complaints in stroke patients, and (2) to study which variables are the best predictors of MSE. Methods: In a cross-sectional study, 136 stroke patients (>18 months after onset) were recruited from April 2008 to November 2009. MSE was measured using the Metamemory in Adulthood questionnaire. Depression, coping and personality were measured using validated questionnaires, and memory performance was measured using the Rivermead Behavioural Memory Test (RBMT) and the Auditory Verbal Learning Test (AVLT). Patients were divided into a ‘complaints’ and a ‘no complaints’ group. Results: A lower MSE score was an independent predictor of having memory complaints (adjusted odds ratio: 0.422; p = 0.000), adjusted for age and depression. The RBMT and AVLT scores did not predict the presence of memory complaints (p > 0.263). Presence of memory complaints and depression were the strongest predictors of MSE (B = –1.748, p = 0.000; B = –0.054, p = 0.000), followed by word fluency, not having a partner and side of stroke (B = 0.038, p = 0.012; B = –0.517, p = 0.082; B = –0.479, p = 0.088). Conclusions: Memory complaints are predicted by MSE rather than memory capacity. MSE memory training might be an effective training strategy for reducing memory complaints in selected chronic stroke patients.

Health-Related Quality of Life 3 Years After Moderate to Severe Traumatic Brain Injury: A Prospective Cohort Study

OBJECTIVES To evaluate the time course of health-related quality of life (HRQoL) after moderate to severe traumatic brain injury (TBI) and to identify its predictors. DESIGN Prospective cohort study with follow-up measurements at 3, 6, 12, 18, 24, and 36 months after TBI. SETTING Patients with moderate to severe TBI discharged from 3 level-1 trauma centers. PARTICIPANTS Patients (N=97, 72% men) with a mean age ± SD of 32.8±13.0 years (range, 18-65y), hospitalized with moderate (23%) or severe (77%) TBI. INTERVENTIONS Not applicable. MAIN OUTCOME MEASURES HRQoL was measured with the Medical Outcomes Study 36-Item Short-Form Health Survey (SF-36), functional outcomes with the Glasgow Outcome Scale (GOS), Barthel Index, FIM, and Functional Assessment Measure, and mood with the Wimbledon Self-Report Scale. RESULTS The SF-36 domains showed significant improvement over time for Physical Functioning (P<.001), Role Physical (P<.001), Bodily Pain (P<.001), Social Functioning (P<.001), and Role Emotional (P=.024), but not for General Health (P=.263), Vitality (P=.530), and Mental Health (P=.138). Over time there was significant improvement in the Physical Component Summary (PCS) score, whereas the Mental Component Summary (MCS) score remained stable. At 3-year follow-up, HRQoL of patients with TBI was the same as that in the Dutch normative population. Time after TBI, hospital length of stay (LOS), FIM, and GOS were independent predictors of the PCS, whereas LOS and mood were predictors of the MCS. CONCLUSIONS After TBI, the physical component of HRQoL showed significant improvement over time, whereas the mental component remained stable. Problems of disease awareness seem to play a role in self-reported mental HRQoL. After TBI, mood status is a better predictor of the mental component of HRQoL than functional outcome, implying that mood should be closely monitored during and after rehabilitation.

Training Memory Self-efficacy in the Chronic Stage After Stroke A Randomized Controlled Trial

Background. Stroke patients with a low memory self-efficacy (MSE) report more memory complaints than patients with a high MSE. Objective. The aim of this study was to examine the effect of a memory-training program on MSE in the chronic phase after stroke and to identify which patients benefit most from the MSE training program. Methods. In a randomized controlled trial, the effectiveness of the MSE training program (experimental group) was compared with a peer support program (control group) in chronic stroke patients. The primary outcome was MSE, measured using the Metamemory-In-Adulthood Questionnaire. Secondary outcomes included depression, quality of life, and objective verbal memory capacity. Changes in outcomes over the intervention period were compared between both groups. Demographic and clinical variables were studied as potential predictors of MSE outcome in the experimental group. Results. In total, 153 patients were included: mean age = 58 years (standard deviation [SD] = 9.7), 54.9% male, and mean of 54 months (SD = 37) after stroke. Of these, 77 were assigned to the training and 76 to the control group. Improvement of MSE (B = 0.40; P = .019) was significantly greater in the training than in the control group. No significant differences were found for the secondary outcomes. An increase in MSE after training was predicted by a younger age (B = −0.033; P = .006) and a better memory capacity (B = 0.043; P = .009), adjusted for baseline MSE. Conclusions. MSE can be improved by the MSE training program for stroke patients. Younger patients and patients with a better memory capacity benefit most from the MSE training program (Dutch Trial Register: NTR-TC 1656).

THE RELATivE EffECT Of COPinG sTRATEGy AnD DEPREssiOn On HEALTH-RELATED QuALiTy Of LifE in PATiEnTs in THE CHROniC PHAsE AfTER sTROkE

OBJECTIVE To investigate the relative associations of coping strategy and depression on health-related quality of life in patients in the chronic phase after stroke. DESIGN Cross-sectional study. SUBJECTS A total of 213 patients after stroke (> 18 months post-onset), mean age 59 years (standard deviation (SD) 9.86 years), 56% men, mean time post-stroke 53 months (SD 37.8 months). METHODS Coping strategy was measured using the assimilative-accommodative coping scale, depression using the Center for Epidemiologic Studies Depression Scale, and quality of life using the World Health Organization Quality of Life-BREF. Multivariable regression analyses were performed, adjusted for patient characteristics. RESULTS Depression score was independently related to all domains of quality of life (Psychological Health (B = -0.924; p = 0.000), Physical Health (B = -0.832; p = 0.000), Social Relationships (B = -0.917; p = 0.000), Environment (B = -0.662, p = 0.000)). Accommodative coping (B = 0.305; p = 0.024) and assimilative coping (B = 0.235; p = 0.070) were independently related to the domain Psychological Health, adjusted for depression and education level. CONCLUSION Coping strategies and depression score were independently associated with Psychological Health in patients in the chronic phase after stroke. Patients who prefer an accommodative coping strategy may show less symptoms of depression. Preferable coping strategies may be trained in order to improve both depression score and health-related quality of life in future research.