Segmentation of health-care consumers: psychological determinants of subjective health and other person-related variables.

BACKGROUND: There is an observable, growing trend toward tailoring support programs - in addition to medical treatment - more closely to individuals to help improve patients' health status. The segmentation model developed by Bloem & Stalpers [Nyenrode Research Papers Series 12:1-22, 2012] may serve as a solid basis for such an approach. The model is focused on individuals' 'health experience' and is therefore a 'cross-disease' model. The model is based on the main psychological determinants of subjective health: acceptance and perceived control. The model identifies four segments of health-care consumers, based on high or low values on these determinants. The goal of the present study is twofold: the identification of criteria for differentiating between segments, and profiling of the segments in terms of socio-demographic and socio-economic variables. METHODS: The data (acceptance, perceived control, socio-economic, and socio-demographic variables) for this study were obtained by using an online survey (a questionnaire design), that was given (random sample N = 2500) to a large panel of Dutch citizens. The final sample consisted of 2465 participants - age distribution and education level distribution in the sample were similar to those in the Dutch population; there was an overrepresentation of females. To analyze the data factor analyses, reliability tests, descriptive statistics and t-tests were used. RESULTS: Cut-off scores, criteria to differentiate between the segments, were defined as the medians of the distributions of control and acceptance. Based on the outcomes, unique profiles have been formed for the four segments: 1. 'Importance of self-management' - relatively young, high social class, support programs: high-quality information. 2. 'Importance of personal control' - relatively old, living in rural areas, high in homeownership; supportive programs: developing personal control skills. 3. 'Importance of acceptance' - relatively young male; supportive programs: help by physicians and nurses. 4. 'Importance of perspective and direction' - female, low social class, receiving informal care; support programs: counseling and personal care. CONCLUSIONS: The profiles describe four segments of individuals/patients that are clearly distinct from each other, each with its own description. The enriched descriptions provide a better basis for the allocation and developing of supportive programs and interventions across individuals.

Significance of FAB subclassification of "acute myeloid leukemia, NOS" in the 2008 WHO classification: analysis of 5848 newly diagnosed patients.

The World Health Organization (WHO) classifies acute myeloid leukemia (AML) via genetic, immunophenotypic, biological, and clinical features. Still, "AML, not otherwise specified (NOS)" is further subdivided based on morphologic criteria similar to those of the French-American-British (FAB) classification. We analyzed the relevance of this practice in patients with newly diagnosed "AML, NOS" with available FAB information undergoing curative-intent therapy in trials of 3 cooperative study groups (Dutch-Belgian Cooperative Trial Group for Hematology/Oncology [HOVON], UK Medical Research Council/National Cancer Research Institute [MRC/NCRI], and the US cooperative group Southwest Oncology Group [SWOG]) or at MD Anderson Cancer Center. Ignoring information on NPM1 and CEBPA, 5848 patients met criteria for "AML, NOS." After multivariate adjustment, FAB M0 was independently associated with significantly lower likelihood of achieving complete remission and inferior relapse-free and overall survival as compared with FAB M1, M2, M4, M5, and M6, with inconclusive data regarding M7. However, restricting attention to known NPM1(neg) patients, FAB M0 was no longer associated with worse outcomes; restricting attention to patients known to be NPM1(neg)/CEPBA(neg) (ie, honoring the provisional entities of "AML with mutated NPM1" and "AML with mutated CEBPA") did not affect this result. In conclusion, in the 2008 WHO classification scheme, FAB subclassification does not provide prognostic information for "AML, NOS" cases if data on NPM1 and CEBPA mutations are available.

Addition of bevacizumab to chemotherapy in acute myeloid leukemia at older age: a randomized phase 2 trial of the Dutch-Belgian Cooperative Trial Group for Hemato-Oncology (HOVON) and the Swiss Group for Clinical Cancer Research (SAKK).

An urgent need for new treatment modalities is emerging in elderly patients with acute myeloid leukemia (AML). We hypothesized that targeting VEGF might furnish an effective treatment modality in this population. Elderly patients with AML were randomly assigned in this phase 2 study (n = 171) to receive standard chemotherapy (3 + 7) with or without bevacizumab at a dose of 10 mg/kg intravenously at days 1 and 15. In the second cycle, patients received cytarabine 1000 mg/m(2) twice daily on days 1-6 with or without bevacizumab. The complete remission rates in the 2 arms were not different (65%). Event-free survival at 12 months was 33% for the standard arm versus 30% for the bevacizumab arm; at 24 months, it was 22% and 16%, respectively (P = .42). The frequencies of severe adverse events (SAEs) were higher in the bevacizumab arm (n = 63) compared with the control arm (n = 28; P = .043), but the percentages of death or life-threatening SAEs were lower in the bevacizumab arm (60% vs 75% of SAEs). The results of the present study show that the addition of bevacizumab to standard chemotherapy does not improve the therapeutic outcome of older AML patients. This trial is registered as number NTR904 in The Nederlands Trial Register (www.trialregister.nl).

Increased aortic stiffness and blood pressure in non-classic Pompe disease.

Vascular abnormalities and glycogen accumulation in vascular smooth muscle fibres have been described in Pompe disease. Using carotid-femoral pulse wave velocity (cfPWV), the gold standard methodology for determining aortic stiffness, we studied whether aortic stiffness is increased in patients with Pompe disease. Eighty-four adult Pompe patients and 179 age- and gender-matched volunteers participated in this cross-sectional case-controlled study. Intima media thickness and the distensibility of the right common carotid artery were measured using a Duplex scanner. Aortic augmentation index, central pulse pressure, aortic reflexion time and cfPWV were assessed using the SphygmoCor® system. CfPWV was higher in patients than in volunteers (8.8 versus 7.4 m/s, p < 0.001). This difference was still present after adjustment for age, gender, mean arterial blood pressure (MAP), heart rate and diabetes mellitus (p = 0.001), and was shown by subgroup analysis to apply to the 40-59 years age group (p = 0.004) and 60+ years age group (p = 0.01), but not to younger age groups (p = 0.99). Except for a shorter aortic reflexion time (p = 0.02), indirect indicators of arterial stiffness did not differ between patients and volunteers. Relative to volunteers (20%), more Pompe patients had a history of hypertension (36%, p = 0.005), and the MAP was higher than in volunteers (100 versus 92 mmHg, p < 0.001). This study shows that patients with non-classic Pompe disease have increased aortic stiffness and blood pressure. Whether this is due to glycogen accumulation requires further investigation. To reduce the potential risk of cardiovascular diseases, we recommend that blood pressure and other common cardiovascular risk factors are monitored regularly.

Risk model and nomogram for dysphagia and xerostomia prediction in head and neck cancer patients treated by radiotherapy and/or chemotherapy.

In our randomized trial on hyperbaric oxygen (HBO), it was shown that HBO could reduce dysphagia and xerostomia, which are frequently encountered after (chemo-) radiotherapy (RT) and/or surgery for head and neck cancer (HNC). A risk model and nomogram are developed to select those patients who most likely will respond to HBO treatment. A total of 434 HNC patients treated from 2000 to 2008 were analyzed and filled out the EORTC QLQC-30 and H&N35 questionnaires. Age, gender, chemotherapy, T and N stages, site, radiotherapy technique, RT boost, surgery of the primary tumor and neck, bilateral RT, and dose were analyzed in a statistical model. The discriminative value of the model was evaluated based on receiver operating characteristics (ROC), the area under the curve (AUC), sensitivity, specificity, and proportion of correctly classified measures. Significant factors in predicting swallowing problems are age, follow-up duration, tumor site, chemotherapy, surgery of the primary tumor and neck, and dose. For dry mouth, the significant factors are age, gender, tumor site, N stage, chemotherapy, and bilateral irradiation. For dysphagia and xerostomia, the area under the ROC curve is 0.7034 and 0.7224, respectively, with a specificity of 89/77%, sensitivity of 27/58%, and a positive predictive value of 83/67% for dysphagia and xerostomia, respectively. The developed predictive risk model could be used to select patients for costly hyperbaric oxygen treatment to prevent or reduce severe late side effects of HNC treatment. Our model serves as a guideline for the Department of Radiation Oncology to reduce costs by excluding patients not amenable to hyperbaric oxygen protocols. The nomogram presented is a useful tool for clinicians in assessing patient risks when deciding on follow-up strategies (e.g., hyperbaric oxygen treatment) after RT or surgery for HNC.

Outcome of microscopic incomplete resection (R1) of colorectal liver metastases in the era of neoadjuvant chemotherapy.

BACKGROUND: Data from patients with colorectal liver metastases (CRLM) who received neoadjuvant chemotherapy before resection were reviewed and evaluated to see whether neoadjuvant chemotherapy influences the predictive outcome of R1 resections (margin is 0 mm) in patients with CRLM. METHODS: Between January 2000 and December 2008, all consecutive patients undergoing liver resection for CRLM were analyzed. Patients were divided into those who did and did not receive neoadjuvant chemotherapy. The outcome after R0 (tumor-free margin >0 mm) and R1 (tumor-free margin 0 mm) resection was compared. RESULTS: A total of 264 were eligible for analysis. Median follow-up was 34 months. Patients without chemotherapy showed a significant difference in median disease-free survival (DFS) after R0 or R1 resection: 17 [95% confidence interval (CI) 10-24] months versus 8 (95% CI 4-12) months (P < 0.001), whereas in patients with neoadjuvant chemotherapy the difference in DFS between R0 and R1 resection was not significant: 18 (95% CI 10-26) months versus 9 (95% CI 0-20) months (P = 0.303). Patients without chemotherapy showed a significant difference in median overall survival (OS) after R0 or R1 resection: 53 (95% CI 40-66) months versus 30 (95% CI 13-47) months (P < 0.001). In patients with neoadjuvant chemotherapy, the median OS showed no significant difference: 65 (95% CI 39-92) months for the R0 group versus the R1 group, in whom the median OS was not reached (P = 0.645). CONCLUSIONS: In patients treated with neoadjuvant chemotherapy, R1 resection was of no predictive value for DFS and OS.

Is the clinical risk score for patients with colorectal liver metastases still useable in the era of effective neoadjuvant chemotherapy?

BACKGROUND: Several clinical risk scores (CRSs) for the outcome of patients with colorectal liver metastases have been validated, but not in patients undergoing neoadjuvant chemotherapy. Therefore, this study evaluates the predictive value of these CRSs in this specific group. METHODS: Between January 2000 and December 2008, all patients undergoing a metastasectomy were analyzed and divided into two groups: 193 patients did not receive neoadjuvant chemotherapy (group A), and 159 patients received neoadjuvant chemotherapy (group B). In group B, the CRSs were calculated before and after administration of neoadjuvant chemotherapy. Results were evaluated by using the CRSs proposed by Nordlinger et al., Fong et al., Nagashima et al., and Konopke et al. RESULTS: In groups A and B, the overall median survival was 43 and 47 months, respectively (P = 0.648). In group A, all CRSs used were of statistically significant predictive value. Before administration of neoadjuvant chemotherapy, only the Nordlinger score was of predictive value. After administration of neoadjuvant chemotherapy, all CRSs were of predictive value again, except for the Konopke score. CONCLUSIONS: Traditional CRSs are not a reliable prognostic tool when used in patients before treatment with neoadjuvant chemotherapy. However, CRSs assessed after the administration of neoadjuvant chemotherapy are useful to predict prognosis.

Fifteen years of external quality assessment in leukemia/lymphoma immunophenotyping in The Netherlands and Belgium: A way forward.

In 1985, external quality assurance was initiated in the Netherlands to reduce the between-laboratory variability of leukemia/lymphoma immunophenotyping and to improve diagnostic conclusions. This program consisted of regular distributions of test samples followed by biannual plenary participant meetings in which results were presented and discussed. A scoring system was developed in which the quality of results was rated by systematically reviewing the pre-analytical, analytical, and post-analytical assay stages using three scores, i.e., correct (A), minor fault (B), and major fault (C). Here, we report on 90 consecutive samples distributed to 40-61 participating laboratories between 1998 and 2012. Most samples contained >20% aberrant cells, mainly selected from mature lymphoid malignancies (B or T cell) and acute leukemias (myeloid or lymphoblastic). In 2002, minimally required monoclonal antibody (mAb) panels were introduced, whilst methodological guidelines for all three assay stages were implemented. Retrospectively, we divided the study into subsequent periods of 4 ("initial"), 4 ("learning"), and 7 years ("consolidation") to detect "learning effects." Uni- and multivariate models showed that analytical performance declined since 2002, but that post-analytical performance improved during the entire period. These results emphasized the need to improve technical aspects of the assay, and reflected improved interpretational skills of the participants. A strong effect of participant affiliation in all three assay stages was observed: laboratories in academic and large peripheral hospitals performed significantly better than those in small hospitals. © 2015 International Clinical Cytometry Society.

Nasal sequelae of Treacher Collins syndrome.

OBJECTIVE: This study aimed to determine external and endonasal deformity, and satisfaction with nasal functioning and appearance, in Treacher Collins syndrome. STUDY DESIGN: A cross-sectional cohort study was conducted. METHODS: Eleven adult patients with Treacher Collins syndrome were compared with 151 controls in terms of satisfaction with nasal functioning and appearance by means of the Nasal Appearance and Function Evaluation Questionnaire. In all patients with Treacher Collins syndrome, external nasal deformities were scored on standardized digital photographs of the nose as rated independently by three experienced physicians. Endonasal deformity was determined by standardized nasal endoscopy. RESULTS: The patients were relatively satisfied with the various esthetic nasal subunits. The most significant functional problems were snoring (P = 0.001) and quality of phonation (P = 0.003). The main external nasal deformities were the dorsal hump (73%), external deviation (≤55%), the bifid or bulbous nasal tip (55%), and columellar septal luxation (55%). In 82% of the patients, a septal deviation was found, often associated with spurs. CONCLUSION: Satisfaction with esthetics of the nose was fair, but these patients suffer from the functional problems of snoring and impaired quality of phonation. A structured nasal ENT physical examination with nasal endoscopy might determine aspects requiring more attention during treatment. Septorhinoplasty can be performed at an adult age if there is a considerable esthetic wish of the patient and/or nasal obstruction combined with septal deviation. Attention should be paid to dorsal hump reduction, correction of the deviated external osseous framework, septoplasty, and correction of the nasal tip shape. LEVEL OF EVIDENCE: 2b.

Use of TransFix™ cerebrospinal fluid storage tubes prevents cellular loss and enhances flow cytometric detection of malignant hematological cells after 18 hours of storage.

Flow cytometry is a sensitive method for detection of leptomeningeal localizations of hematological malignancies (LHM) in cerebrospinal fluid (CSF). Rapid processing of CSF is needed, as leukocyte numbers appear to decline quickly after lumbar puncture. The cell-stabilizing agent TransFix™ may enhance the detection of LHM in CSF by preventing cellular loss. To study the effects of TransFix on leukocyte numbers and the detection of LHM, we prospectively collected 99 CSF samples from patients with suspected or proven LHM in tubes with (i) TransFix; (ii) serum-containing medium; and (iii) no cell-stabilizing agents (native CSF). Presence of LHM and absolute leukocyte numbers were determined by flow cytometry after 30 minutes and 18 hours of storage. Leukocyte numbers in TransFix-stabilized CSF were higher than in the corresponding native samples at both time points (1.4× and 2.3× respectively, P < 0.0001 on each occasion). After 18 hours of storage, TransFix enhanced the detection of LHM in CSF. In all discordant paired observations (13/99, P = 0.005), the level of suspicion (classified as positive, suspicious, or negative) in CSF with TransFix was higher than in native CSF. We conclude that the use of TransFix-containing CSF storage tubes prevents cellular loss and enhances flow cytometric detection of LHM after 18 hours of storage.

The development and validation of a decision-analytic model representing the full disease course of acute myeloid leukemia.

BACKGROUND: The treatment of acute myeloid leukemia (AML) is moving towards personalized medicine. However, due to the low incidence of AML, it is not always feasible to evaluate the cost-effectiveness of personalized medicine using clinical trials. Decision analytic models provide an alternative data source. OBJECTIVE: The aim of this study was to develop and validate a decision analytic model that represents the full disease course of AML. METHODS: We used a micro simulation with discrete event components to incorporate both patient and disease heterogeneity. Input parameters were calculated from patient-level data. Two hematologists critically evaluated the model to ensure face validity. Internal and external validity was tested by comparing complete remission (CR) rates and survival outcomes of the model with original data, other clinical trials and a population-based study. RESULTS: No significant differences in patient and treatment characteristics, CR rate, 5-year overall and disease-free survival were found between the simulated and original data. External validation showed no significant differences in survival between simulated data and other clinical trials. However, differences existed between the simulated data and a population-based study. CONCLUSIONS: The model developed in this study is proved to be valid for analysis of an AML population participating in a clinical trial. The generalizability of the model to a broader patient population has not been proven yet. Further research is needed to identify differences between the clinical trial population and other AML patients and to incorporate these differences in the model.

Screening for obstructive sleep apnea in Treacher-Collins syndrome.

OBJECTIVES/HYPOTHESIS: This study evaluated the accuracy of established obstructive sleep apnea syndrome (OSAS) questionnaires based on presenting symptoms and complaints as screening tools for OSAS in Treacher-Collins syndrome (TCS). STUDY DESIGN: Cross-sectional cohort study. METHODS: In 35 TCS patients (13 children, 22 adults) in whom diagnostic polysomnographic results on OSAS were available, the Brouillette score was evaluated in children and the Epworth Sleepiness Scale in adults. RESULTS: The total Brouillette score showed a sensitivity of 50%, specificity of 71%, and positive and negative predictive values of 60% and 63%, respectively. The answer "No" to the question as to whether a child snored could rule out OSAS in children, and showed positive and negative predictive values of 55% and 100%, respectively. The Epworth Sleepiness Scale showed a sensitivity of 0%, specificity of 92%, and positive and negative predictive values of 0% and 57%, respectively. A positive answer to the question of whether a person falls asleep while sitting and talking to someone (sometimes or more) was able to predict OSAS in adults; this question had positive and negative predictive values of 100% and 72%, respectively. CONCLUSIONS: This cross-sectional cohort study showed that the Brouillette score and the Epworth Sleepiness Scale are of minimal usefulness in TCS. Diagnosis of OSAS based solely on complaints is not reliable, probably due to habituation. Therefore, for a good evaluation and optimal multidisciplinary treatment of this chronic disease in TCS, all newly referred pediatric and adult TCS patients should be screened for OSAS at least once with polysomnography.