Wendy Post

Modest effect of p53, EGFR and HER-2/neu on prognosis in epithelial ovarian cancer: a meta-analysis

Background:P53, EGFR and HER-2/neu are the most frequently studied molecular biological parameters in epithelial ovarian cancer, but their prognostic impact is still unequivocal. We performed a meta-analysis to more precisely estimate their prognostic significance.Methods:Published studies that investigated the association between p53, EGFR and HER-2/neu status and survival were identified. Meta-analysis was performed using a DerSimonian–Laird model. Publication bias was investigated using funnel plots and sources of heterogeneity were identified using meta-regression analysis.Results:A total of 62 studies were included for p53, 15 for EGFR and 20 for HER-2/neu. P53, EGFR and HER-2/neu status had a modest effect on overall survival (pooled HR 1.47, 95% CI 1.33–1.61 for p53; HR 1.65, 95% CI 1.25–2.19 for EGFR and HR 1.67, 95% CI 1.34–2.08 for HER-2/neu). Meta-regression analysis for p53 showed that FIGO stage distribution influenced study outcome. For EGFR and HER-2/neu, considerable publication bias was present.Conclusions:Although p53, EGFR and HER-2/neu status modestly influences survival, these markers are, by themselves, unlikely to be useful as prognostic markers in clinical practice. Our study highlights the need for well-defined, prospective clinical trials and more complete reporting of results of prognostic factor studies.

Dietary Influences on Plasma and Urinary Metanephrines: Implications for Diagnosis of Catecholamine-Producing Tumors

CONTEXT Measurements of the 3-O-methylated metabolites of catecholamines [metanephrines (MNs)] in plasma or urine are recommended for diagnosis of pheochromocytoma. It is unclear whether these tests are susceptible to dietary influences. OBJECTIVE The aim of the study was to determine the short-term influence of a catecholamine-rich diet on plasma and urinary fractionated MNs. DESIGN, SETTING, AND PARTICIPANTS We conducted a crossover study in a specialist medical center involving 26 healthy adults. INTERVENTIONS Subjects consumed catecholamine-rich nuts and fruits at fixed times on one day (about 35 mumol dopamine and 1 mumol norepinephrine) and catecholamine-poor products on another day. Blood and urine samples were collected at timed intervals before, during, and after experimental and control interventions. MAIN OUTCOME MEASURES Isotope-dilution mass spectrometry-based measurements of plasma and urinary concentrations of free and deconjugated 3-methoxytyramine (3-MT), normetanephrine (NMN), and MN were made. RESULTS The catecholamine-rich diet had substantial effects (up to 3-fold increases) on plasma concentrations and urinary outputs of free and deconjugated 3-MT. Dietary catecholamines had negligible influences on free NMN in plasma and urine, but substantial effects (up to 2-fold increases) on deconjugated NMN in plasma and urine. Concentrations of free and deconjugated MN in plasma and urine remained unaffected. CONCLUSIONS Dietary restrictions should be considered to minimize false-positive results for urinary and plasma deconjugated MNs during diagnosis of pheochromocytoma. Similar considerations appear warranted for plasma and urinary free 3-MT, but not for free NMN or MN, indicating advantages of measurements of the free compared to deconjugated metabolites.

Factors associated with phantom limb pain: a 3½-year prospective study

Objective: To analyse the prevalence of phantom (limb) pain over time and to analyse factors associated with phantom (limb) pain in a prospective cohort of amputees. Design: A multicentre longitudinal study. Patients: One hundred and thirty-four patients scheduled for amputation were included. Methods: Patients filled in questionnaires before amputation, and postal questionnaires six months, 1½ years and 2½ years to a maximum of 3½ years after amputation. Preoperative assessment included patients’ characteristics, date, side and level of, and reason for amputation. The follow-up questionnaires assessed the frequencies of the experienced phantom pain, prosthetic use and walking distance. The occurrence of phantom pain was defined as phantom pain a few times a day or more frequently. Results: Pre- and postoperative questionnaires were available filled in by 85 amputees (33 females and 52 males). The percentage of lower limb amputees with phantom pain was the highest at six months after amputation, and of upper limb amputees at 1½ years. In general, more women than men experienced phantom pain. One and a half years and 2½ years after amputation the highest percentages of the lower limb amputees used their prosthesis more than 4 hours a day (66%), after that time this percentage decreased to 60%. The results of the two-level logistic regression analysis to predict phantom pain show that phantom pain was less frequently present in men (odds ratio (OR) = 0.12), in lower limb amputees (OR = 0.14) and that it decreased in due course (OR = 0.53 for 1 year). Conclusion: Protective factors for phantom pain are: being male, having a lower limb amputation and the time elapsed since amputation.

Prospective Study of Long-Term Impact of Adjuvant High-Dose and Conventional-Dose Chemotherapy on Health-Related Quality of Life

PURPOSE To evaluate and compare health-related quality of life (HRQOL) after conventional- and high-dose adjuvant chemotherapy in patients with high-risk breast cancer. PATIENTS AND METHODS Patients were randomly assigned to either a conventional or high-dose chemotherapy regimen; both regimens were followed by radiotherapy and tamoxifen. HRQOL was evaluated until disease progression using the Short Form-36 (SF-36), Visual Analog Scale, and Rotterdam Symptom Checklist and assessed every 6 months for 5 years after random assignment. For the SF-36, data from healthy Dutch women with the same age distribution served as reference values. RESULTS Eight hundred four patients (conventional-dose chemotherapy, n = 405; high-dose chemotherapy, n = 399) were included. Median follow-up time was 57 months. Directly after high-dose chemotherapy, HRQOL decreased more compared with conventional chemotherapy for all SF-36 subscales. After 1 year, the reference value of healthy women was reached in both groups. Small differences were observed between the two groups in the role-physical and role-emotional subscales, but 1 year after treatment, these differences were minor and not clinically relevant. During follow-up, patients with a lower educational level and many complaints before chemotherapy experienced a worse HRQOL. CONCLUSION Shortly after high-dose chemotherapy, HRQOL was more affected than after conventional-dose chemotherapy. One year after random assignment, differences were negligible. Identifying patients who have a higher chance of persistent impaired quality of life after treatment (which, in the present study, included patients with a lower educational level and many complaints before chemotherapy) is important and may open the way for better patient-tailored prevention strategies.

Correlation between imaging and pathology in ductal carcinoma in situ of the breast.

BackgroundIt is helpful in planning treatment for patients with ductal carcinoma in situ (DCIS) if the size and grade could be reliably predicted from the mammography. The aims of this study were to determine if the type of calcification can be best used to predict histopathological grade from the mammograms, to examine the association of mammographic appearance of DCIS with grade and to assess the correlation between mammographic size and pathological size.MethodsMammographic films and pathological slides of 115 patients treated for DCIS between 1986 and 2000 were reviewed and reclassified by a single radiologist and a single pathologist respectively. Prediction models for the European Pathologist Working Group (EPWG) and Van Nuys classifications were generated by ordinal regression. The association between mammographic appearance and grade was tested with the χ2-test. Relation of mammographic size with pathological size was established using linear regression. The relation was expressed by the correlation coefficient (r).ResultsThe EPWG classification was correctly predicted in 68%, and the Van Nuys classification in 70% if DCIS was presented as microcalcifications. High grade was associated with presence of linear calcifications (p < 0.001). Association between mammograhic- and pathological size was better for DCIS presented as microcalcifications (r = 0.89, p < 0.001) than for DCIS presented as a density (r = 0.77, p < 0.001).ConclusionsPrediction of histopathological grade of DCIS presenting as microcalcifications is comparable using the Van Nuys and EPWG classification. There is no strict association of mammographic appearance with histopathological grade. There is a better linear relation between mammographic- and pathological size of DCIS presented as microcalcifications than as a density, although both relations are statistically significant.

Which variables relate to the attitudes of teachers, parents and peers towards students with special educational needs in regular education?

While there is an increased interest in describing attitudes of teachers, parents and peers towards students with special educational needs in regular education, there is a lack of knowledge about various variables relating to the attitudes of these three groups. The aims of this study are: (1) to examine which variables relate to the attitudes of teachers (N = 44), parents (N = 508) and peers (N = 1113) towards students with Attention Deficit/Hyperactivity Disorder, Autistic Spectrum Syndrome or a cognitive disability in regular primary education and (2) to examine whether teachers and parents’ attitudes affect the attitudes of peers. An attitude survey was used to assess attitudes and data were analysed by means of multilevel analyses. The variables found in this study relating to attitudes can be used as a foundation to develop interventions to change attitudes.

Seasonality in depressive and anxiety symptoms among primary care patients and in patients with depressive and anxiety disorders; results from the Netherlands Study of Depression and Anxiety

BackgroundLittle is known about seasonality of specific depressive symptoms and anxiety symptoms in different patient populations. This study aims to assess seasonal variation of depressive and anxiety symptoms in a primary care population and across participants who were classified in diagnostic groups 1) healthy controls 2) patients with a major depressive disorder, 3) patients with any anxiety disorder and 4) patients with a major depression and any anxiety disorder.MethodsData were used from the Netherlands Study of Depression and Anxiety (NESDA). First, in 5549 patients from the NESDA primary care recruitment population the Kessler-10 screening questionnaire was used and data were analyzed across season in a multilevel linear model. Second, in 1090 subjects classified into four groups according to psychiatric status according to the Composite International Diagnostic Interview, overall depressive symptoms and atypical versus melancholic features were assessed with the Inventory of Depressive Symptoms. Anxiety and fear were assessed with the Beck Anxiety Inventory and the Fear questionnaire. Symptom levels across season were analyzed in a linear regression model.ResultsIn the primary care population the severity of depressive and anxiety symptoms did not show a seasonal pattern. In the diagnostic groups healthy controls and patients with any anxiety disorder, but not patients with a major depressive disorder, showed a small rise in depressive symptoms in winter. Atypical and melancholic symptoms were both elevated in winter. No seasonal pattern for anxiety symptoms was found. There was a small gender related seasonal effect for fear symptoms.ConclusionsSeasonal differences in severity or type of depressive and anxiety symptoms, as measured with a general screening instrument and symptom questionnaires, were absent or small in effect size in a primary care population and in patient populations with a major depressive disorder and anxiety disorders.

Knowledge of the unknown child: A systematic review of the elements of the Best Interests of the Child Assessment for recently arrived refugee children

Decision-making regarding an asylum request of a minor requires decision-makers to determine the best interests of the child when the minor is relatively unknown. This article presents a systematic review of the existing knowledge of the situation of recently arrived refugee children in the host country. This research is based on the General Comment No. 14 of UN Committee on the Rights of the Child. It shows the importance of knowing the type and number of stressful life events a refugee child has experienced before arrival, as well as the duration and severity of these events. The most common mental health problems children face upon arrival in the host country are PTSD, depression and various anxiety disorders. The results identify the relevant elements of the best interests of the child assessment, including implications for procedural safeguards, which should promote a child rights-based decision in the asylum procedure.

Could the BIC-Q be a decision-support tool to predict the development of asylum-seeking children?

The Best Interest of the Child Questionnaire (BIC-Q) is an instrument to measure the quality of the childrearing environment. We used a sample of asylum-seeking children (N=79) in the Netherlands to determine the relationship between the quality of the childrearing environment and the childs internalizing behavioural problems. In decisions as to whether asylum-seeking children may remain in the Netherlands or must return to their country of origin, those in favour of the childs positive development are in line with the Convention on the Rights of the Child. The aim of the present study is to determine the criterion-related validity of the BIC-Q using internalizing behavioural problems as criteria. In the case of good predictive validity, this instrument might be a suitable tool in judicial decision-making with respect to a possible change in an asylum-seeking childs place of residence. We investigated the criterion-related validity of the BIC-Q using logistical regression analysis and an ROC-curve to determine the relation between the quality of the childrearing environment and the childs internalizing behavioural problems. Logistic regression analysis showed that the current quality of the childrearing environment is negatively related to the risk of internalizing behavioural problems in children. The ROC shows that 81% of the children are correctly predicted whether they have internalizing behavioural problems or not. For seven conditions, the sum of the sensitivity and specificity was at a maximum (.75 and .71, respectively).

Change in health-related quality of life in the first 18 months after lower limb amputation : A prospective, longitudinal study

OBJECTIVE To describe changes in health-related quality of life in people with lower limb amputation, from time of amputation to 18 months, taking into consideration the influence of age and walking distance. In addition, quality of life for people with amputation is compared with the Dutch population norm values. DESIGN Multicentre, longitudinal study. SUBJECTS All people undergoing first amputation: 106 were referred, of whom 82 were included, mean age 67.8 years (standard deviation; SD 13.0), 67% men. A total of 35 remained in the study at 18 months. METHODS Dutch language RAND-36 questionnaire (Research and Development Corporation measure of Quality of Life) was completed at time of amputation, 6 and 18 months after amputation. RESULTS Over time, a significant improvement was seen in physical function, social function, pain, vitality, and perceived change in health (all p < 0.001). Subjects over 65 years of age had a poorer outcome compared with people <65 years for physical function only (p < 0.001). Walking distance was associated with improved scores in social function (p = 0.047). CONCLUSION Quality of life improved significantly in 5 of 7 domains investigated; most change occurred in the first 6 months. Physical function remained well below population norm values. Different domains may be affected in different ways for older and younger age groups, but this requires further research.