Estimating Non-Response Bias in Family Studies: Application to Mental Health and Lifestyle

Non-response to mailed surveys reduces the effective sample size and may introduce bias. Non-response has been studied by (1) comparison to available data in population based registers, (2) directly contacting non-respondents by telephone or single-item reply cards, and (3) longitudinal repetition of the survey. The goal of this paper was to propose an additional method to study non-response bias: when the variable of interest has a familial component, data from respondents can be used as proxy for the data from their non-responding family members. This approach was used with data on smoking, alcohol consumption, physical activity, coffee- and tea-use, education, body mass index, religion, burnout, life events, personality and mental health in large number of siblings and DZ twins registered with the Netherlands Twin Register. In addition, for smoking behavior, we also used the second strategy by sending a reply card. Results show that scores of members from less cooperative families or incomplete twin pairs tended to be more unfavorable than the scores from highly cooperative families or complete twin pairs. For example, family members from less cooperative families cycled less often and scored higher on anxious depression and neuroticism. For smoking, both the results of the reply card and the results of the additional method suggested a higher percentage smokers among the non-respondents but this was only significant with reply card method. In general, differences between highly/less cooperative families and complete/incomplete DZ twins were small. Results suggest that, even for studies with moderate response rates, data collected on health, personality and lifestyle are relatively unbiased.     

Accuracy of the precordial V-Quick patch in persons with cardiac or pulmonary disease

The aim of this study was to demonstrate the equivalence of 12-Lead Electrocardiograms (EKG) obtained with the new V-Quick patch and traditional tab-style electrodes. Using a within-subject design, a convenience sample of 100 subjects with either cardiac or pulmonary disease underwent two 12-lead EKGs, one with the traditional tab-style electrodes and one with the precordial patch. Computer-generated measurements of waveform axes and amplitude were obtained for both EKGs. Comparison of mean and 95% confidence intervals revealed no significant differences in Q, R or S wave amplitude across the six precordial leads. Furthermore, a four-factor ANOVA found no significant difference (p > 0.05) in the Q, R and S wave amplitude between the type of electrode, gender and type of disease. A subset of 29 EKGs read by three experts found intra- (.90) and inter-rater (.84) reliability to be strong. In conclusion, the precordial V-Quick patch provided equivalent EKGs to those obtained using standard tab-style electrodes.     

Intraoperative photodynamic therapy after pleuropneumonectomy in patients with malignant pleural mesothelioma: dose finding and toxicity results

OBJECTIVE: To determine the optimal administered dose of meta-tetrahydroxyphenylchlorin (mTHPC) for intraoperative photodynamic therapy (IPDT) in resected malignant pleural mesothelioma (MPM). The primary objective of this combination treatment was to improve local tumor control. DESIGN: Phase I/II dose escalation study. SETTING: Two Dutch cancer centers. PATIENTS: The study included 28 patients (2 women, 26 men), with pathologically confirmed MPM. The mean age was 57 years (age range, 37 to 68 years), and the World Health Organization performance score was 0 to 1. Epithelial mesotheliomas were found in 17 patients, a sarcomatous mesothelioma was found in 1 patient, and mixed epithelial sarcomatous mesotheliomas were found in 10 patients. METHODS: Patients were injected with 0.075 mg/kg (4 patients), 0.10 mg/kg (19 patients), or 0.15 mg/kg (5 patients) mTHPC 4 or 6 days before undergoing surgery and IPDT. Complete surgical resection (i.e., pleuropneumonectomy) was followed by integral illumination with monochromatic light of 652 nm (10 J/cm(2)). The real-time fluence rate measurements were performed using four isotropic detectors in the chest cavity to calculate the total light dose. RESULTS: Dose-limiting toxicity was reached at the level of 0.15 mg/kg mTHPC. Three patients died in the perioperative period, and one death was directly related to photodynamic therapy. Real-time dosimetry identified 12 patients in whom additional illumination had to be given to the diaphragmatic sinuses, which were unavoidably shielded during integral illumination. In two patients, illumination was cancelled due to the insufficient resectability of the tumor. The median survival time for all 28 patients was 10 months. Local tumor control, 9 months after treatment, was achieved in 13 of the 26 patients treated with IPDT. CONCLUSION: IPDT using mTHPC, combined with a pleuropneumonectomy, resulted in local control of disease in 50% of the treated cases. The considerable toxicity associated with the procedure, however, precludes its recommendation for widespread use. Stricter patient selection and improvements of the IPDT technique may reduce the toxicity.     

Clinical algorithm for cerebrospinal fluid test of 14-3-3 protein in diagnosis of Creutzfeldt-Jacob disease

OBJECTIVE: To study whether an algorithm that includes additional diagnostic information could increase the specificity of the 14-3-3 protein testing in patients suspected to suffer from Creutzfeldt-Jakob disease (CJD). DESIGN: The development of a diagnostic algorithm. METHOD: The 14-3-3 protein was tested in the cerebrospinal fluid from 69 consecutive patients suspected of having CJD. On the basis of a former study and literature research, a diagnostic algorithm was constructed, which restricted the indication for performing the 14-3-3 protein test. RESULTS: By taking into consideration the findings of neuroimaging and routine cerebrospinal fluid examination prior to 14-3-3 testing, the specificity increased to 97% (95%-CI: 85.5-99.9) thus changing the prior probability of having CJD of 35% to a posterior probability of 75-100%, in the case of a positive test result. CONCLUSION: Determining the presence of 14-3-3 protein is a highly sensitive and specific marker for sporadic CJD when used in combination with imaging and cerebrospinal fluid examination.     

Heat-induced superaggregation of amphotericin B modifies its interaction with serum proteins and lipoproteins and stimulation of TNF-alpha

The purpose of the present study was to examine the influence of heat-induced superaggregation of Amphotericin B (AmB) in the Fungizone (FZ) formulation on its interaction with human serum components and relate this to reduced toxicity. Whole serum distribution studies showed that a significantly lower percentage of AmB from HFZ was recovered in the high-density lipoprotein (HDL), low-density lipoprotein (LDL), and triglyceride-rich lipoprotein (TRL) fractions and a greater percentage recovered in the lipoprotein-deficient plasma (LPDP), though the majority of both preparations were recovered in LPDP. Circular dichroism (CD) and difference absorption spectroscopy were used to determine the stability of FZ and heat-treated FZ (HFZ) in the presence of HDL, LDL, serum, and albumin. The CD studies indicate that the "core" aggregate of HFZ is more stable in the presence of HDL and LDL, whereas the FZ is less stable and more dynamic with the core aggregate dissociating to a greater extent in the presence of either purified lipoprotein. Absorption studies with whole serum and purified albumin suggest that FZ aggregates are far less stable in the presence of albumin than HFZ and that interaction with serum albumin is a dominant feature for both drug preparations. HFZ also has a different effect on the cytokine response in vitro. Studies using THP-1 human monocytes show that HFZ provokes a smaller release of tumor necrosis factor (TNF)-alpha than FZ. This cytokine may be associated with the unpleasant side effects of AmB. These findings suggest that heat-induced superaggregation of AmB alters its interaction with HDL, LDL, serum proteins, and monocytes, and these findings may be important in explaining the reduced toxicity of the superaggregated form of AmB.     

A Phase II study of gemcitabine in patients with malignant pleural mesothelioma. European Organization for Research and Treatment of Cancer Lung Cancer Cooperative Group.

BACKGROUND: Gemcitabine has shown activity in patients with less chemosensitive solid tumors. Phase II screening of novel drugs is an accepted method with which to investigate new therapies in malignant mesothelioma. The European Organization for Research and Treatment of Cancer-Lung Cancer Cooperative Group has performed several sequential Phase II trials of new agents for the treatment of mesothelioma over the last 10 years. METHODS: Twenty-seven chemotherapy-naive patients with histologically proven malignant mesothelioma were treated with gemcitabine as a 30-minute intravenous administration of 1250 mg/m2 on Days 1, 8, and 15 of a 28-day cycle. Therapy continued for up to ten cycles unless disease progression or excessive toxicity mandated discontinuation. RESULTS: With a median relative dose intensity of 96%, toxicity was mild and neutropenia of > or = Grade 3 (according to National Cancer Institute criteria) occurred in 30% of patients, without episodes of febrile neutropenia. One case of hemolytic-uremic syndrome, most likely related to gemcitabine use, was observed. Overall, 2 objective responses were observed (response rate of 7%; 95% confidence interval, 1-24%). The median survival was 8 months. CONCLUSIONS: At the prescribed dosage and schedule, single agent gemcitabine appears to have limited activity in chemotherapy-naive patients with malignant pleural mesothelioma.     

Diagnostic value of a psychological test in cases of suspected child abuse

The use of the Bene-Anthony Family Relations Test is described and illustrated by three examples of child abuse. This test should be considered in the investigation of definite or suspected cases of abuse and as part of the preparation of court evidence.     

Complex and simple coronary artery stenoses: a new way to interpret coronary angiograms based on morphologic features of lesions

For many years, atherosclerotic coronary artery lesions have been described by angiographers only in terms of location and degree of narrowing. However, it has become apparent that coronary stenoses generally have distinct morphologic features that can be recognized at angiography and that allow them to be classified as either "simple" or "complex" plaques. Complex plaques are those characterized by ulcerated or ruptured surfaces, subintimal hemorrhage, superimposed partially occluding thrombi, recanalized thrombi, or some combination. Pathologic studies have shown a very high frequency of these lesions at sites of total thrombotic occlusion of coronary arteries. Clinical and angiographic studies have demonstrated a high frequency of such lesions in living patients with both unstable angina and acute myocardial infarction. The presence of complex stenoses has also been found to increase the risk of future myocardial infarction. Plaque morphology thus appears to significantly affect the prognosis of patients with coronary disease and should be carefully evaluated in interpretation of all coronary angiograms.     

The Effect of Soaking Allograft in Bisphosphonate: A Pilot Dose-response Study

Background  

Long-term survival of uncemented total joint replacements relies on osseointegration. With reduced bone stock impacted morselized allograft enhances early implant fixation but is subject to resorption.