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Large Prospective Study (large + prospective_study)
Selected AbstractsMethodological issues in the epidemiological study of the teratogenicity of drugsCONGENITAL ANOMALIES, Issue 2 2005Bengt A.J. Källén ABSTRACT The review presented here discusses and exemplifies problems in epidemiological studies of drug teratogenesis according to methodology: case,control studies, cohort studies, or total population studies. Sources of errors and the possibility of confounding are underlined. The review stresses the caution with which conclusions have to be drawn when exposure data are retrospective or other possible bias exists. It also stresses the problem with the multiple testing situation that is usually present in the studies. It is therefore difficult to draw any firm conclusion from single studies and still more difficult to draw conclusions on causality. As randomized studies are in most cases out of the question, one has to rely on the type of studies which can be made, but the interpretation of the results should be cautious. The ideal study, next to a randomized one, is a large prospective study with detailed exposure information and detailed and unbiased outcome data. Even so, such a study can mainly be used for identifying possible associations which have to be verified or rejected in new studies. Nearly every finding of a risk increase, if not extremely strong, should only be regarded as a tentative signal to be tested in independent studies. [source] A prospective study on the natural course of low-grade squamous intraepithelial lesions and the presence of HPV16 E2-, E6- and E7-specific T-cell responsesINTERNATIONAL JOURNAL OF CANCER, Issue 1 2010Yin Ling Woo Abstract This study investigates the clinical course of low grade squamous intraepithelial lesions (LSIL), HPV status and HPV16-specific immune response in a large prospective study of 125 women with LSIL followed cytologically, virologically and histologically. Women with low-grade abnormal smears were recruited and followed-up for one year. Colposcopy, cervical biopsy for histology and brushings for HPV typing was performed at recruitment, 6 months (no biopsy) and upon completion of the study at one year. HPV16-specific T-cell responses were analysed by interferon-, ELISPOT at entry, 6 and 12 months. Infection with multiple HPV types was detected in 70% of all patients, HPV16 was found in 42% of the patients. LSIL lesions progressed to HSIL in 24%, persisted in 60% and regressed to normal in 16% of the patients. No difference was observed in the clearance rate of infections with single or multiple HPV types among the groups with a different histological outcome. HPV16-specific type 1 T-cell responses were detected in only half of the patients with an HPV16+ LSIL, and predominantly reactive to HPV16 E2 and E6. Interestingly, the presence of HPV16 E2-specific T-cell responses correlated with absence of progression of HPV16+ lesions (p = 0.005) while the detection of HPV16 E6 specific reactivity was associated with persistence (p = 0.05). This large prospective study showed that the majority of LSIL persisted or progressed within the first year. This was paralleled by immune failure as most of the patients with an HPV16+ LSIL failed to react to peptides of HPV16 E2, E6 or E7. [source] Down syndrome serum screening also identifies an increased risk for multicystic dysplastic kidney, two-vessel cord, and hydrocelePRENATAL DIAGNOSIS, Issue 13 2008Jodi D. Hoffman Abstract Objective The FASTER trial compared first and second trimester screening methods for aneuploidy. We examined relationships between maternal serum markers and common congenital anomalies in the pediatric outcome data set of 36 837 subjects. Methods We used nested case,control studies, with cases defined by the most common anomalies in our follow-up database, and up to four controls matched by enrollment site, maternal age and race, enrollment gestational age, and infant gender. Serum markers were dichotomized to , 2 or < 0.5 multiples of the median (MoM). Odds ratios (ORs) and 95% confidence intervals (CI) were estimated. Results Statistically significant (p < 0.05) associations were found between inhibin A , 2 MoM with fetal multicystic dysplastic kidney (MCDK) (OR = 27.5, 95% CI: 2.8,267.7) and two-vessel cord (OR = 4.22, 95% CI:1.6,10.9); hCG of , 2 MoM with MCDK (OR = 19.56, 95% CI: 1.9,196.2) and hydrocele (OR = 2.48, 95% CI: 1.3,4.6); and PAPP-A , 2.0 MoM with hydrocele (OR = 1.88, 95% CI:1.1,3.3). Conclusion In this large prospective study, significant associations were found between several maternal serum markers and congenital anomalies. This suggests potential additional benefits to screening programs that are primarily designed to detect aneuploidy. Copyright © 2008 John Wiley & Sons, Ltd. [source] Etiologic yield of autistic spectrum disorders: A prospective studyAMERICAN JOURNAL OF MEDICAL GENETICS, Issue 1 2006Agatino Battaglia Abstract Studies addressing etiologic yield in childhood developmental disabilities have mainly looked at individuals with developmental delay/mental retardation. The few studies addressing the question of etiologic yield in patients with pervasive developmental disorders (PDDs) had a major drawback, in that the enrolled subjects were diagnosed as having the autistic spectrum disorders based only on history and clinical examination, and/or on unspecified instruments. In addition, only some of these patients underwent a complete laboratory evaluation. To investigate the etiologic yield of PDDs, we undertook a large prospective study on subjects selected according to very strict criteria and diagnosed as having PDD based on the present "gold standard" (ADI-R and ADOS-G), and a clinical diagnosis made by a child psychiatrist. Eighty-five (85) patients with PDD and their first degree relatives participated in this study. These patients were selected from a sample of 236 subjects who had received a clinical diagnosis of PDD at the Stella Maris Institute between March 2002 and 2005. Selection criteria for entering the study were: (1) a diagnosis of PDD (with exclusion of the Rett syndrome) confirmed after the administration of the ADI-R (autism diagnostic interview-revised) and the ADOS-G (autism diagnostic observation schedule-generic). In addition, a clinical diagnosis was made by the child psychiatrist, on the basis of presence or absence of DSM-IV symptoms of autism; (2) chronological age between 4 and 18 years; (3) IQ>30; (4) availability of both biologic parents. Patients, 65/85 (76.5%), had autism, 18/85 (21.2%) had PDD-NOS, and the remaining 2/85 (2.3%) had Asperger syndrome. Ages varied between 4 years 2 months and 12 years 5 months (mean 7.6 years), and there was a marked male preponderance (68/85). All subjects underwent various laboratory studies and neuroimaging. With respect to possible etiologic determination, a detailed history and physical examination in this group of patients with PDD was informative in 10.5% (9/85). HRB karyotype was diagnostic in one, and molecular fragile X studies in one child. Brain MRI was informative in two children (2.3%) with relative macrocrania but no neurological features; and EEG was helpful in one child, identifying a Landau,Kleffner disorder. Audiometry and brainstem auditory evoked potentials (BAEPs) showed a bilateral sensorineural loss in another child. Metabolic evaluation gave normal results in all subjects. The results suggest an evaluation paradigm with reference to etiologic determination for individuals with PDDs that does not presently justify metabolic or neuroimaging on a screening basis. Recurrence risk, treatment implications, and significant and long-lasting emotional relief for the parents suggest that serious consideration be given to clinical genetic examination, genetic testing, EEG study (during wakefulness and sleep), and audiometry, despite a relatively low yield. © 2006 Wiley-Liss, Inc. [source] Evaluation of gender differences in caregiver burden in home care: Nagoya Longitudinal Study of the Frail Elderly (NLS-FE)PSYCHOGERIATRICS, Issue 3 2006Yoshihisa HIRAKAWA Abstract Background:, Japan is presently experiencing a growth in the number of male caregivers and this situation has given rise to some concerns over gender differences. Previous studies have suggested that there are gender differences in caregiver burden in home care, however, it is still unclear whether or not gender differences exist. We therefore conducted this study to attain a better understanding of the Japanese male caregiver burden in home care, using data from the Nagoya Longitudinal Study of Frail Elderly (NLS-FE). Methods:, NLS-FE is a large prospective study of community-dwelling elderly persons eligible for public long-term care insurance who live in Nagoya city and use the services of the Nagoya City Health Care Service Foundation for Older People, which comprises 17 visiting nursing stations and corresponding care-managing centers, from November to December 2003. Data used in this study included the Japanese version of the Zarit Caregiver Burden Interview, caregivers' and dependents' characteristics, and the caregiving situation. The differences in dependent and caregiver characteristics between male and female caregiver groups were assessed using the ,2 -test for categorical variables or the unpaired t -test for continuous variables. Multiple logistic regression was used to examine the association between dependent and caregiver characteristics and caregiver burden. Results:, A total of 399 male caregivers and 1193 female caregivers were included in our analysis. Before and after controlling baseline variables, we did not detect a difference between male and female caregivers with respect to caregiver burden. Conclusion:, Our study suggests that differences in caregiver burden may not necessarily exist between male and female caregivers in Japan. [source] Recurrent ovarian cancer: Treatment with pegylated liposomal doxorubicin; a Westmead Cancer Care Centre experienceASIA-PACIFIC JOURNAL OF CLINICAL ONCOLOGY, Issue 1 2010Rachel F DEAR Abstract Aim: To describe the overall survival, progression-free survival, response rate and toxicity of pegylated liposomal doxorubicin (PLD) in recurrent ovarian cancer. Methods: A retrospective study of 45 patients with recurrent or progressive ovarian cancer was conducted at the Westmead Cancer Care Centre. Patients received PLD at a starting dose of 30,50 mg/m2 every 4 weeks. Results: A total of 43 patients were included for analysis. The starting dose was 40 mg/m2 in 67% of cases, and 21 % had a dose increase. A median of 2 cycles (mean 3, range 1,7) was given. All patients were assessable for response and 77% stopped treatment due to progressive disease. The overall response rate to PLD assessed by CA-125 criteria was 14 percent (six of 43 patients). Five patients (12 percent) were from the potentially platinum-sensitive group and one (2 percent) was from the platinum-resistant group. The overall median progression-free survival was 52 days (2 months), which was greater in the platinum-sensitive than in the platinum-resistant group (4.4 months vs 1.7 months, respectively, P = 0.030). The median overall survival was 296 days (10.6 months) with a trend for this to be longer in the platinum-sensitive than in the platinum-resistant group (13 vs 9 months, P = 0.393). Overall 25 percent of patients had grade 2 or 3 toxicity. Conclusion: The benefit of PLD in platinum-resistant recurrent ovarian cancer is small and the treatment has considerable toxicity. These data support the need to establish whether chemotherapy in this setting has any favorable effect on quality of life. The Australian New Zealand Gynaecological Oncology Group is currently addressing this question in a large prospective study measuring both the subjective and objective benefit (response and survival) of palliative chemotherapy in platinum-resistant or refractory ovarian cancer in Australia. Clinicians are urged to enter their patients in this study to address this important question. [source] Design and Inference for Cancer Biomarker Study with an Outcome and Auxiliary-Dependent SubsamplingBIOMETRICS, Issue 2 2010Xiaofei Wang Summary In cancer research, it is important to evaluate the performance of a biomarker (e.g., molecular, genetic, or imaging) that correlates patients' prognosis or predicts patients' response to treatment in a large prospective study. Due to overall budget constraint and high cost associated with bioassays, investigators often have to select a subset from all registered patients for biomarker assessment. To detect a potentially moderate association between the biomarker and the outcome, investigators need to decide how to select the subset of a fixed size such that the study efficiency can be enhanced. We show that, instead of drawing a simple random sample from the study cohort, greater efficiency can be achieved by allowing the selection probability to depend on the outcome and an auxiliary variable; we refer to such a sampling scheme as,outcome and auxiliary-dependent subsampling,(OADS). This article is motivated by the need to analyze data from a lung cancer biomarker study that adopts the OADS design to assess epidermal growth factor receptor (EGFR) mutations as a predictive biomarker for whether a subject responds to a greater extent to EGFR inhibitor drugs. We propose an estimated maximum-likelihood method that accommodates the OADS design and utilizes all observed information, especially those contained in the likelihood score of EGFR mutations (an auxiliary variable of EGFR mutations) that is available to all patients. We derive the asymptotic properties of the proposed estimator and evaluate its finite sample properties via simulation. We illustrate the proposed method with a data example. [source] A prospective Italian survey on the safety of subcutaneous immunotherapy for respiratory allergyCLINICAL & EXPERIMENTAL ALLERGY, Issue 10 2009M. Schiappoli Summary Background Subcutaneous immunotherapy is effective for the treatment of respiratory allergy, and it is largely used in Italy, but no systematic safety assessment has been carried out so far. Objective To assess prospectively the safety of injection immunotherapy in a multicentre, real-life survey. Methods Eleven Italian allergy departments recorded the clinical characteristics of systemic reactions (SRs) due to immunotherapy. Vaccines were prescribed according to guidelines; only standardized depot extracts were used. SRs were graded according to the EAACI recommendations, and were classified as immediate or delayed. Results One thousand seven hundred and thirty-eight patients (847 males, age range 5,71) received immunotherapy from eight different manufacturers, for a total of 2038 courses (300 patients received two extracts). A total of 60 785 injections were given over a mean immunotherapy duration of 3 years. Overall, 95 reactions were observed in 57 patients (3.28%), corresponding to 4.7% of the courses and 1.56/1000 injections. Twenty-five patients experienced more than one adverse event. There were 34 grade 2, 60 grade 3 and one grade 4 reactions and no fatality. SRs occurred more frequently in patients with asthma than in patients with rhinitis alone (4.1% vs. 1.1%), and were equally distributed between the build-up and the maintenance phase. Ragweed and grass extracts caused significantly more side effects than other allergens. Conclusion In this large prospective study, the rate of SRs was low, thus confirming that injection immunotherapy has an acceptable risk/benefit ratio when prescribed and carried out according to recommendations. [source] | |||||||||||||