Including a time-of-year effect in the analysis of a matched case-control study

Motivated by a matched case-control study to investigate potential risk factors for meningococcal disease amongst adolescents, we consider the analysis of matched case-control studies where disease incidence, and possibly other risk factors, vary with time of year. For the cases, the time of infection may be recorded. For controls, however, the recorded time is simply the time of data collection, which is shortly after the time of infection for the matched case, and so depends on the latter. We show that the effect of risk factors and interactions may be adjusted for the time of year effect in a standard conditional logistic regression analysis without introducing any bias. We also show that, if the time delay between data collection for cases and controls is constant, provided this delay is not very short, estimates of the time of year effect are approximately unbiased. In the case that the length of the delay varies over time, the estimate of the time of year effect is biased. We obtain an approximate expression for the degree of bias in this case.     

Factors affecting the probability of first year medical student dropout in the UK: a logistic analysis for the intake cohorts of 1980-92

BACKGROUND: In the context of the 1997 Report of the Medical Workforce Standing Advisory Committee, it is important that we develop an understanding of the factors influencing medical school retention rates. AIMS: To analyse the determinants of the probability that an individual medical student will drop out of medical school during their first year of study. METHOD: Binomial and multinomial logistic regression analysis of individual-level administrative data on 51 810 students in 21 medical schools in the UK for the intake cohorts of 1980-92 was performed. RESULTS: The overall average first year dropout rate over the period 1980-92 was calculated to be 3.8%. We found that the probability that a student would drop out of medical school during their first year of study was influenced significantly by both the subjects studied at A-level and by the scores achieved. For example, achieving 1 grade higher in biology, chemistry or physics reduced the dropout probability by 0.38% points, equivalent to a fall of 10%. We also found that males were about 8% more likely to drop out than females. The medical school attended also had a significant effect on the estimated dropout probability. Indicators of both the social class and the previous school background of the student were largely insignificant. CONCLUSIONS: Policies aimed at increasing the size of the medical student intake in the UK and of widening access to students from non-traditional backgrounds should be informed by evidence that student dropout probabilities are sensitive to measures of A-level attainment, such as subject studied and scores achieved. If traditional entry requirements or standards are relaxed, then this is likely to have detrimental effects on medical schools' retention rates unless accompanied by appropriate measures such as focussed student support.     

Properties of case/pseudocontrol analysis for genetic association studies: Effects of recombination, ascertainment, and multiple affected offspring

The case/pseudocontrol approach is a general framework for family-based association analysis, incorporating several previously proposed methods such as the transmission/disequilibrium test and log-linear modelling of parent-of-origin effects. In this report, I examine the properties of methods based on a case/pseudocontrol approach when applied to a linked marker rather than (or in addition to) the true disease locus or loci, and when applied to sibships that have been ascertained on, or that may simply contain, multiple affected sibs. Through simulations and analytical calculations, I show that the expected values of the observed relative risk parameters (estimating quantities such as effects due to a child's own genotype, maternal genotype, and parent-of-origin) depend crucially on the ascertainment scheme used, as well as on whether there is non-negligible recombination between the true disease locus and the locus under study. In the presence of either recombination or ascertainment on multiple affected offspring, methods based on conditioning on parental genotypes are shown to give unbiased genotype relative risk estimates at the true disease locus (or loci) but biased estimates of population genotype relative risks at a linked marker, suggesting that the resulting estimates may be misleading when used to predict the power of future studies. Methods that allow for exchangeability of parental genotypes are shown (in the presence of either recombination or ascertainment on multiple affected offspring) to produce false-positive evidence of maternal genotype effects when there are true parent-of-origin or mother-child interaction effects, even when analyzing the true locus. These results suggest that care should be taken in both the interpretation and application of parameter estimates obtained from family-based genetic association studies.     

Spontaneous regression of recurrent squamous cell carcinoma of the tongue

A 73-year-old man presented with well-differentiated squamous cell carcinoma of the tongue (T3N0N0). After the completion of external beam radiotherapy (32Gy) and oral tegafur-uracil (UFT) administration, the tumor had clinically disappeared. Two years later, a recurrent lesion was confirmed histologically. Without any specific therapy, the tumor gradually and spontaneously regressed, from 4 months after the recurrence was diagnosed, and it had completely disappeared both clinically and by computed tomography imaging at 1 year and 4 months after recurrence. There was no evidence suggesting regrowth of the disease in the patient at 3 years and 7 months after the histological confirmation of tumor recurrence.     

Chemoradiotherapy for uterine cancer: current status and perspectives

The conventional local treatment methods (surgery and radiation) for cervical cancer have reached a plateau in terms of survival benefit and, therefore, in this review, new treatment strategies (combined chemotherapy [CT] and local therapy) to overcome the poor prognosis were examined in high-risk groups. The effectiveness of neoadjuvant chemotherapy (NAC) administered prior to radiotherapy (RT) has not been confirmed for any disease stages. But NAC followed by surgery may improve survival in patients with stage Ib2 compared with surgery alone; and in patients with stage Ib2 to IIB compared with RT alone. Five large randomized clinical trials (RCTs) demonstrated a significant survival benefit for patients treated with concurrent chemoradiotherapy (CCRT), using a cisplatin (CDDP)-based regimen, with a 28%–50% relative reduction in the risk of death. In addition, the results of a metaanalysis of 19 RCTs of CCRT (1981–2000) involving 4580 patients showed that CCRT significantly improved overall survival (OS) hazard ratio ([HR] 0.71; P < 0.0001), as well as progression-free survival (PFS; HR 0.61; P < 0.0001). In line with these results, CCRT is currently recommended as standard therapy for advanced cancer (stage III/IVA) in the United States. However, there remains much controversy and uncertainty regarding the optimal therapeutic approaches, especially for patients with advanced cancer. Additional RCTs should be conducted to find the optimal CT regimen and RT for Japanese patients, considering acute and late complications, as well as differences in pelvic anatomy, total radiation dose, and RT procedures between Japan and other countries. Evidence obtained from such studies should establish the optimal CCRT treatment protocol and define the patient population (disease stage) that the protocol really benefits.     

Platelet-activating factor antagonist WEB-2170 inhibits lipopolysaccharide-induced, but not antiprogestin-induced, preterm cervical ripening in timed-pregnant rats

OBJECTIVE: The purpose of this study was to determine whether the platelet-activating factor antagonist WEB-2170 inhibits preterm cervical ripening induced by lipopolysaccharide or by antiprogestin RU 486. STUDY DESIGN: Timed-pregnant rats were killed on day 16 after treatment with (1) WEB-2170, lipopolysaccharide, lipopolysaccharide plus WEB-2170, or vehicle control and (2) with WEB-2170, RU 486, RU 486 plus WEB-2170, or vehicle control. Cervical ripening was assessed by light-induced fluorescence and resistance to stretch. Statistics were assessed by 1-way analysis of variance followed by Tukey-test (P <.05). RESULTS: Light-induced fluorescence and resistance to stretch were significantly lower in the lipopolysaccharide-treated and in the RU486-treated animals compared with vehicle control (lipopolysaccharide:light-induced fluorescence, 7.0+/-0.6 vs 12.8+/-0.8 [P=.001]; resistance to stretch, 0.41+/-0.03 N/mm vs 0.54+/-0.04 N/mm [P <.05]; RU486:light-induced fluorescence, 9.6+/-0.6 vs 11.7+/-0.6 [P <.05]; resistance to stretch, 0.28+/-0.06 N/mm vs 0.61+/-0.02 N/mm [P <.001]). Compared with vehicle control, WEB-2170 alone did not alter cervical light-induced fluorescence or resistance to stretch. Although WEB-2170 significantly blocked cervical ripening after lipopolysaccharide administration (light-induced fluorescence, 11.3+/-1.3 [P <.05]; resistance to stretch, 0.61+/-0.04 [P <.01]), WEB-2170 did not inhibit the RU 486-induced cervical ripening. CONCLUSION: Although infection-related cervical ripening is inhibited by platelet-activating factor antagonists, the physiologic process of cervical ripening appears to be unaffected. Platelet-activating factor inhibition may be of clinical value in the infection-related pathologic processes that are responsible for premature cervical ripening.     

Uterine fibroids and gynecologic pain symptoms in a population-based study

OBJECTIVE: To determine the association between dyspareunia, dysmenorrhea, and noncyclic pelvic pain and the presence and characteristics of uterine fibroids. DESIGN: Population-based cross-sectional study. SETTING: Desio, Italy. PATIENT(S): Six hundred thirty-five non-care-seeking participants of the Seveso Women's Health Study with an intact uterus who underwent transvaginal ultrasound. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Ultrasound-detected presence of uterine fibroids and fibroid characteristics including volume, number, location, and position. Current dyspareunia, dysmenorrhea, and noncyclic pelvic pain was measured by self-report on a visual analog scale. RESULT(S): Uterine fibroids were detected in 96 women (15%). Women with fibroids were more likely to report moderate or severe dyspareunia (adjusted odds ratio [OR] = 2.8, 95% confidence interval [CI] = 0.9-8.3, statistically significant trend) and moderate or severe noncyclic pelvic pain (adjusted OR = 2.6, 95% CI = 0.9-7.6, statistically significant trend) than women without fibroids. Moderate or severe dysmenorrhea was not associated with the presence of fibroids (adjusted OR = 1.1, 95% CI = 0.5-2.6). Number and total volume of fibroids were not related to pain. CONCLUSION(S): This is the first population-based study of gynecologic pain symptoms and fibroids. Dyspareunia and noncyclic pelvic pain, but not dysmenorrhea, increased in severity with the presence of uterine fibroids. Fibroid-associated pain symptomatology in a non-care-seeking population may be different from that of a clinic population.     

Selective uterine artery embolization in the management of uterine myomas

OBJECTIVE: To evaluate the effectiveness of uterine artery embolization in women with uterine myomas in terms of the clinical results for the relief of related symptoms. DESIGN: A pilot study on 26 women affected by uterine single myoma. SETTING: Tertiary level care in an university hospital. PATIENT(S): Twenty-six patients, aged 32 to 54 years, suffering of menorrhagia, pelvic pain, and abdominal mass for single myoma, intramural localization. INTERVENTION(S): Selective uterine artery embolization performed under peridural anesthesia. MAIN OUTCOME MEASURE(S): We measured the x-ray dose to which patients were exposed. Color power Doppler ultrasound examinations were performed during the follow-up evaluations at 1 to 6 months and 1 year after the procedure. RESULT(S): Uterine artery embolization was successfully performed in 100% of cases. The mean fluoroscopy time was of 20 minutes during the procedure. The mean dose of x-ray absorbed by the ovary was estimated at 18.7 cGy and the mean dose of x-ray absorbed by the skin was 126.7 cGy. A reduction of myoma volume of 55% was found at 6 months' ultrasound examination and 75% at the 1-year examination. CONCLUSION(S): Patients are well satisfied and have short recovery times with this procedure. Uterine artery embolization may be a valid alternative to traditional surgery.     

The Ontario Uterine Fibroid Embolization Trial. Part 2. Uterine fibroid reduction and symptom relief after uterine artery embolization for fibroids

OBJECTIVE: To evaluate fibroid uterine volume reduction, symptom relief, and patient satisfaction with uterine artery embolization (UAE) for symptomatic fibroids. DESIGN: Multicenter, prospective, single-arm clinical treatment trial. SETTING: Eight Ontario university and community hospitals.Five hundred thirty-eight patients undergoing bilateral UAE. INTERVENTION(S): Bilateral UAE performed with polyvinyl alcohol particles sized 355-500 microm. MAIN OUTCOME MEASURE(S): Three-month follow-up evaluations including fibroid uterine volume reductions, patient reported symptom improvement (7-point scale), symptom life-impact (10-point scale) reduction, and treatment satisfaction (6-point scale). RESULT(S): Median uterine and dominant fibroid volume reductions were 35% and 42%, respectively. Significant improvements were reported for menorrhagia (83%), dysmenorrhea (77%), and urinary frequency/urgency (86%). Mean menstrual duration was significantly reduced after UAE (7.6 to 5.4 days). Improvements in menorrhagia were unrelated to pre-UAE uterine size or post-UAE uterine volume reduction. Amenorrhea occurring after the procedure was highly age dependent, ranging from 3% (1%-7%) in women under age 40 to 41% (26%-58%) in women age 50 or older. Median fibroid life-impact scores were significantly reduced after UAE (8.0 to 3.0). The majority (91%) expressed satisfaction with UAE treatment. CONCLUSION(S): UAE reduced fibroid uterine volume and provided significant relief of menorrhagia that was unrelated to initial fibroid uterine size or volume reduction. Patient satisfaction with short-term UAE treatment outcomes was high.