Search

Objective Referral for colposcopy because of abnormal Pap test results is likely to be distressing, but the extent and duration of these effects are unknown. We aimed to fill this gap. Methods We conducted a prospective observational study at two departments of Obstetrics and Gynecology (an academic and a non-academic setting). Women referred for colposcopy completed questionnaires before colposcopy, and at 1, 3, and 6months afterwards. A reference group of 706 screen participants, aged 29–60years old, was included and completed questionnaires once. Main outcome measures were generic health-related quality of life (HRQoL), assessed through the EQ-5D and the SF-12 physical and mental scores (PCS-12 and MCS-12); anxiety as assessed by STAI-6, and screen-specific anxiety as assessed by the psychological consequences questionnaire (PCQ). Results 154 women responded to the questionnaire, of whom 132 were included in the analyses. Histological results were CIN 1 in 17/115 women (15%) and CIN 2+ in 62 (54%). In 36 women (31%) there was no histologically confirmed neoplasia. Before colposcopy physical HRQoL scores were similar or slightly better than in the reference group, while mental HRQoL (MSC-12) and (screen-specific) anxiety were worse (p Conclusions Referral for gynecological evaluation because of abnormal PAP-test results was distressing. Anxiety – and not the physical burden of management – seemed to be the most bothersome to women. For all CIN-grades, distress disappeared over six months following colposcopy, suggesting a reassuring effect of gynecological management.

Objective To call attention to the influence of the number of birth-cohorts used in cost-effectiveness analysis (CEA) models on incremental cost-effectiveness ratios (ICERs) under differential discounting. Methods The consequences of increasing the number of birth-cohorts are demonstrated using a CEA of cervical cancer prevention as an example. The cost-effectiveness of vaccinating 12-year-old girls against the human papillomavirus is estimated with the MISCAN microsimulation screening analysis model for 1, 10, 20, and 30 birth-cohorts. Costs and health effects are discounted with equal rates of 4% and alternatively with differential rates of 4% and 1.5% respectively. The effects of increasing the number of cohorts are shown by comparing the ICERs under equal and differential discounting. Results The ICER decreases as the number of cohorts increases under differential discounting, but not under equal discounting. Conclusions The variation of ICERs with the number of cohorts under differential discounting prompts questions regarding the appropriate specification of CEA models and interpretation of their results. In particular, it raises concerns that arbitrary variation in study specification leads to arbitrary variation in results. Such variations could lead to erroneous policy decisions. These findings are relevant to CEA guidance authorities, CEA practitioners, and decision makers. Our results do not imply a problem with differential discounting per se, yet they highlight the need for practical guidance for its use.

Background and Objective: The International Germ Cell Consensus (IGCC) classification defines good, intermediate, and poor prognosis groups among patients with nonseminomatous germ cell cancer. In the database used to develop the IGCC classification (n = 5,202), >40% of patients were excluded because of missing values (n = 2,154). We looked for effects of this exclusion on survival estimates in the three IGCC prognosis groups. Study Design and Setting: We imputed missing values using a multiple imputation procedure. The IGCC classification was applied to patients with complete data (n = 3,048) and with imputed data (n = 2,154), and 5-year survival was calculated for each prognosis group. Results: Patients with missing values had a lower 5-year survival than those without missing values: 76% vs. 82%. Five-year survival in the complete and imputed data samples was 92% and 87% for the good prognosis groups and 80% and 70% for the intermediate prognosis groups, whereas 5-year survival for the poor prognosis groups in both samples was similar (50% and 47%, respectively). This difference in survival was largely explained by a higher proportion of missing values among patients treated before 1985, who had a worse survival than patients treated after 1985. Conclusion: Multiple imputation of the missing values led to lower survival estimates across the IGCC prognosis groups, compared with estimates based on the complete data. Although imputation of missing values gives statistically better survival estimates, adjustments for year of treatment are necessary to make the estimates applicable to currently diagnosed patients with testicular cancer.

Objective: Various prognostic models have been developed to predict outcome after traumatic brain injury (TBI). We aimed to determine the validity of six models that used baseline clinical and computed tomographic characteristics to predict mortality or unfavorable outcome at 6 months or later after severe or moderate TBI. Study Design and Setting: The validity was studied in two selected series of TBI patients enrolled in clinical trials (Tirilazad trials; n = 2,269; International Selfotel Trial; n = 409) and in two unselected series of patients consecutively admitted to participating centers (European Brain Injury Consortium [EBIC] survey; n = 796; Traumatic Coma Data Bank; n = 746). Validity was indicated by discriminative ability (AUC) and calibration (Hosmer-Lemeshow goodness-of-fit test). Results: The models varied in number of predictors (four to seven) and in development technique (two prediction trees and four logistic regression models). Discriminative ability varied widely (AUC: .61-.89), but calibration was poor for most models. Better discrimination was observed for logistic regression models compared with trees, and for models including more predictors. Further, discrimination was better when tested on unselected series that contained more heterogeneous populations. Conclusion: Our findings emphasize the need for external validation of prognostic models. The satisfactory discrimination indicates that logistic regression models, developed on large samples, can be used for classifying TBI patients according to prognostic risk.

Sixteen vignettes of subfertile couples were constructed by varying fertility history, post-coital test, sperm motility, FSH concentration and Chlamydia antibody titre (CAT). Thirty-five gynaecologists estimated probabilities of treatment-independent pregnancy, intrauterine insemination (IUI) and IVF. Thereafter, they chose IUI, IVF or no treatment. The relative contribution of each factor to probability estimates and to subsequent treatment decisions was calculated. Duration of subfertility and maternal age were the most important contributors for gynaecologists' estimates of treatment-independent pregnancy [relative contribution (RC) 41, 26%]. Maternal age and FSH concentration were the most important contributors in the estimates for IUI (RC: 51, 25%) and for IVF (RC: 64, 31%). The decision to start IVF was mainly determined by maternal age, duration of subfertility, FSH concentration and CAT. The relative contribution of maternal age and duration of subfertility was in concordance with existing prediction models, whereas previous pregnancy and FSH concentration were under- and overestimated respectively. In conclusion, maternal age, duration of subfertility and FSH concentration are the main factors in clinical decision-making in subfertility. Gynaecologists overestimate the importance of FSH concentration, but underestimate that of a previous pregnancy, as compared with their importance reported in prediction models and guidelines.

This observational study shows that the antral follicle count is a better predictor of ongoing pregnancy in IVF patients aged >38 years of age than is basal FSH. Patients aged

The use of the term 'infertility' and related terms in reproductive medicine is reviewed. Current terminology is found to be ambiguous, confusing, and misleading. We recommend that the fertility investigation report of a couple should consist of statements concerning description, diagnosis, and prognosis. The description concerns the duration of nonpregnancy before consulting the clinician. A system for prognostic grading is proposed. The fertility investigation report forms the basis for further action, including the possibility of waiting with treatment in case of almost normal or only slightly reduced fertility. The use of the terms 'infertility', 'subfertility', and 'fecundity' is not necessary, and it is recommended to avoid them.

Objective: To develop a prognostic model for the outcome of IUI. Design: Retrospective cohort study. Setting: Four fertility centers in The Netherlands. Patient(s): Couples of whom the female partners had a regular cycle and who had been treated with IUI. Intervention(s): Intrauterine insemination with and without ovarian hyperstimulation. Main Outcome Measure(s): Ongoing pregnancy. Result(s): Overall, 3,371 couples were included who underwent 14,968 cycles. There were 1,229 (8.2%) pregnancies, of which 1,000 (6.7%) pregnancies were ongoing. Logistic regression analysis demonstrated that increasing maternal age, longer duration of subfertility, presence of male factor subfertility, one-sided tubal pathology, endometriosis, uterine anomalies, and an increasing number of cycles were unfavorable predictors for an ongoing pregnancy. Cervical factor and the use of ovarian hyperstimulation were favorable predictors. The area under the receiver operating characteristic curve was 0.59. When couples were divided into four categories based on prognosis, the difference between the predicted and observed chance, that is, the calibration, was less than 0.5% in each of the four groups. Conclusion(s): Although our model had a relatively poor discriminative capacity, data on calibration showed that the selected prognostic factors allow distinction between couples with a poor prognosis and couples with a good prognosis. After external validation, this model could be of use in patient counseling and clinical decision making. (C) 2004 by American Society for Reproductive Medicine

Objective Randomized controlled trials (RCTs) with dichotomous outcomes may be analyzed with or without adjustment for baseline characteristics (covariates). We studied type I error, power, and potential reduction in sample size with several covariate adjustment strategies. Study Design and Setting Logistic regression analysis was applied to simulated data sets ( n = 360) with different treatment effects, covariate effects, outcome incidences, and covariate prevalences. Treatment effects were estimated with or without adjustment for a single dichotomous covariate. Strategies included always adjusting for the covariate (“prespecified”), or only when the covariate was predictive or imbalanced. Results We found that the type I error was generally at the nominal level. The power was highest with prespecified adjustment. The potential reduction in sample size was higher with stronger covariate effects (from 3 to 46%, at 50% outcome incidence and covariate prevalence) and independent of the treatment effect. At lower outcome incidences and/or covariate prevalences, the reduction was lower. Conclusion We conclude that adjustment for a predictive baseline characteristic may lead to a potentially important increase in power of analyses of treatment effect. Adjusted analysis should, hence, be considered more often for RCTs with dichotomous outcomes.

The objective of this article was to evaluate the utility of high-risk human papillomavirus (HR-HPV) testing for triage of women referred for colposcopy because of abnormal smears. We considered women with persistent mild or moderate dyskaryosis and women with severe dyskaryosis who were referred for colposcopy. For both patient groups we evaluated three alternative management policies: (1) conventional management based on histological assessment; (2) HR-HPV-triage with direct treatment without prior histologic assessment for HR-HPV-positive women and conventional management for HR-HPV-negative women; and (3) direct treatment without histologic assessment for all referred women. For each policy the average number of medical procedures, doctor visits, and the costs per referred woman were calculated. Based on a literature review, the results were tested and translated to other patient groups. Per woman with persistent mild or moderate dyskaryosis and compared with conventional policy, HR-HPV-triage will avoid 0.51 colposcopically directed biopsies, but adds 0.05 local treatments of the cervix (i.e., loop excision of the transformation zone) and 0.09 outpatient visits, and will cost $134 extra. HPV triage is less efficient in women with borderline or mildly dyskaryotic cytology. In women with severe dyskaryosis, direct treatment is more efficient as conventional management or HPV triage. The decision to introduce HPV testing or direct treatment in women with persistent mild or moderate dyskaryosis strongly depends on the relative burden attributed to a colposcopically directed biopsy and an outpatient visit compared to loop excision of the transformation zone treatment of the cervix. For women with severe dyskaryosis, direct treatment should be seriously considered.

The performance of a predictive model is overestimated when simply determined on the sample of subjects that was used to construct the model. Several internal validation methods are available that aim to provide a more accurate estimate of model performance in new subjects. We evaluated several variants of split-sample, cross-validation and bootstrapping methods with a logistic regression model that included eight predictors for 30-day mortality after an acute myocardial infarction. Random samples with a size between n = 572 and n = 9165 were drawn from a large data set (GUSTO-I; n = 40,830; 2851 deaths) to reflect modeling in data sets with between 5 and 80 events per variable. Independent performance was determined on the remaining subjects. Performance measures included discriminative ability, calibration and overall accuracy. We found that split-sample analyses gave overly pessimistic estimates of performance, with large variability. Cross-validation on 10% of the sample had low bias and low variability, but was not suitable for all performance measures. Internal validity could best be estimated with bootstrapping, which provided stable estimates with low bias. We conclude that split-sample validation is inefficient, and recommend bootstrapping for estimation of internal validity of a predictive logistic regression model.

Background The aim of this study was to evaluate whether in patients with myocardial infarction, the intensity and duration of myocardial ischemia as measured by continuous ST monitoring are associated with infarct size and residual left ventricular function. Methods and Results The analyses included patients with myocardial infarction, receiving thrombolytic therapy, who were enrolled in the electrocardiographic substudy of GUSTO-I, monitored by a vector-derived 12-lead electrocardiographic recording system, and in whom either infarct size (defined as cumulative release of α-hydroxybutyrate dehydrogenase activity per liter of plasma over a 72-hour period [Q(72)]) or left ventricular ejection fraction (LVEF) was determined. With the use of linear regression analysis, we investigated the association of various ST-trend characteristics with Q(72) (206 patients) and with LVEF (180 patients). A higher area under the ST trend since thrombolysis until 50% ST recovery and a higher area under recurrent ischemic episodes (ST reelevations) were significantly associated with a higher Q(72), whereas only a higher area under recurrent ischemic episodes was significantly associated with a lower LVEF. These associations remained after adjusting for other patient characteristics such as age, sex, infarct location, and time to treatment. Conclusions These findings support the physiologic hypothesis that both the intensity and duration of myocardial ischemia (both reflected by the estimated areas under the ST-trend curve) determine myocardial damage and thus are associated with infarct size and ejection fraction in patients with acute myocardial infarction who receive thrombolytic therapy. (Am Heart J 1999;138:525-32.)

Incidence of and preoperative predictors for postoperative delirium were studied in 296 patients (age 26-83 years, mean age 63 years) undergoing elective cardiac surgery. Delirium occurred in 40 (13.5%) patients. Predictors included old age, low level of albumin, poor physical condition, use of nifedipine, and a high ratio of the amino acids phenylalanine to the sum of isoleucine, leucine, valine, tyrosine, and tryptophan. These findings suggest that preoperative physical condition and amino acid disturbances may be related to delirium after cardiac surgery in the elderly.

Objective To investigate the effect of mild ovarian hyperstimulation on hormonal and sonographic variables of the subsequent natural cycle. Design Prospective study of three consecutive cycles. Setting University Hospital, Department of Reproductive Medicine, Division of Obstetrics and Gynecology. Patients Twelve couples with subnormal semen as the only identifiable cause of subfertility. Interventions Subjects were offered IUI for three cycles. In the second cycle, mild ovarian hyperstimulation with 75IU IM hMG was applied daily and ovulation was induced with 5,000IU hCG. In the first and third both natural cycles, serum samples were obtained for hormone measurements and ultrasound (US) scanning of the ovaries was performed. Main Outcome Measure To determine whether there was a carryover effect of mild ovarian hyperstimulation as applied in the second cycle, hormone levels and US scans of cycle 3 were compared with those of cycle 1. Results None of the variables of cycle 3 were significantly different from those of cycle 1. Conclusion Because hormonal and sonographic variables in the subsequent natural cycle remain unchanged, a carryover effect of mild ovarian hyperstimulation with gonadotropins seems unlikely.

Objective: To determine the effect of moderate alcohol intake on probability of conception. Design: Prospective cohort study. Setting: Normal healthy women enrolled in an artificial donor insemination program. Patients: Women starting artificial donor insemination for the very first time were selected. Interventions: Alcohol exposure was measured through a self- administered questionnaire at intake of study. Main Outcome Measure: A first positive pregnancy test as indicative for conception. Results: Women with moderate alcohol intake had a slightly higher, though not significant, probability of conception compared with nondrinkers (Hazard Ratio 1.20; 95% confidence interval 0.90 to 1.60). Conclusion: Moderate alcohol intake has no negative impact on female fecundity.

OBJECTIVE: We determined the prognostic value of the postcoital test in subfertile couples. STUDY DESIGN: A retrospective study relates the result of the postcoital test to the occurrence of a spontaneous pregnancy. In a fertility center of a university hospital, data from the complete fertility workup of 956 couples who were examined because of infertility due to cervical hostility, male subfertility, or unexplained causes were collected. Statistical analysis was done with Cox regression. RESULTS: The postcoital test result 9 to 12 hours after intercourse is strongly associated with future pregnancy during the first year after intake; the association is also present when the relation with other prognostic variables is taken into account. CONCLUSIONS: The postcoital test result is a strong predictor of possible fertility within the following year.

To reassess the relations between postulated risk factors and seizure recurrence after a first febrile seizure (FS), the individual data from five follow-up studies that used similar definitions of FSs and risk factors were pooled and reanalyzed. The risk of frequent recurrent seizures and of the occurrence of complex seizures in previously healthy, untreated children was studied. Seizure recurrence hazard was described as a function of the child's attained age. The influence of various risk factors on the recurrence hazard was assessed, with control for other factors. Of a total of 2496 children with 1410 episodes of recurrent seizures, 32% had one, 15% had two, and 7% had three or more recurrent seizures after a first FS; 7% had a complex seizure. The hazard of recurrent seizures was highest between the ages of 12 and 24 months. After a first and a second recurrence, the risk of further FSs was two and two and one-half times higher, respectively. A history of febrile or unprovoked seizures in a first-degree family member and a relatively low temperature at the time of the first seizure were also associated with an increased risk of subsequent recurrences. Young age at onset (

As part of a study towards determinants of survival in nursing home patients with dementia, the prognostic value of a behavioral rating scale for nursing home patients is assessed in an 8-year follow-up study. The 2-year survival rate for the entire cohort (n = 569) was 56%. Women (n = 459) had a 2-year survival rate of 62%, and men (n = 110) had a 2-year survival rate of 40%. Items indicating physical impairment, dependency and apathy had most prognostic value. Items measuring aggressive or depressive behavior, and cognitive impairment were less predictive. These results were confirmed in a multivariate proportional hazards analysis. A prognostic model with age, gender and five behavioral items (needs help when walking, occupied in useful activity, restless at night, utters physical complaints, and socializes with other patients) substantially differentiated in survival chances in patients with dementia. The model gives a predicted 2-year survival chance of less than 20% or more than 80% in 80 of the 569 patients. When adjusted for the variables in the model, previous residence had no prognostic value anymore. Possibilities for further work in this area of research are discussed.

Objective To develop a model that can predict the chance to conceive spontaneously in subfertile couples. Design In a cohort study, a consecutive series of patients consulting infertility was followed up. We related information from previous history, physical examination, postcoital tests (PCT), semen analyses, and sperma penetration meter tests with the occurrence of a spontaneous pregnancy. Setting Fertility center in a university hospital. Patients Nine hundred ninety-six couples consulting for infertility due to cervical hostility, male subfertility, or unexplained infertility. Interventions None. Main Outcome Measure(s) Time between intake and occurrence of the first spontaneous pregnancy. Results Information from the previous history (duration of infertility, primary or secondary female infertility, age of the woman, fertility problems in male's family), the percentage motile sperm in the first semen analysis, and the result of the first PCT are sufficient to predict the chance to conceive. A pocket chart is presented for easy use of the model. Conclusions With a limited amount of diagnostic information, the chance to conceive spontaneously can be predicted.

Mass treatment with antifilarial drugs is the mainstay of the Global Programme to Eliminate Lymphatic Filariasis a parasitic disease which is an important cause of chronic morbidity in tropical countries. Current drugs—diethylcarbamazine or ivermectin usually given with albendazole—effectively kill the microfilariae (larval offspring of the parasite) but their effect on the macrofilariae (adult worms) is incomplete. The search for macrofilaricides remains a research priority. One of the most promising leads is treatment directed at Wolbachia the intracellular bacterial symbiont of filarial parasites. In today’s Lancet Mark Taylor and colleagues provide convincing evidence that depletion of Wolbachia by doxycycline kills most adult worms without causing severe side-effects. (excerpt)

Basal FSH measurements in general infertility patients should be considered as a screening and not as a diagnostic test. Excluding patients from assisted reproduction technology on the basis of an elevated FSH level should be restricted to those with a poor ovarian response to gonadotropin hyperstimulation.

We analyzed the importance of five factors (the nature and extent of adhesions, the macroscopic aspect of the endosalpinx, the thickness of the tubal wall, and the diameter of the hydrosalpinx) for the prediction of subsequent conception in 108 patients treated for hydrosalpinx. Each factor was classified into a score immediately after operation. After follow-up study, each factor was correlated with the pregnancy outcome. The prognostic information of the four most promising factors was combined with Bayes' discriminant analysis. The results clearly indicate the presence of three prognostic classes: a good one (n = 27); an intermediate one (n = 44); and a poor one (n = 37) with a probability of intrauterine pregnancy of 77%, 21%, and 3%, respectively. Moreover, the results allow for a simple classification of each future patient into the appropriate prognostic group. In the present era of in vitro fertilization, this differentiation may have consequences for an optimal treatment of patients.