Biomedical subjects

Marinus J C Eijkemans

Publications and source records attributed to Marinus J C Eijkemans.

At least 19 recordsLinked to original sources

PubMed2006

Intrauterine insemination with controlled ovarian hyperstimulation versus expectant management for couples with unexplained subfertility and an intermediate prognosis: a randomised clinical trial.

BACKGROUND: Intrauterine insemination with controlled ovarian hyperstimulation is commonly used as first-line treatment for couples with unexplained subfertility. Since such treatment increases the risk of multiple pregnancy, a couple's chances of achieving an ongoing pregnancy without it should be considered to identify those most likely to benefit from treatment. We aimed to assess the incremental effectiveness of intrauterine insemination with controlled ovarian hyperstimulation compared with expectant management in couples with unexplained subfertility and an intermediate prognosis of a spontaneous ongoing pregnancy. METHODS: 253 couples with unexplained subfertility and a 30-40% probability of a spontaneous ongoing pregnancy within 12 months were randomly assigned either intrauterine insemination with controlled ovarian hyperstimulation for 6 months or expectant management for 6 months. The primary endpoint of this hospital-based study was ongoing pregnancy within 6 months. Analysis was by intention to treat. This trial is registered with the Dutch Trial Register and as an International Standard Randomised Clinical Trial, number ISRCTN72675518. FINDINGS: Of the 253 couples enrolled, 127 were assigned intrauterine insemination with controlled ovarian hyperstimulation and 126 expectant management. In the intervention group, 42 (33%) women conceived and 29 (23%) pregnancies were ongoing. In the expectant management group, 40 (32%) women conceived and 34 (27%) pregnancies were ongoing (relative risk 0.85, 95% CI 0.63-1.1). There was one twin pregnancy in each study group, and one woman in the intervention group conceived triplets. INTERPRETATION: A large beneficial effect of intrauterine insemination with controlled ovarian hyperstimulation in couples with unexplained subfertility and an intermediate prognosis can be excluded. Expectant management for 6 months is therefore justified in these couples.

Adult↗

PubMed2006

Comparison of Carpentier-Edwards pericardial and supraannular bioprostheses in aortic valve replacement.

OBJECTIVE: This study aimed at calculating and comparing the long-term outcomes of patients after aortic valve replacement with the Carpentier-Edwards bovine pericardial and porcine supraannular bioprostheses using microsimulation. METHODS: We conducted a meta-analysis of eight studies on the Carpentier-Edwards pericardial valves (2,685 patients, 12,250 patient-years) and five studies on the supraannular valves (3,796 patients, 20,127 patient-years) to estimate the occurrence rates of valve-related events. Eighteen-year follow-up data sets were used to construct age-dependent Weibull curves that described their structural valvular deterioration. The estimates were entered into a microsimulation model, which was used to calculate the outcomes of patients after aortic valve replacement. RESULTS: The annual hazard rates for thrombo-embolism after aortic valve replacement were 1.35% and 1.76% for the pericardial and supraannular valves, respectively. For a 65-year-old male, median time to structural valvular deterioration was 20.1 and 22.2 years while the lifetime risk of reoperation due to structural valvular deterioration was 18.3% and 14.0%, respectively. The life expectancy of the patient was 10.8 and 10.9 years and event-free life expectancy 9.0 and 8.8 years, respectively. CONCLUSIONS: The microsimulation methodology provides insight into the prognosis of a patient after aortic valve replacement with any given valve type. Both the Carpentier-Edwards pericardial and supraannular valve types perform satisfactorily, especially in elderly patients, and show no appreciable difference in long-term outcomes when implanted in the aortic position.

Aged↗

PubMed2006

Staging of esophageal carcinoma in a low-volume EUS center compared with reported results from high-volume centers.

BACKGROUND: It is well known that a learning curve exists for performing EUS. OBJECTIVE: To determine whether the number of EUS investigations performed in a center affects the results of esophageal cancer staging. DESIGN: We compared EUS in the evaluation of T stage and the presence of regional and celiac lymph nodes in a low-volume center where <50 EUS/endoscopist/y were performed with reported results from 7 high-volume EUS centers. SETTING: A reference center for esophageal cancer (>90 cases/y) but a low-volume center for EUS when it comes to individual endoscopists. PATIENTS: From 1994 to 2003, 244 patients underwent EUS, without specific measures to pass a stenotic tumor or FNA and with postoperative TNM stage as the criterion standard in the low-volume EUS center. In the high-volume centers, 670 EUS investigations for esophageal cancer were performed, if needed, with dilation, and with postoperative TNM stage and/or FNA as the criterion standard. INTERVENTIONS: Retrospective analysis. MAIN OUTCOME MEASUREMENTS: Sensitivity and specificity of EUS for esophageal cancer staging. RESULTS: In the low-volume center, results of EUS for T3 staging in patients in whom passage of the EUS probe was possible were almost comparable for sensitivity (85% vs 88%-94%) but were lower for specificity (57% vs 75%-90%), whereas both sensitivity (58% vs 75%-90%) and specificity (87% vs 94%-97%) for T1 or T2 stages were lower than those reported in the high-volume centers. In the low-volume center, sensitivities of EUS for regional (45% vs 63%-89%) and celiac (19% vs 72%-83%) lymph nodes were lower, whereas specificities (75% vs 63%-82% and 99% vs 85%-100%, respectively) were comparable with those from high-volume centers. Results in the low-volume EUS center were worse if the EUS probe could not pass the stricture, which occurred in almost 30% of patients. LIMITATIONS: Both FNA and dilation before EUS for stenotic tumors were not performed in the low-volume EUS center. CONCLUSIONS: The results of EUS performed in a low-volume EUS center compared unfavorably with those reported from high-volume EUS centers. The results of this study suggest that preoperative staging by EUS should be performed by experienced and dedicated EUS endoscopists to optimize staging of esophageal cancer.

Aged↗

PubMed2006

Long-term survival after non-small cell lung cancer surgery: development and validation of a prognostic model with a preoperative and postoperative mode.

OBJECTIVE: At present, there is no prognostic model that is specific for prediction of survival after non-small cell lung cancer surgery. We aimed to develop a prognostic model that can be used to estimate the postoperative survival of individual patients. METHODS: A total of 766 patients underwent resection for primary non-small cell lung cancer. Comorbid conditions were scaled according to the Charlson comorbidity index (CCI). Cox proportional hazard analyses were used to determine risk factors for survival. A prognostic model for survival with a preoperative and postoperative mode was established. Performance of the prognostic model, the CCI, and pathologic tumor stage were quantified by a concordance statistic to indicate discriminative ability. RESULTS: The factors associated with an impaired survival were male sex, age, chronic obstructive pulmonary disease, congestive heart failure, any prior tumor, moderate-to-severe renal disease (preoperative and postoperative mode), clinical tumor stage (preoperative mode), type of resection, and pathologic tumor stage (postoperative mode). The discriminative performance was poor for the CCI (c = 0.55), better for pathologic tumor stage (c = 0.60) and for the preoperative mode (c = 0.61), and best for the postoperative mode (c = 0.65). The discriminative performance of the postoperative mode was better than the discriminative performance of the CCI (P < .0001), the preoperative mode (P < .0002), and pathologic tumor stage (P < .0001). The discriminative performance of the preoperative mode was better than the discriminative performance of the CCI (P < .0001) and similar (P = .90) to a model that only included pathologic tumor stage. CONCLUSIONS: The prognostic model, particularly the postoperative mode, successfully estimates long-term survival of individual patients and could help clinicians in clinical decision-making and treatment tailoring.

Aged↗

PubMed2006

Use of ovarian reserve tests for the prediction of ongoing pregnancy in couples with unexplained or mild male infertility.

The chance of infertile patients conceiving is related to factors like female age and duration of infertility. This prospective observational study evaluated whether the results of ovarian reserve tests, including the novel marker serum anti-Mullerian hormone (AMH), were of additional value in predicting ongoing pregnancy. Two hundred and twenty-two patients diagnosed with unexplained infertility or mild male factor (total motile count>10x10(6)) on the basis of the infertility work-up were prospectively included. Antral follicle count, AMH, inhibin B, FSH and oestradiol concentrations were determined during the early follicular phase. Outcome measures were treatment-dependent and treatment-independent ongoing pregnancy and time to ongoing pregnancy. There were 159 ongoing pregnancies, 52 of which occurred spontaneously. Pregnant patients were significantly younger than those who did not become pregnant (median age 32.4 versus 34.9 years, P<0.001) and FSH concentrations were higher in non-pregnant patients (median 6.8 versus 7.6 IU/l, P=0.04). Only age (hazard ratio 0.93, 95% CI 0.90-0.97) and whether or not the patient was undergoing treatment (hazard ratio 8.10, 95% CI 5.66-11.61) were significantly associated with time to ongoing pregnancy. Ovarian reserve tests, other than chronological age, seem of limited value in predicting (time to) ongoing pregnancy in patients with unexplained and mild male infertility.

Adult↗

PubMed2006

Which factors play a role in clinical decision-making in subfertility?

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.

Adult↗

PubMed2006

A comparison between low-volume referring regional centers and a high-volume referral center in quality of preoperative metastasis detection in esophageal carcinoma.

BACKGROUND AND AIM: An inverse correlation between hospital volume and esophageal resection mortality has been reported. In this study, we compared the quality of preoperative metastasis detection between a high-volume referral center with that of low-volume referring regional centers. METHODS: In 573 patients diagnosed with esophageal cancer (1994-2003), the results of preoperative staging investigations (CT-scan, ultrasound of abdomen and neck, and chest x-ray) performed in 61 regional centers were re-evaluated and/or repeated in one referral center. The gold standards were a radiological result with > or =6 months follow-up, fine-needle aspiration, or the postoperative TNM-stage. RESULTS: In the same group of patients, the preoperative investigations performed in regional centers detected true-positive malignant lymph nodes in 8% of patients and true-positive distant metastases in 7% of patients, whereas these percentages were 16% and 20%, respectively, in the referral center. In 72/573 (13%) patients, one or more metastases detected in the referral center had been missed in the regional centers. After allowing resectability in the presence of M1a lymph nodes, this would still have resulted in futile esophageal resections in 6% of patients. In contrast to the higher diagnostic sensitivity in the referral center, specificity was comparable between referral and regional centers. CONCLUSIONS: This study found that, in assessing the operability of esophageal cancer, the diagnostic sensitivity of metastasis detection in a high-volume referral center was higher than that in referring regional centers. This resulted from both better CT-scanning equipment and more experienced radiologists in the referral center. Should the decision to perform esophagectomy have only been based on metastasis detection in these regional centers, over 1 in 20 patients would have undergone resection in the presence of metastases.

Biopsy, Fine-Needle↗

PubMed2006

Serial echocardiographic assessment of neo-aortic regurgitation and root dimensions after the modified Ross procedure.

BACKGROUND AND AIM OF THE STUDY: Concern exists regarding progressive root dilatation after the modified Ross procedure. The present prospective echocardiographic study aimed to provide further insight into neo-aortic regurgitation (nAR) and neoaortic root dimensions over time in adult Rotterdam Ross root patients, and to study potential risk factors for nAR and dilatation. METHODS: All Rotterdam Ross patients aged > or = 16 years at surgery were subjected to a prospective biennial standardized echocardiographic protocol. Analysis over time of nAR according to the jet length and jet diameter method, autograft annulus and sinotubular junction (STJ) diameters was carried out using a multilevel linear model in 90 patients who had two or more echocardiographic measurements (mean 5; range 2-9; total 458) up to 14 years (mean 7 years) after surgery. RESULTS: The mean (+/- SE) initial postoperative jet length nAR was grade 0.9 +/- 0.09, and the annual increase 0.1 +/- 0.02 (p < 0.001). Initial annulus and STJ diameters were 25 +/- 0.5 mm and 36 +/- 0.6 mm, while annual increases were 0.4 +/- 0.07 mm and 0.5 +/- 0.09 mm, respectively (p < 0.001). Patients who eventually underwent an autograft reoperation (n = 10) had significantly greater initial nAR and greater progression of nAR, and a greater initial annulus diameter. The annual annulus and STJ diameter increase was greater in patients who underwent autograft reoperation. Compared to freestanding root replacement, patients with inclusion cylinder aortic root replacement had smaller initial annulus and STJ diameters that did not increase over time. Female gender was associated with a greater initial jet length and jet diameter nAR and a greater increase over time in jet diameter nAR. Preoperative aortic regurgitation or combined aortic stenosis and regurgitation were associated with greater initial annulus and STJ diameters. Neither bicuspid valve disease, patient age, preoperative ascending aorta aneurysm, prior aortic valve surgery nor hypertension had an effect on initial or progression of nAR, annulus, and STJ diameter. CONCLUSION: The annual increase in nAR and root dimensions is small, but persistent, after autograft aortic root replacement in adults, and further reoperations should be anticipated. Use of the inclusion cylinder root replacement technique seems to prevent neo-aortic dilatation.

Adolescent↗

PubMed2005

Randomized controlled trials with time-to-event outcomes: how much does prespecified covariate adjustment increase power?

PURPOSE: We evaluated the effects of various strategies of covariate adjustment on type I error, power, and potential reduction in sample size in randomized controlled trials (RCTs) with time-to-event outcomes. METHODS: We used Cox models in simulated data sets with different treatment effects (hazard ratios [HRs] = 1, 1.4, and 1.7), covariate effects (HRs = 1, 2, and 5), covariate prevalences (10% and 50%), and censoring levels (no, low, and high). Treatment and a single covariate were dichotomous. We examined the sample size that gives the same power as an unadjusted analysis for three strategies: prespecified, significant predictive, and significant imbalance. RESULTS: Type I error generally was at the nominal level. The power to detect a true treatment effect was greater with adjusted than unadjusted analyses, especially with prespecified and significant-predictive strategies. Potential reductions in sample size with a covariate HR between 2 and 5 were between 15% and 44% (covariate prevalence 50%) and between 4% and 12% (covariate prevalence 10%). The significant-imbalance strategy yielded small reductions. The reduction was greater with stronger covariate effects, but was independent of treatment effect, sample size, and censoring level. CONCLUSIONS: Adjustment for one predictive baseline characteristic yields greater power to detect a true treatment effect than unadjusted analysis, without inflation of type I error and with potentially moderate reductions in sample size. Analysis of RCTs with time-to-event outcomes should adjust for predictive covariates.

Computer Simulation↗

PubMed2005

Individualized cost-effective conventional ovulation induction treatment in normogonadotrophic anovulatory infertility (WHO group 2).

BACKGROUND: Conventional treatment in normogonadotrophic anovulatory infertility (WHO 2) consists of clomiphene citrate (CC), followed by exogenous gonadotrophins (FSH) and IVF. Response to these treatments may be predicted on the basis of individual patient characteristics. We aimed to devise a patient-tailored, cost-effective treatment algorithm involving the above-mentioned treatment modalities, based on individual patient characteristics. METHODS: Sixteen prognostic groups are defined, according to the presence or absence of: age >30 years, amenorrhea, elevated androgen levels and obesity. The chances of response with each of the three treatments were calculated using prediction models. Treatment costs were based on the data of 240 patients visiting a specialist academic fertility unit. Outcome was an ongoing pregnancy within 12 months after initiation of treatment. The costs per pregnancy of three different strategies were compared, with a threshold for cost-effectiveness of 10 000. RESULTS: The strategy CC + FSH + IVF compared with FSH + IVF generated more pregnancies against lower costs. Compared with CC + IVF, it also produced more pregnancies, but at higher costs. For <30 years of age with normal androgen levels, costs per pregnancy were less than 10 000. For women >30 years old, costs per pregnancy were 25 000 and over 200 000, when presenting with normal or elevated androgen levels, respectively. CONCLUSIONS: The conventional treatment protocol is efficient for women aged <30 years with normal androgen levels. For women >30 years old with elevated androgen levels, FSH may be skipped.

Adult↗

PubMed2005

Investigation of the infertile couple: a basic fertility work-up performed within 12 months of trying to conceive generates costs and complications for no particular benefit.

The current approach of the basic fertility work-up has been questioned recently in this journal. Based on new data on human fecundity, the authors advocated starting the fertility work-up after just 6 months of trying to conceive instead of the usual 12 months. In women younger than 39 years and with a regular cycle, there are several arguments why the basic fertility work-up should not be done earlier than after 12 months of child wish. Firstly, 50% of couples who have tried to conceive for 6 months without success will conceive in the next 6 months without any treatment. Secondly, the prevalence of fertility diseases is lower in couples who have been trying to conceive for 6 months as compared with those who have been trying for 12 months. Performance of a fertility work-up at this stage will lead to an increase in false-positive diagnoses compared with performing them at 12 months of subfertility. Thirdly, fertility treatment will have fewer additional effects in couples with good spontaneous conception prospects (6-12 months child wish), compared with subfertile couples who have poor prospects. At present, none of the available fertility treatments have success rates comparable with no intervention in these women, and postponement of treatment in such couples will prevent complications such as ovarian hyperstimulation syndrome and multiple pregnancies. We argue that the fertility work-up should not be offered to couples with a duration of child wish of <12 months, except for women with ovulation disorders and women of 39 years and older.

Adult↗

PubMed2005

Prospective validation of two models predicting pregnancy leading to live birth among untreated subfertile couples.

BACKGROUND: Models predicting clinical outcome need external validation before they can be applied safely in daily practice. This study aimed to validate two models for the prediction of the chance of treatment-independent pregnancy leading to live birth among subfertile couples. METHODS: The first model uses the woman's age, duration and type of subfertility, percentage of progressive sperm motility and referral status. The second model in addition uses the result of the post-coital test (PCT). For validation, these characteristics were collected prospectively in two University hospitals for 302 couples consulting for subfertility. The models' ability to distinguish between women who became pregnant and women who did not (discrimination) and the agreement between predicted and observed probabilities of treatment-independent pregnancy (calibration) were assessed. RESULTS: The discrimination of both models was slightly lower in the validation sample than in the original sample which provided the model. Calibration was good: the observed and predicted probabilities of treatment-independent pregnancy leading to live birth did not differ for both models. CONCLUSIONS: The chance of pregnancy leading to live birth was reliably estimated in the validation sample by both models. The use of PCT improved the discrimination of the models. These models can be useful in counselling subfertile couples.

Birth Rate↗

PubMed2005

Patients' preferences in deciding between intrauterine insemination and expectant management.

BACKGROUND: Intrauterine insemination (IUI) is a commonly used treatment in subfertile couples. We assessed patients' preferences for IUI relative to expectant management. METHODS: Forty subfertile couples were offered scenarios in which the treatment-independent pregnancy chance was varied against a fixed pregnancy chance after IUI without or with controlled ovarian hyperstimulation (COH) of 8% and 12% per cycle, respectively. The treatment-independent pregnancy chance within 12 months was initially set at 100%, and subsequently reduced until couples switched preferences. We also investigated the impact of the risks of ovarian hyperstimulation syndrome (OHSS) and multiple pregnancy on couples' preferences. RESULTS: When pregnancy was guaranteed within a year, all couples would opt for expectant management. Most couples switched to IUI without COH at a 60% chance of a treatment-independent pregnancy and to IUI with COH between a 40% and 60% chance. Where the risk of OHSS was set at 10%, a large majority of the couples preferred expectant management to IUI. At a multiple pregnancy risk of 100%, 77% of the couples would still prefer IUI. CONCLUSIONS: The majority of couples prefer IUI with or without COH when the treatment-independent pregnancy chance in the next 12 months is <50% and <40%, respectively. The risk of a multiple pregnancy does not affect their preference for IUI, whereas IUI is rejected when the risk of OHSS exceeds 10%.

Adult↗

PubMed2005

Applicability of clinical prediction models in acute myocardial infarction: a comparison of traditional and empirical Bayes adjustment methods.

INTRODUCTION: Several clinical prediction models have been developed to predict outcome after acute myocardial infarction. Updating to local circumstances may be required to make such models better applicable. We aimed to compare traditional and empirical Bayes (EB) methods to perform such updating. METHODS: We focused on 16 geographical regions within the GUSTO-I trial, which included 40,830 patients with acute myocardial infarction; of whom, 2851 (7.0%) had died by 30 days. Differences in mortality between regions were studied with traditional adjustment for case mix in logistic regression models and with EB methods. These methods updated predictions for new patients while accounting for the uncertainty in the traditionally estimated mortality differences. RESULTS: The case mix in the regions differed with respect to important predictive characteristics such as age, presence of shock, and anterior infarct location (all P < .001). These differences did not explain regional differences in 30-day mortality, which varied between 80% and 120% with traditional analyses (P < .01). The EB estimates for regional differences were much smaller (between 93% and 107%). CONCLUSIONS: Statistically significant differences in case mix and 30-day mortality were noted between geographical regions. The practical implications of this heterogeneity were, however, limited when model predictions were updated with EB methods.

Bayes Theorem↗

PubMed2005

Prognosis after aortic valve replacement with the Carpentier-Edwards pericardial valve: use of microsimulation.

BACKGROUND: The second-generation Carpentier-Edwards pericardial valve (Edwards Lifesciences LLC, Irvine, CA) is widely used for aortic valve replacement. However, knowledge on the long-term outcomes of patients after valve implantation is incomplete. We used microsimulation to calculate the long-term outcome of any given patient after aortic valve replacement with the Carpentier-Edwards pericardial valve. METHODS: A meta-analysis of 8 reports on aortic valve replacement with the Carpentier-Edwards pericardial valve (2,685 patients; 12,250 patient years) was used to estimate the hazards of valve-related events other than structural valvular deterioration. Structural valvular deterioration was described by age-dependent Weibull curves calculated from 18-year follow-up, premarket approval, Carpentier-Edwards pericardial primary data. These estimates provided the input data for the parameters of the microsimulation model, which was then used to calculate the outcomes of patients of different ages after valve implantation. The model estimates of survival were validated using two external data sets. RESULTS: The Weibull analysis estimated a median time to reoperation for structural valvular deterioration ranging from 18.1 years for a 55-year-old male to 23.2 years for a 75-year-old male. For a 65-year-old male, microsimulation calculated a life expectancy and event-free life expectancy of 10.8 and 9.1 years, respectively. The lifetime risk of at least one valve-related event was 38% and that of reoperation due to structural valvular deterioration 17%, respectively, for this patient. The model estimates of survival showed good agreement with external data. CONCLUSIONS: Microsimulation provides detailed insight into the long-term prognosis of patients after aortic valve replacement. The Carpentier-Edwards pericardial valve performs satisfactorily and offers a low lifetime risk of reoperation due to structural valvular deterioration, especially for elderly patients requiring aortic valve replacement.

Adult↗

PubMed2005

Substantial effective sample sizes were required for external validation studies of predictive logistic regression models.

BACKGROUND AND OBJECTIVES: The performance of a prediction model is usually worse in external validation data compared to the development data. We aimed to determine at which effective sample sizes (i.e., number of events) relevant differences in model performance can be detected with adequate power. METHODS: We used a logistic regression model to predict the probability that residual masses of patients treated for metastatic testicular cancer contained only benign tissue. We performed standard power calculations and Monte Carlo simulations to estimate the numbers of events that are required to detect several types of model invalidity with 80% power at the 5% significance level. RESULTS: A validation sample with 111 events was required to detect that a model predicted too high probabilities, when predictions were on average 1.5 times too high on the odds scale. A decrease in discriminative ability of the model, indicated by a decrease in the c-statistic from 0.83 to 0.73, required 81 to 106 events, depending on the specific scenario. CONCLUSION: We suggest a minimum of 100 events and 100 nonevents for external validation samples. Specific hypotheses may, however, require substantially higher effective sample sizes to obtain adequate power.

Humans↗

PubMed2005

Equally valid models gave divergent predictions for mortality in acute myocardial infarction patients in a comparison of logistic [corrected] regression models.

OBJECTIVE: Models that predict mortality after acute myocardial infarction (AMI) contain different predictors and are based on different populations. We studied the agreement and validity of predictions for individual patients. STUDY DESIGN AND SETTING: We compared predictions from five predictive logistic regression models for short-term mortality after AMI. Three models were developed previously, and two models were developed in the GUSTO-I data, where all five models were applied (n =40,830, 7.0% 30-day mortality). Agreement was studied with weighted kappa statistics of categorized predictions. Validity was assessed by comparing observed frequencies with predictions (indicating calibration) and by the area under the receiver operating characteristic curve (AUC), indicating discriminative ability. RESULTS: The predictions from the five models varied considerably for individual patients, with low agreement between most (kappa <0.6). Risk predictions from the three previously developed models were on average too high, which could be corrected by re-calibration of the model intercept. The AUC ranged from 0.76-0.78 and increased to 0.78-0.79 with re-estimated regression coefficients that were optimal for the GUSTO-I patients. The two more detailed GUSTO-I based models performed better (AUC approximately 0.82). CONCLUSION: Models with different predictors may have a similar validity while the agreement between predictions for individual patients is poor. The main concerns in the applicability of predictive models for AMI should relate to the selected predictors and average calibration.

Aged↗

PubMed2005

Does metformin modify ovarian responsiveness during exogenous FSH ovulation induction in normogonadotrophic anovulation? A placebo-controlled double-blind assessment.

OBJECTIVE: To assess whether the addition of metformin to gonadotrophin ovulation induction in insulin-resistant, normogonadotrophic, anovulatory women alters ovarian responsiveness to exogenous FSH. DESIGN: Placebo-controlled double-blind assessment in an academic hospital. RESULTS: After a progestagen withdrawal bleeding, patients were randomised for either metformin (n = 11) or placebo (n = 9) treatment. In cases of absent ovulation, exogenous FSH was subsequently administered to induce ovulation. Only during metformin treatment did body mass index and androgen (androstenedione and testosterone) levels decrease, whereas FSH and LH levels increased significantly. In the metformin group, a single patient ovulated before the initiation of exogenous FSH. Significantly more monofollicular cycles and lower preovulatory oestradiol concentrations were observed in women receiving FSH with metformin compared with FSH alone. CONCLUSIONS: Metformin co-treatment in a group of insulin-resistant, normogonadotrophic, anovulatory patients resulted in normalization of the endocrine profile and facilitated monofollicular development during the FSH induction of ovulation.

Adolescent↗