Complications after benign hysterectomy, according to procedure: a population-based prospective cohort study from the Danish hysterectomy database, 2004-2015.

OBJECTIVE: To compare the risk of complications associated with benign hysterectomy according to surgical procedure. DESIGN: Register-based prospective cohort study. SETTING: Danish Hysterectomy Database, 2004-2015. POPULATION: All Danish women with benign elective hysterectomy (n = 51 141). METHODS: Multivariate log-binomial regression to compute relative risks (RRs) stratified by calendar period, and adjusted for age, height, weight, smoking habits, use of alcohol, comorbidity, indications, uterine weight and adhesions. Multiple imputation and 'intention to treat' analyses were performed. MAIN OUTCOME MEASURES: Major (grades III-V) and minor (grades I-II) Clavien-Dindo modified complications within 30 days. RESULTS: Overall, major complications occurred in 3577 (7.0%) hysterectomies and minor complications occurred in 4788 (9.4%). The proportions of major and minor complications according to type of hysterectomy were: 10.3 and 9.6% for abdominal hysterectomy (AH); 4.1 and 12.1% for laparoscopic hysterectomy (LH); and 4.9 and 8.0% for vaginal hysterectomy (VH) for non-prolapse, and 2.3 and 6.4% for prolapse. In multivariate analyses, compared with VH for non-prolapse, the risk of major complications was higher for AH (RR 1.82, 95% CI 1.63-2.03) but lower for both LH (RR 0.78, 95% CI 0.68-0.90) and VH for prolapse (RR 0.55; 95% CI 0.41-0.75). For LH, the risk of major complications reduced from a RR of 0.96 (95% CI 0.75-1.22) in the time period 2004-2009 to an RR of 0.72 (95% CI 0.60-0.87) between 2010 and 2015. CONCLUSION: Laparoscopic hysterectomy and VH for uterine prolapse are associated with fewer major complications, and AH is associated with more major complications, compared with VH performed in the absence of uterine prolapse. TWEETABLE ABSTRACT: Laparoscopic hysterectomy has fewer major complications compared with vaginal hysterectomy, in the absence of uterine prolapse.

Randomized trial to examine procedure-to-procedure transfer in laparoscopic simulator training.

BACKGROUND: Laparoscopic simulation has become a standard component of surgical training, but there is limited knowledge regarding skills transfer between procedural tasks. The objective was to investigate the specificity of procedural simulator training. METHODS: This was randomized single-centre educational superiority trial. Surgical novices practised basic skills on a laparoscopic virtual reality simulator. On reaching proficiency, participants were randomized to proficiency-based training. The intervention group practised two procedures on the simulator (appendicectomy followed by salpingectomy), whereas the control group trained on only one procedure (salpingectomy). The main outcomes were number of repetitions and time to proficiency for the second procedure. RESULTS: Ninety-six participants were randomized, of whom 74 per cent were women, with a median age of 26 years. The intervention group needed significantly fewer attempts than the control group to reach proficiency in the second procedure: median (i.q.r.) 22 (17-34) versus 32 (26-41) attempts, which corresponded to 24·1 per cent fewer attempts as assessed by multivariable analysis (P = 0·004). The intervention group required significantly less time than the control group to reach proficiency: median (i.q.r.) 88 (63-127) versus 131 (101-153) min respectively, corresponding to a difference of 31·1 min as assessed by multivariable analysis (P = 0·001). CONCLUSION: Practising two procedures, compared with only one, reduced the number of attempts and time to reach proficiency in the second procedure. Skills transfer is seen between two tasks in laparoscopic simulator training; however, task specificity is still present when practising procedures. REGISTRATION NUMBER: NCT02069951 (http://www.clinicaltrials.gov).

Development of knowledge tests for multi-disciplinary emergency training: a review and an example.

BACKGROUND: The literature is sparse on written test development in a post-graduate multi-disciplinary setting. Developing and evaluating knowledge tests for use in multi-disciplinary post-graduate training is challenging. The objective of this study was to describe the process of developing and evaluating a multiple-choice question (MCQ) test for use in a multi-disciplinary training program in obstetric-anesthesia emergencies. METHODS: A multi-disciplinary working committee with 12 members representing six professional healthcare groups and another 28 participants were involved. Recurrent revisions of the MCQ items were undertaken followed by a statistical analysis. The MCQ items were developed stepwise, including decisions on aims and content, followed by testing for face and content validity, construct validity, item-total correlation, and reliability. RESULTS: To obtain acceptable content validity, 40 out of originally 50 items were included in the final MCQ test. The MCQ test was able to distinguish between levels of competence, and good construct validity was indicated by a significant difference in the mean score between consultants and first-year trainees, as well as between first-year trainees and medical and midwifery students. Evaluation of the item-total correlation analysis in the 40 items set revealed that 11 items needed re-evaluation, four of which addressed content issues in local clinical guidelines. A Cronbach's alpha of 0.83 for reliability was found, which is acceptable. CONCLUSION: Content and construct validity and reliability were acceptable. The presented template for the development of this MCQ test could be useful to others when developing knowledge tests and may enhance the overall quality of test development.

Five-year follow up of a randomised controlled trial comparing subtotal with total abdominal hysterectomy.

OBJECTIVES: To compare the rates of urinary incontinence (UI) and other complications of subtotal abdominal hysterectomy (SAH) with total abdominal hysterectomy (TAH) at 5 years after surgery. DESIGN: Randomised clinical trial with central, computer-generated randomisation. SETTING: Danish multi-centre trial performed in 11 departments of gynaecology. POPULATION: Women referred with benign uterine diseases scheduled for abdominal hysterectomy. METHODS: Women were randomised to either SAH (n = 161) or TAH (n = 158). Follow-up data were collected from participants using postal questionnaires sent out 5 years after surgery. Complications of hysterectomy were further examined by scrutinising registered discharge summaries following hospitalisation. Intention-to-treat and per-protocol analyses were conducted. Potential bias caused by missing data was handled using multiple imputation. MAIN OUTCOME MEASURES: The primary outcome was UI. Secondary outcomes included constipation, prolapse of the vaginal vault or cervical stump, satisfaction with sexual life, pelvic pain, postoperative complications and vaginal bleeding. RESULTS: The response rate was 234/319 (73.4%). A significantly higher proportion of respondents had urinary incontinence 5 years after SAH 34/113 (30.1%) than TAH 21/119 (17.6%) (RR 1.71, 95% confidence interval 1.06-2.75, P = 0.026). This difference reduced after multiple imputation to account for missing data (RR 1.37, 95% confidence interval 0.99-1.89, P = 0.052). Eleven of the 101 women (11%) in the SAH group still experienced vaginal bleeding. No other differences were found between the two types of abdominal hysterectomy. AUTHORS' CONCLUSIONS: A smaller proportion of women suffered from UI after TAH than after SAH 5 years postoperatively. Around one in ten women continued to experience vaginal bleeding 5 years after SAH.

Assessment of performance measures and learning curves for use of a virtual-reality ultrasound simulator in transvaginal ultrasound examination.

OBJECTIVE: To assess the validity and reliability of performance measures, develop credible performance standards and explore learning curves for a virtual-reality simulator designed for transvaginal gynecological ultrasound examination. METHODS: A group of 16 ultrasound novices, along with a group of 12 obstetrics/gynecology (Ob/Gyn) consultants, were included in this experimental study. The first two performances of the two groups on seven selected modules on a high-fidelity ultrasound simulator were used to identify valid and reliable metrics. Performance standards were determined and novices were instructed to continue practicing until they attained the performance level of an expert subgroup (n = 4). RESULTS: All 28 participants completed the selected modules twice and all novices reached the expert performance level. Of 153 metrics, 48 were able to be used to discriminate between the two groups' performance. The ultrasound novices scored a median of 43.8% (range, 17.9-68.9%) and the Ob/Gyn consultants scored a median of 82.8% (range, 60.4-91.7%) of the maximum sum score (P < 0.001). The ultrasound novices reached the expert level (88.4%) within a median of five iterations (range, 5-6), corresponding to an average of 219 min (range, 150-251 min) of training. The test/retest reliability was high, with an intraclass correlation coefficient of 0.93. CONCLUSIONS: Competence in the performance of gynecological ultrasound examination can be assessed in a valid and reliable way using virtual-reality simulation. The novices' performance improved with practice and their learning curves plateaued at the level of expert performance, following between 3 and 4 h of simulator training.

Which factors are associated with trainees' confidence in performing obstetric and gynecological ultrasound examinations?

OBJECTIVE: To explore the association between clinical training characteristics and trainees' level of confidence in performing ultrasound scans independently. METHODS: A cross-sectional e-survey was distributed to members of the national societies of junior obstetricians/gynecologists in Denmark, Sweden and Norway (n = 973). Multiple linear regression models were used to explore the effect that amount of time spent in specialized ultrasound units and clinical experience had on trainees' confidence in performing ultrasonography independently. Exploratory factor analysis was used to identify factors that contributed to trainees' confidence in performing ultrasonography. Trainees' ultrasound confidence was finally compared with their expected levels of performance. RESULTS: Of the 682 respondents (response rate 70.1%), 621 met the inclusion criteria. Clinical experience and time spent in specialized ultrasound units were predictors of trainees' confidence in performing ultrasonography independently (P < 0.001). Trainees required more than 24 months of clinical experience and 12-24 days of training in specialized ultrasound units in order to feel confident about performing transvaginal and transabdominal ultrasound scans independently. Three factors were related to ultrasound confidence: technical aspects, image perception and integration of scan into patient care. There were significant differences between trainees' level of confidence and their expected levels of performance (P < 0.001). CONCLUSIONS: Clinical experience and time spent in specialized ultrasound units were predictors of trainees' confidence in performing ultrasonography independently. Discrepancies between trainees' confidence and their expected levels of performance raised concerns about the adequacy of current ultrasound training programs.

Reliable and valid assessment of ultrasound operator competence in obstetrics and gynecology.

OBJECTIVES: To explore the reliability and validity of a recently developed instrument for assessment of ultrasound operator competence, the Objective Structured Assessment of Ultrasound Skills (OSAUS). METHODS: Three groups of 10 doctors with different levels of ultrasound experience in obstetrics and gynecology were included. The novices had less than 1 month of experience, the intermediate group had 12-60 months of experience and the senior participants were all consultants. Fifteen participants performed transabdominal fetal biometry and the other 15 participants performed systematic transvaginal gynecological ultrasound scans. All scans were video-recorded and assessed by two blinded consultants using the OSAUS scale. The OSAUS scores were compared between the groups using the Kruskal-Wallis test, and pass/fail scores were determined using the contrasting-groups method of standard setting. RESULTS: For the transabdominal fetal biometry examinations, the mean ± SD OSAUS scores of the novices, intermediates and senior participants were 1.5 ± 0.4, 3.3 ± 0.6 and 4.4 ± 0.4, respectively (P = 0.003). For the systematic transvaginal scans, the mean ± SD OSAUS scores of the novices, intermediates and senior participants were 1.8 ± 0.2, 3.1 ± 0.1 and 3.9 ± 0.5, respectively (P = 0.003). Post-hoc comparisons showed significant differences between each of the groups for both types of scans. The pass/fail score was 2.5 for the transvaginal scan and 3.0 for the transabdominal biometry examinations. The inter-rater reliability was 0.89. CONCLUSIONS: Ultrasound competence can be assessed in a reliable and valid way using the OSAUS scale. The pass/fail scores may be used to help determine when trainees are qualified for independent practice.

Socio-demographic factors, comorbidity and diagnostic delay among women diagnosed with cervical, endometrial or ovarian cancer.

This study investigates the association between socio-demographic factors, comorbidity and diagnostic delay among gynaecological cancer patients. A questionnaire was sent to 1052 women diagnosed with cervical, endometrial or ovarian cancer between October 2006 and December 2007 in Denmark. Long patient delays were associated with diagnosis with a greater risk of experiencing long delays among women diagnosed with cervical and endometrial cancer as opposed to ovarian cancer. The risk of experiencing long GP referral delays was associated with residential area, with a greater risk of long delays in rural vs. urban areas. Long gynaecologist appointment delays were associated with younger age, while long secondary care delays were associated with living in a capital area and having comorbidity. Long total delays were associated with diagnosis with greater risk of experiencing long delays among women diagnosed with cervical and endometrial cancer as opposed to ovarian cancer, and with working as opposed to being retired. In conclusion, this study found that socio-demographic factors and comorbidity play a role in the probability of experiencing long delays. If delays in diagnosis are to be reduced, there must be increased recognition of the significance of symptoms among patients and interventions aimed at ensuring timely care by specialists.

The association between leisure time physical activity in the year before pregnancy and pre-eclampsia.

UNLABELLED: In order to investigate the association between leisure time physical activity in the year before pregnancy and pre-eclampsia, stratifying for maternal BMI, a prospective study was carried out from 1996 to 1998. Pregnant women attending their first antenatal care visit, were invited to participate in the study. INCLUSION CRITERIA: Danish-speaking, > OR =18 years of age, gestational age <22 weeks, no psychiatric disease, or abuse. The participants (n = 2,793) self-filled a questionnaire at 12-18 gestational weeks. Leisure time physical activity was categorised as sedentary, light and moderate-to-heavy. The results showed that pre-eclampsia occurred in 4.2%, 4.2% and 3.1% of women with sedentary, light and moderate-to-heavy leisure time physical activity, respectively. Although we found a tendency towards a lower risk of pre-eclampsia in women with the highest degree of physical activity during leisure time, especially in overweight women, no significant associations were found. It was concluded that leisure time physical activity the year before pregnancy does not protect against pre-eclampsia.

Risk indicators for dystocia in low-risk nulliparous women: a study on lifestyle and anthropometrical factors.

We examined background information and course of labour from a cohort of 2,810 low-risk nulliparas to identify possible lifestyle and anthropometrical risk indicators for dystocia. Criteria for dystocia: cervical dilatation <2 cm over 4 h during labour's active phase, or no descent during 2 h (3 h with epidural) in the descending phase, or no progress for 1 h during the expulsive phase. After adjustments, athletics or heavy gardening > or =4 h per week appeared protective for dystocia (OR 0.63, CI 0.45-0.89), contrary to a non-significant finding of intensive physical training (OR 1.57, CI 0.84-2.93). Caffeine intake of 200-299 mg/day was associated with dystocia (OR 1.37, CI 1.04-1.80); also high maternal age (OR 2.25, CI 1.58-3.22), small stature (OR 2.18, CI 1.51-3.15) and pre-pregnancy overweight (OR 1.28, CI 1.02-1.61). No association was found between dystocia and alcohol intake, smoking, night sleep and options for resting during the day.

Sports and leisure-time physical activity in pregnancy and birth weight: a population-based study.

We examined the association between sports and other leisure-time physical activities during pregnancy and birth weight of babies born after 37 completed weeks of gestation. All Danish-speaking pregnant women attending routine antenatal care at the Department of Obstetrics, Aarhus University Hospital, Denmark, from August 1989 to September 1991 were invited to participate in the study. A total of 4458 healthy women who delivered after 37 completed gestational weeks participated in this study. The associations between sports (0, 1-2, 3+ h/week) or leisure-time physical activity (sedentary, light, and moderate to heavy) and birth weight were examined by linear and logistic regression and adjusted for potential confounding factors such as smoking, parity, schooling, pre-pregnancy body mass index and gestational age. The results showed that pregnant women who practiced sports or were moderate to heavy leisure-time physical active during the early second or the early third trimester gave birth to infants with a similar birth weight as inactive women. The proportion of newborns with a low (<2500 g) or a high birth weight (>/=4500 g) was also unchanged. In conclusion, in this large population-based study, we found no association between sports and leisure-time physical activity and low-birth weight, high-birth weight, or average-birth weight.

Objective assessment of surgical competence in gynaecological laparoscopy: development and validation of a procedure-specific rating scale.

OBJECTIVE: The purpose of this study was to develop a global- and a procedure-specific rating scale based on a well-validated generic model (objective structured assessment of technical skills) for assessment of technical skills in laparoscopic gynaecology. Furthermore, we aimed to investigate the construct validity and the interrater agreement (IRA) of the rating scale. We investigated both the gamma coefficient (Kendall's rank correlation), which is a measure of the strength of dependence between observations, and the kappa value for each of the ten individual items included in the rating scale. DESIGN: Prospective cohort, observer-blinded study. SETTING: Departments of Obstetrics and Gynaecology in Zealand, Denmark. POPULATION: Twenty one gynaecologists or gynaecological trainees. MATERIAL AND METHODS: Twenty-one video recordings of right side laparoscopic salpingectomies were collected prospectively, eight from novices (defined as <10 procedures), seven from intermediate experienced (20-50 procedures) and six from experts (> 200 procedures). All operations were performed by the same operative principles and using a standardised technique. The recordings were analysed by two independent, blinded observers. MAIN OUTCOME MEASURES: Construct validity of the rating scale based on operative performance (median of total score) and interrater reliability. RESULTS: There were significant differences between the three groups: median score of novices 24.00 versus intermediate 29.50 versus expert 39.50, P < 0.003) The IRA was 0.83 overall. The gamma correlation coefficient was 0.91. The kappa values varied from 0.510-0.933 for each of the individual items of the rating scale. CONCLUSIONS: The procedure-specific rating scale for laparoscopic salpingectomy is a valid and reliable tool for assessment of technical skills in gynaecological laparoscopy.

Objective assessment of gynecologic laparoscopic skills using the LapSimGyn virtual reality simulator.

BACKGROUND: Safe realistic training and unbiased quantitative assessment of technical skills are required for laparoscopy. Virtual reality (VR) simulators may be useful tools for training and assessing basic and advanced surgical skills and procedures. This study aimed to investigate the construct validity of the LapSimGyn VR simulator, and to determine the learning curves of gynecologists with different levels of experience. METHODS: For this study, 32 gynecologic trainees and consultants (juniors or seniors) were allocated into three groups: novices (0 advanced laparoscopic procedures), intermediate level (>20 and <60 procedures), and experts (>100 procedures). All performed 10 sets of simulations consisting of three basic skill tasks and an ectopic pregnancy program. The simulations were carried out on 3 days within a maximum period of 2 weeks. Assessment of skills was based on time, economy of movement, and error parameters measured by the simulator. RESULTS: The data showed that expert gynecologists performed significantly and consistently better than intermediate and novice gynecologists. The learning curves differed significantly between the groups, showing that experts start at a higher level and more rapidly reach the plateau of their learning curve than do intermediate and novice groups of surgeons. CONCLUSION: The LapSimGyn VR simulator package demonstrates construct validity on both the basic skills module and the procedural gynecologic module for ectopic pregnancy. Learning curves can be obtained, but to reach the maximum performance for the more complex tasks, 10 repetitions do not seem sufficient at the given task level and settings. LapSimGyn also seems to be flexible and widely accepted by the users.

Spontaneous abortion: a prospective cohort study of younger women from the general population in Denmark. Validation, occurrence and risk determinants.

OBJECTIVE: To assess the occurrence of spontaneous abortion, comparing two different data sources. To estimate the rate of spontaneous abortion over a 2-year period, and examine potential predictors of the risk for incident spontaneous abortion. METHODS: We used interview data from a population-based prospective cohort study comprising 11,088 women and data from a linkage of the cohort with the Hospital Discharge Register to compare spontaneous abortions as reported in the interview with those identified in the register. Based on interview data, we estimated the rate of spontaneous abortion during the two-year follow-up. Finally, risk determinants for incident spontaneous abortion were analyzed by means of logistic regression. RESULTS: A total of 654 spontaneous abortions before enrolment in the study were reported by the women compared to 531 abortions found in the register. More than 80% of the spontaneous abortions identified from both sources were recorded in the same year. During follow-up a total of 20.9% of pregnancies intended to be carried to term ended as a spontaneous abortion. In the risk factor analysis, we found that previous spontaneous abortion, being single, never having used oral contraceptives, and use of intrauterine device were associated with increased risk of subsequent spontaneous abortion. In addition, it was indicated that a short interpregnancy interval following a spontaneous abortion may confer an increased risk of abortion in the subsequent pregnancy. CONCLUSION: We found a high rate of spontaneous abortion in the present study and an acceptable agreement between information obtained by interview and register information. More than 25% of the spontaneous abortions were only reported by the women, and this could not be explained by erroneously reported induced abortions, and may be early, nonhospitalized abortions. We confirm that number of previous spontaneous abortions is a strong determinant, and our data may also indicate a role of previous contraceptive habits. A role of the length of interpregnancy interval in the risk of spontaneous abortion cannot be ruled out.

The association between early menopause and risk of ischaemic heart disease: influence of Hormone Therapy.

UNLABELLED: Randomised clinical trials find no protection against development of ischaemic heart disease by use of Hormone Therapy (HT) after the age of 50 years. Observational studies suggest that early menopause is a risk factor for ischaemic heart disease. Yet, a clinical very relevant question is whether HT reduces this risk associated with early menopause. OBJECTIVE: To analyse whether early menopause based on various causes are independent risk factors for ischaemic heart disease, and to investigate whether the risks are modified by use of HT. METHODS: In a prospective cohort study questionnaires were mailed to Danish female nurses above 44 years of age in 1993. Information on menopause, use of HT and lifestyle was obtained. In total 19,898 (86%) nurses fulfilled the questionnaire, among them 10.533 were postmenopausal with definable menopausal age, free of previous ischaemic heart disease, stroke or cancer. Through individual linkage to national register incident cases of ischaemic heart disease were identified until end of 1998. RESULTS: Menopause below both age 40 and 45 was associated with an increased risk of ischaemic heart disease, seeming most pronounced for women who had an early ovariectomy but also among spontaneous menopausal women. Generally HT did not reduce the risk except for the early-ovariectomised women, where no increased risk of ischaemic heart disease for HT users was found. CONCLUSION: We found an increased risk of ischaemic heart disease associated with early removal of the ovaries that might be reduced with HT. The present study need confirmation from other studies but suggests that early ovariectomised women could benefit from HT.

Different cerebrovascular effects of medroxyprogesterone acetate and norethisterone acetate in the New Zealand White rabbit.

OBJECTIVE: The lack of a cardioprotective effect of hormone replacement therapy (HRT), as suggested by the Heart and Estrogen/progestin Replacement Study (HERS) and Women's Health Initiative (WHI) may in part be explained by the progestin used. The aim of this study was to elucidate the effect of different progestins on cerebrovascular reactivity in an animal model. METHODS: Fifty-six ovariectomized New Zealand White rabbits were randomized into seven groups receiving hormone treatment for 4 weeks: medroxyprogesterone acetate (MPA) (10 mg/day); norethisterone acetate (NETA) (3 mg/day); conjugated equine estrogens (CEE) (1.25 mg/day); 17beta-estradiol (E2) (4 mg/day); MPA + CEE (10 mg/day + 1.25 mg/day); NETA + E2 (3 mg/day + 4 mg/day); or placebo. Segments from the basilar and posterior cerebral arteries were mounted in myographs for tension recordings. Concentration-response curves to potassium, acetylcholine, sodium nitroprusside, L-NAME (N(omega)-nitro-L-arginine methyl ester), calcium and endothelin-1 were established. RESULTS: Treatment with MPA caused a significant increase in vasoconstriction, expressed as E(max) (mN/mm, mean +/- SEM; p < 0.05), in response to potassium (3.18 +/- 0.19 vs. 2.47 +/- 0.19) and calcium (4.00 +/- 0.22 vs. 3.34 +/- 0.14) in the posterior cerebral artery, and to endothelin-1 (6.88 +/- 0.69 vs. 5.22 +/- 0.30) in the basilar artery, when compared with NETA. This difference was neutralized in the groups receiving the combined treatment of MPA + CEE and NETA + E2. No overall differences were seen between CEE and E2. CONCLUSIONS: In rabbit cerebral arteries, MPA treatment causes a higher development in arterial tension compared with NETA, indicating that different progestins may display different cerebrovascular effects. However, when accompanied by estrogens, as in the case of HRT, this difference is eliminated.

Breast cancer with different prognostic characteristics developing in Danish women using hormone replacement therapy.

The aim of this study is to investigate the risk of developing prognostic different types of breast cancer in women using hormone replacement therapy (HRT). A total of 10 874 postmenopausal Danish Nurses were followed since 1993. Incident breast cancer cases and histopathological information were retrieved through the National Danish registries. The follow-up ended on 31 December 1999. Breast cancer developed in 244 women, of whom 172 were invasive ductal carcinomas. Compared to never users, current users of HRT had an increased risk of a hormone receptor-positive breast cancer, but a neutral risk of receptor-negative breast cancer, relative risk (RR) 3.29 (95% confidence interval (CI): 2.27-4.77) and RR 0.99 (95% CI: 0.42-2.36), respectively (P for difference=0.013). The risk of being diagnosed with low histological malignancy grade was higher than high malignancy grade with RR 4.13 (95% CI: 2.43-7.01) and RR 2.17 (95% CI: 1.42-3.30), respectively (P=0.063). For breast cancers with other prognostic characteristics, the risk was increased equally for the favourable and non favourable types. Current users of HRT experience a two- to four-fold increased risk of breast cancer with various prognostic characteristics, both the favourable and non favourable types. For receptor status, the risk with HRT was statistically significantly higher for hormone receptor-positive breast cancer compared to receptor-negative breast cancer.

Does caffeine and alcohol intake before pregnancy predict the occurrence of spontaneous abortion?

BACKGROUND: Consumption of caffeine and alcohol is suspected to affect pregnancy outcome. Use of both stimulants is widespread and even minor effects on fetal viability are of public health interest. METHODS: We performed a nested case-control study using prospective data from a population-based cohort comprising 11088 women aged 20-29 years. From this cohort, women who experienced either a spontaneous abortion (n = 303) or who gave birth (n = 1381) during follow-up [mean time: 2.1 years (range: 1.6-3.4)] were selected. Associations between self-reported exposures to caffeine and/or alcohol at enrolment and spontaneous abortion were analysed by means of logistic regression. RESULTS: Compared with women with a pre-pregnancy intake of <75 mg caffeine per day, the adjusted odds ratio (95% confidence interval) for spontaneous abortion was 1.26 (0.77-2.06), 1.45 (0.87-2.41), 1.44 (0.87-2.37) and 1.72 (1.00-2.96) for a pre-pregnancy intake on 75-300, 301-500, 501-900 and >900 mg caffeine per day respectively (P = 0.05 for trend). A pre-pregnancy intake of alcohol was not a predictor for spontaneous abortion. CONCLUSIONS: A high intake of caffeine prior to pregnancy seems to be associated with an increased risk of spontaneous abortion, whereas a low-to-moderate alcohol intake does not influence the risk.

Acute effects of tibolone on cerebral vascular reactivity in vitro.

OBJECTIVE: To evaluate the acute effects of tibolone and its metabolites on cerebral vascular reactivity in vitro. METHODS: Ring segments of the posterior cerebral artery from female rabbits were mounted in myographs for isometric tension recordings. Concentration-response curves with tibolone, 3alpha-OH-tibolone, 3beta-OH-tibolone, Delta(4) isomer and 17beta-estradiol were obtained before and after addition of the NO blocker N(omega)-nitro-L-arginine methyl ester (L-NAME, 10(-4) mol/l) or the potassium-channel blocker tetraethylammonium chloride (TEA, 10(-2) mol/l). Additionally, the effects of the hormones on the concentration-response curves with calcium were examined. RESULTS: Tibolone and its metabolites induced a concentration-dependent relaxation comparable to that of 17beta-estradiol (area under the curve (AUC); tibolone vs. 17beta-estradiol: 242 vs. 251; p < 0.05, analysis of variance). L-NAME increased the AUC for all substances compared with controls (p < 0.05, Student's t test), except for 17beta-estradiol. Preincubation with TEA induced no changes. The concentration-dependent contraction curves with calcium were shifted rightward by all hormones. CONCLUSIONS: The study demonstrates that the acute relaxation induced by tibolone and its metabolites in cerebral arteries in vitro is comparable to that with 17beta-estradiol, and seems to be mediated by inhibition of voltage-gated calcium channels and possibly partly by a nitric oxide-dependent mechanism.