Modeling the impact of changes in tobacco use on individual disease risks.

Reduced Risk Products (RRPs) do not burn tobacco and produce lower levels of toxicants than in cigarette smoke. The long-term effects of using RRPs on health are difficult to assess in a pre-market setting and a modeling approach is required to quantify harm reduction. The Population Health Impact Model (Weitkunat et al., 2015) follows a hypothetical population of individuals over time, creating their tobacco use histories and, based on these, estimating relative and absolute risks of lung cancer, ischemic heart disease, stroke and chronic obstructive pulmonary disease. Linking the tobacco use to the risk profile allow us to assess how the relative and absolute risks of these diseases vary between individuals aged 20, 30, 40 or 50 at baseline who have never smoked or who initiated smoking at 19 years old and either continued to smoke, quit smoking, or switched to RRPs with varying degrees of harm reduction. The simulations suggest that, for smokers in their 20s-30s quitting, or switching to RRP primarily prevents the accrual of risk, while in their 40s-50s it reduces risk. Though tobacco prevention has been the primary approach to limit smoking-related diseases, RRPs can also substantially reduce risks in individuals who do not quit.

[Historical cohort study of delivery in women of forty years of age and older]. / Etude cohorte historique de l'accouchement a 40 ans et plus a Yaoundé-Cameroun.

In a recent study at the Yaounde-Cameroon University Teaching Hospital, we found that delivery at extreme ages of reproductive health was associated with increased foetal and maternal risks. However we were not able to evaluate the impact of advanced age on exposure do different risks observed. The purpose of this study was to test the hypothesis that deliveries of women aged 40 years and above were associated with increased risk. Data collection was retrospective from delivery room registers at the Yaoundé University Teaching Hospital Between 01/01/1991 - 31/12/2000. The deliveries of 180 women in their forties were compared with those of 532 women in their twenties. The software EPI Info 6 and SPSS were used in analysis. At unvaried analysis, the risk of delivery by caesarean section for women in their forties (16.1%) was significantly high compared to women in their twenties (10.0%), (HR: 1.7; 95% CI: 1.1-2.8; p = 0.027). After adjustment for different factors associated with the occurrence of delivery by caesarean section, its risk for women aged 40 and above remained significantly increased (HR: 1.7; 95% CI: 1.0-2.9; p = 0.039). Similar observation was found for stillbirth with 11.7% by women aged 40 and above compared to 5.8% by women in their twenties (HR: 2.1; 95% CI: 1.1-3.9; p = 0.011). After adjustment for different factors associated with mortinatality, its occurrence remained significantly increased at age 40 and above (HR: 1.9; 95% CI: 1.1-3.6; p = 0.032). Women aged 40 years and above had an increased risk of stillbirth and delivery by caesarean section than those in their twenties. Studies are needed to establish the exact causes of these risks and evaluate management options in these women.

[Outcome of delivery at extreme ages of reproductive life]. / Devenir de l'accouchement aux âges extrêmes de la vie reproductive.

BACKGROUND: Deliveries in adolescents and in elderly are separately known as associated with high foetal and maternal risks. The purpose of this study was to test the hypothesis that the outcome of deliveries might be comparable in these distinct age groups. POPULATION AND METHODS: The deliveries of 99 adolescents aged 16 and under were compared with that of 183 women aged 40 years and above with respect to complications of the delivery and the outcome of pregnancy. Data collection was retrospective using delivery room registers from 01/01/1991 to 31/12/2000. RESULTS: Some risks were comparable in both groups as delivery by caesarean section, intra uterine growth retardation, and stillbirth. Other risks were significantly higher in teenagers as post-term delivery, premature delivery, and neonatal foetal distress. The risk of macrosomia was significantly higher in aged women. CONCLUSION: There are risks that are similar in both extremes of age. Other risks are higher particularly in teenagers or in aged women. A common prenatal care unit can be used for these two categories of population, but a few different practices will have to be considered according to the specific age group.

Positive peritoneal cytology in early-stage endometrial cancer does not influence prognosis.

The aim of this study was to assess the prognostic importance of positive peritoneal cytology in early-stage endometrial cancer. All 278 stage I and 53 stage IIIA (without cervical involvement) endometrial cancer patients operated between 1980 and 1996, recorded at the Geneva Cancer registry, were included. Stage IIIA cancers were recategorised into 'cytological' stage IIIA (positive peritoneal cytology alone, n=33) and 'histological' stage IIIA (serosal or adnexal infiltration, n=20). Survival rates were analysed by Kaplan-Meier method and compared using log-rank test. The prognostic importance of cytology was analysed using a Cox model, accounting for other prognostic factors. The 5-year disease-specific survival of cytological stage IIIA cancer was similar to stage I (91 vs 92%) and better than histological stage IIIA cancer (50%, P<0.001). After adjustment for age, myometrial invasion, differentiation and radiotherapy, cytological stage IIIA patients were still at similar risk to die from endometrial cancer compared to stage I patients (hazard ratio (HR) 0.7, 95% confidence interval (CI): 0.18-2.3), while histological stage IIIA patients were at a four-fold increased risk to die from their disease (HR 4.2, 95% CI: 1.7-10.3). This population-based study shows that positive peritoneal cytology in itself has no impact on survival of patients with localised endometrial cancer. Based on the present and previous studies, FIGO (Fédération Internationale de Gynécologie et d'Obstétrique) might consider reviewing its classification system.

Impact of peritoneal cytology on survival of endometrial cancer patients treated with surgery and radiotherapy.

Stage IIIA endometrial cancer includes patients with serosal or adnexal invasion and patients with positive peritoneal cytology only. In this study, we assessed the impact of peritoneal cytology on endometrial cancer survival. All endometrial cancer patients receiving surgery and radiotherapy at the Geneva University Hospitals between 1980 and 1993 were included. Stage IIIA cancers were categorised into 'cytological' stage IIIA (only positive peritoneal cytology) and 'histological' stage IIIA (serosal or adnexal infiltration). Survival rates were analysed by Kaplan-Meier method and compared using log-rank test. The prognostic importance of peritoneal cytology was analysed by multivariate regression analysis. This study included 170 endometrial cancers (112 stage I, 17 cytological stage IIIA, 18 histological stage IIIA, 9 stage IIIB+). Disease-specific survival of cytological stage IIIA was not different from stage I (94 vs 88% respectively, P=0.5) but better than histological stage IIIA (94 vs 51% respectively, P<0.01). Histological stage IIIA patients were at increased risk to die from cancer compared to stage I patients (HR 2.7, 95% CI 1.0-7.7), while cytological stage IIIA patients were not (HR 0.3, 95% CI 0.3-2.0). Cytological stage IIIA endometrial cancer has similar prognosis as stage l and better prognosis than histological stage IIIA. Additional research, definitively separating stage and cytology is warranted.

High efficacy of photodynamic therapy on rat endometrium after systemic administration of benzoporphyrin derivative monoacid ring A.

BACKGROUND: The aim of this study was to evaluate the effect of the benzoporphyrin derivative monoacid ring A (verteporfin)-mediated photodynamic therapy (PDT) on rat endometrium and to determine the optimal drug concentration for endometrial ablation. METHODS: Five minutes after i.v. injection of different concentrations of verteporfin into 24 female Sprague-Dawley rats, 630 nm light treatment was delivered for 500 s (120 J/cm2) to the left horn of the uterus. The 24 rats were divided into six groups according to the drug dose injected, four rats per group: group I (2 mg/kg), group II (1 mg/kg), and groups III, IV, V and VI with 0.5, 0.25, 0.125 and 0.0625 mg/kg respectively. Four days later, the rat uteri were analysed by light microscopy. RESULTS: Endometrial destruction was seen in all six groups, with the most significant result in group I (P<0.008). Conservation of the myometrium was most significant in groups III, IV, V and VI. Acute inflammatory cells in the stromal endometrium were recorded mainly in groups I and II. However, the drug dosage that was most significant in destroying the glands with conservation of the myometrium and not causing severe inflammation was between 0.5 and 0.125 mg/kg. CONCLUSIONS: Verteporfin was effective in endometrial ablation in all our animal groups, and the dose range of 0.5-0.125 mg/kg appeared to be adequate. This observation will have to be scaled for clinical application.

Photodynamic diagnosis of ovarian cancer using hexaminolaevulinate: a preclinical study.

The unfailing detection of micrometastases during surgery of patients suffering from ovarian cancer is mandatory for the optimal management of this disease. Thus, the present study aimed at determining the feasibility of detecting micrometastases in an ovarian cancer model using the intraperitoneal administration of the photosensitiser precursor hexaminolaevulinate (HAL). For this purpose, HAL was applied intraperitoneally at different concentrations (4-12 mM) to immunocompetent Fischer 344 rats bearing a syngeneic epithelial ovarian carcinoma. The tumours were visualised laparoscopically using both white and blue light (D-light, Karl Storz, Tuttlingen, Germany), and the number of peritoneal micrometastases detected through HAL-induced photodiagnosis (PD) was compared to standard white light visualisation. Fluorescence spectra were recorded with an optical fibre-based spectrofluorometer and the fluorescence intensities were compared to the protoporphyrin IX (PpIX) fluorescence induced by 5-aminolevulinic acid under similar conditions. The number of metastases detected by the PD blue light mode was higher than when using standard white light abdominal inspection for all applied concentrations. Twice as many cancer lesions were detected by fluorescence than by white light inspection. The hexyl-ester derivative produced higher PpIX fluorescence than its parent substance aminolevulinic acid at the same concentration and application time. Fluorescence contrast between healthy and cancerous tissue was excellent for both compounds. To overcome poor diagnostic efficiency and to detect peritoneal ovarian carcinoma foci in the large surface area of the human peritoneal cavity, HAL fluorescence-based visualisation techniques may acquire importance in future and lead to a more correct staging of early ovarian cancer.

[Premenstrual dysphoric disorder: approach and treatment]. / Trouble dysphorique prémenstruel : approche et traitement.

The premenstrual dysphoric disorder corresponds to a severe form of the premenstrual syndrome that mainly shows psychiatric symptoms. The incidence is about 3 to 8% of women in the reproductive age. The essential characteristics are depressive mood, a marked anxiety, emotional instability, and decrease of activity, appearing during the luteal phase and ceasing in the follicular phase of the menstrual cycle. Several factors are implied in the pathogenesis of this disorder. Neurobiological and psychobiologic effects concerning the metabolism of serotonin and the melatonin play a role. Several therapies were proposed. The most effective treatment seem to be the selective inhibitors of the of serotonin reuptake.

Contraception and sexuality after termination of pregnancy: a comparison between Lugano and Geneva.

OBJECTIVE: To evaluate the impact of a voluntary termination of pregnancy (TOP) on contraceptive practice and sexual well-being in women. STUDY DESIGN AND METHODS: Comparative evaluation of a retrospective study conducted in Lugano in 1995 with 85 women interviewed 3-6 months post-TOP, and a prospective study carried out in Geneva in 1998 with 103 women interviewed pre-TOP and 6 months post-TOP. In both studies TOP was performed during the first 12 weeks of pregnancy by vacuum aspiration and curettage. RESULTS: Oral contraceptive use in the Lugano group increased from 21% pre-TOP to 47% post-TOP, and in the Geneva group from 19% pre-TOP to 69% post-TOP. Condom use decreased in both groups. Those practising unprotected intercourse also decreased by half (around one in five). No effect on sexual well-being was reported by almost two-thirds of both groups. CONCLUSIONS: Despite large differences between these two populations, the two studies show a similar evolution. The majority of women appeared to be able to cope well with a TOP. About one third presented sexual dysfunction.

Dose finding in a low-dose 21-day combined oral contraceptive containing gestodene.

An open label, non-comparative study was carried out in 22 women over a total of five cycles. After an untreated cycle, oral administration of 20 microg ethinyl estradiol (EE) with 50 microg gestodene (GST) (tablets taken daily for 21 days with a break of 7 days) was commenced, and three treatment cycles were followed by an untreated follow-up control cycle. The ability of this formulation to inhibit ovulation and suppress ovarian activity was assessed by using hormonal parameters and ultrasound. One ovulation occurred during treatment. Luteinized unruptured follicles were observed in three cases in the second treatment cycle and in one case during the third treatment cycle. Follicle-like structures larger than 13 mm associated with a serum estradiol level of more than 30 pg/mL were noted in 19% of the women in the first treatment cycle. The rate of active follicle-like structures was 43% in the second treatment cycle and 28% in the third treatment cycle. The results were compared with previously reported findings of a preparation containing 20 microg EE and 75 microg GST. With regard to ovarian grading and endogenous hormone secretion, considerably more residual ovarian activity, with all parameters examined, was found in the 20 microg EE and 50 microg GST preparation compared to the 20 microg EE and 75 microg GST preparation. It was concluded that the 20 microg EE and 50 microg GST preparation administered for 21 days does not meet the requirements of a combined oral contraceptive with respect to ovulation inhibition.

High- and intermediate-risk human papillomavirus infection in sexually active adolescent females.

STUDY OBJECTIVE: To determine the prevalence of high- and intermediate-risk type human papillomavirus (HPV) infection and cervical dysplasia in an urban Swiss adolescent population attending the local Adolescent Clinic, using a liquid-based Pap test combined with risk type HPV DNA testing. To determine the prevalence of Chlamydia trachomatis in the same study population. DESIGN: Observational study. SETTING: The Adolescent Clinic of the Department of Obstetrics and Gynaecology at the University Clinic, Geneva, Switzerland. PARTICIPANTS: 134 women between 14 and 20 years of age were enrolled in the study. MAIN OUTCOME MEASURES: A standardized patient file on demographic and sexual history information was compiled and completed by physical examination, including a Pap test with adjunct high- and intermediate-risk type HPV DNA detection. RESULTS: Of the 134 specimens analyzed for HPV, 115 patients were negative and 19 (14.2%) were positive for HPV types 16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, or 68. A significant association between HPV infection and having had more than one lifetime sexual partner was found (P <.05). Six (31.6%) of the HPV-positive and three (2.6%) of the HPV-negative specimens had a low-grade squamous intraepithelial lesion (SIL) by cytology. Abnormal Pap test was related to HPV infection (odds ratio, 46.2; 95% confidence interval, 7.4 to 287.4) and, inversely, to age at first sexual intercourse (odds ratio, 0.98; 95% confidence interval,.97 to 1.0). CONCLUSION: High- and intermediate-risk type HPV infection is a frequent finding in our study group and is linked to having had more than one lifetime sexual partner. No association was found between HPV infection and other potential risk factors such as patient's age, age at first intercourse, frequency of intercourse during the three months prior to the investigation, smoking habits, or alcohol consumption.

Reproductive health in eastern Europe: a collaborative training project in Romania.

Since the fall of the Berlin Wall, fundamental political changes in eastern Europe have affected the Soviet-style health care systems that formerly provided basic care for everyone. Many of these systems have collapsed, and the new systems of social insurance that have replaced them often are inadequate. Advanced Training in Reproductive Health in Romania aimed to create an authority in family planning and reproductive health in selected Romanian university centers and to improve training and research capabilities. Initially, the project had 2 main goals: to provide advanced training in reproductive health and family planning to Romanian obstetrics-gynecology specialists from the main university centers-which would allow them to train other physicians (obstetricians, gynecologists, and general practitioners) and medical students-and to develop, test, and finalize specific training materials in Romanian to be used by the new trainers.

Effect of a combined oral contraceptive containing 3 mg of drospirenone and 30 microg of ethinyl estradiol on the human endometrium.

OBJECTIVE: To provide an in-depth assessment of the effects of the combined oral contraceptive containing 30 microg of ethinyl estradiol and 3 mg of drospirenone (Yasmin, Schering AG, Berlin) on the endometrium by means of endometrial morphometry in comparison to an untreated cycle. DESIGN: The open, multicenter study consisted of one untreated precycle and 13 treatment cycles. SETTING: Four gynecologic clinics in Belgium, The Netherlands, and Switzerland were involved. PATIENT(S): Forty women with a history of regular menstrual cycles. INTERVENTION(S): Before the commencement of the trial, 3 months without any hormonal intake was obligatory. The first endometrial sample was done in the untreated precycle, adjusted to the day of LH peak plus 5 to 6 days. During the medication phase, endometrial samples were taken at cycle 3, 6 and 13. MAIN OUTCOME MEASURE(S): Primary outcome measure of the study was the morphologic assessment of the endometrium with measures such as glandular diameter, glandular epithelial height, and number of vacuolated cells per 1,000 glandular cells. Furthermore, the endometrial thickness was measured by ultrasound. RESULT(S): After 13 cycles of medication use the endometrium had an atrophic appearance in 63% of the subjects. The size of the glands, the glandular epithelial height, and the number of glands per square millimeter were already significantly reduced after 3 months' use. Histological and ultrasonographical evaluation of the endometrium indicated a suppression of the proliferative activity of the endometrium. CONCLUSION(S): The combination of 30 microg of ethinyl estradiol with 3 mg of drospirenone induces changes of the endometrium that are comparable with other combined oral contraceptives and exhibits a marked antiproliferative effect on the endometrium. The medication was proven to be an effective oral contraceptive and revealed good cycle control characteristics.

Sexuality, partner relations and contraceptive practice after termination of pregnancy.

The aim of this study was to determine the impact of termination of pregnancy (TOP) on women's sexual well-being, the couple and contraceptive practice. In a prospective qualitative and quantitative study, 103 women undergoing induced abortion by vacuum aspiration were interviewed before the abortion and 6 months later. The interview was performed by means of a questionnaire including open and closed questions, and two psychological tests (Locke-Wallace and Horowitz). After TOP, the majority of women did not report changes in their sexual behavior and satisfaction. Eighteen per cent of women reported a decrease in sexual desire and 17% reported orgasmic disorders. About one-third of women described psychosomatic symptoms, but a minority were traumatized by the event. Ninety-eight per cent of the women were informed about, and had practiced, contraception in the past; 69% had actually used some kind of contraception during the menstrual cycle that had resulted in pregnancy (31% had had unprotected intercourse). Six months later, 83% practiced contraception, and only 17% did not. Fourteen out of 84 couples separated after TOP (one in six). Six months after TOP, the large majority of women interviewed seemed able to cope with TOP. A minority presented some persisting sexual dysfunction and/or some psychosomatic symptoms.

Association between weather conditions and the incidence of emergency gynecological consultations.

OBJECTIVE: This study examined the influence of weather conditions on the incidence of outpatient emergency consultations at the Department of Obstetrics and Gynecology at the Regional Hospital in Lugano, Switzerland. STUDY DESIGN: The medical records of all women who attended the outpatient emergency unit at the Department for Obstetrics and Gynecology over the 1-year study period were reviewed. The final diagnosis was pelvic pain of unidentified origin in 180 cases, menorrhagia and/or metrorrhagia in 95 cases, threatened abortion in 56 cases and spontaneous abortion in 54 cases. The meteorological factors considered were atmospheric pressure, temperature, humidity and global radiation. A logistic regression model was used to correlate the occurrence of symptoms with the chosen weather factors. RESULTS: High mean daily temperature was found to be a significant predictor of pelvic pain (p < 0.001). A rise in barometric pressure compared to the previous day increased the probability of menorrhagia and/or metrorrhagia (p = 0.001). Higher minimal temperature (p = 0.011) and an increase in atmospheric pressure (p = 0.006) were identified as positive predictors of threatened abortion. None of the meteorological factors considered seemed to influence the frequency of spontaneous abortions. CONCLUSION: Meteorological factors such as temperature and barometric change appear to affect the probability of emergency admissions for gynecological symptoms including uterine bleeding, threatened abortion and pelvic pain.

An exploratory pilot study of acupuncture on the quality of life and reproductive hormone secretion in menopausal women.

The majority of menopausal women suffer from climacteric symptoms. The purpose of this study was to assess the effects of acupuncture on the quality of life and reproductive hormones secretion in menopausal women. Eleven (11) menopausal women with climacteric symptoms entered this prospective study. The Menopause Specific Quality of life Questionnaire was filled out by the patients before the first acupuncture session, after the last one (5 weeks later), and 3 months after the last acupuncture session. Reproductive hormones including follicular-stimulating hormone (FSH), luteinizing hormone (LH), estradiol, progesterone, and prolactin were measured before and after treatment. Acupuncture significantly improved menopausal vasomotor symptoms (p = 0.001 and p = 0.003 for the end of treatment and 3 months later, respectively) and physical symptoms (p = 0.014 at the end of treatment and p = 0.046 3 months later). It did not change psychosocial or sexual symptoms, nor did it change the measured reproductive hormones. In conclusion, acupuncture is shown to be effective in relieving vasomotor and physical disturbances of menopausal women with effects lasting at least up to 3 months after termination of the treatment. Acupuncture may be a useful treatment alternative for women who are unable or do not want to receive hormone replacement therapy. A prospective study with larger sample sizes will be needed to define the role of acupuncture in the management of menopausal symptoms.

Contraception and induced abortion in Armenia: a critical need for family planning programs in eastern Europe.

OBJECTIVES: The purpose of this study was to determine the number of induced abortions per woman and the reasons for selecting induced abortion among parous Armenian women. METHODS: A consecutive series of 200 women attending an abortion clinic in Yerevan, Armenia, were queried by a physician about their reproductive histories. RESULTS: Women younger than 20 years of age reported a median of 1 and women older than 40 years reported a median of 8 induced abortions in their lifetimes (overall median = 3). Lack of contraceptive information was the major reason cited for not using contraception. CONCLUSIONS: Induced abortion is the major form of birth control among parous Armenian women. Concerted public health campaigns are needed to inform women and their physicians in Armenia and other Eastern European countries about alternative contraceptive methods.