Sample Size Calculation for Clinical Studies on the Efficacy of a New Contraceptive Method

The current guideline of the European Agency for the Evaluation of Medicinal Products (EMEA) on the clinical investigation of steroid contraceptives in women, which was prepared by the Committee for Proprietary Medicinal Products (CPMP), calls for the calculation of a confidence interval for the Pearl Index, a widely used measure to describe the reliability of a contraceptive method. The key studies should be large enough to give a Pearl Index with a 95% confidence interval such that the difference between the upper limit of the confidence interval and the corresponding point estimate does not exceed a given margin. As a consequence of this guidance, the success probability of a Pearl Index study is given by its capability, i.e. probability to fulfil this criterion. The resulting power function based on the necessary exposure time does not increase strictly. The minimum exposure time T_min should be calculated such that this function exceeds a given probability for all T ≥ T_min. In this paper, the underlying model is discussed, and definitions and formulae are given for the assumption of a Poisson model. The necessary total exposure time is calculated as a function of a given true pregnancy rate. In addition, some simulations were conducted for the model where a drop‐out mechanism is incorporated into the process. Assuming an exponential distribution for the time to drop‐out the phenomenon that the power does not increase strictly with exposure time is less pronounced. (© 2004 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)     

Contraceptive Use and Pregnancy Outcomes among Opioid Drug-Using Women: A Retrospective Cohort Study

Objective

The contraceptive needs of illicit opioid users differ from non-drug users but are poorly understood. The aim of this study was to describe contraceptive use and pregnancy outcomes in opioid-using women, and to examine their association with a range of risk factors.

Method

This retrospective cohort study used UK general practice records, Treatment Outcomes Profile and National Drug Treatment Monitoring System data, and a nested data validation exercise. A cohort of 376 women aged 20–61 years were in active treatment for opioid addiction in October 2010 at two specialised primary care practices in North-East England. Outcomes were age-adjusted prevalence estimates for contraceptive use and pregnancy outcomes in users of illicit opioids. The association between lifestyle-related risk factors and contraception was explored.

Results

Drug-using women made lower use of planned (non-condom) contraception (24% vs 50%, p<0.001), had more frequent pregnancy terminations (0.46 vs. 0.025, p = 0.004) and higher annual incidence of chlamydia (1.1% vs. 0.33%, p<0.001), when compared with age-matched population data. Specifically, there was low use of oral contraceptives (4% vs. 25%, p<0.001), IUCD (1% vs. 6%, p<0.001), and sterilisation (7% vs. 6%, p = 0.053), but higher rates of injectable contraceptives (6% vs. 3%, p = 0.003). A total of 64% of children aged <16 years born to this group did not live with their mother. No individual risk factor (such as sex-working) significantly explained the lower use or type of non-condom contraception.

Conclusions

This is the first study to describe planned contraceptive use among drug-users, as well as the association with a range of risk factors and pregnancy outcomes. The low uptake of planned contraception, set against high rates of terminations and sexually transmitted disease demonstrates the urgent clinical need to improve contraceptive services, informed by qualitative work to explore the values and beliefs influencing low contraceptive uptake.     

Contraceptive use and efficacy in a genetically counseled population

Abstract

This paper reports contraceptive use and efficacy rates among 648 married women aged 15 to 44 who had received genetic counseling six months previously. Over half (53.5 per cent) of the counseled population were using non‐surgical contraception; 20 per cent were pregnant or postpartum; 10 per cent were seeking to become pregnant; 11 per cent were sterilized. Only 4.5 per cent were neither using contraceptives nor seeking to become pregnant. Women who were certain about their reproductive intentions after counseling utilized contraceptives effectively, with only two pregnancies at six months among those seeking to delay wanted pregnancies and only one pregnancy among those seeking to prevent pregnancy. This represents six‐month contraceptive failure rates of 4.3 and 2.1 per cent respectively for the two groups, rates similar to those with comparable intentions in the U. S. population at large. A distinguishing characteristic of the genetically counseled group was that 32 per cent of contraceptive users reported that their reproductive intentions were uncertain after counseling. The six‐month pregnancy rate in this uncertain group was 10 per cent.     

Mental Health in Bariatric Surgery: Selection,Access, and Outcomes

Severe obesity has many psychiatric consequences that can be influenced by bariatric surgery. The goal of this article is to review these challenges, including the mental health status of patients with severe obesity, the evaluation of surgical candidates, and the early and late effects of the operations, and to offer some recommendations to manage these challenges. The failure of the insurance‐mandated preoperative psychosocial evaluation is also discussed.     

Clinical Evaluation of a New Sequential Oral Contraceptive Agent

One hundred and seventy-eight patients were placed on a new sequential oral contraceptive preparation (Ortho-Novum SQ) and observed through a total of 1785 months in an effort to determine the effectiveness of the agent and its acceptability to patients. Patients with varicose veins and/or previous thrombophlebitis were not excluded from the study. The most frequent side effect was “breakthrough bleeding” which occurred in 19 patients. One patient became pregnant while apparently taking the tablets as directed, and another was already pregnant when started on the drug. However, in spite of at least four weeks'' continued ingestion after conception, both gave birth to normal female infants. Chloasma, noted in four patients while on combination oral contraceptives, cleared on this medication. There was no aggravation of thrombophlebitis or varicose veins. The acceptance of this sequential preparation by patients was excellent.     

Contraceptive Charms Among the Plains Indians

Abstract

Although Clark Wissler and Sister M. Inez Hilger have recorded the use of contraceptive charms by the Blackfoot and Arapaho, the Piegan specimen illustrated here may be unique to museum collections. Indications that use of these charms survived into the middle years of the present century suggest the possibility of obtaining more detailed information about their use among other tribes of Plains Indians through field work.     

Gonorrhoea and the Intrauterine Contraceptive Device

Though pelvic infection in women fitted with an intrauterine device (I.U.C.D.) is reported to be rare, three cases, gonococcal in origin, are presented. These case histories suggest that the presence of an I.U.C.D. increases the severity of gonorrhoea, while removal of the device before antibiotic therapy is probably essential for proper management. The literature and our experience suggest that where pelvic infection and an I.U.C.D. coexist gonorrhoea should be considered a likely diagnosis.     

Selection of Yeasts for Breadmaking by the Frozen-Dough Method

Eleven yeast strains suitable for frozen dough were selected from over 300 Saccharomyces strains. All of these were identified as Saccharomyces cerevisiae from morphological, cultural, and physiological characteristics. The selected yeast cells accumulated a higher amount of trehalose than did commercial bakers' yeast cells.     

Clinical and Laboratory Findings in a Trial of Norgestrel,a Low-dose Progestogen-only Contraceptive

Norgestrel, a progestogen-only oral contraceptive, was given continually at a dose of 75 μg/day to 144 women of proved fertility. It was an efficient contraceptive with a failure rate of 2·1% (assessed by the “life-table” method) within the first 12 cycles and 3·6% within the first 30 cycles (or 2·0 conceptions per 100 woman-years when assessed by the Pearl index). The overall conception rate for the entire trial period was 2·1% and 1·3 pregnancies per 100 woman-years respectively. Norgestrel caused a high proportion of irregular and generally short bleeding intervals, about one-fifth of the cycles lasting less than 17 days. This irregularity appeared to be due to individual variance in cycle length between women rather than that between their successive cycles. No confirmed instances of thromboembolism were observed. Norgestrel apparently exerts its contraceptive action by several mechanisms: reduction in the sperm penetrability of the cervical mucus and an impairment of luteal function appear important. The serum concentrations of cholesterol and globulin were significantly reduced in women taking norgestrel. Preliminary observations suggest that on discontinuing the medication fertility is promptly restored. Of the 144 women originally enrolled 57 (40%) withdrew for reasons connected with the method before completing 30 months on trial, over half of them because of the irregular menstrual pattern. Nonetheless, in view of its main clinical and laboratory characteristics and simple mode of administration, norgestrel appears to be a useful alternative to the combined type of pill for women unsuitable for, or unable to tolerate, oestrogen-containing preparations.     

An Evaluation of Diazacon as a Potential Contraceptive in Non-Native Rose-Ringed Parakeets

ABSTRACT Rose-ringed parakeets (Psittacula krameri) have become widely established outside their native range through accidental or deliberate release. Potential economic impacts on agriculture, conservation concerns, and mixed public opinion regarding the species have highlighted the need to develop effective but humane management options. Fertility control might provide such a solution if a safe and environmentally benign contraceptive was available. The chemical 20,25-diazacholesterol dihydrochloride (diazacon) has previously been used to reduce reproductive output in avian species through reduction of blood cholesterol and cholesterol-dependent reproductive hormones. We orally dosed captive rose-ringed parakeets with a solution of either 9 mg/kg or 18 mg/kg of diazacon for up to 10 days and found that a dose of 18 mg/kg for 10 days temporarily reduced blood cholesterol levels with no adverse side effects. We evaluated this dose level in a captive population in semi-natural conditions during the 2008 breeding season and found a significant decrease in fertility. We concluded that diazacon has potential for fertility control in this species if a suitable formulation and delivery system is developed for free-living populations.     

PBL教学模式在我国医学本科生中教学效果的Meta分析

目的:系统评价我国以问题为基础的教学(problem-based learning,PBL)模式在医学本科生中的教学效果。方法:运用计算机检索中国知网、万方数据库、维普数据库收录的国内公开发表以问题为基础的本科医学生教育相关的临床研究文献,同时进行Meta分析。结果:共检索出783篇相关文献,通过筛选共有9篇文献纳入研究,共计纳入986例教学对象。纳入文献Jadad评分2-3分,纳入文献均说明基线资料均有可比性。对所有文献进行合并分析显示,PBL教学法的教学效果与传统教学组有显著差异(Z=6.52,P0.00001),PBL教学法优于传统教学法[SMD=7.72,95%CI[5.4,10.04],P0.00001]。结论:采用PBL教学法的教学效果优于传统教学法。但我国医学教育应用此方法仍不普及,其原因有待深入探讨,现有研究质量普遍不高,有待普及规范标准的研究方法。     

Efficacy of a Y-Design Silastic Elastomer Intrauterine Device as a Horse Contraceptive

To successfully manage population growth rates of free-roaming horses (Equus ferus caballus), an effective, long-acting contraceptive could be beneficial. We evaluated the efficacy and safety of an intrauterine device (IUD) in a breeding trial using seasonal pasture assemblages of 2 males individually pastured in large enclosures (~81 ha) each with 10 females per male. The study took place at a large animal research facility at Oklahoma State University in Stillwater, Oklahoma, USA. Specific objectives of the study were to evaluate the effectiveness of IUDs in preventing pregnancy over 20.5 months with return to fertility assessed over the subsequent 6 months and to evaluate potential effects of this IUD on ovarian function and uterine health (e.g., endometrial inflammation, infection, fibrosis). We developed a Y-design IUD, made of silastic elastomer, and set the desired retention rate at 75%. After procurement of endometrial biopsies, we inserted IUDs into the uteri of 20 females and examined them via transrectal ultrasound every 2 weeks for detection of the device and assessment of uterine health. After 20.5 months we removed the remaining 15 IUDs, obtained a second endometrial biopsy for comparision, and returned the females to their respective males for continued breeding in efforts to assess uterine return to health as indicated by pregnancy rates. The Y-design IUD met the 75% retention rate goal, with 100% contraception in females that retained the device; 12 of 20 treated females became pregnant (i.e. returned to fertility) after removal of the IUD. Based on these results, we conclude that the Y-design IUD is a safe and effective device to control fertility in free-roaming horses. © 2021 The Wildlife Society.     

Direct Selection of Clostridium acetobutylicum Fermentation Mutants by a Proton Suicide Method

Clostridium acetobutylicum ATCC 10132 mutants altered in acetic acid synthesis or in the shift to solventogenesis were directly selected by a proton suicide method after mutagenic treatment, by using bromide and bromate as selective agents. The mutants were characterized according to their solvent and acid production. On the selection plates they differed in colony phenotype from the parent strain.     

A Method for the Simultaneous Estimation of Selection Intensities in Overlapping Genes

Inferring the intensity of positive selection in protein-coding genes is important since it is used to shed light on the process of adaptation. Recently, it has been reported that overlapping genes, which are ubiquitous in all domains of life, seem to exhibit inordinate degrees of positive selection. Here, we present a new method for the simultaneous estimation of selection intensities in overlapping genes. We show that the appearance of positive selection is caused by assuming that selection operates independently on each gene in an overlapping pair, thereby ignoring the unique evolutionary constraints on overlapping coding regions. Our method uses an exact evolutionary model, thereby voiding the need for approximation or intensive computation. We test the method by simulating the evolution of overlapping genes of different types as well as under diverse evolutionary scenarios. Our results indicate that the independent estimation approach leads to the false appearance of positive selection even though the gene is in reality subject to negative selection. Finally, we use our method to estimate selection in two influenza A genes for which positive selection was previously inferred. We find no evidence for positive selection in both cases.     

Contraceptive potential of antibodies to the zona pellucida

The notion of a contraceptive vaccine based on gamete-specific surface antigens was first proposed over a decade ago, as the result of in-vitro and in-vivo studies, and in recent years has been the subject of intensive research. In particular, the zona pellucida has attracted much attention as a potential target for immunological intervention in the fertilization process. Such is the rapidly-expanding nature of research into the biochemical and biological characterization of this structure, that a review of the implications for the development of a contraceptive vaccine seems timely.