Women’s health—what’s new worldwide

A roundup of patents, guidelines and trials from around the globe

Authors

  • Shona Kirtley,

  • Catriona Murray,

  • Stephen Kennedy


Patent news

Granted patents

US7447542: A US patent was granted in November 2008 for a system using an electromyogram, incorporating position sensors to enable three-dimensional monitoring of myographic activity in muscles, such as the contracting uterus during labour. This invention aims to improve monitoring of uterine activity by assessing the effectiveness of contractions. It also aims to help prevent premature birth as well as research generally in obstetrics and gynaecology settings.

Calderon I, Ben-David G. Three-dimensional monitoring of myographic activity.

http://www.patentlens.net/patentlens/structured.cgi?patnum=US_7447542#show

The potential benefits of a device that might be able to improve the accuracy of measuring uterine activity noninvasively, particularly if it can more reliably predict preterm labour, are considerable.

US7445621: This patent, granted in November 2008, relates to an instrument that combines the benefits of both monopolar and bipolar endoscopic coagulating forceps, reducing the need for surgeons to change instruments during certain surgical procedures. The forceps have been modified to include a shaft fitted with moveable jaws and a connector to enable each of the jaws to be connected to an electrical source. This allows the jaws to operate in a bipolar mode conducting electricity through tissue to coagulate, seal or cut the tissue. The forceps can also be used in monopolar mode independent of the bipolar mode. This invention is a continuation of patent number US7232440.

Dumbauld PL, Garrison DM, Guerra P, Peterson D, Dycus ST. Bi-polar forceps having monopolar extension.

http://www.patentlens.net/patentlens/structured.cgi?patnum=US_7445621#show

Patent applications

WO2008/132153 A1: This invention relates to novel tetrahydrocarbazole derivatives that act as ligands of G-protein-coupled receptors (GPCRs), but especially as antagonists of luteinizing hormone-releasing hormone. These compounds could be used to prevent or treat physiological or pathological conditions, which are mediated or modulated by GPCRs, such as gynaecological cancers, endometriosis and uterine fibroids.

Schuster T, Paulini K, Schmidt P, Baasner S, Polymeropoulos E, Günther E, Teifel M. Novel tetrahydrocarbazole derivatives as ligands of G-protein coupled receptors.

http://www.patentlens.net/patentlens/structured.cgi?patnum=WO_2008/132153_A1#show

GPCRs represent a superfamily of cell membrane-associated receptors that play an important part in numerous biochemical processes. They mediate and control diverse physiological stimuli, such as photosensitivity, taste and smell, as well as fundamental processes, such as metabolism, reproduction and development. Peptide hormones, biogenic amines, amino acids, nucleotides and lipids have been identified as ligands.

Tetrahydrocarbazole carboxylic acids have previously been described as prostaglandin antagonists and 5HT1 agonists; however, their use for this indication is novel.

US2008/0275363 A1: This patent application relates to an instrument for examining the wall of a body cavity, in particular the uterus, which includes a catheter through which fluid can be inserted into the cavity, an outflow opening, a sealing element (preferably a cervix cone) to prevent leakage of the fluid from the cavity, a gripping attachment for ease of use and a vacuum.

Schoot BC. Device and Method for Examination of a Body Cavity.

http://www.patentlens.net/patentlens/structured.cgi?patnum=US_2008/0275363_A1#show

The simplicity of this invention compared with previously proposed, more complex devices and its similar mode of action to the microsuction curette may improve its acceptability.

US2008/0275026 A1: This patent application relates to the use of novel nonpeptide oxytocin agonists and vasopressin antagonists in pharmaceutical compounds for treating a range of conditions including primary dysmenorrhoea. Currently, only one oxytocin receptor has been well researched and only three vasopressin receptors are known. Peptide analogues of oxytocin are well known, but little has been reported on nonpeptide oxytocin receptor agonists, which have the advantage over peptide versions of oral administration (as well as penetration of the central nervous system). High levels of vasopressin have been found in women with dysmenorrhoea, and it is hoped that by reducing the stimulation of V1A receptors, vasopressin antagonists would reduce the symptoms. This application is a division of patent number US7407949.

Hudson P, Batt AR, Heeney CM, Baxter AJ, Roe MB, Robson PA. Benzamide derivatives as oxytocin agonists and vasopressin antagonists.

http://www.patentlens.net/patentlens/structured.cgi?patnum=US_2008/0275026_A1#show

There is currently a surge of interest in this area: we reported in a previous issue (December 2008) on a patent application for triazole antagonists, which may be useful as vasopressin antagonists.

International guidelines/reports

Uncertainty factors in risk assessment

To establish toxicity to human health and in order for exposure limits to be set by regulators, detailed information is required from animal experiments and epidemiological research about novel substances. Such information is available for a few substances, but for the majority, data sets are rarely adequate enough and a degree of extrapolation is required. This advisory report from the Health Council of the Netherlands considers ‘uncertainty factors’ that aid extrapolation and hence allow determination of both health-related recommended exposure limits and toxicological risk assessment. These ‘uncertainty factors’ allow for interspecies and intraspecies variations in the effect of substances (and hence the differing toxic dose of the same substance on laboratory animals and between one human and the next). Various scientific disciplines and methodologies are discussed, and current scientific thought regarding numeric values for these ‘uncertainty factors’ are examined. Recommendations include encouraging the use of new toxicological analysis techniques such as quantitative structure-activity relationship; the use of allometric scaling factors (which adjust for the relationship between biological activity and physical size); defining chemical-specific adjustment factors and promoting the use and further development of probabilistic methodologies.

http://www.gr.nl/samenvatting.php?ID=1764

Best practice statement on urological surgery: antimicrobial prophylaxis

This updated statement from the Best Practice Policy Panel of the American Urological Association aims to assist urologists in the appropriate use of perioperative antimicrobial prophylaxis. Guidance is provided on specific indications, agents and durations of prophylaxis for surgery, including cystourethroscopy, vaginal surgery and open laparoscopic surgery as well as cystography and urodynamic studies. Tables have been provided with guidance regarding patient-related factors affecting host response to surgical infections and antimicrobial prophylaxis for patients with orthopaedic conditions.

http://www.auanet.org/content/guidelines-and-quality-care/clinical-guidelines/main-reports/antimicroprop08.pdf

This document includes a useful discussion regarding the rationale behind antibiotic choices for urological procedures. This adds further detail to the recent SIGN guidelines (July 2008) for antibiotic prophylaxis in surgery (http://www.sign.ac.uk/pdf/sign104.pdf), which may be useful to gynaecologists carrying out the procedures listed above.

Medical Oncology Status in Europe Survey Phase III

The ESMO (European Society for Medical Oncology) Medical Oncology Status in Europe Survey (MOSES) Task Force has released their latest report providing the results of a survey to assess the status of medical oncology in Europe. The principal aims of the MOSES III survey were to investigate two areas: the teaching of medical oncology for both undergraduates and postgraduates in Europe and the adoption of a multidisciplinary approach to cancer treatment across Europe. The report concludes that there has been a slow increase in the level of education in medical oncology (in parallel with a greater role for medical oncologists) in Europe but that this varies from country to country; plenty of improvement is required in terms of the organisation of the discipline of medical oncology and there is an increasing role for EMSO on a political level both nationally and internationally.

http://www.esmo.org/fileadmin/media/pdf/surveys/ESMO_MOSES_Phase_III_2008.pdf

The report includes an interesting table summarising specialist (i.e. medical oncologist, radiologist, gynaecologist etc.) involvement in the diagnosis, investigation and management of women with ovarian and cervical cancer. There is considerable heterogeneity between countries in the pregraduate and postgraduate training of medics: approximately 85% of the countries surveyed have training in oncology, but only about half have training in medical oncology.

Family planning: a global handbook for providers

This guidance handbook, published by the Information and Knowledge for Optimal Health project at Johns Hopkins Bloomberg School of Public Health, has been developed in collaboration with a range of organisations worldwide. The handbook is one of the World Health Organization’s four cornerstones of family planning guidelines providing the technical information required for healthcare providers to deliver effective and appropriate family planning methods to women. This handbook includes guidance, laid out in a clear and comprehensive manner, regarding the main methods of contraception and their effectiveness, STIs, reproductive health issues, family planning provision and medical eligibility criteria for contraceptive use. Useful job aids and tools have also been provided for comparing contraceptives, male and female anatomy, pregnancy checklists, missed pills and a contraceptive effectiveness chart. The handbook is available online and in hard copy and has been translated into French, Portuguese, Spanish and Russian. Online versions will be available in Arabic, Farsi, Hindi, Swahili and Urdu.

http://www.infoforhealth.org/globalhandbook/remindersheets/msword.shtml

Clinical trial recruitment

Clinicians keen to keep up to date regarding clinical trials that are currently recruiting may find the following informative.

Observing pelvic organ prolapse symptoms and treatment outcomes

http://clinicaltrials.gov/ct2/show/NCT00784602?term=prolapse&recr=Open

This observational study aims to monitor the natural history of pelvic organ prolapse in women and assess the outcomes of both conservative and surgical treatment. Outcomes, assessed by questionnaire, will include urinary, bowel and sexual function, quality of life, patient satisfaction, cost and achievement of patient-determined treatment goals. Questionnaires will be sent to all women at enrolment and then yearly. Those women who receive surgical treatment will be sent an additional questionnaire at 6 months after surgery.

Inclusion criteria: Female; pelvic organ prolapse; able to provide informed consent; able to complete study assessment.

Primary outcome measures: changes in urinary, bowel and sexual function as measured on validated questionnaires.

Trial site: Michigan, USA.

Anticipated trial end date: December 2028.

This observational study aims to collect data over a 20-year period from women presenting to gynaecologists with prolapse symptoms who themselves opt for conservative management or surgery. Although nonrandomised, it will nevertheless provide interesting long-term, prospectively collected data to inform clinicians and patients about the natural history of this condition.

Safety and efficacy of Proellex in premenopausal anaemic women with symptomatic uterine fibroids

http://clinicaltrials.gov/ct2/show/NCT00785356?term=menopause&recr=Open

This randomised double-blind trial aims to determine the safety and effectiveness of the selective progesterone receptor modulator (SPRM) Proellex (CDB-4124) in anaemic, premenopausal women with symptomatic uterine fibroids requiring hysterectomy.

Women will be randomly assigned to receive one of three treatment arms: Proellex 25 mg; Proellex 50 mg or placebo. All women will receive 325 mg of iron supplements to be taken twice daily for the duration of the drug treatment.

Inclusion criteria: Female; age 18–48 years, body mass of 18–39; anaemic (haemoglobin ≤ 10.5 g/dl); uterine fibroid-associated symptoms indicated by a history of excessive menstrual bleeding; surgical interventions for uterine fibroids planned/anticipated after the study; willing to comply with all study procedures including endometrial biopsies, blood draws for all visits.

Primary outcome measure: comparison between the 50 mg Proellex dose level and placebo in the change in haemoglobin from baseline to 3 months.

Trial site: Various locations in Mexico.

Anticipated trial end date: June 2009.

The effects of Proellex are thought to be antiproliferative and pro-apoptotic (programmed cell death). It is hoped that this drug will prove useful in the management of diseases, such as endometriosis and uterine fibroids. However, readers should be aware that development of another SPRM, Asoprisnil, was discontinued after concerns about endometrial safety in phase III studies.

Evaluation of endocrine and metabolic parameters in the new diagnostic phenotypes of patients with polycystic ovary syndrome

http://clinicaltrials.gov/ct2/show/NCT00784615?termmenstrualdisorders&recrOpen

This observational study aims to investigate the endocrine and metabolic characteristics of different polycystic ovary syndrome (PCOS) phenotypes to determine if these phenotypes predispose women with PCOS to cardiovascular disease.

Inclusion criteria (two of the following): ovulatory dysfunction (clinically defined by oligomenorrhoea or amenorrhoea); clinical hyperandrogenism (defined by the presence of hirsutism, acne, androgenic alopecia); polycystic ovaries (defined by the presence, in one ovary, of 12 or more follicles).

Primary outcome measures: serum levels (total bioavailable testosterone, free androgen index, total low-density lipoprotein and high-density lipoprotein cholesterol, triglycerides, insulinaemia, OGTT, HOMA index, adiponectin, C-reactive protein); transvaginal ultrasound to determine the number and size of ovary follicles and ovary volume.

Trial site: Cordoba, Argentina.

Guidelines for the diagnosis of PCOS were updated in 2003 by a committee of experts in Rotterdam under the auspices of the American Society for Reproductive Medicine and the European Society for Human Reproduction and Embryology. It is possible that certain women diagnosed with PCOS, who regularly ovulate or show no signs of hyperandrogenism, may not have the same cardiovascular risk factors as those whose diagnosis is reached using other criteria. This needs to be established to aid planning of preventative strategies in those at risk and to avoid unnecessary treatments in others.

Amnioinfusion initiative

http://clinicaltrials.gov/ct2/show/NCT00787163?termpregnancy&recrOpen

This randomised trial aims to compare perinatal survival rates in women who present with early spontaneous preterm prelabour rupture of membranes (PPROM) and persistent oligohydramnios managed either conservatively or with serial amnioinfusions.

Inclusion criteria: single pregnancy; early spontaneous PPROM <24.3 weeks; oligohydramnios for at least 4 days and no longer than 15 days at enrolment; normal structural examination as much as possible; at least two ultrasound examinations after PPROM for gestational age confirmation and diagnosis of persistent oligohydramnios; follow-up ultrasound examinations weekly in the treatment group; acceptance of randomisation.

Primary outcome measures: survival of neonate at discharge after serial amnioinfusions compared with survival after expectant management.

Secondary outcome measures: gestational age at birth; latency time from PPROM to delivery; indication for delivery; number of days of ventilatory support; serious neurological morbidity; neonatal sepsis prevalence; need for oxygen at 36 weeks postconception.

Trial site: Milan, Italy.

Anticipated trial end date: December 2013.

The perinatal mortality and neonatal morbidity associated with rupture of membranes prior to 24 weeks is extremely high. In uncontrolled series, serial infusions have been shown to substantially reduce mortality. However, the last systematic review of the subject identified only one randomised controlled trial (Cochrane Database Syst Rev 2000;CD000942), which showed that the intervention was not beneficial. Further research into this distressing condition will be greatly appreciated.

Legal matters

South Dakotans reject abortion ban

The Centre for Reproductive Rights reports that for the second time in 2 years voters in South Dakota have voted against a measure that would have prohibited nearly all terminations in the state. The ban would have required all women in South Dakota to carry their pregnancy to term regardless of any risks to their own physical and mental health. It had been anticipated that, if successful, this ballot may have been just the start of a campaign that could have been destined for the US Supreme Court in an attempt to overturn the landmark decision brought about by Roe v. Wade (1973). In a separate ballot, voters in both Colorado and California have also rejected bans that aimed to jeopardise women’s reproductive rights in the USA.

http://www.reproductiverights.org/pr_08_1105SDBan.html

Indian activist sues state for neglecting maternal mortality

The co-ordinator of a network of local NGOs in India, Sandesh Bansal, has begun a public interest lawsuit against the state of Madhya Pradesh. He claims that the state has not properly implemented maternal health polices resulting in Madhya Pradesh having the third highest maternal mortality ratio in India (498 deaths for every 100 000 live births). The lawsuit aims to order the state to set-up health facilities and provide free health services for those who need them. It also aims to ensure that the state establish a reporting system to review maternal deaths.

http://www.reproductiverights.org/ww_asia.html

The progress of this lawsuit will be fascinating to observe and is likely to be followed closely by regions that find themselves in similar situations. Action in certain countries and regions is certainly required to facilitate achievement of Millennium Development Goal 5 (reduction of the maternal mortality ratio by three-quarters by 2015).

Footnotes

  1. Shona Kirtley, Catriona Murray and Stephen Kennedy, Women’s Health Specialist Library, Nuffield Department of Obstetrics and Gynaecology, University of Oxford. To keep up to date with the latest evidence-based women’s health information visit the Women’s Health Specialist Library: http://www.library.nhs.uk/womenshealth

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