The Research Snippets are extracts from a monthly service called the Journal Article Summary Service. It is a service that summarises new articles in obstetrics and gynaecology published over the preceding month. If you would like to have information on how to subscribe, please email the editor Athol Kent at firstname.lastname@example.org or visit the website www.getjass.com.
Shona Kirtley, Research Information Specialist, Centre for Statistics in Medicine, Botnar Research Centre, Oxford, UK and Patrick Chien, Consultant Obstetrician and Gynaecologist, Ninewells Hospital, Dundee, UK.
The USA spends more on health care per annum than the Gross Domestic Product (GDP) of France. One in every five dollars is consumed by health care and the proportion of spending relative to other expenses has been rising since the 1960s and continues to do so at an annualised rate of 2.4%. Presently, 18% of the US GDP is attributable to health care.
The new American national healthcare system starts in earnest on 1 January 2014 when the Affordable Care Act coverage begins. All US citizens will have to be registered with one of the many insurance plans on offer and enrolment is well under way. Each person will have their own health account that they will have chosen from a commercial insurer or an insurance scheme run by a federally backed organisation. Whichever plan is chosen, it must have a set of minimal requirements for healthcare coverage and prescribed prices so that it falls within the ‘Affordable’ guidelines.
For many Americans, this Act will have arrived just in time as health—or more accurately sickness—costs are moving beyond their financial means with medical bills now being ‘a leading cause of financial harm’, often resulting in a loss of savings or even homes. The article entitled ‘First, Do No (financial) Harm’ makes for sobering reading (Moriates et al. JAMA 2013;310:577–8).
Obviously, choosing what constitutes the minimal healthcare requirements has been a formidable task, which has been guided by a definitive evaluation of the average health needs of Americans.
The resulting document called The State of US Health, 1990–2010. Burden of Diseases, Injuries and Risk Factors by (US Burden of Disease Collaborators JAMA 2013;310:591–608) pulls no punches, stating that although the country has improved its health, it has not kept pace with other developed nations who have advanced the provision of health care at superior rates.
From the report, which includes the world's wealthiest nations, the top countries in order of longevity and healthy life expectancy are:
more than 82 years: Japan, Iceland and Switzerland
more than 81 years: Australia, Italy, Sweden, Spain and Israel
more than 80 years: France, Norway, New Zealand, Canada, Austria, the Netherlands, Germany, Luxembourg and Finland
next come countries like Great Britain with the USA some ten places lower down the list at 27th place (seven rankings further down this list since 1990).
For the USA, the diseases and injuries leading to the greatest number of ‘years of life lost’ are heart disease, lung cancer, stroke, chronic obstructive pulmonary disease and road injuries followed by self harm, diabetes, cirrhosis, Alzheimer's disease and colorectal cancer.
The top five risk factors were:
consumption of tobacco
high blood pressure
high body mass index
lack of exercise.
On reflection, it is clear that factors within the control of its citizens dominate most of the remediable conditions. This work highlights where effort should be focused by individuals, which is not in more health care, but in more care of themselves.
Every person in every country can learn from this major piece of work.
Responding to intimate partner violence
Intimate partner violence (IPV) is a scourge for all societies. Men who perpetrate violence against women exploit their perceived weaker partners. This is done with physical, psychological, societal or controlling ways when the woman is demeaned. It can be overt or covert, disguised as a religious or cultural norm, but it is still unacceptable.
It has to be opposed in all cultures and in all walks of life. The medical profession should play a pivotal role in exposing its evils through research; it should draw awareness to it, identify it wherever possible and respond to it appropriately. Gynaecologists may be the first-line of contact for victims/survivors and should be aware of the basic risk factors and trigger symptoms as well as the recommended interventions for dealing with IPV when confronted by it.
The World Health Organization guidelines make salient points:
Awareness that IPV is not confined to any social status or class.
IPV can be experienced not only by sexual or physical means but by verbal, intellectual or provisional abuse.
Unexplained injuries, symptoms and psychological states should raise an index of suspicion about IPV.
Disclosure should be responded to with support that includes first-line measures/privacy, confidentiality and primary safety.
The best approach condemns the violence and is never judgemental, pitying, blaming or trivialising.
Provision of assistance or referral to services or places of safety.
Referral to expert help is best and the primary point of disclosure should be compassionate.
IPV is always a complex psychological problem but evidence-based interventions do exist to combat such situations. It is of note that survivors may respond most positively if ‘not pressurised to disclose information, leave the relationship or pursue charges and are allowed to progress at their own therapeutic pace’ (Feder et al. JAMA 2013;310:479–80).
The evidence for any benefit with routine enquiry by healthcare professionals at every gynaecological visit for IPV is unclear with the latest Cochrane Review concluding that there is insufficient evidence to justify such screening but there is every reason to have an increased awareness of high-signalling behaviours and have a low threshold for enquiry.
The fact that more than a third of female homicides are perpetrated by the woman's intimate partner reflects the extent of the problem (Stöckl et al. Lancet 2013;382:859–65). The highest rates were recorded in mainly affluent countries.
Source: Drawn from US Burden of Disease Collaborators. JAMA 2013;310:591–608.
Venous thromboembolism treatment
Venous thromboembolism (VTE) is a serious condition that is the third leading cause of vascular deaths after myocardial infarction and stroke. It can present as deep-vein thrombosis or pulmonary embolism and the incidence of these conditions increases with age.
Objective evidence is essential for the diagnosis because conventional treatment is arduous and not without risk. Standard therapy is usually with parenteral heparin-type anticoagulation (like subcutaneous enoxaparin) followed by warfarin, which is given for at least 3 months. These daily injections with bridging to a regimen requiring close monitoring and dose adjustment are demanding, so news of an alternative approach is welcome.
Apixaban is an oral factor Xa inhibitor that acts rapidly, can be given as a fixed-dose regimen and does not require monitoring. It has been shown to be effective in preventing recurrences of deep-vein thromboses so Agnelli et al. (The AMPLIFY Trial. N Engl J Med 2013;369:799–808) investigated its effectiveness in the acute deep-vein thrombosis situation. They randomised over 5000 patients around the world who had proven VTEs to either conventional therapy or apixaban (10 mg twice daily for 7 days followed by 5 mg twice daily for 6 months). The aim of the study was to prevent further VTE or death while avoiding major bleeding complications. The apixaban was at least as effective as the standard treatment for preventing recurrences or death while reducing the risk of bleeding by one half to two thirds.
These outcomes, together with the ease of administration and lack of need for laboratory follow-up, will have a major influence on how VTEs are managed in future. Changes from tried and trusted therapeutic regimens for life-threatening conditions are usually slow but the results of research with rivaroxaban and dabigatram (other new oral anticoagulants) and now apixapan will undoubtedly make their management simpler, safer and potentially less expensive. Tight consent and compliance agreement will be needed (Cushman N Engl J Med 2013;369:865–6) but the portents are promising for a new way of treating acute and chronic VTEs.
New prenatal testing
All prospective parents are keen to know if their expected child is normal. With maternal serum markers plus ultrasound it is possible to reassure them (or not) about the possibility of their fetus having a trisomy. Abnormal results need confirmation using definitive amniocentesis or chronic villus sampling, the former being by far the commoner and is performed at around 15 weeks of gestation with the results available by a week or two later.
Now with sophisticated methodology, cell-free DNA is recoverable from maternal serum as early as 9 weeks of gestation, which can be genomically sequenced to detect trisomies 21, 18 and 13. The sensitivity of the test exceeds 98% with a specificity above 99.5%, which clearly outperforms conventional screening (Morain et al. N Engl J Med 2013;369:499–501). The fetus can also be sexed.
This all seems good news but the introduction of the test into clinical practice to screen the whole population may not be straightforward as large-scale studies on the screening of low-risk groups are lacking, the technology is demanding and the cost is substantial. Furthermore, women with positive screen results need to be confirmed by conventional methods negating the gestational age advantage of the initial test.
In the USA, the test is available through commercial channels but costs between US$ 800 and US$ 1600. In India, early sex testing for nefarious purposes has been associated with an unwelcome reputation. It is a significant step forward for medical science but as with many new inventions, it comes at a price and an ethical challenge.
This training package, which is available on-line and developed by ReproLine Plus, is aimed at all frontline health workers who provide care to women during labour and delivery. The resources provided include a graphic action plan, which is designed to aid clinical decision making to detect, prevent and manage postpartum haemorrhage; an illustrated training flip book (highlighting key points and key skills), which focuses on using simulation and role play to teach the prevention and management of postpartum haemorrhage and includes facilitator's notes, discussion points and details of what supplies are required for carrying out practical demonstrations; and a provider's guide, intended for both participants and facilitators, which summarises key points and performance expectations, and sets out important information regarding what the healthcare provider needs to know and do. The key points of the training package include the principles of establishing good communication with delivery team members and the woman, the administration of intramuscular oxytocin or oral misoprostol to reduce postpartum haemorrhage, the clamping of the umbilical cord, the delivery of the placenta with controlled cord traction, the assessment of uterine tone and checking the completeness of the delivered placenta, checking for perineal tears, administration of uterine massage and compression if uterine atony or bleeding is still present and the emergency transport to advanced care with continuing vaginal bleeding. All the materials are designed to be easy to understand and use and include helpful illustrations. The one-day training course is designed to be delivered on site using a model to facilitate practice. It is expected that participants will continue to practise on the model after the end of the course to reinforce the skills learnt during the course. The French, Swahili, Portuguese and Hindi translations of this resource will be available soon.
This toolkit, developed by EngenderHealth, the Johns Hopkins' Center for Communication Programs, Family Health International 360, and the US Agency for International Development, is aimed at programme managers, health service providers, and policy makers involved in the provision of family planning services. The toolkit specifically focuses on permanent methods of birth control involving female sterilisation and vasectomy. The toolkit comprises detailed information regarding essential knowledge about male and female sterilisation, relevant policies and guidelines (including World Health Organization guidelines), logistics and training resources, recommendations for programme management and service delivery, links to communication guides, advocacy tools and useful communication materials such as brochures and posters currently used in many countries. Individual country experiences (from Asia, Latin America and the Caribbean, North America and Sub-Saharan Africa) are also included providing experiences of introducing and implementing family planning programmes that include sterilisation, addressing awareness and acceptability of sterilisation and highlighting experiences of different approaches to training. The toolkit is freely accessible and can be downloaded as a PDF.
This report produced by the World Health Organization, the United Nations, the World Bank and the United Nations Children's Fund (UNICEF) documents the progress that has been made in achieving Millennium Development Goal (MDG) 4, which aims to reduce the mortality rate in under-fives by two thirds between 1990 and 2015. The report states that substantial progress has been made in achieving this target as overall the under-five mortality rate has fallen by 47%—from 90 deaths per 1000 live births in 1990 to 48 deaths per 1000 live births in 2012. However, progress is still slow with only 13 of the 61 countries required to reduce their under-five mortality rates on track to achieve this. Around half of all under-five deaths are reported to occur in only five countries: India, Nigeria, Democratic Republic of Congo, Pakistan and China. Neonatal mortality rates have been reported to have increased by 19% since 1990. Sub-Saharan Africa, which has the highest risk of death in the first month of life, is one of the regions showing the least progress towards a reduction. For MDG 4 targets to be achieved by 2015, the report states that the annual rate of reduction in the under-five mortality would need to increase substantially to 15.6% for 2012–15 (the reported under-five mortality rate from 2005 to 2012 was only 3.9%).
Medical Aid Films have recently released five new training films available for free download from their website. The films were produced in collaboration with the Somaliland Nursing and Midwifery Association (SLNMA) who together with the Somaliland Ministry of Health and UNICEF identified the need for specific training for nurses and midwives on the prevention and management of emergencies in childbirth. Four of the new training films, which have been developed specifically for skilled health workers, cover emergency obstetric and newborn care and include training films on: the administration of parenteral antibiotics; how to use the partograph; manual removal of the placenta and focused antenatal care. The fifth newly released film has been developed for community education to support health worker initiatives to encourage antenatal care attendance and highlight the importance of focused antenatal care. The content of each of these films is based on widely recognised guidelines, protocols, manuals and expert opinion and the animations aim to encourage good practice and teach practical techniques. The French, Somali and Swahili versions of these films will be released soon.
Methods of detecting aneuploidy in human embryos AU2012220540 (A1). This patent application relates to the time-lapse imaging and evaluation of human embryos in order to predict their viability and/or detect aneuploidy. Specifically, this patent outlines methods and kits for determining, in vitro, whether an embryo has the capability to develop into a blastocyst.
This application claims priority to US Provisional Application Numbers 61/445,863, filed 23 February 2011 and 61/537,336, filed 21 September 2011, both of which are incorporated by reference herein in their entireties for all purposes. Chavez, S.L., Loewke, K.E., Behr, B., Reijo, P.R.A. 12 September 2013.
Ovarian neuromodulation and associated systems and methods WO2013134548 (A2). This patent application proposes methods for treating polycystic ovary syndrome with therapeutic ovarian neuromodulation. Specifically, methods for treating conditions caused by increased ovarian sympathetic activity are discussed involving either the partial or complete disruption or incapacitation of nerves serving the ovaries. The modulation can be achieved, for example, using an intravascularly positioned catheter carrying a therapeutic assembly.
The present application claims priority to US Provisional Patent Application No.61/608,452, filed 8 March 2012, entitled Ovarian neuromodulation and associated systems and methods, which is incorporated herein in its entirety by reference. Sobotka, P. 12 September 2013.
Uterine electrical stimulation system and method EP2632328 (A2). This patent application proposes systems and methods for treating a woman with insufficient uterine contractions after labour and delivery by applying a stimulating current. The device may potentially be used to treat or prevent postpartum haemorrhage due to uterine atony. Specifically, this patent outlines the placing of stimulating electrodes (either a balloon electrode array device, a ring electrode array device, an electrode probe device, or a mesh electrode array device) along the uterus, cervix, vaginal wall and abdominal wall of a woman that would then apply a stimulating current to the woman.
This application claims priority under 35 U. S. C. $ 119 to US Provisional Patent Application No. 61/407,397 filed on 27 October 2010, the entire contents of which is incorporated herein by reference. Garfield, R.E., Carp, H., Maner, W.L. 4 September 2013.
Optimal gonadotrophin dosage WO2013132036 (A1). This patent application outlines a method predicting a woman's ovarian response to ovarian stimulation with a gonadotrophin. The ability to achieve this prediction will be relevant to women undergoing in vitro fertilisation for infertility. Specifically, this patent proposes that predicting ovarian response can be determined by obtaining monocyte or macrophage cells from the woman and assessing the in vitro uptake of the gonadotrophins into these cells. The inventors state that specifically an increased in vitro uptake of gonadotrophins into monocyte or macrophage cells may indicate a reduced response to ovarian stimulation. Fedorcsak, P., Raki, M. 12 September 2013.
The High Court of Justice in Israel has recently rejected a lesbian couple's request to be allowed to undergo a surrogacy procedure completely within the country. The Court ordered that the couple would be permitted to have the egg extracted in Israel but that the implantation of the embryo(s) must take place overseas. Currently, Israeli law allows heterosexual couples to undergo surrogacy procedures within Israel but homosexual couples wishing to undergo this procedure are required to go overseas. The Israeli Government has signalled that changes to the current legislation regarding this issue will be put forward in the next few months but it has not been made clear what form these changes may take. www.bionews.org.uk/page_336743.asp
Mixed messages on surrogacy maternity leave from European Court
Expert advisors to the Court of Justice of the European Union (CJEU) recently gave opposing recommendations regarding very similar surrogacy cases. The cases involved the right to paid maternity leave for mothers who had a child via a surrogate with one Advocate General advising that ‘a mother without enduring the physical and mental effects of pregnancy and childbirth’ does not qualify for paid maternity leave under current EU law whilst another ruled that maternity leave was 'intended to protect the special relationship between a woman and her child over the period which follows pregnancy and childbirth' and that new mothers should split the paid maternity leave provided under EU law with the surrogate. Opinions obtained from an Advocate General are not legally binding on the CJEU but these two cases have highlighted the problems of a lack of consistency in applying current EU laws to those involved in surrogacy. http://www.bionews.org.uk/page_347497.asp
Clinicians keen to keep up-to-date regarding clinical studies that are currently recruiting may find the following informative.
Preoperative chemoradiotherapy combined with nimotuzumab for cervical cancer
This phase II study aims to investigate the efficacy and feasibility, in women with initially inoperable locally advanced cervical cancer, of nimotuzumab 200 mg/week combined with concurrent platinum-based chemotherapy and intensity-modulated radiation therapy.
Primary: treatment-related toxicities; tumour response after preoperative treatment.
This phase IV randomised placebo-controlled study aims to assess the effectiveness, among nulliparous women who were managed according to a standard intrapartum protocol, of an intravenous injection of 10 mg metoclopramide at enrolment and then every 2 hours (up to a maximum of three doses) in reducing the duration of spontaneous labour. In the control group, women will be administered intravenous 0.9% sodium chloride instead.
This observational study aims to investigate the pharmacokinetics of oral contraceptive agents in obese women (body mass index > 30 kg/m2) born with a low birthweight (<5.5 lb [2.5 kg]) and obese women born with a normal birthweight (5.5–8.0 lb [2.5–3.6 kg]) to determine whether an adverse in utero environment in subsequently obese women can alter the expression and function of the enzymes and transporters that underlie the pharmacokinetics of oral contraceptives and lead to oral contraception failure. Ovulatory obese women with normal and low birthweight will be placed on oral contraceptives for 1 month during the study.
Primary: measure pharmacokinetic parameters of oral contraceptives including drug clearance.
Secondary: measure levels of gonadotrophins and ovarian hormones.
Anticipated study end date: June 2014.
The impact of mentor mothers on PMTCT service outcomes in Nigeria (MoMent)
This randomised study aims to assess the effectiveness of the use of Trained Mentor Mothers (women with HIV who are trained peer counsellors) in improving the rates of enrolment in and successful completion of prevention of mother-to-child transmission (PMTCT) programmes in Nigeria and their effect on overall outcomes for mothers and babies in terms of general HIV-related health, HIV transmission rates and survival.
Primary: proportion of HIV-exposed infants receiving early (within 2 months old) DNA HIV polymerase chain reaction testing.
Secondary: proportion of HIV+ mothers who were compliant with highly active antiretroviral therapy (HAART); proportion of exposed infants who completed 6 weeks of nevirapine prophylaxis; proportion of exposed infants who received the first dose of nevirapine syrup prophylaxis within 72 hours of life; proportion of HIV+ mothers who exclusively breastfed for 6 months; proportion of mother–infant pairs who remained in the PMTCT services at 12 months after delivery; proportion of HIV-exposed infants who received post-weaning HIV testing.
Anticipated study end date: September 2016.
Lower-limb drainage mapping in pelvic lymphadenectomy for gynaecological cancer (SENTIJAMBE)
This phase IV, non-randomised study aims to investigate the feasibility of using an isotopic technique to detect and map lower-limb lymphatic nodes during pelvic lymphadenectomy for gynaecological cancer. A radiopharmaceutical agent will be injected into both feet on the day before surgery. Pelvic lower-limb drainage nodes will be identified using preoperative single photon emission computed tomography and an intraoperative isotopic probe, and then electively removed before complete pelvic lymphadenectomy. Lower-limb drainage nodes and pelvic lymphadenectomy specimens will then be subjected to separate histological evaluation.
Primary: lower-limb drainage intraoperative isotopic detection rate in women with pelvic lymphadenectomy for gynaecological cancers.
Secondary: anatomy of lower-limb drainage; percentage of women with metastatic lower-limb sampling; follow up of women to identify complications, particularly lower-limb lymphoedema.