Insights from outside BJOG

Abstract

There was a kerfuffle when it was discovered that the UK national breast-screening programme had failed to send invitations to a group of women to attend for mammography. The women were aged 68–71 years. The UK's Secretary of State for Health and Social Care said that some women ‘have had their lives shortened as a result’ in a written statement, but did not give the full picture that others had been spared mammography and had escaped having their lives shortened as a result of overdiagnosis and its unintended consequences (Gøtzsche & Jørgensen Cochrane Database Syst Rev 2013;6:CD001877). Mammography screening has been a matter of debate for decades, with the benefit of diagnosing some breast cancers early needing to be weighed against the harms of overdiagnosis, which leads to women being exposed to procedures and medications that add to morbidity and raise mortality. There is no net reduction in all-cause mortality from screening mammography. The balance is even less well understood in women aged 70 years or older; the UK view is that the impact of screening in this group ‘is very uncertain’ (Marmot et al. Br J Cancer 2013;108:2205–40). The perspective from the USA, which is pro-screening, has been less assured, with each recommendation from trusted sources advising moving from annual screening for women in midlife to biennial screening in individuals aged 50–69 years. An editorial in JAMA on the topic concedes that the ‘likelihood that a woman with average risk will experience harm from mammography screening is consistently higher than the likelihood that she will benefit’ (Keating & Pace JAMA 2018;319:1814–15). The BMJ weighed in with a catchy piece entitled ‘Breast cancer screening error: fatal mistake or lucky escape?’ (Hawkes BMJ 2018;361:k2036), which suggests that the medical authorities have been ‘elegantly hoisted by their own petard’. By siding with the more benefit faction, those in charge have caused many women to be concerned. They will need to explain to women with breast cancer and their families just how the missing mammogram letters would have changed outcomes and whether this constituted negligence. Recommendations should be based on all the facts and not those convenient to the person giving advice. Medical advisors should openly discuss mammography with all women, and should be clear that all-cause mortality is unaffected by screening. Every woman should be allowed to make up her own mind (McCartney BMJ 2018;361:k2055). Breast cancer is the most common malignancy in women, affecting about one in eight in high-income countries. Its incidence rose toward the end of the previous century, but has stabilised over the past decade. The disease accounts for the second highest number of cancer-related deaths after lung cancer, although mortality is decreasing at a rate of 2% per year, mainly as a result of increased awareness and improved treatments. Treatment consists of surgery (less radical than it was in the past), site radiation, chemotherapy (in selected cases) and endocrine follow-up therapy. The aim is to reduce local or distant recurrence and mortality, and what is recommended depends on the initial stage at presentation, tumour type, hormone and human epidermal growth factor (HER) receptor status, plus more recently the genetic make-up of the tumour. It is this genetic ‘signature’ that is now the focus of research to define the role of chemotherapy in each case. About half of diagnosed breast cancers are hormone-receptor positive, HER negative and axillary-node negative. Women with these tumours have been selected for research into genetics and chemotherapy. The most widely used gene expression test is ‘Oncotype DX’, which gives prognostic scores that depend on the expression of 21 different genes. Each tumour is given a recurrence score between 0 and 100. Scores below ten indicate a low chance of recurrence over the next 10 years (<2%). Chemotherapy can offer little additional benefit and the balance of probability is that it will cause harm, so it is not recommended. Scores more than 25 indicate an increased chance of recurrence and the benefits of chemotherapy are likely to be greater than its adverse effects. However, 70% of patients have a score between 11 and 25 and to date have been given chemotherapy to err on the conservative side. Women from this group were invited to join a trial of chemotherapy plus endocrine therapy or endocrine therapy alone as part of the latest leg of the TAILORx trial (Sparano et al. N Engl J Med 2018;379:111–21). More than 9000 patients underwent randomisation and were followed up for a mean of 9 years. There was no difference in survival rates (94% in both groups), invasive disease-free survival (83% in the endocrine-therapy group and 84% in the chemoendocrine-therapy group) or in freedom from distant or local recurrence (92% and 93%, respectively). It was concluded that adding chemotherapy to endocrine therapy in women older than 50 years with genetic test scores of 11–25 was unnecessary. The practical implications are that the majority of women with the most common form of breast cancer can safely avoid chemotherapy. These outcomes will encourage research into the prognostic assessment of other tumours and usher in more individualised treatment – a significant advance toward precision medicine. The failure of a pregnancy to progress beyond 12 weeks is most commonly due to genetic aberrations or embryonic maldevelopment. Ultrasonic demonstration of the absence of a fetal heartbeat or an anembryonic pregnancy may or may not be accompanied by symptoms and signs, but either way it is a distressing situation requiring resolution. The options are expectant, medical or surgical management. Observation may be desirable emotionally, but it is unpredictable and action is often preferred. Surgical evacuation or aspiration is definitive but invasive, requires admission and has cost considerations. Medical management using 800 micrograms of misoprostol given orally or vaginally offers a reasonable alternative. Among women who have pain and bleeding, success rates are near 90% but many pregnancies that are asymptomatic do not respond as readily to the exclusive use of misoprostol. Pretreatment with mifepristone could improve success rates (meaning that evacuation of the uterus is not required) although evidence of the efficacy of this combined approach has been lacking. A trial of vaginal misoprostol alone versus mifepristone pretreatment (200 mg orally) has shown that expulsion of the products of conception within 3 days is the most likely result (Schreiber et al. N Engl J Med 2018;378:2161–70). At 1-month follow up, surgical evacuation was required more often among women receiving misoprostol alone than dual therapy (Figure 1). The number needed to treat with the adjuvant medication to meet the criteria for success was 6. This information could sway many gynaecologists to recommend medical therapy with an editorial suggesting that these ‘results support the use of the sequential regimen as the standard of care’ (Westhoff N Engl J Med 2018;378:2232–3). Mifepristone needs to be less expensive and more readily available if women are to be offered this improved non-invasive option when choosing medical over surgical or expectant care. The costs of infertility are high whether at individual, couple, family or community level. The condition is independent of socio-economic status, and public opinion is that more resources should be allocated to it. People are prepared to pay the costs of treating infertility and, because women are choosing to start families later, the demand for services is rising. In high-income countries, the mean age of a woman having her first child is 29 years, which means that half of pregnancies are conceived after fecundity has started to decline. Infertility affects 6% of couples. After investigations and infertility diagnosis, the resort to in vitro fertilisation (IVF) is becoming ever more rapid. Data from the UK reveal a situation – probably applicable to other high-income countries – in which more than half of IVF cycles are funded privately and cost between £2500 and £3500 depending on ‘add-ons’ (Howard BMJ 2018;361:k2204). The average number of cycles is six, with a success rate of one in three below the age of 35 years. Registration costs, depending on clinic status, plus ‘add-ons’ are sources of concern because these are not regulated and can exploit couples for profit without proven added value in terms of live-birth outcomes. Examples are endometrial scratching, assisted hatching, embryo glue, protein injections and acupuncture. The last of these has a chequered record, and the latest research from Australia and New Zealand provides no support (Smith et al. JAMA 2018;319:1990–8). A sample of over 800 women underwent real or sham acupuncture as part of their IVF programme both at the follicle stimulation stage and at embryo transfer. Live-birth rates were 18% in both groups. There are other hidden costs of IVF – ovarian hyperstimulation affects nearly one-third of women – and even if successful, a higher-than-average frequency of pregnancy loss can be anticipated, plus raised rates of premature birth, neonatal morbidity and a relative risk of birth defects of 1.32. Another potential cost is that of multiple pregnancies. Couples embarking on IVF programmes need to be informed about the practical and psychological costs of the intervention. Failed cycles increase the risks of partnership breakdowns, reiterating the high stakes of infertility in modern society (Martins et al. Hum Reprod 2018;33:434–40). This comprehensive report produced by the Economic Commission for Latin America and the Caribbean (ECLAC) emerged from the 37th session of ECLAC, which was held in Havana on 7–11 May 2018. The report focuses on issues of equality and investigates mechanisms by which inequality affects the Latin American and Caribbean economies. In accordance with the 2030 Agenda and the Sustainable Development Goals, the report focuses on three specific areas: a macroeconomy for development; a welfare state based on rights and productivity gains; and decarbonisation of the production structure, cities and energy sources. Issues regarding unequal access to health and education and the effects of inequality arising from gender, race or ethnic discrimination are discussed. Chapter IV provides a detailed overview of inequality as a development obstacle. Chapter VII part B discusses the welfare state: exercising rights and increasing productivity. Figure I.2 highlights average monthly labour income among employed individuals aged ≥15 years by sex, race or ethnicity and years of schooling around 2015 in selected Latin American countries. Figure III.15 highlights incidence of poverty in households in 2002–17 in Latin America and subregions (15 countries), and figure IV.6 focuses on average length of education of women aged 25–35 years who did and did not become mothers during adolescence in seven countries. The report proposes guidelines that are based on equality and sustainability and are designed to increase the efficiency of the Latin American and Caribbean economies. Capacity building and the construction of welfare states are reported as key areas for development. Available online at www.cepal.org This manual, produced by the World Health Organization (WHO), presents up-to-date information regarding 15 infectious diseases and guidance on how to respond to outbreaks. It is available to all frontline responders to outbreaks including communities, government officials and public health professionals. The diseases covered are Zika, yellow fever, chikungunya, Ebola virus disease, plague, Crimean–Congo haemorrhagic fever, leptospirosis, meningococcal meningitis, avian and other zoonotic influenzas, Lassa fever, monkeypox, seasonal influenza, cholera, pandemic influenza and Middle-East respiratory syndrome. This practically focused manual provides access to response tips and checklists including coordinating responders, health information, communicating risk and health interventions. Detailed information is presented for three focus areas: community engagement during epidemics, risk communication, and treating patients and protecting the health workforce. Page 22 provides a very useful world map (including data for Latin America and the Caribbean region) indicating the 1307 epidemic events reported in 172 countries between 2011 and 2017. Part II focuses on providing ten key facts for each of the 15 diseases followed by detailed individual disease response tips and information about geographic distribution of each disease. A series of five toolboxes are also included covering the role of WHO, the International Coordinating Group (ICG) on vaccine provision, tables for laboratory diagnosis and shipment of infectious substances, transport of infectious substances and vector control during epidemics. Available online at www.who.int This highly practical clinical handbook, produced by WHO, is aimed at health professionals caring for women or girls who have been subjected to any form of female genital mutilation (FGM) and is based on WHO guidelines on the management of health complications from female genital mutilation, which was published in 2016. It is estimated that around 200 million women and girls are living with FGM worldwide and many health professionals have limited knowledge and skills regarding preventing and managing FGM-related complications. The WHO handbook is based on three guiding principles: that girls and women living with FGM have experienced a harmful practice and should be provided with high-quality health care; that medicalisation of FGM (i.e. healthcare providers performing FGM) is never acceptable; and that all stakeholders should initiate or continue actions directed towards primary prevention of FGM. Arranged over nine chapters, the handbook covers: understanding FGM; communicating with girls and women living with FGM; immediate and short-term physical complications arising from FGM; gynaecological and urogynaecological care; caring for women with FGM during pregnancy, labour, childbirth and after delivery; deinfibulation; mental health and FGM; sexual health and FGM; and additional considerations. Step-by-step guidance is provided on clinical assessments, management and follow up. Cultural notes, notes of referral and summary boxes of key aspects to remember are also included. Job aids are provided to help with classification of FGM, visual recording of FGM, deinfibulation procedures and problem management in five steps. Available online at www.who.int The second edition of the comprehensive mental healthcare manual Where there is no psychiatrist has been published by the Royal College of Psychiatrists. The manual, which is freely available, has been developed for health professionals more generally, including community health workers, primary-care nurses, midwives, social workers and family doctors, and does not require specialist knowledge of mental health issues. Part one presents an overview of different mental health problems including core skills for providing mental health care, how to assess someone with a mental health problem and general approaches to treatment. This part of the manual also includes example cases with an explanation of the problem and a diagnosis – including postnatal depression, post-traumatic stress disorder and depression. Part two provides comprehensive and clearly written information about the various specific treatments for different mental health problems, including advice on what to do if the person does not take medication as prescribed, if the person does not improve and if there are adverse effects. Detailed counselling information is also provided in this section, including a table focusing on different counselling strategies and the problems that they address; and a useful summary table highlighting issues that may arise during counselling and how to approach them. Part three focuses on clinical problems and covers emergency management, behaviours causing concern, symptoms that are medically unexplained, individuals with problems due to habits, problems arising from loss and violence, and problems in childhood and adolescence. Parts four and five focus on integration of mental health care into health care and community platforms, and how to localise this manual for the readers’ particular region or setting. Available online at www.cambridge.org Royal College of Obstetricians and Gynaecologists (RCOG) The following guideline is now available at www.rcog.org.uk Mesh safety alert American College of Obstetricians and Gynecologists (ACOG) The following guideline is now available at www.acog.org Low-Dose Aspirin Use During Pregnancy (Committee Opinion) No 743 Society for Maternal-Fetal Medicine The following guideline is now available at www.smfm.org SMFM Consult Series #45, Mild fetal ventriculomegaly: diagnosis, evaluation, and management Society of Obstetricians and Gynaecologists of Canada (SOGC) The following guidelines are now available at www.jogc.com No. 362-Ovulation Induction in Polycystic Ovary Syndrome No. 361-Caesarean Delivery on Maternal Request Faculty of Sexual and Reproductive Healthcare (FSRH) The following guideline is now available at www.fsrh.org RCOG and FSRH statement on taking misoprostol at home in Wales WO2018091906 (A1) Device for self-collection of a biological sample from a vaginal or anal orifice. This patent application discusses the invention of a device for self-collection of a biological sample from a vaginal or anal orifice and a kit for collection of the sample. Specifically, the device consists of an applicator with a handle at one end and an absorbent swab at the other, allowing the user to easily insert the swab to obtain the biological sample. A locking mechanism protects the swab after the sample has been obtained. Smith L, Wetton J. 24 May 2018. US2018147171 (A1) Trans10:CIS12 isomer of conjugated linoleic acid as a therapeutic and preventative agent for hypertension specific to pregnancy. This patent application proposes compositions and methods for using t10:c12 conjugated linoleic acid to reduce hypertension in pregnant women (particularly women at risk of pre-eclampsia) by reducing blood pressure and therefore reducing the risk of preterm birth. Another aspect of this patent discusses a prenatal vitamin comprising t10:c12 conjugated linoleic acid. This application claims priority to US Provisional Application 61/623,815 filed on 13 April 2012. Bird IM, Patankar MS, Boeldt DS, Shahzad MMK. 31 May 2018. US2018164323 (A1) Use of soluble CD146 as a biomarker to select in vitro-fertilized embryo for implantation in a mammal. This patent application relates to the use of a soluble CD146 protein (sCD146) as a biomarker to determine whether an embryo can be selected for implantation or not. Specifically, the authors state that sCD146, when measured in an embryo culture medium, can be used to identify an embryo that may have a high-risk of implantation failure, an implantable embryo, or to aid selection of the embryo that has the greatest implantation potential. Bardin N, Blot-Chabaud M, Bouvier S, Lacroix O, Dignat-George F, Gris J-CR. 14 June 2018. A referendum was recently held in Ireland regarding whether to repeal the current Irish constitutional ban on termination of pregnancy. The result was in favour of repealing the current legislation and reforming access to termination of pregnancy in Ireland, which will bring it into line with most other European countries. Source: www.reproductiverights.org A Canadian member of parliament (MP) has recently tabled a private member's bill in the Canadian House of Commons aiming to legalise payments for sperm and egg donation and for the use of surrogates. Currently, the 2004 Assisted Human Reproduction Act in Canada states that surrogacy should be altruistic and that payments to gamete donors is prohibited. The MP reportedly has the support of eight other MPs with the bill yet to be debated. Source: www.bionews.org.uk Clinicians keen to keep up-to-date regarding clinical studies that are currently recruiting may find the following informative.