12 December, 2008

Interesting article on drug makers and journals

The New York Times has an interesting article on HRT and a drug maker.

09 December, 2008

Flu immunisation in pregnancy

Pregnant women should be vaccinated against influenza viruses. Being immunised reduces their chances of being hospitalised during pregnancy and decreases the risk of fetal anomalies. Although immunisation with inactivated flu vaccine is recommended by the World Health Organisation and national health bodies, few mothers receive the vaccine and little is known about its effect on neonates.

What is known is that natural maternal antibodies protect babies in the first few months of life but there are no data on whether vaccinating the mother also offers protection. Zaman et al (NEJM 2008;359:1556-64) now report on a trial that looked at the effectiveness of a trivalent inactivated vaccine in reducing flu in pregnant women and their offspring for 6 months after delivery.

Compared to mothers and infants not given the vaccine, babies whose mothers received the vaccination intervention had a two-thirds reduction in the risk of having laboratory- proven flu while the mothers had a one-third reduction in their likelihood of respiratory fever. The study was carried out in Bangladesh and showed that the remarkable effectiveness of the vaccine conveyed infant immunity for a longer duration than that offered by passive antibody acquisition from the mother. The “two for the price of one” benefit to mother and infant is an additional incentive, with 5 pregnant women needing to be treated to prevent one illness in her or her baby.

The cost of time saving

In developed countries people turn their clocks forward in spring and backwards in autumn. Forward-turning in spring means an hour is “lost” which usually means an hour less sleep and this reduction can be stressful until people's physiology adjusts. But can losing one hour of rest have a real effect? It seems so if the incidence of myocardial infarcts is anything to go by.

Janszky & Ljung from Sweden (NEJM 2008;359:1966-8) showed that coronary events are more common when people are deprived of their extra hour when they turn their clocks forward. Hospital admissions for infarcts rose significantly across the land, especially 2 days after change-over, compared to 2 weeks earlier or 2 weeks later. The effect was consistent over many years and most pronounced in people younger than 65 years old.

As if to prove the point, the opposite effect was found in autumn when the Swedes had fewer than average heart attacks immediately after the “extra hour” was added. The work suggests there are subtle relationships between sleep patterns, stress and cardiac events.

03 December, 2008

The Six Habits of Highly Respectful Physicians

A good article on The Six Habits of Highly Respectful Physicians in the New York Times.

18 November, 2008

Is there a cognitive cost of being a twin?

Multiple pregnancies have come under intense scrutiny because they are associated with prematurity and growth restriction. In developed countries, high rates of multiple pregnancies following assisted reproductive technology have been cited as a reason why preterm delivery rates remain stubbornly high and perinatal statistics have plateaued.

Long-term outcomes of twins take decades to be determined and it is described that twins born in developed countries half a century ago had lower IQs and academic performances than singletons. However, recent figures from Scandinavian studies show no differences between singletons and twins as measured by all cause mortality and academic achievement (Christensen & McGue BMJ 2008;337:a651:245-6). Perhaps modern antenatal care and catch-up interventions have nullified the discrepancies, but there is strong evidence that disadvantage no longer applies in these sophisticated environments.

It is of interest that a Taiwanese study of twins born in the mid-1980s shows that the subjects had lower academic achievements than singletons and had a lesser probability of attending college (Tsou et al pp 277-80). Is it possible that developing socio-economic factors play a role still, while these factors have been eradicated in developed countries?

HRT and quality of life

Women take hormone replacement therapy (HRT) to improve their quality of life. Symptoms such as hot flushes, sleep difficulties, vaginal dryness, unsatisfactory sexual function and emotional disturbances are the main indications for commencing HRT. These will remain the reasons for prescribing HRT despite the Women's Health Initiative trial casting doubt on the balance of benefits for women starting treatment 10 to 15 years after the menopause.


Another study running in parallel to the WHI trial was the women's international study of long duration oestrogen after the menopause (WISDOM) investigation (Welton et al BMJ 2008;337:a1190 (550-3). It was scuppered by the WHI results but there were sufficient data to look at quality of life outcomes over one year in women taking combined HRT or placebo. The domains in which the replacement therapy proved significantly better were vasomotor symptoms, sexual functioning, sleep problems, night sweats, vaginal dryness and aching joints or muscles. On the downside, more women complained of breast tenderness and vaginal discharge.


These women were also initiating treatment a considerable time after their menopause which is not ideal but the fact that they derived benefits restores some faith in the role of HRT in its primary function - symptomatic relief of hypo-estrogenic effects. There was no discernable influence on depression or other climacteric symptoms over the short-term. The jury is still out on the possible protective effects on cognitive function, protection from Alzheimer disease and cardio-vascular effects when HRT is started soon after menopause and continued for many years.


Another feature of HRT may be its effect on gastro-esophageal reflux. Jacobson et al (Arch Int Med 2008;168:1798-804) report on a large observational study in which women using estrogens were more at risk of experiencing heartburn than non-users. Their odds ratio was 1.66 and those taking combined HRT had only slightly less risk. The larger the dose and the longer the duration of use, the greater the likelihood of symptoms. The absolute risk is approximately 1 in 4 women will report such effects, and taking estrogens increases a woman's chances of being in the symptomatic category.

25 June, 2008

UK breast screening

“All screening programmes do harm; some do good as well and, of these, some do more good than harm”. This is the leading statement in an article by Gray et al discussing the introduction of the UK national breast screening programme 20 years ago (BMJ 2008;336:480-3). To maximise the good - early detection - and minimise harm - unnecessary investigations - any programme has to have ongoing quality assurance to ensure minimum standards and set improvement targets. The quality of any service depends on the skill and experience of those running it, as well as the resources allocated, especially the equipment.

The UK scheme aims to detect 5 breast cancers for every 1 000 women screened and send less than 70 per 1 000 for unnecessary further testing. All women aged 50 - 70 years are offered screening every 3 years with 2 views now the norm, resulting in more than 18 million sets of mammograms since the programme's inception. It is estimated that 100 000 breast cancers have been detected with the saving of about 1 400 lives per year (Mayor p 527).

Multidisciplinary centres have replaced diagnostic clinics and employ radiography experts, pathologists, surgeons, radiotherapists and oncologists, resulting in better comprehensive services with faster turn-around times and improved data collation. Since the screening programme was introduced, breast cancer in the UK is no longer the most common cause of death from cancer in women.

08 June, 2008

Overweight in pregnancy

Being overweight or obese is endemic in the United States. A body mass index between 25 and 30 is overweight, over 30 obese, over 35 grossly obese and over 40 morbidly obese. According to these criteria, more than 25% of women are obese when they conceive. There are 4 million births each year in the US, so about a million deliveries involve obese women.

The consequences are enormous. Routine care is more difficult starting with basic clean-catch urine specimens and venipuncture no longer being straightforward. Palpation, blood pressure measurement and ultrasound readings are compromised so monitoring presents problems. Co-morbid conditions of diabetes and hypertension are exacerbated or develop during pregnancy so these pregnancies move towards the high-risk category with increasing surveillance requiring more frequent visits, wider investigations and greater expense.

As BMI increases, so do complications and caesarean section rates, both of which add to costs according to an in-depth study by Chu et al (NEJM 2008;358:1444-153). Their research showed the increased use of all antenatal facilities with rising obesity and these strongly favoured doctors rather than nurses as well as more frequent outpatient attendance and longer in-patient stays. The greater the BMI, the greater the complications and the costs, which is a huge concern to health management organisations.

There is a strong association of rising BMI with decreasing socio-economic status in the US, so it appears those who can least afford to are placing themselves at risk and need most medical care at greater financial hardship.

05 June, 2008

May Jass Out

These are genuinely interesting times as new means of investigating old problems are being found. The work on the genetic signatures of breast tumours, the anti-immune treatment of vulvar neoplasia and the detection of the fetus' Rh blood group are all developments that could have implications for practice - and all published in one month.

Equally important is the information about the acceptability of medical evacuation after a miscarriage and advice about HPV screening as a routine. These articles could inform a change in our practice.

Also practically, it seems safe to prescribe bisphosphonates to post-menopausal women but giving testosterone to pre-menopausal women with unhappy sex lives looks unpromising.

Finally, the trends in exclusive breast feeding appear to be improving in developed countries and we can all influence attitudes in this regard. Perhaps in 10 years time mothers will regard 4-6 months of breast feeding as a positive action to benefit their children. Let us hope so.

Click on the link to JASS Online on the right, and sign up to subscribe to read the latest issue.

31 May, 2008

Cord blood storage - a new idea

Commercial opportunists encourage new parents to have their baby's cord blood stored for the next 25 years in case it could save his or her life in the future. Indeed, stem cell transplants from cord blood are used for the equivalent of bone marrow donations, often to patients with leukaemia. There may also be future advances where mesenchymal cells could be useful in treating chronic disorders and these potential applications have encouraged private businesses to lure the up-front costs of £1500 for the collection and storage of neonates' cord blood.

But the odds of the blood ever being used are low - estimated to be between 1 : 2 700 and 1 : 20 000 - and the commonest indication, childhood leukaemia, may require stem cells from a donor who does not have the carcinogenic mutation. Also, insufficient blood is available, so cord banks offer a more realistic solution and that is the view of all recognised expert groups, including the Royal College of Obstetricians and Gynaecologists. The problem is that cord banks developed altruistically have not taken off in the public sector, with less than 1% of live births contributing their cord blood in Europe.

A possible public / private partnership has been initiated by Virgin Health in the UK whereby, for the same cost, 20% of the blood is set aside for personal use and 80% donated to a communal bank (Fisk & Atun BMJ 2008;336:642-4). It is an intriguing proposition and may offer an alternative for those wishing to protect their own interests - no matter how remote - and assist those less financially well-off.

10 April, 2008

Assisted reproduction and multiple pregnancies

Multiple pregnancies resulting from assisted reproductive manoeuvres are often blamed for the rising preterm delivery rates in developed countries. Indeed, a multiple pregnancy is deemed to be the most significant risk of in-vitro fertilisation.

Transferring two or more embryos at the day 2 single-cleavage stage results in higher pregnancy rates per cycle, but also more multiple pregnancies. It now appears that transferring a single embryo at a later stage of in-vitro development (day 5) might lead to higher implantation rates, together with lowered multiple pregnancy rates, especially in women with a good prognosis. The philosophy is that by selecting women who are likely to have successful outcomes (because at least four eight-cell embryos of quality are achieved) and allowing for the development of their embryos to the blastocyst stage prior to implantation of single embryos, better clinical pregnancy rates could be achieved.

Whether such a policy in a large assisted conception unit would be feasible and give superior results is not known. To test the hypothesis, Khalaf et al (BJOG 2008;115:385-90) changed their guidelines and recorded their results for 18 months before and after the implementation of the new protocols. Despite only a selected group of patients fulfilling the criteria for single blastocyst transfer, they improved their clinical pregnancy rates from 27% to 32% while reducing their multiple pregnancy rates from 32% to 17%.


It is therefore feasible to use selective single embryo transfers in a busy IVF unit without sacrificing overall pregnancy rates and at the same time reducing twin and higher order multiple pregnancy risks. The policy had the extra spin-off of having more supernumerary embryos for cryopreservation and later use.

A Canadian study has found that singleton preterm babies and multiple birth babies have similar outcomes at the same gestational age, except for multiples having a greater predisposition to respiratory distress (Qui et al Obstet Gynecol 2008;111:365-71).

The extra costs of multiple pregnancies are considerable. As Wood points out (BJOG 2008;115:416) a twin pregnancy costs £1826 more than a low-risk singleton in antenatal and intrapartum care but other expenses have to be added in such as neonatal intensive care which could add another £3500 plus further infant in-patient care at £4800. These figures do not take into account other costs should complications arise like postnatal depression, a handicapped survivor never mind the emotional and societal costs of the stresses of ongoing care. A proper audit is indeed sobering.

Elective delivery of twins can safely include a vaginal option according to Schmitz et al who describe their experience in a French tertiary referral unit (Obstet Gynecol 2008;111:695-703). With an active intervention policy aimed at facilitating the delivery of the second twin about 5 minutes after the first, they had morbidity and mortality rates similar to those delivered by caesarean section.

08 April, 2008

New JASS out

Much is being published on preventative measures.

The journals carry large, long-term studies which show that antenatal supplementation with broad-spectrum vitamin nutrients are superior to iron plus folate alone in reducing the incidence of how birth-weight in developing countries.

Bolstering nutrition in early childhood also has long-term benefits in terms of greater earning capacity in adulthood. Breastfeeding and basic hygiene are cheap and effective interventions (Lancet 2008;371 Haddinott et al 411-6, Bhutto et al 417-40, Vaidya et al 492-9, Bryce et al 510-26, Ruel et al 588-95, Morris et al 608-21).

Later in life smoking is the most common preventable cause of death. It killed 100 million people last century and is predicted to kill 1 billion this century. Half of all smokers will die prematurely, with men's lives being shortened by 6 years and women's by 8 years (NEJM 2008:doi:10.1056) (Britton & Edmunds pp 441-5).

If you doubted the link between obesity and cancer, the article by Renehan et al (Lancet 2008;371:569-75 will convince you of the association.

Meanwhile JASS this month is dominated by twins and embolic phenomena. It's fascinating what turns up serendipitously!

18 March, 2008

Latest JASS

The messages from this month's summaries are hugely important from the international perspective.

Modern research in the epidemiological field would have been unthinkable last century because the long-term data would not have been available and the resources to capture it unaffordable. Massive financial and human investment in nutritional studies, plus the technology to interpret the information, are leading to global conclusions.

The macro- and micro-nutrition of mothers and children up to two years of age are clearly shown to determine long-term outcomes, while longitudinal studies of oral contraceptive (OC) use forty years ago are now affecting old women's health.

Concepts such as disability-adjusted life-years (DALYs) and intra-uterine settings are just the start as mega- and meta-analysis drive our views to include new confounding variables in our assessments in Obstetrics and Gynaecology. The positive news about OCs must surely eventually lead to their wider and easier availability which will breach so many existing hindrances to women's health.

10 March, 2008

Pfizer and Medical Journal Referees

Pfizer tries to make journal reveal referees

05 March, 2008

HRT and breast cancer

The role of hormonal replacement therapy is controversial in the development of breast cancer. What does seem clear is that combined estrogen with progesterone taken orally either continually or sequentially does raise the risk by a quarter to a third if taken over a decade. Looking more closely into this group of women, it appears that C-19 progestins have a lower risk than C-21 progestins and the mechanism of action may be the potentiation of the proliferative effect of estrogens in breast tissue.

In contrast, taking estrogens alone or the delivery of estrogens with progesterone transdermally does not increase the risk of breast cancer (Opatrny et al BJOG 2008;115:169-75). The authors carried out a large observational case-control study on UK women with a mean age of 61 years that takes into account the hormone therapy women took at all stages of their post-menopausal lives as the Women's Health Initiative (WHI) study caused many to swap preparations. This new data confirms the estrogen-only arm of findings of the WHI study which showed no increased risk of breast cancer.

It is interesting that transdermal preparations were not associated with increased risk either. They provide constant low hormone levels in the blood which avoids hepatic protein synthesis which does occur with the oral route, causing peaks and troughs from one dose to the next. Transdermal estrogens alone or with progesterone did not raise the risk of breast cancer.

Tibolone is a selective tissue estrogen activity regulator which has estrogenic activity on the vagina and bone without similar effects on breast and endometrial tissue. The study summarised here showed that women using tibolone alone were not at increased risk of breast cancer but the numbers were small.

Information continues to become available showing that selected prescriptions of replacement hormones should be tailored to each woman's requirements in terms of the type of medication, the dosage, the route of administration and the duration of use if unwanted side-effects are to be avoided.

06 February, 2008

Urban legends

The end-of-year BMJ is a light-hearted issue which allows us to raise our eyes above the temperature charts and dwell on the funny side of our profession. Vreeman & Carroll (BMJ 2007;335:1288-9) bust a few medical myths that we may have wondered about:

Drink 8 glasses of water a day - not necessary. There is far more fluid in our food than we realise and our thirst signals when more is needed.

We use 10% of our brains - no areas of our brains are inactive for long despite many functions being localised.

Hair and fingernails grow after death - untrue but skin retraction from desiccation can give that appearance.

Reading in dim light ruins your eyes - poor lighting may make restaurant menus difficult to read but by next morning your eyes will be fine.

Shaving makes hair grow faster - shaving your chin or your legs removes the dead part of the hair and does not encourage growth.

Mobile phones are dangerous in hospitals - no serious consequences of mobile (cellular) phone use in hospitals have been reported and certainly no deaths.
Conversely, the use of mobile phones reduces errors from delays in communication.

Eating turkey makes you drowsy - turkey contains no specific sedatives but usually forms part of a large meal, redirecting blood flow from the brain to the abdomen, causing drowsiness.

08 January, 2008

OCs and cervical cancer

Overall oral contraceptives are not associated with an increased risk of cancer. Since they prevent pregnancy and thus the risk of maternal mortality, it is far safer for a woman to take OCs than not take them.

But within these broad statements are detailed changes of risk of various conditions which have been studied to confirm or refute the role of combined estrogen and progesterone medication in their aetiology. One such condition is cervical cancer and OCs have long been linked to its increased risk, with some suggesting their carcinogenic role (Sasieni Lancet 2007;370:1591-2).

Despite the causative nature of HPV in cervical cancer, by no means all such infections lead to malignancy, so the quest is now to find what causes some HPV infections to end up as precancerous or invasive cancer while others regress harmlessly.

Given that recurrent HPV infections are part of the process, contraceptive use has been scrutinised to see if barrier methods reduce risk or hormonal methods increase the risk of recurrent infection. Data have now been published for combined OC use which give consistent results from all around the world by the International Collaboration of Epidemiological Studies of Cervical Cancer - Lancet 2007;370:1609-21. They have shown that using OCs for 5 to 10 years doubles the risk, but this diminishes soon after stopping their use and is negligible after a decade.

The authors point out the absolute risks remain very small and the other factors such as screening, smoking and other infections - especially those associated with altered immunity - are more important in the long-term. So, for women taking OCs in their twenties and thirties in developed countries, the additional risk from OCs of eventually developing cervical cancer is very small - something of the order of 0.002% and, for a woman in sub-Saharan Africa, this rises to 0.4%.

In perspective, OCs and other hormones do fit into the complex pathology of cervical cancer but their aetiological role is minor - in the extreme.