What’s new in the other journals?


  • Athol Kent

  • These snippets are extracts from a monthly service called the journal Article Summary Service. It is a service that summarises all that is new in obstetrics and gynaecology over the preceding month. If you would like to know the details of how to subscribe, please email the editor Athol Kent at atholkent@mweb.co.za or visit the website http://www.jassonline.com.

Genetic prediction of breast cancer risk

Sometimes it is important to know what does not work. It is a fact of life in the world of medical journal publication that more articles with positive results get published than articles with negative results. There are plenty of good ideas that look promising but turn out not to work. Not only is it intellectually honest to publish these findings, it is also vital to inform future research direction to know that one avenue of exploration has proved futile or at best ‘not yet promising’.

Nearly a decade ago the Human Genome Project was completed. By deciphering the human genotype it was keenly anticipated that the genetic risk factors for diseases would soon be pinpointed. The reasoning was that because some disorders had strong family history components, there would be discernable genetic fingerprints which would be identified by an individual’s detailed genomic make-up. The illnesses targeted were not the known hereditary disorders but major disease complexes like diabetes, hypertension and cancers.

For example, it was hypothesised that women at risk from developing breast cancer would carry certain abnormal alleles that could be recognised by micro-array probing and these women should be screened more regularly than those with the normal alleles—hence focusing on a high-risk cohort of women. Apart from the genes BRCA1 and BRCA2 there are at least ten single nucleotide polymorphisms (SNP or colloquially SNIPS) which are associated with women who develop breast cancer. Each of the ten confers only a small increase in risk, so testing for each SNP separately does not assist in defining high-risk status. Testing for all ten SNPs may, however, yield clinically helpful results.

Such testing was carried out on over 5000 middle-aged women by Wacholder et al. (N Engl J Med 2010;162:986–93), but even the composite findings did not work in predicting susceptibility any better than the established Gail model, which is based on history alone. The Gail model takes into account the woman’s age at menarche, her age at the birth of her first child plus her family history of breast cancer.

There are other factors indicating low risk such as abstinence from alcohol, normal BMI, multiparity plus extended breastfeeding and avoidance of hormone therapy.

Adding SNP testing to the Gail model did not increase the predictive value, probably because gene–gene or gene–environment interactions are not yet understood so at our present state of knowledge SNP investigations are of no added value, despite unscrupulous advertising suggesting otherwise. Statistically, a woman with a first-degree relative who has breast cancer is at roughly double the population risk herself and embarking on sophisticated genetic investigations does not indicate lowered or increased risk (Devilee and Rookus N Engl J Med 2010;162:1043–5).

Miscarriage and human papillomavirus vaccines

If the human papillomavirus (HPV) vaccines are to be widely given to young women then safety information about pregnancy is essential. In the efficacy trials half the subjects were given the vaccine and half were given placebo but all were instructed to use contraception. Nevertheless, some did conceive and the numbers of miscarriages in each group were compared to establish early pregnancy risk. The vaccine evaluated was Cervarix® and the results were reported by Wacholder et al. (BMJ 2010;340:c712).

The miscarriage rates varied between 9 and 15% depending on the interval between inoculation, conception and miscarriage but the differences between vaccine and placebo recipients did not reach significance. There was also no evidence that there was an effect on undetected pregnancies. Further monitoring is ongoing, but so far there is no cause for concern.

Reversing sterilisation

Female sterilisation by tubal division or occlusion is supposed to be permanent. Given the fluidity of modern society, changing relationship norms and occasional disasters the word permanent has become relative. The options for women seeking reversal of the procedure are surgical—either open laparotomy or laparoscopy—or in vitro fertilisation (IVF). The IVF techniques seem logical but superovulation, cost and the possibility of multiple pregnancies, together with overall lower success rates mean that surgery cannot be discounted.

A paper by Tan and Loh (Ann Acad Med Singapore 2010;39:22–6) records the outcomes of open and laparoscopic operations to re-establish tubal patency. Although the series comprised only 20 women, the results were promising with live births in two-thirds of women using either type of surgery, with costs considerably less than IVF–even including ectopic pregnancy expenses, as these were the commonest complications.

Provided that the candidates are younger than 40 years and that laparoscopic skills are available there does seem to be a place for surgery for those women wishing to conceive after tubal sterilisation.

Cold relief

Colds and flu cause unpleasant symptoms and are the commonest cause of loss of work hours. The viruses involved are neutralised by our immune systems over the period of a few days but the question arises as to whether vitamin and other supplements can shorten the duration of the illness.

A balanced diet will provide all the nutrients and minerals required for immunity and only deficiency states or at-risk population groups require supplementation with vitamins as protection against common viruses. Now there is evidence that extra micronutrients do not shorten cold and flu symptoms (Weichselbaum, Nutrition Bull 2010;35:26–9). The researchers show that large doses of vitamins C, A, D or E or zinc, iron or selenium are potentially more harmful than beneficial and their costs are usually prohibitive.

Analgesics, fluids and constant temperature control remain the only way to respond positively to these conditions—so save your money.

The obesity epidemic

The obesity epidemic enjoys wide publicity in all medical journals. The range of articles includes statistics, bariatric surgery, diets and implications for diseases such as metabolic disorders, cardiovascular disease and cancers as well as the enormous costs in terms of health and humanity.

All countries are affected but it seems the more affluent are the more vulnerable. According to Colagiuri et al. (Med J Aust 2010;192:260–4) being overweight or obese directly costs Australia’s citizens vast amounts of money, the figure being A$ 21 billion in 2005, which was double the estimates for that year. No wonder serious research is going into combating the epidemic with interesting data emerging on the effects of taxing junk foods such as fizzy drinks containing large quantities of sugar and fast foods with high fat contents (Duffey et al., Arch Int Med 2010;170:420–6). In the USA it is calculated that an 18% increase in the tax on junk food would decrease individuals intake by 56 kcal/day, resulting in a 2-kg weight loss per adult annually.

This apparent straight-line approach does not take into account the social complexities of being overweight, the legal implications of targeting one industry and the right-of-choice so enshrined in the American psyche (Reohr BMJ 2010;340:c1370).

Again from the USA, where one in three people are obese, there comes a study of 34 000 middle-aged women followed over 13 years. They ate their normal diet and the researchers compared those that exercised regularly with those who did not in terms of weight gain (Lee et al. J Am Med Assoc 2010;303:1173–9). Unsurprisingly, those who engaged in physical activity more often had less weight gain, but the amount of time needed per day was higher than previously recommended. Moderate to hard physical activity for an hour a day was the amount required to prevent weight gain, which is considerably more than the 20 minutes a day quoted in earlier assessments. Nevertheless, exercise is the one thing that costs nothing and is of proven benefit and it now seems the more the better.

Oral contraceptives and mortality

One of the longest running surveys is the UK General Practitioners’ study in the UK, of the effects of oral contraceptives (OCs). Forty years ago GPs started tracking the health of OC users and a control group of nonusers to see if OCs were linked to increased or decreased mortality rates (Hannaford et al., BMJ 2010;340:c927). Initial reports suggested an increased risk of cardiovascular problems in older women and smokers but the latest data show users to be at a lowered risk compared with never-users. There were fewer deaths from cancer and circulatory disease leading to an overall reduction in all-cause mortality of 52 per 100 000 woman-years.

Sexually active life expectancy

As life expectancy increases, so does the interest in the quality of life of older people. Pharmaceutical companies, health providers and governments are mindful of the needs and buying power of its aging citizens.

There is some coyness about defining age groups but it is generally accepted that middle age ends at 64 and at 65 years old age begins. At 80 you are very old. Presumably at 90 you become extremely old and maybe over 100 you become ancient? Too often euphemistic terms are bandied about trying not to offend anyone but generally confusing scientific accuracy such as ‘second adulthood’, ‘older generation’, ‘later life’ or ‘older adults’, which do not assist when groups are being compared.

Life expectancy is about 80 years in developed countries with women outliving men by a mean 2 years. In the USA 60% of the population is old and this percentage is predicted to rise to 70% over the next two decades. The health, including the sexual health, of this group is being increasingly monitored. Lindau and Gavrilova (BMJ 2010;340:C810) surveyed men and women about their sex lives and found that regular sex, defined as coitus at least once a week, was strongly related to age and general health. They coined the phrase ‘sexually active life expectancy’ which turned out to be 65 years old for women and 70 years old for men, with a 5-year variation between those rating their own health poor to fair or very good to excellent.

Their data were collected cross-sectionally in the USA where the medical management of the postmenopause and erectile dysfunction excite the interest of big pharmaceutical companies, so we can expect more publications on this previously under-researched topic.