Journal Article Summary Service

Predicting pre-eclampsia

2011-06-09T18:33:00.003+03:00

Pre-eclampsia remains unpredictable, despite numerous biochemical and biophysical efforts to provide pointers. Working on history taking may prove of some value so North et al (BMJ 2011;342:d1875) embarked on an international study of over 3000 healthy nulliparous women which screened for pregnancy endpoints (the SCOPE study).

The women were interviewed at the start of the second trimester, routine biometry and Doppler studies were carried out around 20 weeks and the later development of pre-eclampsia tracked. It turned out that 5% did show signs and symptoms of pre-eclampsia with the following points on history indicating an increased risk: young maternal age, higher mean arterial blood pressure, raised BMI, family history of pre-eclampsia, family history of coronary heart disease, the woman having a low birth weight, vaginal bleeding for at least 5 days during early pregnancy or a duration of the sexual relationship of six months or less. The only protective predictor was a previous miscarriage of at least 10 weeks gestation with the same partner.

Adding the ultrasonic data did not improve the SCOPE prediction tool which raises the predictability of history taking to about 10%. Maybe adding the biochemical markers will increase the value of this interesting but inconclusive line of investigation.

Nifedipine & preterm labour

2011-04-04T00:16:00.000+03:00

The management of preterm labour involves the acute suppression of uterine contractions. By inhibiting the end-organ response it is presumed the initial stimulus will not remain operative or the incident producing it has passed. It is a conveniently uninvestigated aspect of preterm labour research – so are randomized trials using placebo controls which are scarce and nifedipine has never been subjected to this gold-standard form of investigation (Caritis AJOG 2011;204:95-6).

Most trials of uterine activity suppression test one drug against another and look at relative efficacy and side-effects rather than neonatal outcomes. However in the present ethical climate it may be that comparative efficiency is the best that can be hoped for and the best evidence comes from a meta-analysis by Conde-Anudelo et al (AJOG 2011;204:134 e 1-20).

Their work shows nifedipine to be superior to beta-adrenergics and magnesium sulphate for tocolysis of women in preterm labour, so if a decision is made on clinical grounds to suppress the myometrium then there is guidance in favour of nifedipine for the person in charge of the case.

Hot flush treatment

2011-04-04T00:11:00.000+03:00

There are limited non-hormonal treatments for women seeking relief from hot flushes. Peri- and postmenopausal women may not wish to take estrogens and selective serotonin reuptake inhibitors (SSRIs) offer a reasonably good option for decreasing the frequency, severity or bothersome effects of hot flushes.

A report by Freeman et al (JAMA 2011;305:267-74) indicates that the SSRI escitalopram is effective in controlling flushes in healthy menopausal women.
As usual in controlled trials for flushes about one third of volunteers had a 50% reduction in symptoms on the placebo but more than half had a similar beneficial effect from 10 – 20 mg per day of escitalopram over 8 weeks. The active substance had few side effects and it was convincing that 3 weeks after the trial ended those who took the escitalopram had the return of more hot flushes than those “coming off” the placebo.

For the record the participants had at least 4 flushes or night sweats a day before treatment and there were no racial differences between African-American and white women who were equally represented in the sample population. Estrogens are the treatment of choice for menopausal symptoms but escitalopram appears to be an option in reducing the frequency, severity and bother of menopausal vasomotor symptoms.

Treatment of depression in pregnancy

2010-01-04T05:55:00.000+03:00

Women during their childbearing years are susceptible to depression. In developed countries more than 10% of women take antidepressants during their reproductive life - most commonly selective serotonin reuptake inhibitors (SSRIs). The safety of these drugs in pregnancy is critical and a study by Pedersen et al from Denmark adds to prescribing principles (BMJ 2009; 339: b3569).

The researchers correlated congenital malformations with maternal antidepressant use in half a million children and found no overall increased risk. However the drugs were associated with septal defects of the heart. This was found for all SSRIs, especially when combinations were used or different drugs were prescribed serially. The absolute increase was from a background rate of 0.5% to 0.9% for single medications and 2% for multiple prescriptions.

This risk must be weighed against the dangers of not treating major depression or using psychotherapy. The American College of O&G has stated that women can continue or start SSRI antidepressants in pregnancy but should be appraised of the risks, however small (Chambers BMJ 2009; 339: b3525).

Preterm infants and infection

2010-01-04T05:54:00.000+03:00

Preterm infants are at risk of a host of morbidities. Most obviously their immature respiratory and metabolic systems place them at a disadvantage while their fragile cardiovascular anatomy and physiology makes them prone to cerebral and gastro-intestinal incidents.

Also linked to poor outcomes, especially in very low-birth-weight infants of less than 1500g, is infection. About 20% of these babies will develop serious infections while in intensive care units. Nosocomial infections occurring after 3 days of age carry major risks of mortality or impaired neuro-development and the smallest are the most vulnerable. There are enormous short-term costs of hospital treatment plus the long-term financial implications of looking after mentally compromised survivors.

Hard on the heels of encouraging magnesium sulphate research to reduce cerebral palsy risk come data on the use of lactoferrin to lower the risk of neonatal infections. Lactoferrin is the major whey protein in human milk and has many functions in early immune processes (Kaufman JAMA 2009; 302:1467-8). Apart from antimicrobial activity, it promotes healthy gut flora and enhances the immature immune system. It is found in higher quantities in colostrum than mature milk, again suggesting a natural boost immediately after delivery.

Manzoni et al (JAMA 2009; 302: 1421-8) studied the administration of bovine lactoferrin, with or without an adjuvant against placebo to a series of very low-birth-weight infants and found some promising results. Subjects receiving the lactoferrin had bacterial and fungal sepsis rates of 6% whereas the placebo group rate was 17%.

The smaller the infant the greater the impact of the lactoferrin so another promising door appears to be opening in the care of preterm infants.

The screening process

2009-07-10T16:31:00.002+03:00

The future of cervical screening is being carefully scrutinised. There is no doubt that cytology is one of the most valuable of all screening modalities, being able to detect pre-cancerous lesions while they are amenable to curative procedures that prevent more serious disease.

The profession and the public are analysing the role of all population screening strategies with the harms being objectively assessed as well as the benefits. There is a temptation to become caught up in the preventative fervour of prophylactic screening without looking at the downside implicit in all programmes. These negative aspects are derived from an over-reaction to minor deviations or difficult-to-interpret results, as well as the psychological and emotional fall-out generated by false positives. There is a spectrum of under-recognised harm from a pre-occupation with abnormal labels, through to the financial interests of business to grow the screening industry.

Health professionals exhort their patients to prevent disease and it is easy to slip into the simplistic mantra of early detection being the equivalent of prevention. Screening is no more preventative than insuring your home is preventative of its burning down. While reminding ourselves of the differences between screening and prevention, it is as well to remember the fundamentals of an effective screening test which should have the following characteristics (Clark Cancer Control 1995;2:485-92):

1. The disease sought should be an important health problem
2. A presymptomatic stage of the disease should exist
3. The natural history of the disease should be well understood
4. There should be an acceptable screening test available
5. Screening tests should be acceptable to the population being tested
6. Outcomes after presymptom diagnosis and treatment should be better than those after symptoms
7. Reduced morbidity/mortality should outweigh harms from false-positive tests
8. Benefits of the test should be achieved at acceptable risk

So does population based cervical cytology measure up to these ideals?

The massive reduction in deaths from cervical cancer in countries where programmes have been introduced does not preclude its re-evaluation as every intervention must be reconsidered in the present economic melt down. Fortunately cytology does hold up cost-effectively in developed countries like the United States where the burden of the disease has decreased by 75% but there are other strategies which need to be considered in developing countries where the costs of clinics, laboratories administration and personnel are prohibitive.

The role of HPV DNA testing in screening is starting to emerge. At present HPV tests are used to triage women with equivocal cytology who may or may not need colposcopy.

The next focus for HPV tests has been in women over the age of 30 years. These women are past the stage of self-limiting infections, and if they are HPV negative with normal cytology then they may constitute a group in whom fewer smears are necessary. Less frequent screening carries large financial implications.

Castle et al (Obstet Gynecol 2009;113:595-600) looked at the number of women who had oncogenic HPV positive tests in the general population of California and evaluated their cytology at the same time. Those between 30 and 34 years had 10% HPV oncogenic positive results but this dropped to around 5% in women older than 40 years. In the entire population the HPV positive rate was lower than anticipated thus not realising epidemiologists' fears of a sharply increased need for further investigation if widespread HPV screening is introduced. Conversely women with negative HPV tests plus negative cytology had a very low risk of incipient precancer and their screening can safely be extended beyond 3 years.

In some practices an “annual smear” has become traditional and women may be reluctant to give up their routine check-ups for fear of failing to detecting early disease. Cotesting with both cytology and HPV DNA may resolve this issue.

When to stop screening is an unsettled matter. There is no point in cytological screening in women who have had their cervix removed by hysterectomy for benign indications. Vault smears are not justified, but for older women with a cervix, when should screening end? Recommendations vary from country to country with 65 or 70 being the most frequently advised age on both sides of the Atlantic but this is in low-risk women who are asymptomatic. Certainly the latest data from Denmark (Rebolj et al (BMJ 2009; 338:b1354) indicates that negative smears in women in their fifties have the same predictive value as women in their thirties suggesting continued vigilance is a good idea.

Finally, Strander (BMJ 2009:338:b809) believes the story will unfold as the technology improves with computer generated risk factors guiding the frequency and duration of screening. Surely algorithms can be devised which include lifestyle considerations plus previous cytology and HPV results which would streamline services, save unnecessary retesting as well as indicating when to stop screening?

Breast Cancer Screening

2009-04-23T16:22:00.000+03:00

The national routine breast screening programme in the UK has doubled the number of women screened in the last 10 years and it is now approaching 2 million per year. This is due to more women availing themselves of the service and an extension of the previously restricted age offer to 50 - 65 year-olds by a further 5 years. The latest data reveal twice the number of cases detected compared with a decade ago, with most being invasive and half being less that 1.5cm in size which are not detectable by hand (Mayor BMJ 2009;338:315).

The claim is made that the programme is serving an “increasing number of women's lives” but this is not a universally accepted point of view.

A spirited rebuttal to unconditional screening programmes is made by Gotzsche et al (BMJ 2009;338:446-8) in which the point is made that mammography has a downside - cost, discomfort, false-positive findings and over-treatment. The authors castigate programmes whose information leaflets fail to mention the harmful effects of screening and over-emphasize the benefits. They argue that choices about screening can only be made by healthy women if the cons as well as the pros are presented. They looked at 31 leaflets from publicly-funded programmes and found them all to be biased so they have produced their own evidence-based contribution (see www.bmj.com).

Women should not be coerced or made to feel guilty if they choose not to undergo screening - informed choice implies unbiased information.

While on the topic of screening for women, the latest figures of cervical screening in the UK are quoted by Kmietowicz (BMJ 2009;338:497). Since the national programme was introduced 30 years ago, the number of diagnoses of cervical cancer have halved. The disease has dropped from the 6th to the 13th most common cancer in women and mortality rates have plummeted. The only negative data show fewer young women are taking up screening invitations but, as a group, those under the age of 35 remain vulnerable.

Antioxidants and cancer prevention

2009-03-11T17:34:00.001+03:00

Antioxidants are the hope of the healthy. Millions of people take supplements, usually vitamins or antioxidants, in the hope that these extras will prevent chronic conditions. The supplement industry is vast but many of the popular products so eagerly ingested lack scientific evidence of benefit.

The latest casualties are selenium and vitamin E for the prevention of cancer in men. In the largest randomised controlled trial ever undertaken, comprising over 35 000 people, these substances were no more effective than placebo in reducing the rates of prostate or any other cancers in middle-aged and elderly men. The trial was supposed to last 12 years but was stopped half-way when an interim audit shown no effect of each agent or a combination (Lippman et al JAMA 2009;301:39-51).

In a second smaller trial of 15 000 male doctors - also middle-aged - vitamins E and C were pitted against placebo and, again, after 8 years there was no decreased risk of any cancer found (Gazanio et al pp 52-62).

It seems clear that healthy men and women do not lower their chances of developing cancer by taking vitamins C, E or selenium. Half of all American adults take supplements. Will these definitive studies change their habits?

At the other end of the age spectrum, other additives have also not been faring very well. Theoretically, giving preterm infants high doses of polyunsaturated fatty acids in their diets could assist brain structure and function. Babies born before 33 completed weeks of gestation are at risk of developmental and behavioural problems, but it is unclear whether standard or high dose fatty acids in their early feeds will make any difference to long-term outcomes.

Makrides et al (JAMA 2009;301:175-82) supplemented the diet of the mothers whose expressed breast milk formed the bulk of the infant's nutrition. The intervention group took capsules containing tuna oil while the controls had a standard diet, resulting in the babies receiving either high or low doses of docosahexanoic acid (DHA) from birth to the date when they would have reached term in utero. Examining both groups at 18 months there was no difference in the neuro-developmental outcome between those receiving the DHA supplementation or not. However, the girls did better than the boys which may lead to even higher dose trials.

Miscarriage and the next pregnancy

2009-01-26T22:07:00.001+03:00

Women who miscarry their first pregnancy are naturally distressed, but what reassurance about the next pregnancy is appropriate? If she conceives again and the pregnancy continues to viability, is she at increased obstetric risk, or not?

Battacharya et al (BJOG 2008;115:1623-9) followed up a large group of women who experienced a spontaneous early pregnancy loss and compared them to women whose first pregnancy reached viability and to women having their second pregnancy after a first normal outcome.

Unsurprisingly, the lowest risk was found in the group who had an initial uncomplicated pregnancy, followed by primigravidas, then those who had experienced a miscarriage. One miscarriage was associated with more obstetric complications, such as threatened miscarriage, pre-eclampsia, induced labour, instrumental delivery, preterm delivery and a low birth-weight infant, compared with those who had a successful pregnancy. Compared with primigravidas, they were more at risk of threatened miscarriage, induction, preterm labour and post-partum haemorrhage.

It is not clear whether this expectation of behaving like a “virtual primigravida” is related to the way the miscarriage was dealt with - by surgical evacuation, expectant management or medical evacuation. It is equally unclear whether waiting before trying for a replacement pregnancy will give a woman a better chance of a successful outcome. Steer suggests that an interval of 18 months may improve her chances (Editor's Choice BJOG Dec 2008).

Interesting article on drug makers and journals

2008-12-12T21:37:00.001+03:00

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

Flu immunisation in pregnancy

2008-12-09T17:54:00.000+03:00

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

2008-12-09T17:53:00.000+03:00

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.

The Six Habits of Highly Respectful Physicians

2008-12-03T22:36:00.000+03:00

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

Is there a cognitive cost of being a twin?

2008-11-18T06:12:00.001+03:00

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

2008-11-18T06:11:00.001+03:00

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.

UK breast screening

2008-06-25T17:28:00.000+03:00

“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.

Overweight in pregnancy

2008-06-08T21:05:00.001+03:00

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.

May Jass Out

2008-06-05T16:42:00.002+03:00

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.

Cord blood storage - a new idea

2008-05-31T21:47:00.001+03:00

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.

Assisted reproduction and multiple pregnancies

2008-04-10T18:00:00.001+03:00

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.

New JASS out

2008-04-08T16:53:00.001+03:00

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!

Latest JASS

2008-03-18T17:04:00.000+03:00

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.

Pfizer and Medical Journal Referees

2008-03-10T19:00:00.001+03:00

Pfizer tries to make journal reveal referees

HRT and breast cancer

2008-03-05T06:13:00.001+03:00

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.

Urban legends

2008-02-06T17:38:00.001+03:00

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.

OCs and cervical cancer

2008-01-08T14:04:00.000+03:00

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.

HPV testing

2007-12-04T18:22:00.000+03:00

The HPV circus is still in town with plenty of sound and fury. Before we climb on the bandwagon and start expensive HPV DNA testing - as we are encouraged to do by commercial interests - let us be quite sure we are acting in our patients' best interests and not using technological improvements for the sake of science.

As our editorial points out, healthy young women will not thank you for a cancer scare, no matter how diligently you explain its significance. The evidence does not exist that HPV DNA screening reduces deaths from cervical cancer.

There is plenty else to amaze or amuse as the festive season approaches - so hang onto your sense of humour.

The following pieces are recommended reading for subspecialists and those in training:

Diagnosis and management of cervical cancer. Petignat & Roy BMJ 2007;335:765-8

Epilepsy in pregnancy. Thomson & Hiilesmaa BMJ 2007;335:769-73

Cancer and Oral Contraception

2007-11-06T17:42:00.001+03:00

Do oral contraceptives increase the risk of cancer? The answer is no, but it has taken 40 years to prove it. In 1968 GPs recruited a large group of women who had, or had not, taken oral contraceptives and followed them to see if the pill had carcinogenic effects.

The UK Royal College of GPs has now published the results of over a million women-years and the outcomes are reassuring (Hannaford et al BMJ 2007;335:651-4).

Most of the 46 000 women are now post-menopausal and moving into the years when cancers are more common but pill use is more distant, so the detection of protection or enhancement of risk is now measurable.

Overall, pill-users had a lower risk of cancers of the colon, rectum, uterus, ovaries and tumours of unknown site. The differences were statistically significant trends with absolute values of 1 to 5 per 10 000 women years. The authors believe that today's lower doses of estrogen will have similar effects, so we can reassure our patients that there are benefits rather than risks as far as cancer and the pill are concerned.

HPV vaccine policy

2007-10-24T21:21:00.000+03:00

HIV vaccines are receiving ongoing high profile. Their potential is huge but the implementation of vaccination programmes the source of rich debate (BMJ 2007;335 Lo 357-8, Raffle 375-7 & Franco 378-9).

The first argument is that existing cervical cancer screening programmes in developed countries reduce deaths by 80% and it is difficult to argue with these success rates. The costs may even come down with HPV triaged follow up, and the expenditure on a vaccine initiative is formidable. There is no doubt the conventional screening policies will be required on an ongoing basis, but with the opportunity for protecting future generations from primary HPV infection and preventing precancerous and cancerous lesions is too inviting to reject.

The second point is those who would benefit most are the at-risk populations, all in developing countries. Again implementation would be the most challenging but the rewards the greatest.

Finally, the attention to the benefits of screening and prophylaxis will probably be the greatest spin-off. The debate, the rhetoric, the policies, the arguments for and against, the money, the political stances, the religious views and the medical science all contribute to the opening of discussions about women's health.
Should we not all engage as vociferously as we dare on promoting interaction on sexual and adolescent health questions and provide the medical science to inform opinion?

This is an entrée not to be missed.

Soy phytoestrogens

2007-10-04T16:43:00.001+03:00

Natural estrogens have great appeal to women as an alternate to conventional hormones at and beyond the menopause. Concerns about the negative effects of standard drugs persuade some women to try phytoestrogens as a “softer option”.

It is difficult for clinicians to advise on such preparations as evidence of benefit - and more importantly harm - is lacking, and it has taken massive trials to uncover the small absolute detrimental effects of estrogens. Until equally stringent trials show the safety of phytoestrogens we will have to rely on smaller studies to show the way.

Marini et al (Ann Int Med 2007;146:839-47) have demonstrated in a RCT of 400 women that genistein, which is found in soy products, increases bone mineral density in osteopenic postmenopausal women. 54 mg of genistein daily for 2 years had positive effects on bone density and turnover compared with placebo, opening the way for long-term trials on fracture effects as well as uterine and breast safety.

Diet and health

2007-09-07T15:56:00.001+03:00

The long-term prognosis for breast cancer survivors continues to improve. Better treatment, adjuvant chemo- and hormonal therapies offer women an excellent outlook, especially if the disease is detected early.

In addition, support groups give psychological comfort, exercise seems to be beneficial, and now a large study has looked at diet and survival. Pierce et al (JAMA 2007;298:289-98) allocated women after early stage breast cancer care to either a diet very high in fruit, vegetables and fibre but low in fat or a comparison dietary pattern which recommended “5-A-Day” fruit and vegetables.

The “extra fruit, fibre 'n veg” with low fat did not make a difference to recurrence, metastases or all-cause mortality over a period of seven years. Perhaps if the control group had been given no dietary instructions, and gained weight, there might have been a difference but failing to advise women about diet would be considered unethical. Where patients gain weight by not balancing intake and expenditure, the prognosis is poorer, so energy balance may be more important than extreme diets (Grapstur & Khan pp 335-6).

Depression in pregnancy

2007-08-08T18:57:00.000+03:00

Women are more likely than men to suffer from depression, especially during their reproductive years. Rates of depression are higher where stressful circumstances exist such as poverty, lack of education, sexual inequality, poor social support and in pregnancy. Single and adolescent pregnant women are especially at risk.

Pregnancy is a socially and physiologically demanding time and a woman who is just coping with the stresses of life may find the additional burden unmanageable. Mood regulation is modified by sex steroids, specifically the cortisol stress system mediated via the hypothalamic-pituitary-adrenal axis which is overactive in depressed people.

In developed countries, the rate of depression in pregnancy is at least 10% and double that in poorer countries. Irrespective of their socio-economic status, women with affective disorders have a high relapse rate in pregnancy which, in turn, is reflected in poorer maternal and fetal outcomes - mostly early delivery and growth restriction. Again, the common pathway of depression and social adversity is likely to be through the cortisol stress hormone system (O'Keane & Marsh BMJ 2007;334:1003-5).

Given these high rates of occurrence, depression should be specifically enquired about antenatally and actively managed if present. Since two-thirds of women stopping antidepressants during pregnancy will relapse, discontinuation is seldom advisable as the resultant depression can lead to unhealthy behaviours such as smoking, drinking alcohol, substance abuse and poor clinic attendance. About a quarter of those remaining on treatment will relapse, so surveillance levels must remain high.

The teratogenicity of antidepressants has been prominent in the journals recently. Selective serotonin reuptake inhibitors (SSRIs) were introduced in the 1980s as safe mood elevators because of their reasonably rapid onset of action, which is ten days according to the latest reports, plus fewer side effects and lower risk when taken in overdose. Nevertheless, there were incidental reports of birth defects such as nervous system or cardiac abnormalities, and cautions were issued. Now two large studies are reported in NEJM (Louik et al 2007;356:2675-83 and Alwan et al 2007;356:2684-92) which are case-controlled evaluations showing a small absolute risk of SSRIs being causative of defects if taken in the first trimester. These are certainly nothing like the risk posed by thalidomide or isotretinoin. In the US the use of these drugs is increasing and the latest data suggest that 10% of all pregnant women are taking an SSRI (Cooper et al AJOG 2007;196:544-5).

In an editorial, Greene (NEJM 2007;356:2732-3) says it would be pleasing to say there is no risk from SSRIs, but that is not possible. To quote from these major studies, “it is important to keep in perspective that the absolute risks of these rare defects are small” and “the absolute risks associated with SSRIs appear small in comparison with the baseline risks of birth defects that exist in every pregnancy”.

Aspirin and colorectal cancer

2007-07-04T16:51:00.000+03:00

Many studies have shown that the regular use of aspirin reduces the risk of colorectal neoplasms. Quite how this works is not clear but it is thought to be related to prostaglandin metabolism or, more specifically, to aspirin's ability to inhibit the enzyme cyclo-oxygenase-2 (COX-2).

If this is the mechanism by which aspirin reduces colorectal cancers then it would be cancers that over-express COX-2 that would occur less frequently in aspirin users. Chan et al (NEJM 2007;356:2131-42) looked at this theory by histochemical assays of cancers removed from men and women in two large surveys and matched these against aspirin intake. They found that cancers that over-express COX-2 were reduced by aspirin but not cancers that had weak COX-2 expression.

The effect was found relative to increasing aspirin dose and duration of use. Flossmann et al (Lancet 2007;369:1603-13) showed that 300mg per day for 5 years is effective in primary prevention but the latency time is 10 years so patients have to be dedicated to their health.

Does Viagra work for women?

2007-06-30T02:12:00.000+03:00

This is a deliberately provocative title. A more accurate heading would be: Does improving a man's erectile dysfunction improve his partner's sexual satisfaction?

The intuitive response is that it should. If a man's problem is reduced, confidence, frequency and performance could be expected to improve, resulting in the couple's greater enjoyment of sex and the woman being more satisfied with this aspect of their relationship.

But sexual function does not work in straight lines. For example, when a man experiences erectile dysfunction (ED), he may be embarrassed or fear ridicule and withdraw, starting a series of events in his partner's mind about self-blame or being unattractive which can reduce her confidence or may arouse suspicions of unfaithfulness. Because the age at which men seek aid for ED is about 58 years and their partners' age about 54 years, these events are likely to coincide with her menopause with its attendant loss of libido and physical symptoms.

For these reasons, research is complex in the field of women's satisfaction from sildenafil (Viagra ® - Pfizer) treatment of men. However, Heiman et al (BJOG 2007;114:437-47) were able to carry out such a study comparing sildenafil with placebo and measuring the woman's perception of outcomes. Unsurprisingly, provided the woman had no dysfunction herself, her satisfaction with their sexual relationship improved significantly if he received sildenafil compared with those whose partners received the placebo. The scores were better for overall satisfaction as well as more detailed questions probing erectile function, orgasmic function, libido, arousal and intercourse satisfaction.

Side effects in the men were infrequent and mild to moderate. Maybe the manufacturers can add another side-effect - increased partner satisfaction?

Simple health tips - salt

2007-06-28T16:35:00.001+03:00

Adult women and men, who reduce their salt intake, reduce their blood pressure. This effect is independent of age, race, baseline blood pressure or body mass. Such information has been around for years but a study by Cook et al (BMJ 2007;334:885-8) now shows that this leads to a long-term reduction in cardiovascular events.

We should restrict our daily intake to 5g per day, or less. We can reduce what we add to our food and support the profession's efforts to have salt levels on foods labeled. Legislation would help and the new data will add weight to the arguments encouraging less salt in prepared foods and declaring how much there is, so prudent purchasing is possible.

HRT and breast cancer

2007-06-04T15:40:00.001+03:00

Breast cancer risk is not increased in estrogen-only HRT but when estrogens are combined with progestins, there is a raised risk that is cumulative. However, there is no evidence of increased mortality and after quitting HRT risk ratios return to normal.

If these data are correct, and if there is a causal or unmasking effect of hormonal therapy on breast cancer, then the rapid reduction in HRT use in America following the Women Health Initiative trial results would have led to a concomitant reduction in cancers detected.

Ravdin et al (NEJM 2007;356:1670-4) report that such a drop in estrogen-receptor-positive breast cancers did occur in 2002-2003 as the number of prescriptions fell from about 50 million to 25 million. This change occurred in postmenopausal women only, strongly implying an association with hormone therapy. The change was of the order of 7% relative risk and the incidence levelled off thereafter.

These findings support a link between combined hormone therapy and breast cancer, but the interpretation should be cautious. The observations concern a particular set of products, a particular age group and a particular type of breast cancer.

The absolute risk of breast cancer for any woman considering hormonal therapy in America remains around 0.30% per annum and this changes to 0.36% per annum on HRT and the effects are cumulative.

This sort of evidence moves our collective wisdom forward but does not answer other questions, such as will these incidences start to rise as the occult cancers reveal themselves later? Or will other forms of hormonal therapy remain free of breast cancer “encouragement”?

So where is the evidence that taking HRT for 10 years after the menopause is harmful?

Is this another example of medicine discovering a magic bullet that is first hailed, then discredited and then, finally, finds its appropriate niche?

JASS certainly believes that the notion of “feminine forever” was a grossly optimistic concept but, equally, there has been an over-reaction to the harmful effects of HRT because of inappropriate hormones given to women long past their menopause - and who were not in the best of health.

Perhaps the pendulum is reaching sanity and hormonal therapy will be useful in the treatment of menopausal symptoms AND offer protection against chronic conditions if used appropriately in terms of initiation, dose, mode of delivery and duration which may well turn out to be 10 years.

The bottom line in 2007 is that starting therapy at the menopause and continuing for a number of years carries little, if any, risk in healthy women. The experts appear in equipoise so it is up to women and their advisors to decide.

It seems clear that initiating combined HRT in women 10 years or more after their menopause does not turn back the clock and probably, on balance, does harm.

Donating eggs

2007-05-17T16:35:00.001+03:00

Women donate eggs for two reasons. Firstly for other women to conceive and, secondly, for research. Both are dogged by controversy on medical, societal and financial grounds. The US and the UK are currently trying to create guidelines and legislation that will allow workers in assisted reproduction and laboratory research to operate without fear of prosecution.

Infertile women undergoing IVF are usually given some form of gonadotropin-releasing hormone to stimulate multiple oocyte production. This hyperstimulation and harvesting results in more oocytes than can be used in fertilisation and embryo transfer in any given cycle, so there are spare oocytes for later use by the woman, or for donation.

Whether the stimulation should be with GnRH agonists or antagonists is one debate and another is whether one or two embryos should be transferred. What is not in question is that the demand for oocytes far exceeds supply. Women below the age of 35 years have significantly higher IVF success rates than older women, precisely the group who are now more often seeking reproductive assistance. The result is that the donation or sale of oocytes has become a big issue.

Clearly the unauthorised harvesting of oocytes is illegal as an Israeli doctor has found to his cost (BMJ 2007;334:557), but what about consented donations to infertile women? The free donation of “extra ova” from women to their infertile fellow patients seems straight-forward enough, but already the problem of incentives has arisen. In private clinics, can these spare oocytes be bought or can the woman be given a discount for her treatment if she donates? This discount for donation occurs in the UK where 75% of all IVF procedures are funded by the patients themselves despite decrees that all infertile couples are entitled to four IVF cycles within the NHS (Ledger Lancet 2007;369:717-8). Moving further along the continuum, is it acceptable for a woman who has no fertility problems to supply oocytes for payment? In the US it is, where thousands of babies are born annually from oocytes acquired from women who receive an average of $5 000 per harvest (Spar NEJM 2007;356:1289-91).

The UK has the Human Fertilisation and Embryology Authority which is the regulator of IVF treatment. It has now ruled that altruistic oocyte donation, in conjunction with fertility treatment or not, is acceptable. The report by Mayor (BMJ 2007;334:445) made no mention of discounts for donations in the private sector - also known as “egg sharing” - so compensation for co-operation remains a grey area. Other places such as Singapore, Israel and South Korea allow donations but without payment or personal benefit.

The role of oocytes in research is more complex, despite the fact they may not be bought for study purposes. Research falls into two categories - infertility or stem cell research. The former is not as contentious, despite using human reproductive material, but the latter is highly controversial using somatic-cell nuclear transfer (SCNT) to create lines of stem cells from which the US administration has withheld federal funding. The arguments go that without payment women will not donate oocytes for research but, attracted by pay, women could be tempted to “sell their eggs” in a competitive market to their own potential detriment.

OCs and ovarian cancer

2007-05-15T20:35:00.000+03:00

Oral contraceptives (OCs) are known to decrease a woman's risk of developing epithelial ovarian cancer. However, the dose of estrogens and progestins in OCs have come down in recent years so it is unclear if the protection previously offered still holds.

Lurie et al (Obstets Gynecol 2007;109:597-607) conducted a case-controlled study on over 700 women with epithelial ovarian cancer that took into account the woman's OC history and matched them with controls who may or may not have used OCs. Their results were conclusive. OCs were effective in decreasing the risk of cancer and the lowest formulations offered the strongest protection. The authors postulate that the antiovulatory mechanisms of OCs are the key factor in reducing malignancy rates and that women taking the lower dose pills are more likely to be compliant compared to high-dose users.

Consistency of use, rather than the hormonal dose probably explains the effect and a reduction in ovarian cancers may well continue due to OC use.

Contralateral breast cancer

2007-05-07T19:15:00.000+03:00

Some women diagnosed with early breast cancer in one breast are later found to have cancer in the other breast. Even careful clinical examination and mammography can fail to identify early lesions, so the question arises as to whether more extensive investigations - such as magnetic resonance imaging (MRI) - should not be carried out routinely at the time of the initial diagnosis.

Lehman et al (NEJM 2007;356:1295-303) report on nearly 1 000 women across the US who had early cancer in one breast with negative mammography and clinical examination in the other who then had MRI of the “cancer-free” breast. Within one year of the initial diagnosis they found 3% of the women had or developed cancer in the contralateral breast.

The sensitivity and specificity were not as high as ideally required in a screening test but, with a negative predictive value of 99%, women may well find it acceptable. The cancers found in the contralateral breast were all early and had not spread so MRI evaluation should be considered if malignancy is found in one breast, even if routine investigations are apparently negative.

Exercise after breast cancer

2007-05-06T19:57:00.000+03:00

There is evidence that regular exercise is associated with a decreased risk of breast cancer. What is less clear is whether supervised exercise for women recovering from early breast cancer treatment is beneficial. A controlled trial from Scotland now answers some quality-of-life questions.

Mutrie et al (BMJ 2007;334:517-20) followed 100 women allocated to group exercise and 100 controls for three months after their initial treatment and found the exercise group derived functional and psychological benefit, which was immediate and sustained at six months.

It is suggested that the diagnosis of cancer affords a “teachable moment” when people are receptive to changes in lifestyle behaviours and the rigorous research indicates recovery from breast cancer therapy can be enhanced by seizing that moment.

Cardiology News

2007-05-03T17:20:00.000+03:00

An interesting article on MI outcomes.

Women's diets

2007-05-03T16:46:00.000+03:00

Obesity is at an all-time high. Humans throughout the world are consuming more calories than they expend, and BMIs continue to rise. Medically this is not good news as there are virtually no benefits from being overweight - and considerable risks.

Obesity is linked to risks of cardiovascular disease, metabolic disorders, cancer incidence, increased mortality and, in women, reproductive dysfunction. Science has produced evidence of the risks and no-one in the developed world can claim ignorance of the dangers of obesity.

Socially, some developing cultures perceive obesity as a marker of success or status but the ample figure is not admired or respected in Western culture. Over the last half century, affluence seems to have changed our views and being overweight has become a feature of society. Whether it has become socially acceptable or not is a sociological question, but medically it simply increases the burden of disease.

The aesthetics are in the eye of the beholder.

Premenopausal women are traditionally figure-conscious, and diets feature in conversations, magazines and respected medical journals. Arguments about diets will continue as “easier” ways to lose weight are touted by the popular press. But is there science to back one diet against another?

Gardner et al from California (JAMA 2007;297:969-77) explored the relative merits of diets that varied in their carbohydrate components. They diligently followed four groups of women in their forties over one year who were randomly allocated to the following diets - Atkins (very low carbo), Zone (low carbo), LEARN (moderate carbo) and Ornish (very high carbo). They looked at metabolic effects and gave the women every incentive - including a modest financial stipend - to stick to their regimens.

The Atkins diet gave the best results biochemically and cardiovascularly and in terms of sustained weight loss compared to the three others which were equally inferior. However, the overall results were only modest, with the Atkins diet women losing about 4.5kg and the others about 2kg over the year.

Since their mean weight at the start was 85kg, the reward for these women's efforts was small and the drop-out rates not insignificant. Obesity is a problem of lifestyle and the individual effects are there for everyone to ponder. Medicine can highlight what each person can eat for optimal health and emphasise through large studies how our society is slumping into soft-option acceptance of unhealthy food consumption.

April JASS

2007-05-03T16:45:00.000+03:00

Colleague,

Life-style continues to be a theme that the journals publish for women's health.

There are healthy, weight-reducing diets and exercise on the one hand, and the disadvantages of obesity on the other. Scientific evidence backs sensible eating and physical activity.

These are refreshing data because one might have anticipated research in the 21st century to be moving towards molecular and genetic studies. The fact that epidemiology which describes the maintenance of health is reported, allows us to advise patients about what they can do to help themselves to better health.

The issue of supplementation to prevent congenital abnormalities seems a “no brainer” but most European countries have yet to implement the practice. Is it democracy gone mad that makes them kowtow to mavericks and often whacky science that opposes such enhancement to prevent neural tube and facial cleft defects?

Evidence-based medicine has resulted in major changes in obstetric management yet it seems politicians are reluctant to heed its logic. It should be a cause that O&G societies in each country should be lobbying for - as well as fluoride addition to drinking water.

Obesity and pregnancy

2007-04-16T17:58:00.000+03:00

The three major specialist journals carry articles on obesity and pregnancy this month. The definitions are; a BMI over 25 is overweight, over 30 obese, over 35 grossly obese, and over 40 morbidly obese.

The BJOG (Heslehurst 2007;114:187-94) traces maternal obesity over the last 15 years which shows the incidence has increased from 10% to 16% and, if the trend continues, by 2010 the rate will be 22%. This carries implications for hospital staff, facilities and special clinics all requiring more resources.

Some of those requirements will be far more caesarean sections. Bergholt et al (AJOG 2007;196:163-5) tracked a group of uncomplicated primipara and worked out their chances of an emergency CS in labour. Taking women with a BMI of less than 25 as controls, CS rates rose with BMI with those who were grossly obese having four times the risk of a CS. Failure to progress and suspected fetal distress were the main indications while one-quarter of the remaining women had an instrumental delivery.

The authors advise telling women with raised BMIs about their increased risk of CS delivery. Clinicians and patients should be aware of these statistics and share them with labour ward staff.

In the US, more than half of women of reproductive age are overweight and 30% are obese. The lower the socio-economic status, the greater the incidence of obesity. There is a spread of related problems which Catalano (Obstets Gynecol 2007;109:419-33) iterates sequentially: greater risk of miscarriage and congenital abnormalities, later manifestations of the metabolic syndrome including diabetes, cardiac dysfunction, proteinuria, sleep apnoea and fatty-liver disease, greater risk of caesarean section with anaesthetic difficulties, operative challenges, wound disruption or infection and clotting risks. Fetal risks in the short-term are macrosomia and obesity with related poorer outcomes plus long-term consequences in adolescence and adulthood of the metabolic syndrome.

Is fish safe in pregnancy?

2007-04-03T12:59:00.001+03:00

Some long-chain omega-3 fatty acids are essential for optimal neuro-development in the fetus. Fish is a rich source of these nutrients but there have been suggestions that fish could contain toxins like mercury that could be detrimental to brain function. Indeed, the current US governmental recommendations advise not more than three servings of seafood per week for pregnant women, but there may be a danger that such restrictions could be counter-productive and can result in fetal brain malnutrition.

This is quite an issue so the study by Hibbeln et al (Lancet 2007;369:578-85) is a welcome source of information. They investigated 12 000 children whose mothers had recorded how much seafood they ingested during the index pregnancy and measured it against the child's intellectual, social, communication and fine-motor development up to 8 years of age. They found that the lower the seafood intake, the greater the risk of dysfunction. Fish was protective of normal development and function - exactly the opposite of the US advice. On balance, women are not putting their unborn child at risk by eating three or more portions of fish per week.

As Myers & Davidson say in an editorial (Lancet 2007;369:537-8), the dangers of fish-eating in pregnancy have been misrepresented and are misleading and are not based on any evidence of harm.

March JASS is out

2007-04-03T12:57:00.000+03:00

“We are what we eat” is an old chestnut.

The journals are full of articles on how diets affect risk of disease and, with the prevalence of obesity at an all-time high, there is no lack of publications on diets that affect weight. The dangers of being overweight in pregnancy are well documented and the review by Catalano (see summary) highlights these.

Those wishing to supplement their diets with healthy additives should do so with caution. More is not necessarily better and the antioxidant story is sobering.

Pregnant women's intake is also revealing and the article on the dangers of eating fish is a real “myth-buster”.

Also in the life-style paradigm, sex is enjoying a greater press with the tensions between medicalising sexual function and suppressing information receiving attention. What is normal function and what is dysfunction?

You decide how much is enough of what!

Density or detection in breast cancer

2007-03-05T21:35:00.000+03:00

Radiologically, the breast varies according to its tissue composition. Fat is radiographically translucent and appears dark on the film. Epithelium and stroma are radiographically opaque or dense and appear light on the film. The amount of radio-opaque tissue is referred to as the breast's density and generally the higher a woman's breast density, the greater her risk of developing breast cancer.

As well as the increased risk, high breast density makes the interpretation of mammography films more difficult, so early lesions may go undetected, leading to poorer outcomes. It is difficult to say whether it is the breast density per se which increases the risk or the delay in diagnosis because of the density which is the problem.

In an attempt to resolve the issue, Boyd et al from Canada (NEJM 2007;356:227-36) noted the woman's breast density at her first mammography and then carefully tracked her risk of subsequent cancer using modern techniques. Thus they hoped to eliminate the detection problem and quantify the risk of high density breast tissue. Their results were conclusive in that women with densities over 75% were five times more likely to develop breast cancer than those with densities below 10%.

Kerlikowske in an editorial (pp 297-9) draws these data together with other risk factors, such as age, family history, BRCA status, and makes a plea for defining each woman's risk status and advise her about mammography accordingly. The density factor is a major risk and seems especially important in women aged 50 to 55 years. Better detection methods, possibly with digital as opposed to film screening may help but the bottom line remains - the greater the breast density, the greater the risk.

The latest JASS is out

2007-03-05T21:33:00.000+03:00

The medical journals are changing. The BMJ looks more like Time magazine than a medical journal with attention-grabbing coloured text and photos. The American Journal of O&G has reduced itself to summaries-only for the paper version, leaving subscribers to go to the electronic version for the full text.

The content is changing too with summaries from other journals, Cochrane abstracts in Obstets Gynecol, as well as articles on politics, prostitutes and sexual behaviour. These changes may be responses to the challenge of information technology with the delivery of data via the internet or podcasts. It seems even television is threatened by the popularity of mobile phones, iPods, SMS and personal communication networks. If you don't believe this - ask your children!

There really does seem to be an honest move away from the stereotyped medical journalism of the last century and certainly the journals' willingness to prod the establishment on moral matters seems healthy to JASS.

All of this competition for attention means more work for JASS to distill the wisdom from the razzamatazz.

With pleasure.

Remember, what you see on this blog is just a sample of the full JASS you can receive by going to the website and subscribing.

SIDS

2007-02-14T17:30:00.000+03:00

The sudden infant death syndrome (SIDS) is the leading cause of infant mortality in developed countries. The risk is greatest in the first six months of life while the autonomic nervous system matures to control the homeostatic functions of respiratory drive, blood pressure regulation, temperature, airway reflexes and arousal. It appears that the functioning of these mechanisms requires serotonin (5 hydroxytryptamine 5HT) to be normally produced, released and cleared in the region of the medulla and brain stem. Where this is not achieved, the risk of SIDS rises, as found in post-mortem demonstrations of excess 5HT by a Californian group led by Paterson (JAMA 2006;296:2134-32).

They showed that 5HT dysregulation was a neuro-chemical abnormality far more frequently found in SIDS victims than controls which may explain an underlying vulnerability and partially explain the male predisposition. Wease-Mayer in an editorial (pp 2143-4) alludes to the preventable factors in SIDS, namely putting all children to sleep on their backs on firm surfaces, avoiding soft bedding and overheating, as well as reducing exposure to antenatal or postnatal smoking. It was found in a recent US survey that two-thirds of children succumbing to SIDS were sleeping prone when they died, so it is time to re-launch the “Back-to-Sleep” campaign.

Interesting

2007-01-26T00:17:00.000+03:00

An article about the impact of the 'impact factor' on scientific journals.

Breast feeding and intelligence

2007-01-25T01:56:00.000+03:00

There are many advantages to breast feeding - to mother and baby. These include the effect of colostrum on immunity, fewer diarrhoeal diseases, the benefits of omega 3 fatty acids on visual developments in small infants, as well as improved bonding and less breast diseases later. It remains unclear whether the child's intelligence is affected by breast feeding, although it remains an unequaled way of providing ideal nutrition.

To look at the effect of breast feeing on IQ, Der et al defined the known variables in over 5 000 children and teased out factors such as education, race, wealth, smoking, birth order, birth weight and home environment (BMJ 2006;333:945-8). In general, breast-fed babies scored four points higher in testing than formula-fed infants, but almost all this effect was attributable to the mother's IQ. In other words, inheriting the mother's cognitive abilities was more important than being fed her breast milk as measured by intelligence tests.

These findings can be used to reassure mothers who cannot breast feed, but in no way detract from the many other plus factors which should persuade as many women to breast feed as possible for at least six months.

Chemotherapy for breast cancer

2007-01-15T18:46:00.000+03:00

Thirty years ago, Bonadonna and his colleagues proved that adjuvant chemotherapy made a difference to survival following initial surgery in women with early breast cancer (Levine & Whelan NEJM 2006;355:1920-2). The original agents, cyclophosphamide, methotrexate and flurouracil (CMF) have been the gold standard against which newer drugs are assessed.

There have been numerous trials of chemotherapy mainly studying anthracyclines and taxanes in various combinations which are of interest to oncologists, but gynaecologists and GPs need to know that:

* adjunct postoperative chemotherapy has a modest benefit on survival
* it has considerable toxicity and is expensive
* its use is determined by the risk of recurrence which in turn depends on tumour size, axillary node status and pathology grade
* receptor status for human epidermal growth factor (HER2) and treatment with trastuzumab is a promising development
* oestrogen receptor status and hormonal treatment with tamoxifen greatly reduces recurrence.

Trials like that of Poole et al (pp 1851-62) will continue to refine the best combination of agents but the next major step forward will be the use of microarray techniques to identify each tumour's gene profile and then tailor the therapy individually.

December JASS out

2007-01-05T21:55:00.000+03:00

JASS started in early 1997 so this is our tenth birthday.

It has gone from strength to strength and is now subscribed to in 44 countries.

We thank you for your support and will be offering even better opportunities in 2007. May we remind you that if you belong to an academic institution you may wish to enquire about our corporate subscription rates which allow for onward distribution to staff at attractive rates.

The year ends with global concerns about the lack of progress in women's health in developing nations and generally the ever-widening gap between the haves and the have-nots. The have-nots get the worst deals from the pharmaceutical industry, bear the largest burden of disease with the fewest resources, lose their health care workers to richer countries and seen to have less wise leadership.

Perhaps the new WHO leadership under Dr Chan from China will make a difference.

For those wishing JASS to supply CPD certificates, please complete the 2006 Annual Answer Sheet for the year and send it to us for review and points allocation.

We wish you good health personally from Team JASS and a peaceful New Year.

Cerebral palsy and obstetrics

2006-12-22T23:50:00.001+03:00

The European Cerebral Palsy Study Group looked at the correlation of MRI findings and clinical outcomes. MRI scans plus detailed clinical assessments were carried out on over 400 children from the age of 2 years on and it was found that the scans could provide information about the timing and extent of their lesions (Bax et al JAMA 2006;296:1602-8).

The commonest finding was that of white matter damage of immaturity with nearly 90% of the subjects having defined structural abnormalities which would allow clear prognoses to be made. The authors strongly advocate MRI scan for all children with CP.

The possibility of obstetric mishaps being the cause of CP in their study group was small which is in keeping with all similar studies. The most frequent cause was infection which obstetrically is associated with preterm labour and placental damage. When this leads to preterm delivery, the hypoxic insult can result in white matter damage. This mechanism is also thought to account for the cortical damage of those born at term with CP, the infection being either clinical or sub-clinical at an early stage of the pregnancy. Multiple pregnancies are an at-risk group accounting at least 10%, with the same numbers attributable to cerebral malformations and genetic or metabolic disorders.

Only 20% of those born after 34 weeks gestation could be considered to have CP on the basis of an intrapartum mishap. Such mishaps are unlikely to be the result of obstetric mismanagement and the proportion amenable to intervention low. The authors agree with previous findings that asphyxiated encephalopathic infants are not necessarily the result of labour malpractice or lack of vigilance in pregnancy. They suggest the treatment of infections in pregnancy, the reduction in assisted reproduction twin pregnancies and the better, earlier diagnoses of CP are the preventative measures that will reduce the burden of CP. See also the editorial by Msall (pp 1650-2).

Cord blood collection

2006-12-18T18:07:00.000+03:00

Should cord blood be collected for the future benefit of the child? The current debate about stem cell research has focused attention on cord blood and commercial firms are cashing in by offering to collect and store cord blood for future purposes.

Companies are advertising collection as a biological insurance whereby the blood is kept for possible transfusion if the child develops leukaemia or some metabolic disease. Claims, which are presently speculative, suggest that future medical advances will use the blood to cure diseases such as diabetes, breast cancer, ovarian and testicular cancer, melanoma, rheumatoid arthritis or for the regeneration of damaged heart valves. More accurate predictions would be that better treatments for childhood leukaemias will be found that do not require autologous cells. In any event, donor cord blood can be used.

The scientific arguments are in fact pseudoscience in that they talk about future “yet to be discovered” developments. Maybe there will be inventions that will need the patient's own cord blood, but research will be extremely difficult as trials testing “own versus other” blood will be a recruiting nightmare. At present, the likelihood of stored blood being used is very low - quoted at between 1 in 1 400 and 1 in 20 000 (Edozien BMJ 2006;333:801-4).

The Royal College of O&G says storage cannot be recommended because of insufficient scientific evidence and logistic problems. The American and Canadian Colleges are also critical of the process, as are midwifery, paediatric and ethical bodies. There are also medico-legal issues, like whose responsibility is it to take the blood, ensure it is free of contamination, correctly consent its collection, labelling, storage and testing for viral and other dangers? To whom does the blood belong - mother or child? Does the collection process take priority over other labour ward procedures?

It is clear that it cannot be a routine practice, but should those with sufficient resources be advised to pay for it? Parents-to-be want the best for their unborn child and can be considered vulnerable to promotion of this “just in case” philosophy. Yes, personal cord blood may be useful in future situations but at present it is more likely that other measures will overtake autologous transfusions. Medical science says “no” right now but there are other sciences and other beliefs, so it is up to individuals to decide whether recommending cord collection is medical paternalism or sound advice.

Magnesium sulphate and eclampsia

2006-12-06T20:22:00.000+03:00

Magnesium sulphate is given intravenously to prevent initial or subsequent eclamptic fits in peripartum women. Its efficacy in fit prophylaxis is unquestioned but when it should be commenced and stopped are challenging questions. Two American surveys help in the decision making process in high-risk hypertensive patients.

Alexander et al from Texas (Obstet Gynecol 2006;826-32) reviewed their unit's records when changing from an intramuscular to an intravenous regime and at the same time from treating all hypertensive women to treating only those qualifying for treatment according to strict criteria which would label them as severe preeclamptics. The criteria used were

* BP of 140/90 in a previously normotensive woman
* proteinuria of 2+ or greater on a catheter specimen
* serum creatinine more than 1.2mg/dl or platelets less than 100 000/ml
* aspartate transaminase of double the upper limit of normal
* persistent headache or visual disturbances
* persistent epigastric or right upper-quadrant pain.

As expected, the selective rather than broad spectrum use of magnesium resulted in more eclamptic fits but the numbers needed to treat and the side effects of magnesium therapy make an optimal policy difficult to set. If the net is too fine, it cannot be dragged through the water, and the authors speak of an “irreducible minimum” of unpreventable cases.

A second study from Ohio looked at the duration of magnesium treatment postpartum in mild preeclamptics. Ehrenberg & Mercer (pp833-8) randomly allocated women receiving prophylactic magnesium sulphate but who did not have severe disease, to have 12 or 24 hours of postpartum treatment. Women whose condition deteriorated after being selected to one or other arm of the trial were immediately excluded. Incidentally they found that chronic hypertensive and insulin-dependent diabetics were the most at-risk groups for such deterioration.

Of those not showing progressive disease, it seemed that 12 hours of treatment was sufficient and that carrying on the magnesium for a total of 24 hours had no advantage. Of course, lesser duration of treatment means fewer intensive nursing hours, less chance of side-effects and less maternal mobility, so this article provides useful practical information.

New JASS out

2006-12-06T20:19:00.000+03:00

This month we have a focus on American health.If you are wondering about JASS' highlighting of American reproductive health, then reflect on the fact that the US spends more on health than the GNP of most developing countries. Their pharma behemoths dictate where drug research spending is directed - on which much of the rest of the world depends. Their administration's stance on drugs is vital - especially in women's health, but let's hope their moral lead is not one we all have to follow.

Our own government's policies on contraception, abortion, HIV, violence against women and obesity are all issues that directly affect our practice. We seem less and less able to influence political dictates which is leading to frustration and lowered morale.

It is good that the journals are speaking out for the profession rather than siding with our political masters.

There are practical summaries too. What to do about cord blood collection, acute uterine bleeding in gynaecology and postpartum, as well as facts to support our patients who wish to eat fish - and stay slim!

Sound waves and breast cancer

2006-12-05T00:12:00.000+03:00

Interesting news on breast cancer detection using sound waves.

October JASS is out

2006-11-03T18:41:00.000+03:00

A snippet from the just released October JASS:

Tea and olive oil

Tea is made from the leaves of the Camellia sinensis plant. There are basically three kinds of tea - green, oolong and black tea - three billion kilograms of which are consumed each year which makes tea the most popular beverage in the world.

Green tea contains polyphenols which have a theoretical role in the prevention of cardiovascular disease, but it is unclear if this has any effect on tea drinkers in the real world. To test the effects, Kuriyama et al (JAMA 2006;296:1255-65) followed 40 000 Japanese adults for a decade and related their mortality rates from cardiovascular disease to their tea consumption.

They found the more green tea people drank, the lower their risk of dying from cardiovascular disease. There was a “dose-related” response and the effect was more marked in women. The strongest association was with a decrease in stroke mortality. There was no link with cancer mortality.

And while on the subject of polyphenols, it appears that virgin olive oil is better than refined olive oil when it comes to raising your high-density lipoproteins and decreasing your oxidative stress markers. Covacs et al (Ann Int Med 2006;145:333-41) showed that taking an unrefined olive oil supplement as opposed to a refined olive oil one, positively affected serum markers of good cardio-vascular health. These effects were in addition to olive oil being a monounsaturated fat, so it seems the Mediterranean diet using virgin olive oil is underpinned by solid science.

Spelling

2006-10-13T03:20:00.000+03:00

Putting JASS online has made us acutely aware of trans-atlantic spelling issues. The most important of these is 'gynaecology' (the UK spelling obviously) and 'gynecology' (the American spelling). Both are of course, correct. For instance, articles from AJOG will use the 'gynecology' spelling, and BMJ, we'll use 'gynaecology'. We have been using 'gynaecology' , but are considering adding the American spelling when used by the journal article being summarized.

Wound closure

2006-10-03T22:21:00.000+03:00

There is little hard evidence as to which is the best way to close the subcutaneous layer of incisions. With the increasing prevalence of obesity, the question of what to do when the fat layer is 3cm or more will be asked more frequently.

Cardosi et al from Florida (AJOG 2006;195:607-16) randomly allocated obese patients to three ways of dealing with the subcutaneous layer following vertical midline incisions for gynaecological procedures. The three methods were suturing the layer closed with an absorbable stitch, no stitching but placing a suction drain in situ, or no intervention.

All incisions had staples for skin closure that were left in place for at least 7 days. All patients received pre-operative antibiotic prophylaxis and the wounds were diligently observed in hospital and at 2 and 6 weeks post-operatively.

In the over 200 patients in the trial, the method of closure made no difference in terms of disruption, cellulitis, seroma or haematoma formation or abscess occurrence. It seems subcutaneous technique is irrelevant in these circumstances, so preference and resources can dictate practice.

Tailpiece

2006-09-19T15:44:00.001+03:00

More and more women of childbearing age are sporting lumbar tattoos. Irrespective of your attitude to the practice, does this preclude her from having an epidural in labour?

Kuczkowski from California, where a fifth of the population have some “epidermal enhancement” believe a lumbar tattoo is not a contraindication to neuraxial analgesia (Arch Gynecol Obstet 2006;274:310-2). It is suggested that pigmented areas are best avoided and Touhy needles used routinely to circumvent possible tattoo puncture-related complications.

Tamoxifen and infertility

2006-09-19T15:44:00.000+03:00

Tamoxifen citrate is sometimes used empirically in the treatment of unexplained infertility. The rationale for using an anti-oestrogen is unclear but rebound endogenous ovarian stimulation has been suggested, unencumbered by scientific proof.

Now a study by Shokeir (Arch Gynecol Obstet 2006;274:279-83) shows that tamoxifen has no benefit in improving pregnancy rates in infertile women. In fact, there was a statistically significant decrease in conception rates in those taking tamoxifen compared to placebo. This effect may have been mediated by altered cervical mucus or endometrial suppression - either way tamoxifen for infertility is bad news.

The Journals in August

2006-09-19T15:38:00.000+03:00

The articles pouring out of the American journals are impressive. There seems a flood of data on lifestyle, diet, exercise and smoking. There is also a serious self-examination of their public health needs and their ability to provide these.

There is a strong tension between the medical profession, the legislation and big pharma. There seems no resolution in sight. The UK NHS is also being seriously re-examined, with private care being more and more debated as a “partner” in providing the needs of its citizens, while the medical governing bodies are realigning themselves.

JASS tries to keep out of politics but doesn't always manage to do so!

One point about the hormonal replacement trials. The differences that are being uncovered are exceedingly small. The RUTH trial summarised this month confirms this. We are talking in points of one percent differences in outcomes. What concerns me is the lack of data from women starting HRT at their menopause and then continuing - not women aged 68 on a trial. And what about quality of life measures? I know the problems of global scores, but that is what it's all about in the end.

Please visit www.jassonline.com for information about JASS for GPs or tell your Family Physician friends about it.

In silico ?

2006-08-02T02:16:00.000+03:00

For those at the cutting edge of computers and parturition, there is a gem of an article by Errol Norwitz from Yale (AJOG 2006;194:1510-2). It is about how computers can extract patterns from data fed into them and recognise sequences that are too complex to be picked up by standard computer programmes or our brains. This artificial intelligence resembles human intelligence but can hold and connect more variables simultaneously than can our innate software.

The multi-factorial initiation of labour may yield to such scrutiny and the unravelling may have already begun. These sophisticated programmes make in silico redictions - a term Norwitz uses to describe the complex solutions the computers come up with, as compared to in vitro or in vivo evidence. Presumably in silico will take its place in our new lexicon, so drop it into a ward round casually to impress non JASS readers.

For those needing to be conversant with the modern views of the onset of labour, this editorial is highly recommended.

JASS expanding

2006-07-27T03:56:00.000+03:00

We are pleased to report that JASS continues to grow in circulation. We are also expanding the range of JASS with introduction of JASS for GPs. JASS for General Practitioners is aimed at GPs and physicians who are not O&G specialists. JASS for GPs is now available for subscription on the website.

JASS for Nurses will be coming soon! In addition, we also plan to offer podcasts with discussion of the latest from the journals. Imagine being able to listen to the most-to-date research anywhere you like - quite a thought.

Clotting and flying

2006-07-07T18:55:00.000+03:00

Much debate has arisen around a link between flying and thrombosis. Long-haul flights do expose us to prolonged periods of relative hypoxia at low pressure, combined with inactivity, but does the combination make thrombosis more likely – even if we have no risk factors?

It seems not. Toff et al (JAMA 2006;295:2251-61) simulated an 8-hour flight by placing volunteers in an oxygen chamber set to commercial aircraft conditions, then at ground settings and checked their clothing factors. It appears that lowering the environment to hyperbaric and hypoxia flight levels makes little difference to laboratory testable thrombosis propensity. If you are a Factor V Leiden positive or taking oral contraceptives, then take extra precautions, otherwise keep well hydrated, flex and extend your ankles and knees and walk around the cabin as often as you can.

Gross statistics

2006-06-28T22:23:00.000+03:00

In the last quarter of a century the prevalence of obesity in the United States has doubled. Officially one third of the US population is now obese being defined as having a Body Mass Index of greater than 30.

7% are morbidly obese with a BMI above 40. There seems little likelihood of the figures growing smaller in the immediate future as 17% of adolescents are overweight – a significant increase over the last 5 years (Ogden et al JAMA 2006;295:1549-55).

Over-assisted reproduction?

2006-06-28T05:21:00.000+03:00

2% of babies born in Europe are the result of assisted reproduction. This has helped countries of the European Union raise their birth rates but these are still nowhere near population replacement levels (Int J Andr 2006;29:12-6).

Surely one of the most bizarre stories about assisted reproduction must be that of Mrs Z from Russia, reported by the appropriately named Mr Leidig in the BMJ (2006;332:627). She is a 55-year old headmistress whose son was dying of cancer, so she persuaded doctors to freeze some of his semen before treatment was started. This was done and two years after his eventual demise she requested his sperm be used to fertilise a donor egg and be implanted into a surrogate mother.

The child, Mrs Z’s grandson, was born alive and well but the Russian authorities say she is too old to adopt him. The situation is further complicated by the fact that the sperm donor died two years ago and cannot be legally registered as the father. Since the oocyte was donated, the baby doesn’t have a mother either, and since he has no parents he does not officially exist. The Registry Office wants to take him away from Mrs Z and place him in an orphanage. The case is going to court.

Blogs

2006-06-25T04:11:00.000+03:00

This is a medical blog aggregator:

http://www.medlogs.com/

UK statistics on O&G popularity

2006-06-24T19:50:00.000+03:00

In the UK the popularity of our speciality is falling fast. Ten years ago 5% of all graduates wanted to specialise in O&G but this dropped to 3% in 2002 and is now estimated at 2%. This is way below the numbers required to maintain staffing levels, especially with consultants becoming increasingly required on labour wards.

Long hours and the exercising of “patients’ rights” in declining students’ presence are noted by the Royal College as disincentives to choosing O&G. Foreign doctors are being looked to as numbers dwindle (Brettingham BMJ 2006;332:323).

Herbs for menopausal symptoms

2006-06-24T19:48:00.001+03:00

Most herbal remedies for menopausal symptoms give under-whelming results – in fact, most research shows they are no better than placebo. There is always a placebo effect in these trials so any claims at improvements must show a reduction in symptoms well below possible “suggestion or Hawthorne” effects.

At last one such study has appeared (Uebelhack et al Obstet Gynecol 2006;107:247-55) from Germany using black cohosh plus St John’s wort. Black cohosh extract in the dosage of 1mg triterpene glycoside, the active ingredient, is said to relieve symptoms of hot flushes, night sweats and sleep disturbances without exerting oestrogenic effects. St John’s wort has proved effective in the treatment of depression and mood disorders at a dose of 0.25 mg hypericine, so the combination of the two herbs was tested against placebo in the hope of relieving menopausal physiological and psychological symptoms without the side effects of oestrogens or selective serotonin reuptake inhibitors.

Over a 16 week trial period, the women’s menopause rating scores were reduced by 50% in the active ingredient group and by 20% in the placebo group. In the depression rating scale treatment resulted in a 40% reduction in symptoms with a 12% placebo effect. The authors claim the relatively low placebo effect was due to a single investigator being employed who did not accentuate the psychotherapeutic approach.

The side effects were minimal and it appears that the combination of a fixed dose of black cohosh and St John’s wort has a place in the management of climacteric complaints with a pronounced psychological component.

Fibroid embolisation outcomes

2006-06-24T19:48:00.000+03:00

The long-term outcomes of fibroid embolisation look promising. The FIBROID Registry in the US is a voluntary multi-centre database that chronicles the results of fibroid embolisation. There are records of over 2000 women and they have a unique symptom score method which allows quality-of-life measurements to be made and compared prospectively.

The results are available for the first year after embolisation and 95% of patients had significantly improved symptoms and quality-of-life scores. Only 3% underwent hysterectomy within a year of treatment. The results are remarkable with the best outcomes being achieved when the fibroids were small, submucosal and presented with heavy menstrual loss (Spies et al Obstets Gynecol 2005;106:1309-18).

Ultimate sex discrimination

2006-06-24T19:46:00.000+03:00

There are more boys than girls born in India. The discrepancy is becoming more marked with every census, and is greater in urban than rural areas and amongst higher socio-economic groups. It is not a natural process as there are more male than female stillbirths and infant mortality ratios are equal.

The situation is even more apparent in households where the first-born is a girl – the next child is much more likely to be a boy – rather than another girl. In other words, the sex of the existing child or children affects the sex of the next born.

Jha et al (Lancet 2006;367:211-8) traced these trends by conducting interviews in over one million households. They postulate that prenatal sex testing with abortion of female fetuses is the most likely explanation which fits with India’s common ideology. Although illegal and officially condemned (Sheth pp 135-6) the practice of ultrasonic or amniocentesis sex determination is widespread and it is calculated that in that country alone 10 million female fetuses have been aborted in the last two decades. China is also suspected of having a similarly discriminatory attitude, and the world figure of “missing presumed dead” female babies is estimated at 100 million.

Oestrogens only and breast cancer

2006-06-24T18:55:00.000+03:00

Part of the Women’s Health Initiative study of hormonal replacement therapy in the late 1990s included a group of hysterectomised women who received oestrogen alone. Over 10 000 post-menopausal women were randomised to 0.625mg of conjugated equine oestrogen (CEE) daily or placebo over a period of seven years before the trial was stopped because of an increase in stroke incidence without cardiovascular benefit.

Unlike the main study of combined progesterone plus CEE in women with an intact uterus, the incidence of breast cancer in those receiving CEE alone decreased modestly with a hazard ratio of 0.80. However, this reduction has to be balanced against an increase of abnormal mammograms in the CEE alone group, especially in the first year of follow-up. The cumulative percentages requiring follow-up for mammogram abnormalities was 36% for CEE alone recipients and 28% for those on the placebo.

This study had the same flaws as the larger combined progesterone plus CEE research, with most of the women being over 60 years old on recruitment and being overweight, but it does raise interesting reflections that oestrogen alone does not increase breast cancer risk. Would women in their fifties with a progesterone-releasing intrauterine system be able to use oestrogen alone with the same protection from breast cancer? (Stefanick et al JAMA 2006;295:1647-57)

Some interesting links

2006-06-14T20:35:00.000+03:00

This is an interesting link of a journal-club search.

The Public Library of Science has an open-access medical journal.

The Cochrane Centre for evidence-based medicine

Center for Evidence-based medicine at Oxford.

Welcome

2006-06-06T02:13:00.000+03:00

Welcome to the JASS blog. This is where the editor-in-chief of the Journal Article Summary Service will be recording his thoughts on state of the art in obstetrics and gynaecology research. Posts will include opinion on the latest research and practice, as well as what is happening in the leading journals.

Your feedback is always welcome.