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.
23 April, 2009
11 March, 2009
Antioxidants and cancer prevention
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.
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.
26 January, 2009
Miscarriage and the next pregnancy
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).
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).
12 December, 2008
Interesting article on drug makers and journals
The New York Times has an interesting article on HRT and a drug maker.
09 December, 2008
Flu immunisation in pregnancy
Pregnant women should be vaccinated against influenza viruses. Being immunised reduces their chances of being hospitalised during pregnancy and decreases the risk of fetal anomalies. Although immunisation with inactivated flu vaccine is recommended by the World Health Organisation and national health bodies, few mothers receive the vaccine and little is known about its effect on neonates.
What is known is that natural maternal antibodies protect babies in the first few months of life but there are no data on whether vaccinating the mother also offers protection. Zaman et al (NEJM 2008;359:1556-64) now report on a trial that looked at the effectiveness of a trivalent inactivated vaccine in reducing flu in pregnant women and their offspring for 6 months after delivery.
Compared to mothers and infants not given the vaccine, babies whose mothers received the vaccination intervention had a two-thirds reduction in the risk of having laboratory- proven flu while the mothers had a one-third reduction in their likelihood of respiratory fever. The study was carried out in Bangladesh and showed that the remarkable effectiveness of the vaccine conveyed infant immunity for a longer duration than that offered by passive antibody acquisition from the mother. The “two for the price of one” benefit to mother and infant is an additional incentive, with 5 pregnant women needing to be treated to prevent one illness in her or her baby.
What is known is that natural maternal antibodies protect babies in the first few months of life but there are no data on whether vaccinating the mother also offers protection. Zaman et al (NEJM 2008;359:1556-64) now report on a trial that looked at the effectiveness of a trivalent inactivated vaccine in reducing flu in pregnant women and their offspring for 6 months after delivery.
Compared to mothers and infants not given the vaccine, babies whose mothers received the vaccination intervention had a two-thirds reduction in the risk of having laboratory- proven flu while the mothers had a one-third reduction in their likelihood of respiratory fever. The study was carried out in Bangladesh and showed that the remarkable effectiveness of the vaccine conveyed infant immunity for a longer duration than that offered by passive antibody acquisition from the mother. The “two for the price of one” benefit to mother and infant is an additional incentive, with 5 pregnant women needing to be treated to prevent one illness in her or her baby.
The cost of time saving
In developed countries people turn their clocks forward in spring and backwards in autumn. Forward-turning in spring means an hour is “lost” which usually means an hour less sleep and this reduction can be stressful until people's physiology adjusts. But can losing one hour of rest have a real effect? It seems so if the incidence of myocardial infarcts is anything to go by.
Janszky & Ljung from Sweden (NEJM 2008;359:1966-8) showed that coronary events are more common when people are deprived of their extra hour when they turn their clocks forward. Hospital admissions for infarcts rose significantly across the land, especially 2 days after change-over, compared to 2 weeks earlier or 2 weeks later. The effect was consistent over many years and most pronounced in people younger than 65 years old.
As if to prove the point, the opposite effect was found in autumn when the Swedes had fewer than average heart attacks immediately after the “extra hour” was added. The work suggests there are subtle relationships between sleep patterns, stress and cardiac events.
Janszky & Ljung from Sweden (NEJM 2008;359:1966-8) showed that coronary events are more common when people are deprived of their extra hour when they turn their clocks forward. Hospital admissions for infarcts rose significantly across the land, especially 2 days after change-over, compared to 2 weeks earlier or 2 weeks later. The effect was consistent over many years and most pronounced in people younger than 65 years old.
As if to prove the point, the opposite effect was found in autumn when the Swedes had fewer than average heart attacks immediately after the “extra hour” was added. The work suggests there are subtle relationships between sleep patterns, stress and cardiac events.
03 December, 2008
The Six Habits of Highly Respectful Physicians
A good article on The Six Habits of Highly Respectful Physicians in the New York Times.
18 November, 2008
Is there a cognitive cost of being a twin?
Multiple pregnancies have come under intense scrutiny because they are associated with prematurity and growth restriction. In developed countries, high rates of multiple pregnancies following assisted reproductive technology have been cited as a reason why preterm delivery rates remain stubbornly high and perinatal statistics have plateaued.
Long-term outcomes of twins take decades to be determined and it is described that twins born in developed countries half a century ago had lower IQs and academic performances than singletons. However, recent figures from Scandinavian studies show no differences between singletons and twins as measured by all cause mortality and academic achievement (Christensen & McGue BMJ 2008;337:a651:245-6). Perhaps modern antenatal care and catch-up interventions have nullified the discrepancies, but there is strong evidence that disadvantage no longer applies in these sophisticated environments.
It is of interest that a Taiwanese study of twins born in the mid-1980s shows that the subjects had lower academic achievements than singletons and had a lesser probability of attending college (Tsou et al pp 277-80). Is it possible that developing socio-economic factors play a role still, while these factors have been eradicated in developed countries?
Long-term outcomes of twins take decades to be determined and it is described that twins born in developed countries half a century ago had lower IQs and academic performances than singletons. However, recent figures from Scandinavian studies show no differences between singletons and twins as measured by all cause mortality and academic achievement (Christensen & McGue BMJ 2008;337:a651:245-6). Perhaps modern antenatal care and catch-up interventions have nullified the discrepancies, but there is strong evidence that disadvantage no longer applies in these sophisticated environments.
It is of interest that a Taiwanese study of twins born in the mid-1980s shows that the subjects had lower academic achievements than singletons and had a lesser probability of attending college (Tsou et al pp 277-80). Is it possible that developing socio-economic factors play a role still, while these factors have been eradicated in developed countries?
HRT and quality of life
Women take hormone replacement therapy (HRT) to improve their quality of life. Symptoms such as hot flushes, sleep difficulties, vaginal dryness, unsatisfactory sexual function and emotional disturbances are the main indications for commencing HRT. These will remain the reasons for prescribing HRT despite the Women's Health Initiative trial casting doubt on the balance of benefits for women starting treatment 10 to 15 years after the menopause.
Another study running in parallel to the WHI trial was the women's international study of long duration oestrogen after the menopause (WISDOM) investigation (Welton et al BMJ 2008;337:a1190 (550-3). It was scuppered by the WHI results but there were sufficient data to look at quality of life outcomes over one year in women taking combined HRT or placebo. The domains in which the replacement therapy proved significantly better were vasomotor symptoms, sexual functioning, sleep problems, night sweats, vaginal dryness and aching joints or muscles. On the downside, more women complained of breast tenderness and vaginal discharge.
These women were also initiating treatment a considerable time after their menopause which is not ideal but the fact that they derived benefits restores some faith in the role of HRT in its primary function - symptomatic relief of hypo-estrogenic effects. There was no discernable influence on depression or other climacteric symptoms over the short-term. The jury is still out on the possible protective effects on cognitive function, protection from Alzheimer disease and cardio-vascular effects when HRT is started soon after menopause and continued for many years.
Another feature of HRT may be its effect on gastro-esophageal reflux. Jacobson et al (Arch Int Med 2008;168:1798-804) report on a large observational study in which women using estrogens were more at risk of experiencing heartburn than non-users. Their odds ratio was 1.66 and those taking combined HRT had only slightly less risk. The larger the dose and the longer the duration of use, the greater the likelihood of symptoms. The absolute risk is approximately 1 in 4 women will report such effects, and taking estrogens increases a woman's chances of being in the symptomatic category.
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.
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