All you need to read in the other general journalsBMJ 2011; 343 doi: http://dx.doi.org/10.1136/bmj.d4562 (Published 20 July 2011) Cite this as: BMJ 2011;343:d4562
Androgen suppression improves survival in some men with localised prostate cancer
External beam radiotherapy is an established option for men with localised prostate cancer. A short burst (for four months) of androgen suppression given at the same time prolonged survival for some but not all men in a trial from the US. The benefit, which was modest, was confined to men who had localised cancers of “intermediate risk,” defined using a combination of stage, Gleason score, and baseline concentration of prostate specific antigen. In this subgroup, antiandrogen treatment prolonged overall survival at 10 years compared with radiotherapy alone (61% v 54%; hazard ratio 1.23, 95% CI 1.02 to 1.49).
These men began the trial with a mean age of 70, tumours staged T1 or T2, and prostate specific antigen concentrations no higher than 20 ng/ml. Antiandrogen treatment reduced deaths from prostate cancer (4% v 8%; 1.87, 1.27 to 2.74), but again, the benefit was greatest for men with intermediate risk tumours.
Erectile dysfunction was a problem for both groups of men in this trial. It was significantly more of a problem for those given short term antiandrogen treatment. US regulators already warn prescribers that gonadotrophin releasing hormone agonists increase the risk of heart attack, stroke, diabetes, and even sudden death in vulnerable adults, says an editorial (p 169). The benefits are unlikely to outweigh the risks for men with low risk localised prostate cancer.
Unpicking the placebo effect in adults with asthma
The power of the placebo is well known, particularly in medical conditions with subjective symptoms such as asthma. In one experiment, adults with mild to moderate asthma reported the same improvement in symptoms after inhaled albuterol, an inhaled placebo, and sham acupuncture (50%, 45%, and 46% improvement). Participants did not notice the significant improvement in objective lung function associated with albuterol (20% increase in forced expiratory volume in one second (FEV1)), but they did notice a difference between any treatment and no treatment⇓.
In this small pilot, placebo effects were obvious for the self reported subjective outcome (the placebos worked as well as the real drug and better than no treatment). Placebo effects were missing in comparisons that used the objective hard outcome (the placebos worked less well than the drug and about the same as no treatment). The authors argue that patients’ perceptions can be unreliable, so doctors and trialists should look for objective evidence of improvement instead.
Although this approach makes sense to scientists and doctors, it makes less sense to patients, whose subjective symptoms brought them to the surgery in the first place, says an editorial (p 171). In a truly patient centred world we would prioritise symptoms over spirometry, and be much less hung up about controlling for everything but the biological effects of treatments. All treatments, active or inactive, can be meaningful if they work for patients, don’t cost too much, and above all, do no harm.
Number of lifetime partners not concurrency drives the HIV epidemic in Africa
A study from KwaZulu-Natal in South Africa challenges the widespread belief that having multiple sexual partners at the same time is the main driver of the HIV epidemic in sub-Saharan Africa. The authors, who constructed detailed maps of men’s sexual behaviour from local surveys, found that uninfected women living in areas where men had multiple concurrent partners were no more likely to acquire HIV than women living elsewhere⇓.
The average number of lifetime sexual partners reported by local men was a better indicator of risk of HIV in this study. A woman’s risk of incident HIV increase by 8% for each extra lifetime partner reported by men living within 3 km (adjusted hazard ratio 1.08, 95% CI 1.03 to 1.14). The researchers followed up 7284 HIV negative women for five years. Almost 700 acquired the infection (3.60 cases/100 person years).
The link between incident infection in women and the number of partners reported by local men survived adjustments for the women’s own sexual behaviour and demographic variables known to be associated with HIV. International agencies and some national governments have already launched campaigns against concurrency in sexual relationships, says a linked comment (p 203). These campaigns need to shift their focus towards discouraging multiple partners, whether or not partnerships overlap. KwaZulu-Natal is a hyperendemic area, where a quarter of the adult population and half of all women aged 25-29 are infected with HIV.
Support from peers helps African women stick with breast feeding
Breast milk can be life saving for babies in developing countries, and a cluster randomised trial in three countries in sub-Saharan Africa shows that it is possible to double the proportion of women who exclusively breast feed simply by providing regular support from peers. Home visits from trained local women starting in the third trimester worked well, doubling rates of exclusive breast feeding at 12 weeks in all three countries and maintaining a significant difference between intervention and control communities for at least six months, when compared with usual care (73% v 22% in Burkina Faso, 59% v 15% in Uganda, and 2% v <1% in South Africa).
Peer support and higher rates of breast feeding did not help prevent infant diarrhoea in these 82 communities in Burkina Faso, Uganda, or South Africa, however. Mothers in intervention and control communities reported recent diarrhoea in 5-10% of infants at 12 weeks, and slightly more at 24 weeks.
Women in South Africa breast fed substantially less than women in the other two countries. Even with peer support the rate of exclusive breast feeding here peaked at just 10%. The authors blame a political and regulatory climate that encourages uncontrolled marketing of infant formula milk.
Study supports a moratorium on new fast food chains in poor neighbourhoods
US government policies to encourage supermarkets to come to poor neighbourhoods and fast food chains to leave may not have the hoped for effect on local residents’ diets, say researchers. Their cohort study found little evidence that living close to a supermarket encouraged healthier eating, and somewhat patchy evidence that living close to fast food chains did the opposite⇓.
The researchers matched dietary information from a longstanding cohort of US adults with commercial information about the food outlets close to where they lived. One modest but significant association emerged from several adjusted analyses—fast food consumption in men on low incomes went up in line with the number of fast food chains operating within 3 km of home.
Policy makers should press on, says an editorial (p 1171), encouraged by this one result from a good longitudinal study. It may help some people in some places if new fast food outlets were banned, and this has already been done in the food deserts of south Los Angeles. More nuanced initiatives to improve everyone’s food environment can be launched and then evaluated prospectively, it says. Policies may have to target the type of food that outlets sell and how they sell it, as well as where they open.
Early treatment helps prevent sexual transmission of HIV
Early treatment of adults with HIV helps prevent transmission to uninfected sexual partners, according to a new trial. The emphatic findings were released less than two years into a six year trial, when interim analyses suggested that earlier treatment with antiretroviral drugs was associated with 96% fewer transmissions than later treatment (95% CI 73% to 99%).
Researchers in Africa, Asia, Brazil, and the US enrolled 1763 mostly heterosexual couples in stable relationships. All were discordant for HIV infection and were counselled about safe sex. Half the HIV infected partners started treatment immediately, when their CD4 counts were 350-550 cells per mm3. The other half had no treatment until their CD4 count dropped to 250 cells per mm3, or they developed an illness related to HIV.
Twenty eight participants infected their partners during 1.7 years of follow-up. Just one had started treatment early (hazard ratio 0.04, 95% CI 0.01 to 0.27). The other 27, including 18 women, were in the delayed treatment group and transmitted HIV before they were eligible for antiretroviral drugs.
Adults treated early were significantly less likely than controls to develop serious illnesses related to HIV, particularly tuberculosis. They had no more clinical side effects but significantly more abnormal blood tests than controls.
The researchers hope that ongoing trials will confirm their preliminary findings. Preventing infections and curbing transmission through communities remains the best hope for long term control of HIV.
Preserving ovarian function through chemotherapy for breast cancer
Permanent loss of fertility is one of the biggest fears for young women having chemotherapy for early breast cancer, and researchers are trying to establish whether suppressing ovarian function during treatment can help prevent an early menopause. In the latest and largest trial, the gonadotrophin releasing hormone (GnRH) analogue triptorelin seemed to work well, reducing the absolute risk of an early menopause by 17% (8.9% v 25.9%; odds ratio 0.28, 95% CI 0.14 to 0.59) in 281 women under 45 years with stage I-III breast cancers.
Should all young women be offered this kind of protection? Not yet, says an editorial (p 312). Important questions remain about the long term safety of GnRH analogues in women with breast cancer, particularly those with hormone sensitive tumours. Observational studies have hinted that amenorrhoea may improve survival, and we need to know more about what happens to women in the long term before we start using these analogues routinely. The latest trial reports results up to one year after treatment. It is too early to explore breast cancer outcomes, including deaths, and too early for a definitive answer to the leading question for young childless women: will treatment help me conceive?
These new findings are an encouraging step in the right direction, says the editorial, but for now cryopreservation of embryos or oocytes remains the most effective way to preserve fertility through chemotherapy for breast cancer.
Cite this as: BMJ 2011;343:d4562