BMJ  2006;333:643-644 (23 September), doi:10.1136/bmj.333.7569.643

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Chemotherapy prevents local recurrence but doesn't prolong survival in patients with rectal cancer

Preoperative radiotherapy is a standard treatment option for patients with stage T3 or T4 rectal cancers. The role of chemotherapy is less clear. A clinical trial found that additional chemotherapy based on fluorouracil had no impact on patients' survival, but it did help to prevent local recurrences whether it was given before or after surgery.

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Four groups of patients (total 1011) had preoperative radiotherapy plus either preoperative chemotherapy, postoperative chemotherapy, both, or neither. About 65% of them survived for five years regardless of their assigned treatment. But patients who had no chemotherapy at all were more likely to have a local recurrence (17%) than the other three groups (8.7%, 9.6%, and 7.6%, P = 0.002).

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The timing of the chemotherapy didn't seem to matter, except that patients who had their treatment before surgery were more likely complete it. Less than half the patients who were meant to have postoperative chemotherapy managed to complete the course specified by the protocol of the trial. Over a quarter failed to start, mostly because they had postoperative complications, disease progression, or simply said no.

The authors conclude that preoperative chemotherapy with fluorouracil is probably worth considering for some patients.

N Engl J Med 2006;355: 1114-23[Abstract/Full Text]

Children with otitis media do well with optional antibiotics

American doctors often prescribe antibiotics for children with acute otitis media, even though there is good evidence from Europe that a "wait and see" policy can work just as well. They now have their own culturally specific evidence from a large trial set in an urban emergency department in New Haven, Connecticut. Children whose parents were given a delayed prescription to fill in if their child wasn't better (or got worse) over the next two days had similar short and medium term outcomes as children who were given antibiotics immediately. Immediate antibiotics made no difference to the children's fever, use of analgesics for ear pain, or rate of otalgia after a few days or two weeks. Antibiotics did not prevent vomiting, or further visits to a doctor. Children given antibiotics immediately had a few hours less ear pain over the first few days (2.0 days v 2.4 days; P = 0.02), but they also had more diarrhoea (23%, 31/133 v 8%, 10/132 P < 0.001). Most importantly though, delayed prescriptions reduced parents' use of antibiotics from 87% to 38%, a significant effect that can only help in the fight against antibiotic resistance.

The parents in this setting seemed willing to try the delayed prescription approach, and those that managed without antibiotics were more likely to say they would do without next time (63% v 28%, P < 0.001).

JAMA 2006;296: 1235-41.[Abstract/Full Text]

Green tea is associated with longer life for Japanese adults

Many claims have been made about the potential benefits of green tea. Research in humans has been inconsistent, possibly because the studies have been too small to find a modest effect. The largest study so far reports that drinking several cups a day is associated with a reduced risk of death, and a reduced risk of cardiovascular death, particularly stroke. The same study, which included over 400 000 Japanese adults, found no evidence that green tea can help prevent cancer deaths.

Green tea is one of the most popular drinks in Japan and most of the participants regularly drank at least one small cup a day. A Japanese cup measures about 100 ml. The inverse associations between green tea and all cause and cardiovascular mortality were strongest in women and were significant for those drinking three or more cups a day (hazard ratio for cardiovascular mortality 0.69, 95% CI 0.52 to 0.93 for three to four cups and 0.53 to 0.90 for five or more). In men, the associations were significant only for those who drank five or more cups a day, and even then the benefit seemed smaller.

Green tea contains polyphenols which scavenge free radicals among other things. So a link with good cardiovascular health is biologically plausible. Ultimately though, only prospective clinical trials can establish for certain whether or not green tea can prolong your life.

JAMA 2006;296: 1255-65[Abstract/Full Text]

Young women with hepatitis C are more likely to die from drugs than from liver disease

Between 1990 and 2002, 117 547 new cases of hepatitis B or C were notified to the New South Wales state health department in Australia, including 2604 new cases of mixed infection with both viruses. All three groups had a higher mortality rate than the general population in a recent study, and by linking the notifiable diseases database with the Australian death register, researchers have pieced together a comprehensive picture of what they died of.

Perhaps unsurprisingly, deaths coded as viral hepatitis and its sequelae dominated the picture, with standardised mortality ratios between about 36 (for patients with hepatitis B) and 113 (for patients with both viruses). Similarly, liver related mortality was 12 to 33 times greater than in the general population—liver cancer accounting for the greatest number of excess deaths in people with hepatitis B.

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The group with hepatitis C, however, was characterised by a large excess of drug related deaths, presumably because intravenous injection of illegal drugs is a leading cause of hepatitis C worldwide. With a standardised mortality ratio of nearly 20, patients in this group were significantly more likely to die from drug use than from the ensuing liver disease. The link between hepatitis C and a drug related death was particularly strong in young women aged between 15 and 40 years.

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Lancet 2006; 368: 938-45[CrossRef][Medline]

A new pill for multiple sclerosis deserves further study

An oral treatment for relapsing multiple sclerosis looked promising in an early clinical trial. For six months 255 patients took the drug fingolimod or a matching placebo, during which time the drug significantly reduced the number of brain lesions, as measured by magnetic resonance imaging, and reduced the risk of relapse. In a six month extension to the core trial, patients who switched from placebo to fingolimod also improved. The trial tested two doses that seemed to work equally well.

Safety remains an issue, however. Fingolimod is an immunomodulator that acts mainly on lymphocytes, locking them in lymph nodes and reducing the peripheral lymphocyte count. In this study, lymphocyte counts fell quickly by about 70% to 80% in both treated groups. Upper respiratory tract infections were common, particularly in patients taking the higher dose, and there were two serious infections—one patient developed facial herpes zoster and another developed enterocolitis. Fingolimod was also associated with transient reduction in heart rate, asymptomatic abnormalities in liver enzymes, and one case of posterior reversible encephalopathy syndrome (a serious abnormality in the occipital region of the brain that causes temporary blindness, dysarthria, and ataxia).

N Engl J Med 2006;355: 1124-39[Abstract/Full Text]

Redistributing wealth is good for health

Politicians set the public health agenda according to the political aspirations and ideology of the party in power. So you might expect those aspirations and ideologies to have a measurable impact on the health of the population. Proving it is easier said than done, but a team from the United States, Canada, and Spain have made a start by showing that political ideologies encouraging the redistribution of wealth are associated with lower infant mortality, and to a lesser extent with longer life expectancy.

They studied a group of developed countries belonging to the Organisation for Economic Cooperation and Development, categorising them according to dominant political tradition into social democracies, Christian democracies, liberal conservative democracies, or dictatorships. Roughly speaking, these four traditions are in a descending hierarchy of wealth redistribution with social democracies, such as Norway and Sweden, at the top and dictatorships, such as those that ruled Spain and Portugal, at the bottom. The US and UK, as liberal conservative democracies are somewhere in the middle.

The researchers found a clear and inverse correlation between infant mortality since 1972 and the length of time a country had been ruled by political parties that were for redistribution (correlation for 1996 -0.747). Further analysis suggested that the benefits of egalitarian political ideology were mediated by policies encouraging full employment, generous public health expenditure, and universal social benefits.

Lancet 2006 doi 101016/S0140-6736(06)69341-0

Fatty fish may protect women from renal cancer

A diet rich in fatty fish such as salmon, herring, and mackerel seems to be associated with a lower risk of renal cell carcinoma in women, according to a large prospective cohort study from Sweden. Women in the cohort who ate fatty fish at least once a week were 44% less likely to develop renal cancer over a 15 year follow-up than women who ate no fatty fish (adjusted rate ratio 0.56, 95% CI 0.35 to 0.91). The researchers found no link between incidence of renal cancer and any other type of fish or seafood including the lean fish types such as cod and tuna.

The study included over 60 000 Swedish women aged between 40 and 76 who filled in a food frequency questionnaire at baseline between 1987 and 1990. A subgroup of 36 664 filled in a second questionnaire 10 years later, which allowed the researchers to assess the impact of consistent and long term consumption of fatty fish. The risk reduction was an even bigger 74% (rate ratio 0.26, 0.1 to 0.67), even after adjustment for a long list of confounding factors including age, education, body mass index, other aspects of diet, smoking, alcohol intake, hypertension, and diabetes.

JAMA 2006;296: 1371-6[Abstract/Full Text]

Syncope is the best predictor of cardiac arrest or death in young people with long QT syndrome

Adolescents with hereditary long QT syndrome have an increased risk of ventricular arrythmias and death. Catastrophic events are unpredictable, but a new study has identified three factors that might help doctors stratify these adolescents according to their risk: gender, the length of the QT interval, and history of syncope. They followed up 2772 patients on a US register between the ages of 10 and 20 years. Adolescents with a recent history of syncope had the highest risks of a life threatening arrhythmia or death before the age of 20, with a hazard ratio of 18.1 (95% CI 10.4 to 31.2, P < 0.001) for those with two or more syncopal attacks in the past two years. The two other factors were less important, but still significant. Boys had higher risks than girls, but only before the age of 12 years (hazard ratio 4.0, 95% CI 1.8 to 9.2, P = 0.001), as did those of either sex with a QTc of 530 ms (2.3, 1.6 to 3.3, P < 0.001).

The effects of treatment are hard to assess from this kind of study, although ß blockers did seem to help patients at very high risk.

Overall, 45 of the 2772 patients in this study had sudden cardiac death before the age of 20. Another 81 were successfully rescued from cardiac arrest.

JAMA 2006;296: 1249-54[Abstract/Full Text]

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