No correlation between MMR vaccination and autism, study shows
MMR vaccination in Scotland
Pneumococcal vaccine reduces otitis media incidence, study shows
Pneumococcal vaccine to be launched
Preventive aspirin use "not justified" in patients at low-risk of heart disease
Change to vaccination advice for pilgrims travelling to Saudi Arabia
Malaria prophylaxis guidelines to be updated
Tamoxifen may protect the heart, trial results suggest
Patient demand for antibiotics is decreasing, survey finds
New oral treatment for colorectal cancer
New rheumatoid arthritis guidelines
Dietary advice tips: (12) Premenstrual syndrome

No correlation between MMR vaccination and autism, study shows

A new study has shown that there is no evidence of a correlation between the prevalence of combined measles, mumps and rubella (MMR) vaccine use and the increased incidence of autism.

The results of this study follow recent concerns over the proposed causal link between the two (PJ, January 20, p71; January 27, p104).

Researchers from Boston university school of medicine, United States, used the United Kingdom general practice research database to assess the possibility of a temporal relationship between MMR vaccination and the diagnosis of autism.

Dr James Kaye and colleagues identified 305 children aged 12 years or younger, whose diagnosis of autism was first recorded between 1988 and 1999. They estimated that the yearly incidence of diagnosed autism among these children increased seven-fold, from 0.3 per 10,000 person-years in 1988, to 2.1 per 10,000 person-years in 1999. The median age of first diagnosis was 4.6 years and this did not vary substantially over time.

In addition, in a group of 114 boys whose first recorded diagnosis of autism occured between the ages of two and five years, the estimated four-year risk of a first recorded diagnosis increased nearly four-fold, from 8 per 10,000 for boys born in 1988 to 29 per 10,000 boys born in 1993.

In contrast, the researchers found that the prevalence of MMR vaccination among children registered in the database, was virtually constant (about 97 per cent) for each successive birth cohort, and was similar for males and females.

Ninety-five per cent of vaccinated children received their first MMR vaccine by the age of 20 months. Among 110 cases of autism in boys (aged 2-5 years and born in between 1988 and 1993), for whom MMR vaccination could be assessed, 99 per cent were vaccinated, a prevalence which the authors say is nearly identical to that in the general population.

The researchers comment that if the MMR vaccine was a major cause of the increasing incidence of autism, then the risk of autism in successive birth cohorts would be expected to stop rising within a few years of the vaccine being in full use.

They say that "this was not the case in our study" and suggest that the increase in recorded diagnosis of autism could be a result of an increased awareness of the condition among parents and general practitioners, changing diagnostic criteria or environmental factors not yet identified. The article is to be published in the British Medical Journal next week and is currently available on the website www.bmj.com.

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MMR vaccination in Scotland

Scottish parents have been urged to continue to have their children immunised with measles, mumps and rubella (MMR) vaccine. Speaking on February 13, Dr Mac Armstrong (chief medical officer, Scotland) said: "93 per cent of Scots parents are continuing to have their children vaccinated. We need to maintain that record to keep all our children safe." The evidence in support of MMR vaccine’ s safety was "compelling" and the suggestion of a link between the vaccine and autism "unproven".

The introduction of a single vaccine programme would "undoubtedly, lead to a fall in uptake of the vaccines as a whole" and that there was no scientifically assessed programme for giving them separately, he said.

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Pneumococcal vaccine reduces otitis media incidence, study shows

Apneumococcal conjugate vaccine appears to prevent acute otitis media caused by Streptococcus pneumoniae, according to findings from a Finnish study.

The vaccine used in the study contained seven serotypes of S pneumoniae and provided immunity against invasive pneumococcal infections in children.

In the randomised, double-blind study, researchers from the National Public Health Institute, Finland, assigned 1,662 children to receive either the study vaccine (heptavalent pneumococcal polysaccharide-CRM197 conjugate vaccine) or a control (hepatitis B) vaccine, at the ages of two, four, six and 12 months. The primary endpoint was the number of episodes of acute otitis media caused by the pneumococcal serotypes included in the vaccine.

Dr Juhani Eskola and colleagues found that the pneumococcal vaccine group had a 6 per cent reduction in the number of episodes of acute otitis media and a 9 per cent reduction in the frequency of recurrent acute otitis media, compared with the control group.

Although the vaccine reduced the number of episodes caused by the serotypes in the vaccine by 57 per cent, efficacy varied within these serotypes of S pneumoniae.

The pneumococcal vaccine was well tolerated and the majority of reactions seen during the study were mild. During the three days after each dose, more local reactions were associated with the pneumococcal vaccine than with the hepatitis B vaccine.

The researchers conclude that, on the basis of their data, "up to 1.2 million of the 20 million yearly episodes of acute otitis media in the United States could theoretically be prevented if the pneumococcal vaccine was more widely spread".

The study is published in the New England Journal of Medicine (2001;344:403).

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Pneumococcal vaccine to be launched

Prenevar, a pneumococcal saccharide conjugate vaccine for children aged up to two years, is expected to be launched by Wyeth Laboratories in April. The company says that Prenevar contains seven serotypes of Streptococcus pneumoniae and will be licensed for the prevention of invasive pneumococcal disease caused by these serotypes.

Pneumococcal vaccines currently available in the United Kingdom are licensed only for use in children aged over two years.

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Preventive aspirin use "not justified" in patients at low-risk of heart disease

Taking aspirin to prevent a first heart attack or stroke could be harmful to people at low risk of heart disease, say researchers from Sheffield. Dr P. Sanmuganathan and colleagues (clinical pharmacology and therapeutics, Royal Hallamshire hospital) pooled the results of four randomised, controlled trials in which aspirin had been given for primary prevention of heart disease.

They found that aspirin significantly reduced all cardiovascular events by 15 per cent (95 per cent confidence interval [CI], 6 to 22 per cent) and myocardial infarctions by 30 per cent (95 per cent CI, 21 to 38 per cent). However, it increased bleeding complications by 69 per cent (95 per cent CI, 38 to 107 per cent). The number needed to treat to prevent myocardial infarction and the number needed to harm, indicated that the benefits of aspirin treatment for primary prevention outweighed any harm in patients with a coronary event risk of 1.5 per cent per year, or more. However, giving aspirin to patients with an event risk of 0.5 per cent per year could not be justified because of the risk of bleeding.

The authors say that it is important to identify how likely an individual is to have a heart attack before giving them aspirin. To help assess the risk, they have revised the Sheffield table for primary prevention of cardiovascular diseases, which is published in the article. This table allows calculation of risk, and takes into account factors, such as smoking, family history and cholesterol levels. The meta-analysis is published in Heart (2001;85:265).

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Change to vaccination advice for pilgrims travelling to Saudi Arabia

Pilgrims travelling to Saudi Arabia for Hajj or Umrah should receive quadrivalent meningococcal polysaccharide vaccine (ACWY Vax) to protect them against the A, C, W135 and Y strains of meningitis, the Department of Health has advised.

A letter circulated to prescribers on February 13 says that, until now, meningococcal polysaccharide A and C vaccine has been recommended, but an outbreak of meningococcal W135 infection last year made the change necessary.

Doctors are asked to ensure that they indicate which vaccine has been given when issuing a certificate of meningococcal immunisation. Although most people in Britain aged up to 18 years will have received meningococcal C vaccine (MenC), this does not provide protection against strains A and W135, the Department says. A poster that provides information for the public in Arabic, Bengali and Urdu is available from www.doh.gov.uk/traveladvice/hajj.htm.

ACWY Vax is indicated for adults and children aged two years and over (PJ, January 20, p94). The Department says that children at risk, who are aged two months to two years, may be immunised in some circumstances, but their immune response is likely to be short-lived. The vaccine should not be used in children aged under two months.

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Malaria prophylaxis guidelines to be updated

Guidelines for malaria prophylaxis are likely to be updated within the next few weeks, says the Malaria Reference Laboratory. The last published update of the guidelines was in September, 1997.

A number of prescribing changes are to be included in the new guidelines because of increasing resistance. Professor David Warhurst (co-director, Malaria Reference Laboratory) told The Journal on February 9 that doxycycline was now recommended as a first-line alternative to mefloquine for malaria prophylaxis in countries where mefloquine is advised.

Further changes will be made to the guidelines when Malarone (proguanil and atovaquone) — currently only licensed for the treatment of malaria — receives a licence for prophylaxis in the United Kingdom. Glaxosmithkline, the UK manufacturer of Malarone, says that it expects the prophylaxis licence sometime this year.

The National Pharmaceutical Association (NPA) says that it is updating the recommendations on its malaria prophylaxis chart. The update should be sent out to NPA members with the NPA's March Supplement. The NPA has updated its chart on NPAnet. Pharmacists who cannot access the updated chart can telephone the NPA information department (tel 01727 858687, ext 470).

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Tamoxifen may protect the heart, trial results suggest

Tamoxifen has been shown to reduce the levels of two inflammatory markers that have been linked to an increased risk of heart disease.

In an American breast cancer prevention trial, 100 healthy women received either tamoxifen 20mg daily or placebo for six months. Tamoxifen was found to reduce median levels of C-reactive protein (CRP) and fibrinogen by 26 per cent and 22 per cent, respectively. There was no significant change in fibrinogen and CRP levels in the placebo group during the study period. The researchers, led by Dr Mary Cushman (University of Vermont, Burlington) also found that women who received tamoxifen had a 9 per cent reduction in total cholesterol levels.

They conclude: "It is important to note that, although the epidemiological evidence relating C-reactive protein and fibrinogen to vascular disease risk is compelling, a cause-effect relationship is not proven." The reduction of these factors might relate either to altered production or degradation, and any clinical consequences of this is unknown, the researchers add.

The study is published in Arteriosclerosis, Thrombosis, and Vascular Biology (2001;21:255).

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Patient demand for antibiotics is decreasing, survey finds

Patients with coughs, colds or sore throats are making fewer requests for antibiotics, say researchers from Liverpool. Dr Gaynor Bresnen (school of pharmacy and chemistry, Liverpool John Moores university) conducted a survey of pharmaceutical advisers from 16 health authorities and 100 British general practitioners, to assess the impact of a 1998 Standing Medical Advisory Committee report on increasing antibiotic resistance. Bulletins on prescribing issues were the most common form of help provided by pharmceutical advisers to the GPs, followed by cost data and local antibiotic resistance rates from hospitals.

Over a third of the GPs interviewed said that patients were more willing to leave without a prescription for an antibiotic, and over half said that they were seeing significant reductions in requests for antibiotic prescriptions. However, one in 10 said that 75 to 100 per cent of patients with a sore throat still expected to receive an antibiotic.

Many patients were willing to accept alternative treatments to antibiotics and, the authors say, greater reductions in antibiotic prescribing might be possible if patients were better informed about these alternatives.

More than half of the GPs interviewed had distributed leaflets to patients that provided them with information about antibiotics and 41 per cent had regular reviews of prescribing.

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New oral treatment for colorectal cancer

Capecitabine (Xeloda), an oral fluoro- pyrimidine, was launched by Roche Products this week. The product is licensed for first-line treatment of colorectal cancer (see p232).

The summary of product characteristics for capecitabine says that the drug is a precursor of 5-fluorouracil. (See PJ, November 4, p677 for results from phase III trials of capecitabine.)

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New rheumatoid arthritis guidelines

Early treatment of rheumatoid arthritis with disease modifying drugs has been recommended in a new Scottish guideline.

The Scottish Intercollegiate Guidelines Network (SIGN) recommends that all patients with joint inflammation that lasts longer than six to eight weeks should be referred to a rheumatology specialist. If a diagnosis of rheumatoid arthritis is confirmed, the guideline says that early treatment (within 12 weeks of onset of symptoms) with disease modifying anti-rheumatic drugs (DMARDs) will control symptoms, improve quality of life and delay disease progression. The SIGN expects that this preventive strategy could result in considerable cost savings.

The new guideline contrasts with the traditional treatment "pyramid" for the disease, in which DMARDs were used later, and early treatment was based on pain relief.

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Dietary advice tips: (12) Premenstrual syndrome

Premenstrual syndrome (PMS) is a condition which affects many women for up to two weeks before their period starts. Symptoms may be physical (eg, headache, backache, weight gain, abdominal swelling, breast tenderness) or mental (eg, lethargy, marked mood changes, food craving, lack of concentration). The number and type of symptoms varies between women and can be different each month. Many women wish to try nutritional methods to manage their symptoms, and there is evidence that a healthy diet that is low in fat and high in fibre can help to relieve PMS.

• Women who suffer from PMS should take particular care to consume a diet low in fat, sugar and salt, and high in fibre and starch.
• Low blood sugar levels may exacerbate symptoms. It is therefore important that sufferers do not skip meals. Long gaps (ie, more than three hours) between meals and snacks should be avoided. This can be achieved by having three small meals and three small snacks each day. Food portions should be small because of the risk of weight gain. This pattern of eating seems to be particularly important in the luteal phase, when PMS is most likely to occur.
• All meals and snacks should contain a source of starch (eg, bread, potatoes, breakfast cereal, pasta, rice, scones, crispbread). There is evidence that this may help to reduce some PMS symptoms (eg, sugar craving, mood swings) by providing a steady supply of energy and not allowing blood sugar levels to fall too low. Starchy foods are also thought to increase the secretion of serotonin, and this may help to improve mood.
• Excessive caffeine intake should be avoided. This means no more than five cups/glasses of coffee, tea, chocolate and cola a day. Decaffeinated coffee, decaffeinated cola, herbal tea and water are better choices.
• Alcohol can lower blood sugar levels. No more than one to two units a day should be consumed, and it is best to drink with a meal or snack rather than on an empty stomach.
• Gamma-linolenic acid (GLA) supplements (eg, evening primrose oil, starflower oil) may help some women who suffer from PMS. However, consistent benefit in clinical trials has been found only for premenstrual breast pain. A dose of 120-160mg twice a day of GLA (equivalent to three to four 500mg capsules of evening primrose oil) may be tried.
• Vitamin B₆ has been claimed to help reduce the symptoms of PMS. The evidence is controversial, but a recent systematic review of nine published trials representing 940 patients with PMS suggested that doses of vitamin B₆ up to 100mg daily are likely to be of benefit in treating premenstrual symptoms and premenstrual depression. If there is no improvement in symptoms after four months, or if tingling in the hands and feet is experienced, the supplement should be stopped. High doses of vitamin B₆ taken over a prolonged period may cause nerve toxicity, but this is unlikely at doses up to 100mg daily.
• Evidence for the effect of other supplements (eg, zinc, vitamin E) is sparse. Magnesium levels have been found to be low in some women with PMS, although further research is needed. Some clinics recommend a magnesium supplement of 250mg daily, and this may be effective in a number of women.

This series of "dietary advice tips" is intended to be a reminder of the main points to be made by pharmacists when giving nutritional information to the public. The conditions included in the series are those where diet is a well recognised risk factor, those in which diet contributes to the management of the condition, and others for which patients may welcome sound dietary advice. The series is written by Dr Pamela Mason (a pharmacist with a postgraduate qualification in nutrition)

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