• Drug treatment for new Parkinson's patients should await specialist diagnosis
• Major genetic determinant of drug clearance identified
• Phytoestrogens may prevent onset of Alzheimer's disease
• GPRD goes online
• Vaccination reduces mortality in older people
• Influenza vaccine hope for people with egg allergy
• BCG vaccination programme to restart in schools
• Some statins might be safe in renal disease
• Benefits of discharge pharmacists shown
• Trastuzumab of benefit in HER2-positive breast cancer
• Antibiotics for preterm birth
• Insulin manufacturer expresses concerns over NICE guidance

Drug treatment for new Parkinson's patients should await specialist diagnosis

Many people with newly diagnosed Parkinson's disease are not being given appropriate drug treatment, according to the Parkinson's Disease Society (PDS). The development of pharmacy services in this area could improve care.

The PDS says that guidelines recommend that treatment of patients with suspected Parkinson's disease should be delayed until the diagnosis has been confirmed by a specialist, because there is rarely any urgency to prescribe drugs.

However, a survey of 400 general practitioners (GPs) commissioned by the PDS showed that 55 per cent make the decision to start treatment either without, or while awaiting, referral. In addition, 24 per cent said that they initiate drug treatment for all newly diagnosed patients. The survey report says that, of the GPs who initiate treatment themselves, 95 per cent prescribe levodopa and are “possibly unaware that other options are now available”.

Mary Baker (chief executive, PDS) said at a press conference on April 2: “Unfortunately, in their eagerness to help patients, many GPs may not realise that by initiating treatment instead of referring all patients with suspected Parkinson's disease, they could actually be doing more harm than good in the longer term.”

Dr Douglas MacMahon (consultant physician, Cornwall Health Care Trust) added that there had been a rapid expansion in the number of new drugs available to treat Parkinson's disease in recent years, which made it difficult for GPs to keep up to date.

“Levodopa has for many years been the main drug treatment for Parkinson's. ... However, its effectiveness begins to wear off, usually after five years. ... It is prudent to delay treatment with levodopa for as long as possible, provided that adequate relief of symptoms can be achieved with other drugs,” he went on.

Ms Baker said that the PDS does not question GPs' knowledge, just their experience. Dr Stephen Henry (GP, Wiltshire) agreed, saying: “Parkinson's is challenging for GPs. It requires complex medical care, but the average GP only sees a new patient once every five years. There should be primary care group teams who look after these patients.”

He added that pharmacists should be included in these teams: “The only thing holding pharmacists back is pharmacists themselves. Any GP would be thrilled to have the help and advice of a suitably trained pharmacist.”

Ms Baker agreed, saying that, in another survey conducted by the PDS, GPs had said they would welcome the development of pharmacy services in this disease area. The PDS had successfully applied to the Department of Health for funding for a medicines information help line, which was being piloted in Wales and which would advise patients on topics such as compliance and the effect of drugs taken for other diseases on Parkinson's treatment. This was a collaboration between the PDS and the Welsh School of Pharmacy, Cardiff University.

Age discrimination

The PDS says that age discrimination is another problem faced by patients with the disease. Of the GPs surveyed, 95 per cent said that, although they always refer patients aged 50 years or under, only 58 per cent refer those over the age of 71 years.

“Such age discrimination ... has no place in the management of a condition which predominantly affects elderly people. Patients should receive treatment on the basis of clinical need, not on the basis of age,” Ms Baker said.

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Major genetic determinant of drug clearance identified

Expression of cytochrome P450 3A5 (CYP3A5) could be the most important genetic contributor to interindividual and inter-racial differences in CYP3A-dependent drug clearance, say researchers.

Dr Peter Kuehl (University of Maryland, Baltimore, United States) and colleagues analysed the DNA of people from different ethnic groups and looked for associations between differences in their genotypes and drug detoxification. They specifically looked at the genes encoding for CYP3A proteins, which inactivate many drugs.

They estimate that high levels of metabolically active CYP3A5 are expressed by 30 per cent of Caucasians, Japanese, and Mexicans, 40 per cent of Chinese, and more than 50 per cent of African Americans, South East Asians, Pacific Islanders and South Western American Indians. The researchers say that the higher prevalence of CYP3A5 expression indicates that these people are more likely to experience higher clearance of drugs that are inactivated by CYP3A and are therefore less likely to experience dose-limiting toxicity.

The paper is published in Nature Genetics (2001;27:383).

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Phytoestrogens may prevent onset of Alzheimer's disease

Phytoestrogens in soy may protect against the onset of Alzheimer's disease, according to research presented at an American Chemical Society meeting in San Diego this week.

A three-year study that used an animal model of the human menopause (elderly female monkeys whose ovaries had been removed) investigated the effects of soy isoflavones and oestrogen on the brain. The results showed that fewer Alzheimer's disease-linked protein changes occurred in the brains of the monkeys that were given soy isoflavones.

Professor Helen Kim (University of Alabama, United States) and colleagues, who conducted the study, say that these changes were not seen in monkeys given oestrogen. Isoflavones and “real” oestrogens may both be beneficial for the brain but work through different mechanisms, they say.

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GPRD goes online

The General Practice Research Database is now available online. The Medicines Control Agency says that access will be licensed to academics, regulators, pharmaceutical organisations and research service providers.

For further information, visit the GPRD website (www.gprd.com).

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Vaccination reduces mortality in older people

Vaccination against influenza and pneumococcal infection in older people reduces all cause mortality, research shows.

Swedish researchers assessed the effectiveness of the vaccines in a large, prospective study. Of 259,627 people aged over 65 years in the area of the study, 100,242 were vaccinated during an eight-week campaign to encourage vaccine uptake. Of the vaccinated individuals, 76,177 had influenza and pneumococcal vaccines, 23,224 had influenza vaccine only and 841 had pneumococcal vaccine only. The researchers estimated the effectiveness of the vaccines by comparing hospital admissions for influenza and pneumonia in vaccinated and unvaccinated people.

In the first six months after the campaign, vaccination was associated with a 57 per cent reduction in mortality from all causes. “The large overall reduction in death rate from all causes lends support to the assumption that vaccination is beneficial even with respect to pre-existing diseases, such as chronic heart or lung disease,” they say.

In addition, the incidence of hospital treatment was lower in the vaccinated group than in the unvaccinated group. Vaccination resulted in a 46 per cent reduction in hospital admission for influenza and a 29 per cent reduction in admission for pneumonia. The researchers also found a 36 per cent reduction in admission for pneumonococcal pneumonia and a 52 per cent reduction in invasive pneumococcal infection in the vaccinated group.

They comment that the results are an interim analysis and that more detailed results from a three-year follow-up period will follow. The current results were taken from the first six months of the study, a period that included a medium-sized influenza A epidemic caused by a strain that matched the vaccine.

However, important questions remain to be answered, they say. The most important of these is whether the vaccinated and unvaccinated groups were similar in terms of risk from infection that required hospital care. They suggest that differences might result from the fact that healthy older people might be more likely to take part in a vaccination campaign but that, on the other hand, people with underlying chronic diseases might be more aware of the benefits of vaccination (Lancet 2001;357:1008).

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Influenza vaccine hope for people with egg allergy

An egg-free influenza vaccine may be available in Europe next year. Results from phase I, II and III trials in 2,500 people, presented at an American Chemical Society meeting in San Diego this week, have shown that the vaccine is effective in inducing specific antibodies against influenza.

The trials also showed that older patients (aged over 60 years) who received the egg-free vaccine had significantly fewer adverse effects compared with people who received conventional vaccines. No difference was found in younger patients.

The vaccine is produced from a cell line originally derived from kidney cells of the African green monkey. This cell line has a demonstrated safety record and is the only cell line currently licensed for the production of vaccines for human use, the researchers say.

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BCG vaccination programme to restart in schools

The BCG schools immunisation programme is to restart shortly, says the Department of Health.

The programme was suspended in 1999 because of manufacturing problems with the vaccine.

The intention is to restart the immunisation programme before schools break up for summer holidays and to start with students set to leave school this summer.

In a Department of Health press release, Yvette Cooper (Public Health Minister) said that a catch-up programme to immunise all pupils aged between 13 and 15 will start in the next academic year (2001/2002), with routine immunisations being back on track by the academic year 2002/2003.

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Some statins might be safe in renal disease

Some statins can be used safely in patients with renal disease, say researchers from Glasgow.

“The relative risk of cardiovascular mortality among patients with renal disease on dialysis and transplantation is increased about 20-fold compared with the general population,” said Dr Alan Jardine (consultant renal physician, department of medicine and therapeutics, Western Infirmary) at a recent meeting sponsored by Bayer.

However, few received statins because renal physicians were reluctant to introduce drugs that might interact with immunosuppressive agents, such as ciclosporin, he said.

“Ciclosporin and tacrolimus are metabolised by cytochrome P450 3A4. However, they also inhibit this enzyme and with atorvastatin, simvastatin and lovastatin, you get a much greater effect at regular doses, with much more myositis and rhabdomyolysis. However, fluvastatin, pravastatin and cerivastatin are not metabolised by this pathway and do not have the same huge impact, so it is safe to use these drugs in regular doses,” he said.

Since the relationship between deteriorating renal function and cardiovascular disease appeared to be continuous, Dr Jardine suggested it could be factored into cardiovascular risk assessment.

“Analysis of a small subgroup of patients in the Hypertension Optimal Treatment study grouped by serum creatinine levels suggests that those with a serum creatinine of greater than150µmol/L had a risk of about three-times that of patients with serum creatinine of less than 150µmol/L.”

Although the strength of conventional cardiovascular risk factors, such as hypertension and hyperlipidaemia, was weaker among renal patients than in the general population, both remained important targets for intervention.
— Contributed.

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Benefits of discharge pharmacists shown

Integration of a pharmacist into the hospital discharge process improves the timeliness of discharge and reduces drug wastage and overall expenditure for the hospital, according to the results of a new study.

Richard Cattell (clinical pharmacy manager, Bristol Royal Infirmary) and colleagues assigned patients to have their discharge medication organised by a pharmacist (intervention group) or by the existing system (control group). They found that discharge prescription processing time and dispensing time were reduced for patients in the intervention group. In addition, a saving of £6 per patient was achieved through the use of patient's own drugs (PODs). PODs had not been documented in the control group. The researchers comment: “The employment of a discharge pharmacist on a grade C salary equates to an expenditure of approximately £1.50 per patient. Since the reuse of PODs resulted in cost reductions in excess of this, it is evident that the system is financially viable.”

The study is published in The International Journal of Pharmacy Practice (2001; 9:59). The IJPP is available through the Pharmaceutical Press and abstracts appear on PJ Online.

Other papers contained in the new issue of the IJPP

• Community pharmacy management of acute diarrhoea in adults (E. M. Seston, M. Nicolson, K. Hassell, J. A. Cantrill and P. R. Noyce)
• Skin conditions in the pharmacy: consumer satisfaction and economic considerations (A. Plunkett, P. Lau, K. Stewart and R. Marks)
• Community pharmacists' views and experiences of counter-prescribing in pregnancy (S. Hutchinson, K. Mitchell, D. Hansford and D. Stewart)
• Cost implications of the delivery of pharmaceutical care services through Australian community pharmacies (R. Donato, G. March, J. Moss and A. Gilbert)
• Pharmacists' and physicians' perception of antibiotic policies in New South Wales public hospitals (A. Adu, J. M. Simpson and C. L. Armour)
• A preliminary investigation into customers' perceptions of the image of retail pharmacies in South Africa (I. Truter and W. P. van Niekerk)
• Occurrence of potential drug-drug interactions in nursing home residents (K.N. van Dijk, C. S. de Vries, P. B. van den Berg, J. R. B. J. Brouwers and L. T. W. de Jong-van den Berg)
• Work patterns and uptake of continuing education in a two-year cohort of New Zealand pharmacy technicians (V. A. Elmey and R. A. Beresford)

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Trastuzumab of benefit in HER2-positive breast cancer

Trastuzumab (Herceptin) increases clinical benefit of first-line chemotherapy in metastatic breast cancer that overexpresses HER2, say researchers. HER2 is a tyrosine kinase receptor that is overexpressed in 25 to 30 per cent of breast cancers.

Dr Dennis Slamon (University of California, Los Angeles, United States) and colleagues compared weekly trastuzumab plus standard chemotherapy with chemotherapy alone in 459 women with metastatic breast cancer that overexpressed HER2. The addition of trastuzumab to chemotherapy was associated with a longer time to disease progression, a longer duration of response and longer survival (25.1 vs 20.3 months) (New England Journal of Medicine 2001; 344:783).

Dr Elizabeth Eisenhauer (Queen's University, Kingston, Canada) says in a leading article: “The results of the study are important because improvements in survival among women with metastatic breast cancer are rare.” She adds that the study uncovers some important risks. The incidence of cardiotoxicity was significantly higher among the patients who received trastuzumab and chemotherapy and highest among women who received trastuzumab and an anthracycline (ibid, p841).

Standard chemotherapy used in the trial was doxorubicin or epirubicin plus cyclophosphamide for anthracycline-naive women or paclitaxel for women who had previously received adjuvant anthracycline therapy.

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Antibiotics for preterm birth

Erythromycin might have a beneficial effect in some types of preterm birth but co-amoxiclav does not, say researchers.

The ORACLE studies compared the use of the two antibiotics, separately and in combination, with placebo in 4,809 women with preterm, prelabour rupture of foetal membranes (pPROM) and 6,241 women with spontaneous preterm labour.

Erythromycin was found to reduce a combined outcome of death, chronic lung disease and major cerebral abnormality in infants born to women with pPROM. In contrast, co-amoxiclav (alone and in combination with erythromycin) was associated with a significant increase in neonatal necrotising enterocolitis. There was no evidence of benefit for either antibiotic in spontaneous preterm labour without evidence of clinical infection.

The researchers comment that routine prescription of co-amoxiclav for any preterm delivery cannot be recommended (Lancet 2001;357:979 and 989).

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Insulin manufacturer expresses concerns over NICE guidance

Novo Nordisk has written to the National Institute for Clinical Excellence (NICE) expressing concerns over its guidance on rosiglitazone and pioglitazone for type 2 diabetes (see PJ, August 26, 2000, p288, and March 17, 2001, p352). The company says that the guidance could lead to patients receiving delayed insulin therapy or not receiving therapy at all.

A spokeswoman for Diabetes UK told The Journal this week that the charity supports Novo Nordisk's concern that the NICE guidance is not clear. “Glitazones can delay a patient's progress to insulin but are not a replacement for insulin therapy,” she said.

A spokeswoman for the NICE confirmed this week that Novo Nordisk's letter had been received and said that the institute would respond to it after due consideration.

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