March 2001 Therapeutics Letter

March 2001                                        Bruce H. Woolley, Pharm.D., Editor                                        Vol. 8, No. 3
Kenneth J. Hunt, Associate Editor

New Vaccine Against Otitis Media

Acute Otitis Media (AOM) ranks second to the common cold as the most common health problem in preschool children. Fifty percent of children have had at least one episode by one year of age. Between one and three years, 35% will have had repeated episodes. For school children, estimated 5 million school days are missed every year due to AOM.

Several laboratories around the world have been developing vaccines to help battle this common and potentially dangerous infection. In fact, a newly released pneumococcal conjugate vaccine is emerging that appears to be safe and effective in preventing AOM, according to a recent report in the New England Journal of Medicine.

A Finnish Research group randomly selected more than 1600 infants to receive either a hepatitis B vaccine or a pneumococcal polysaccharide conjugate vaccine. The infants were vaccinated at 2, 4, 6 and 12 months of age. During the follow-up period of between 6.5 and 24 months, the researchers reported nearly 2600 episodes of AOM. The number of episodes of acute otitis media from any cause was reduced 6% by the pneumococcal vaccine. Further, cultured-confirmed pneumococcal episodes were reduced by 34%, and the number of episodes of AOM caused by the serotypes in the vaccine was reduced by 57%.

There was also a 51% reduction in episodes caused by serotypes that are cross-reactive with those in the new vaccine. The investigators acknowledge that the efficacy of the vaccine against AOM is not as high as the efficacy of other childhood vaccines but the effect may potentially be substantial. The group calculates that up to 1.2 million of the 20 million yearly episodes of AOM in the US, and particularly invasive infections due to Streptococcus pneumoniae, could theoretically be prevented if the vaccine were used widely.

N Engl J Med 2001;344:403-409

Dietary Supplement Recalled

Anso Comfort Capsules, sold by California-based NuMeridian via phone and mail order, are dietary supplement tablets promoted to treat a wide range of conditions, including high blood pressure and high cholesterol. The supplement is the subject of a nationwide recall after an investigation revealed that the product contains the prescription anxiety drug chlordiazepoxide. The FDA and the California Department of Health Services are warning consumers not to take Chlordiazepoxide (Librium), which is classified by the Drug Enforcement Agency as a controlled substance.

The drug is reported to have potentially dangerous interactions with other medications. It may also intensify the effects of alcohol and other central nervous system depressants, and it may be habit forming. The presence of chlordiazepoxide was not revealed on Anso Comfort Capsules' label. The California State Health Director said that consumers should stop using Anso Comfort Capsules and seek the advice of their physician, particularly if they are taking other prescription medications.

NuMeridian is conducting a voluntary recall of the product under FDA monitoring. The company appears to have violated government regulations under the Dietary Supplement Health and Education Act (DSHEA) by promoting its capsules as a treatment for various illnesses. Under DSHEA, dietary supplements are only permitted to claim that they help maintain a structure or function of the body. Cold Comfort Capsules were manufactured in California using raw materials imported from China.

NuMeridian's owner reported that his company began the recall of Anso Comfort capsules in February by writing letters to all of the firm's US customers. The company's customer base consists of 15 "Chinese clinics" located in California, New York, Illinois and Florida.

The Value of Apgar Scores

The Apgar score is a number assigned by either the physician or nurse who is present during a newborn's delivery. It is simply a number that gives a general idea of how a neonate is adjusting to being outside of the womb in the first few minutes. According to a recent study, the Apgar scoring system is as valuable today for predicting neonatal survival as it was when it was introduced nearly 50 years ago.

A group of researchers at the University of Texas Southwestern Medical Center at Dallas n Texas reviewed outcomes for 145,627 infants born between 1988 and 1998., included infants born no earlier than 26 weeks of gestational age and without major malformations. 178 neonates were assigned 5-minute Apgar scores of 0 to 3, and 1117 were assigned scores of 4 to 6. The remaining infants received scores of 7 to 10. A total of 13,399 infants were born preterm.

The incidence of neonatal death within the first 28 days after birth was highest for infants with 5-minute Apgar scores of 0 to 3, regardless of gestational age. The incidence was 315 per 1000 preterm infants with Apgar scores of 3 or lower, compared with 5 per 1000 for those with scores of 7 to 10. Corresponding rates were 244 and 0.2 per 1000 among infants born at 37 weeks or later.

One concern that has been expressed by physicians is that the score does not accurately identify perinatal asphyxia. There is a seemingly weak relation between low Apgar scores and several indicators of potential perinatal asphyxia. Most agree, however that the 5-minute Apgar score remains valid for rapidly assessing "the effectiveness of resuscitative efforts and the vitality of the newborn."

N Engl J Med 2001;344:467-471,519-520.

Aspirin May Be Unsafe for Heart Disease Prevention

In healthy people at low risk for coronary heart disease, aspirin may actually be harmful, according to a report published in a recent issue of Heart. Researchers from the Royal Hallamshire Hospital in Sheffield, United Kingdom, performed a meta-analysis of four randomized controlled trials that assessed the beneficial and harmful effects of aspirin as a preventive measure for coronary heart disease. From this, the investigators determined the usefulness of aspirin therapy based on a person's risk of a coronary event.

For people with a 1.5% or greater coronary event risk per year, aspirin is a safe and worthwhile means of primary prevention. In people with a 1% risk, aspirin is safe, they found, but it is unlikely to be of much therapeutic value. However, in people with a 0.5% coronary event risk per year, aspirin therapy is actually unsafe, according to the report. The bleeding risks of aspirin in this group are likely to outweigh any beneficial effects.

The researchers emphasize that "Aspirin cannot be prescribed safely for primary prevention of coronary heart disease without formal estimation of coronary disease event risk of the individual." Accurate risk estimation requires identifying the major risk factors for coronary heart disease, using risk functions derived from epidemiologic studies. The authors also revised the Sheffield table for estimating the percentage risk of coronary events; it appears in their report.

Heart 2001;85:265-271.

Drug Addiction and the Genome Map

The human gemone-mapping project carries promise of identifying genes for various traits and diseases with the goal of identification, treatment and prevention. Knowledge gained from the human genome-mapping project is now leading to a better understanding of how drugs and alcohol act on the molecular and cellular mechanisms and brain pathways to cause addiction.

A University of Texas Southwestern Medical Center researcher and his colleagues reported on the progress made in the field of drug addiction in the February 15 issue of Nature, which is dedicated to results of genome research and gains to be expected. The authors stressed that addiction represents a biological process caused by the effects of repeated drug exposure on a vulnerable brain and defined it as the compulsive seeking and taking of a drug or alcohol despite adverse consequences.

They further explain that genome sequencing will advance an understanding of the biology of addiction by enabling researchers to identify specific genes that contribute to individual addiction risk as well as those involved directly in the addiction process caused by drugs. Addiction researchers believe that drugs of abuse act on parts of the limbic system that develop at a much earlier time. These circuits may regulate individual responses to such things as food, sex, or risk-taking activities, any of which may act as "natural reinforcers."

According to the article, there is scientific evidence that natural addictions such as overeating, pathological gambling, compulsive shopping, and perhaps excessive exercise, may involve analogous mechanisms to the chemical kind. A current focus in addiction research is exploring the neurobiology of such addictive conditions, including a person's intense cravings for drugs and the increased risk of relapse the person experiences.

The authors state that addiction may well be associated with memory and/or learning behavior, but limited information is available regarding the molecular and cellular basis of essentially life-long memories. Many changes taking place after multiple drug exposure are now being uncovered. The hope is that new genetic tools combined with advanced models of addiction in animals will allow for the identification of patterns of altered gene expression that are associated with addiction, such as tolerance, sensitization, dependence, craving, and relapse.

Nature 2001;409(6822)

Obesity and Risks of Death

It has been recognized for some time that obesity carries with it several risk factors for mortality. A recent report by the British National Audit Office (NAO) urges more government action on obesity, warning that more than 30,000 deaths per year in England, or 6% of all deaths, can be attributed to excess body weight. The NAO report also states that this death toll is six times higher than that from road accidents.

It is estimated that most adults in England are now overweight, and 20% are classified as obese. The cost to the British National Health Service is at least half a billion pounds a year while the wider costs to the economy could add a further 2 billion pounds a year. Though the problem in England is increasing faster than in most other European countries, it is not significantly more severe than obesity in the United States.

The British government reports that a continued rise in the prevalence of obesity will result in more than one 25% obesity among British adults by 2010. This would significantly increase the incidence of associated diseases, such as coronary heart disease, and would cost the economy over 3.5 billion pounds a year. The cost of treating the consequences of obesity outweighs the actual costs of obesity by nearly 50 times.

It estimates that an obese woman is nearly 13 times more likely to develop type 2 diabetes, four times more likely to become hypertensive and three more likely to have a heart attack than a woman within the healthy weight range. For obese men, the relative risks were 5.2, 2.6 and 1.5, respectively. Even among young adults, the risk of dying for someone with a body mass index of 30 was 50% higher than for someone with a healthy body mass index of 20 to 25. The risk was more than doubled with a body mass index of 35.

Unfortunately, there are wide variations in the way physicians manage overweight patients and some uncertainty about which treatments are most effective. Only 40% of GPs attempt to identify patients at highest risk of excessive weight gain, according to the report. Their solution is a good one: a call for the development of a ubiquitous strategy to promote physical activity through sport, walking or cycling to work, and an improvement in diet.

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