(Complimentary Newsletter from Target Health Inc.)
January 5, 2002
Contents:
I. WHAT'S NEW
Meetings
II. HISTORY OF MEDICINE
Acrodynia (Pink Disease)
III. IMMUNOLOGY
Depression and Immunity
IV. GENETICS
HIV
V. WOMEN’S HEALTH
Pregnancy, Smoking and Disease Risk
VI. CARDIOLOGY
Moderate Drinking and Heart Disease Risk
VII. NEUROLOGY
Schizophrenia
VIII. EPIDEMIOLOGY
Women and Heart Disease Risk
IX. FDA
New Drug Approval
TARGET HEALTH
Meetings
Dr. Jules Mitchel will be attending the annual meetings of the American Society of Clinical Pharmacology and Therapeutics in Atlanta and the American Academy of Dermatology. Please let us know if you will be attending.
Acrodynia (Pink Disease)
Pink disease (acrodynia) is a serious disease of infants and young children, marked by irritability stomatitis, loss of teeth, insomnia, and redness of the fingers, toes, cheeks, nose, and buttocks. The term is derived from the Greek roots meaning extremity and pain. First reports of this disease in the US were in 1920 when 10 cases were reported by Bilderback. These cases, although collectively grouped as acrodynia, still had little resemblance to a similarly described disorder due to arsenic poisoning. The first accurate description should probably be credited to Swift who, in 1914, presented a paper before the Australasian Medical Conference entitled, Erythroedema. In recognition of his discovery acrodynia is often termed Swifts’s disease. The term pink disease is often used interchangeably because of the characteristic red hands and feet. Pink disease baffled the medical world during the first half of the twentieth century until it was shown to be caused by mercury poisoning. In the English-speaking world, the commonest source of the mercury was teething powders, which were widely available and advertised with increasing sophistication. When mercury was finally identified and accepted as the cause of pink disease, pink disease virtually disappeared. However, its consequences emerged much later as a cause of male infertility.
Depression and Immunity
According to an article published in the Journal of Behavioral Medicine (2001;24:537-555), feelings of depression and anger may weaken the immune system for those caring for a spouse with Alzheimer's disease. For the study, the relationship between anger, depressed feelings and the immune system was studied in 82 elderly individuals who cared for a spouse with Alzheimer's disease. Caregivers were compared with a control group of 83 married noncaregivers who were matched for age and sex. At the start of the study, and 18 months later, the participants' physical and psychological health, as well as their physical activity were evaluated. In addition, lymphocyte responses to mitogens [phytohemagglutinin (PHA), concanavalin A, pokeweed] was examined. Data were collected at study entry (T1) and 1518 months later (T2). In men (n = 52), a depressed mood factor was negatively related to all mitogen responses at T1 and PHA at T2. Loneliness was the most important variable in the depressed mood factor. At T2 an anger expression factor (anger-out - anger-control) was negatively related to all mitogen responses in all caregivers. Anger-out was the most important variable for anger expression. Depressed mood at T1 predicted residualized changes in PHA at T2 in men. It was concluded that men with higher depressed mood and caregivers with higher anger expression may be at risk for lower proliferation responses. According to the authors, the combination of anger and chronic stress can result in reduced immune function.
HIV
The MDR1 gene encodes a protein called P-glycoprotein. This protein is important in transporting various substances, including some antiretroviral drugs, throughout the body. P-glycoprotein may affect the immune system's rebound by protecting certain cells from toxic substances, and thus preventing HIV drugs from entering cells. P-glycoprotein is active in many T cells, and low expression of P-glycoprotein, which is seen with the TT gene variant, could potentially allow greater penetration of HIV drugs. According to an article published in The Lancet (2002;359:30-36), variations in a single gene may help determine how well an HIV patient's immune system recovers with treatment. Results showed that patients with a particular variant of the MDR1 gene showed a stronger immune system rebound over 6 months of treatment than patients with one of two other variants. The three variations were also linked to patients' blood concentrations of the HIV drugs nelfinavir and efavirenz. Among the 123 patients in the study, those with the variant MDR1 3435 TT showed lower blood plasma concentrations of nelfinavir and efavirenz and greater recovery in immune system T cells over their first 6 months of treatment. Two other variants, CT and CC, were linked to higher plasma concentrations of the drugs and a lesser immune response to treatment. When these factors were included, the TT variant still strongly predicted a greater immune system recovery. All participants in this study were white and about one quarter of white individuals carry the TT variant.
Pregnancy, Smoking and Disease Risk
According to an article published in the British Medical Journal (2002;324:26-27), the children of women who smoke during pregnancy are at greater risk of developing type 2 diabetes and obesity. The study appears to be the first to link maternal smoking and the risk of diabetes, and suggests that smoking may result in lifelong metabolic abnormalities. For the study, data were derived from the British National Child Development Study of around 17,000 children born in 1958. For the study, midwives obtained information on smoking during pregnancy and smoking among the mothers was also recorded in 1974. Data were collected on the children at ages 7, 16, and 33. Results showed that 15 men and 13 women among those followed throughout childhood and adolescence developed diabetes between the ages of 16 and 33. It was observed that the risk of diabetes was increased more than 4.5-fold in the offspring of women who smoked more than 10 cigarettes a day compared with nonsmokers. The risk in offspring of mothers whose smoked fewer than 10 cigarettes a day was increased by a factor of 4.13. It was also found that smoking during pregnancy increased the risk of obesity independently of diabetes. Offspring of smokers were 34% to 38% more likely than children of nonsmokers to become obese.
Moderate Drinking and Heart Disease Risk
According to an article published in the Journal of the American College of Cardiology (2001;38:1836-1842), men with type 2 diabetes who consume between one-half and two alcoholic drinks per day reduce their risk of heart disease. For the study, data were collected on 2,419 diabetic men who participated in the Health Professionals' Follow-up Study. Altogether, 150 new cases of coronary artery disease were seen during the study's follow-up period, including 69 fatal and 81 non-fatal heart attacks. Results showed that heart disease risk proved to be inversely associated with alcohol use. Compared with nondrinkers, men who consumed half a drink or less per day cut their heart disease risk by 24%, while those who drank one-half to two drinks daily cut their risk by 36%. Men who drank more than two drinks a day had a 41% lower risk of heart disease. Beer, wine and liquor were all associated with lower heart disease risk. According to the authors, the findings are consistent with those of past studies linking light to moderate alcohol intake to lower coronary artery disease risk in patients with type 2 diabetes. The authors added that light-to-moderate drinking with meals may be an attractive and beneficial lifestyle component for the patient with diabetes, but it remains for the clinician to decide whether to include alcohol recommendations as part of the treatment plan. The authors concluded that for most, the benefits would likely outweigh the risks.
Schizophrenia
Prevention of relapse is a major goal of maintenance treatment in patients with psychotic disorders. A study, published in the New England Journal of Medicine (2002; 346:16-22), was performed to compare a newer, atypical antipsychotic drug, risperidone, with an older, conventional neuroleptic drug, haloperidol, in terms of the rate of relapse in patients with schizophrenia and schizoaffective disorder. The study was a randomized, double-blind, prospective study at 40 clinical study sites, in adult outpatients, in stable condition, with chronic schizophrenia or schizoaffective disorder. Patients received flexible doses of either risperidone or haloperidol for a minimum of one year. Of the 397 patients who underwent randomization (177 patients assigned to risperidone and the 188 assigned to haloperidol), data from 2 patients were excluded because they did not receive study medication and data from all 30 patients from one site were excluded by the sponsor, the Janssen Research Foundation, because of concern about the integrity of the data. The median duration of treatment was 364 days in the risperidone group and 238 days in the haloperidol group (P=0.02). Of those assigned to risperidone 44.1% discontinued treatment for reasons other than relapse, while the number in the haloperidol group was 52.7%. The KaplanMeier estimate of the risk of relapse at the end of the study was 34% for the risperidone group and 60% for the haloperidol group (P<0.001); the risk ratio for relapse with haloperidol, from the Cox model, was 1.93 (95% confidence interval, 1.33 to 2.80; P<0.001). Early discontinuation of treatment for any reason was more frequent among haloperidol-treated patients (risk ratio, 1.52; 95% confidence interval, 1.18 to 1.96). Patients in the risperidone group had greater reductions in the mean severity of both psychotic symptoms and extrapyramidal side effects than those in the haloperidol group. It was concluded that adult outpatients with clinically stable schizophrenia or schizoaffective disorder have a lower risk of relapse if they are treated with risperidone than if they are treated with haloperidol.
Women and Heart Disease Risk
According to an article published in the American Journal of Preventive Medicine (2002;22), women who immigrate to the US are more likely to die from heart disease and stroke than their native-born peers. While the reasons for this finding are not clear, the authors suggest that mitigating factors might include consumption of higher levels of dietary fat, as well as lower rates of hormone replacement therapy among postmenopausal immigrants. For the study, 1997 national all-cause mortality rates were calculated for US-born and foreign-born people. Overall, mortality rates for immigrants were significantly lower compared with those for American-born individuals. The death rate from congestive heart disease among foreign-born women was higher compared with that of US-born women (162 versus 122 per 100,000 people). Foreign-born women were also more likely to die from stroke than their native-born peers (58 versus 49 per 100,000) as well as from hypertension. In contrast, diabetes, chronic obstructive pulmonary disease, violence and cancer caused fewer deaths among foreign-born women than their American-born counterparts.
TARGET HEALTH excels in Regulatory Affairs and works closely with many of its clients and FDA. TARGET HEALTH receives daily updates of new developments at FDA. Each week, highlights of what is going on at FDA are shared to assure that new information is expeditiously made available.
New Drug Approval
The formation of clots in the deep veins of the legs is common after surgery for hip fracture, hip replacement, and knee replacement. These clots can lead to serious and potentially fatal consequences, such as when the clots break off and travel to the lungs. The FDA has announced the approval of ARIXTRA?(fondaparinux sodium) Injection for reducing the risk of blood clots after orthopedic surgery for hip fracture, hip replacement, and knee replacement. ARIXTRA?is the first synthetic anticoagulant indicated for use in these types of surgeries and works by inhibiting Factor Xa, a key component involved in blood clotting. FDA based its approval on randomized double-blind clinical trials conducted in 8,000 patients, of whom over 4,000 received ARIXTRA?for hip fracture, hip replacement, or knee replacement surgeries. The population ranged in age from 17 to 97 years and in body weight between 66 and 373 pounds and included both men and women. The major side effect of ARIXTRA?was serious bleeding. ARIXTRA? is, therefore, not to be used in patients with severely impaired kidney function or in patients who weigh less than 110 pounds, because they may have an increased risk for serious bleeding. Elderly patients also may be more likely to experience serious bleeding complications. In addition, the labeling for this product includes a black box warning that states ARIXTRA?is not to be used when spinal anesthesia or spinal puncture is employed. There is a risk of developing a blood clot in the spine, which can result in long-term or permanent paralysis. ARIXTRA?was developed by Sanofi-Synthelabo LLC, and Organon.
TARGET HEALTH INC. is a full service CRO with full-time staff dedicated to all aspects of Regulatory Affairs, including IND, IDE, NDA, 510(k) and PMA submissions, Clinical Research Management, Medical Writing, Internet-based Data Capture and Project Management (Target e*CRF), Biostatistics, Data Management, Strategic Planning and Drug and Device Development. TARGET HEATH's Pharmaceutical Advisory Dream Team (PADT) assists companies in strategic planning from discovery to market launch. Let us help you on your next project.
TARGET HEALTH INC.
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New York, NY 10165
Phone (212) 681-2100; Fax (212) 681-2105
Dr. Jules T. Mitchel, President (julesmitchel@targethealth.com)
Ms. Joyce Hays, CEO, TARGET HEALTH INC. (joycehays@targethealth.com)
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