16 January 2005
I. WHAT'S NEW?
American Academy of Dermatology Poster Presentation
Weekly Quiz
II. HISTORY OF MEDICINE
History of Fever
III. ALTERNATIVE MEDICINE
Acupuncture Treatment for Osteoarthritis
IV. ONCOLOGY
ERS1 and ERS2 Estrogen Receptor Genes and Breast Cancer Risk
V. EPIDEMIOLOGY
You Are What You Eat - Red Meat and Cancer Risk
VI. NEUROLOGY
Overweight and Sleep Deprivation
VII. FDA
FDA Advisory Meeting on COX-2
Inhibitors
American Academy of
Dermatology Poster Presentation
Target Health is pleased to announce that it
will be presenting a poster (#3307) at the annual meeting of the American
Academy of Dermatology, which is being held this year in New Orleans (February
18-23, 2005). The poster entitled, Using the Internet to Enter Data and Manage
a Multinational Clinical Trial in Deep Dermal and 3rd Degree
Burns," is co-authored with Ronit Koren, Ph.D. and Linda Gerstl, B.Sc.
of MediWound, Ltd., Israel and Otto Mills, Ph.D. of the Robert Wood
Johnson School of Medicine. Please contact Dr. Jules T. Mitchel (julesmitchel@targethealth.com)
to let us know if you will be attending the meeting so we can arrange a
get-together, or for more information about Target Health.
Weekly Quiz
Name the organizations that these names
in the news represent: 1) Mark McClellan; 2) Henry McKinnell; 3) Raymond
Gilmartin 4) Lester Crawford - (answer on last page):
History of Fever
The medical concept of fever has undergone
profound changes throughout the centuries. Galen of Pergamon considered fever
as a systemic disease in itself, and it was only between 17th and 18th century
that Hermann Boerhaave provided a more careful evaluation of the clinical
phenomena related to fever. Apart from incorrect theories, a major obstacle to
the development of a rational study of fever has been the lack of appropriate
instruments of measurement. In effect, the clinical thermometer was not
diffusely used in everyday medical practice until the mid 19th century. During
this same period Ignaz Semmelweiss postulated that the pathological-anatomical
changes recorded in women who had died because of puerperal fever represented a
pathological reality clinically suggested by a whole cohort of symptoms and
signs, among them fever. Even if enormous progress has been made in the 20th
century with regard to fever, which is currently considered a clinical sign of
many different diseases, its etiologic assessment remains a challenge. In fact,
in 1961 the clinical picture of 'Fever of Unknown Origin' was officially
defined. Since such diagnostic labeling is in effect a cover for our inability
to discover the real causes of fever, in this case, paradoxically, fever goes
back to being the whole pathological picture, just as it was retained to be
many centuries ago.
Acupuncture Treatment for
Osteoarthritis
Evidence on the efficacy of acupuncture for
reducing the pain and dysfunction of osteoarthritis (OA) has been equivocal. As
a result, a study, published in Archives of Internal Medicine
(2004;141:901-910), was performed to determine whether acupuncture provides
greater pain relief and improved function compared with sham acupuncture or
education, in patients with OA of the knee. The investigation was a randomized,
controlled trial, performed at two outpatient clinics located in academic
teaching hospitals, and at a clinical trials facility. Study participants
included 570 patients with OA of the knee (mean age 65.5 8.4 years). For the
study, patients received 23 true acupuncture sessions over 26 weeks, while the
controls received 6 two-hour sessions over 12 weeks or 23 sham acupuncture
sessions over 26 weeks. The primary outcomes were changes in the Western
Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain and
function scores at 8 and 26 weeks. Secondary outcomes were patient global
assessment, 6-minute walk distance, and physical health scores of the 36-Item
Short-Form Health Survey (SF-36). Results of the study showed that by week
eight (8), participants in the true acupuncture group experienced greater
improvement in WOMAC function scores than the sham acupuncture group (mean
difference, -2.9; P = 0.01), but not in WOMAC pain score (mean
difference, -0.5; P = 0.18) or the patient global assessment (mean
difference, 0.16; P > 0.2). In contrast, at 26 weeks, the true
acupuncture group experienced significantly greater improvement than the sham
group in the WOMAC function score (mean difference, -2.5; P = 0.01),
WOMAC pain score (mean difference, 0.87;P = 0.003), and patient global
assessment (mean difference, 0.26; P = 0.02). One of the flaws of the
study was that at 26 weeks, 43% of the participants in the education group and
25% in each of the true and sham acupuncture groups were not available for
analysis. Nevertheless, according to the authors, acupuncture seems to provide
improvement in function and pain relief as an adjunctive therapy for OA of the
knee when compared with credible sham acupuncture and education control groups.
ERS1 and ERS2 Estrogen
Receptor Genes and Breast Cancer Risk
Many breast cancers depend on estrogen and
progesterone to grow. Cells in these cancers have proteins called estrogen and
progesterone receptors on their surface. Receptors are an outside molecule's
gateway to the cell: molecules bind to and sometimes pass through receptors
into the cell. In breast cancers dependent on these two steroid hormones to
grow, estrogen and progesterone bind to their respective receptors, initiating
signaling pathways that cause the cancer cells to multiply. According to an
article published in Cancer Research (2004;64:8891-8900), a woman's risk of
developing breast cancer is due in part to a group of very small variations in
genes which code for a cell's estrogen receptors. The study evaluated the
association between breast cancer risk and very small differences in the genes
coding for estrogen and progesterone receptors. These variations of the gene
differ by a single nucleotide, the molecular subunit of DNA, and are called
single nucleotide polymorphisms. Though these differences are small, they can
have an impact on how an estrogen receptor performs. Specifically, the
connections between the ESR1 estrogen receptor gene and breast cancer examined.
Results showed that of 17 single nucleotide polymorphisms of ESR1 under study,
there were two polymorphisms associated with breast cancer susceptibility. One
was associated with disease only in women over 50. Interestingly, this
polymorphism was very rare in the African-American population. The other
polymorphism was associated with disease only in Ashkenazi (Central or Eastern
European) Jewish women over 50. In this population, the third most common ESR2
gene was associated with breast cancer susceptibility. The ESR2 polymorphism
was discovered in 1996. No association was found between breast cancer and 13
single nucleotide polymorphisms in the progesterone receptor gene. The study
population included DNA samples from 1,006 women with breast cancer (identities
were masked) who were patients at Memorial Sloan-Kettering in New York City and
613 control subjects from 14 sites that are part of the New York Cancer Study.
The two groups had similar proportions of women over and under 50 and of women
who had menopause before or after age 50. Case and control groups also
contained similar proportions of women in six ethnic groups: those of European,
African, Asian, Hispanic, Ashkenazi, and unknown descent. According to the
authors, three groups of single nucleotide polymorphisms in the ESR1 gene
protected against the risk of the disease across the ethnic and age groups. However,
only one of these was protective when only European- Americans were examined.
The authors expressed hope that pharmaceutical companies will take the results
into account as they develop new drugs that modulate the effects of estrogen on
breast cancer cells.
You Are What You Eat - Red
Meat and Cancer Risk
Consumption of red and processed meat has
been associated with colorectal cancer in many but not all epidemiological
studies; few studies have examined risk in relation to long-term meat intake or
the association of meat with rectal cancer. As a result, a study, published in
the Journal of the American Medical Association (2005;293:172-182), was
performed to examine the relationship between recent and long-term meat
consumption and the risk of incident colon and rectal cancer. The study
included a cohort of 148,610 adults aged 50 to 74 years who provided
information on meat consumption in 1982 and again in 1992/1993 when they were
enrolled in the Cancer Prevention Study II (CPS II) Nutrition Cohort. Follow-up
from time of enrollment in 1992/1993 through August 31, 2001, identified 1,667
incident colorectal cancers. Participants contributed person-years at risk
until death or a diagnosis of colon or rectal cancer. The main outcome measure was
the incidence rate ratio (RR) of colon and rectal cancer. Results from the
study showed that high intake of red and processed meat reported was associated
with higher risk of colon cancer after adjusting for age and energy intake but
not after further adjustment for body mass index, cigarette smoking, and other
covariates. When long-term consumption was considered, persons in the highest
tertile (third) of consumption in both 1982 and 1992/1993 had higher risk of
distal colon cancer associated with processed meat (RR, 1.50), and ratio of red
meat to poultry and fish (RR, 1.53) relative to those persons in the lowest
tertile at both time points. Long-term consumption of poultry and fish was
inversely associated with risk of both proximal and distal colon cancer. High
consumption of red meat reported in 1992/1993 was associated with higher risk
of rectal cancer (RR, 1.71; P = .007 for trend), as was high
consumption reported in both 1982 and 1992/1993 (RR, 1.43). According to the
authors, the results, 1) demonstrate the potential value of examining long-term
meat consumption in assessing cancer risk and 2) strengthen the evidence that
prolonged high consumption of red and processed meat may increase the risk of
cancer in the distal portion of the large intestine.
Overweight and Sleep
Deprivation
Insufficient sleep and
obesity are common in the United States. It is well known that restricted sleep
causes important neurocognitive changes, including excessive daytime sleepiness
and altered mood. This may result in work-related injuries and automotive
crashes. Evidence links sleep loss to hormonal changes that could result in
obesity. As a result, a study, published in the Archives of Internal Medicine
(2005;165:25-30), was performed to examine the association between restricted
sleep and obesity in a heterogeneous adult primary care population. A total of
1001 patients from 4 primary care practices participated in this prospective
study. Patients completed a questionnaire administered by a nurse or study
coordinator concerning demographics, medical problems, sleep habits, and sleep
disorders. Professional staff measured height and weight in the office. The
relationship between body mass index (BMI) and reported total sleep time per 24
hours was analyzed after categorizing patients according to their BMI
(calculated as weight in kilograms divided by the square of height in meters)
as being of normal weight (<25), overweight (25-29.9), obese (30-39.9), or
extremely obese (>40). Study participants included 924 patients
between 18 - 91 years of age. Results showed that (1) the mean BMI was 30; (2)
women slept more than men; (3) overweight and obese patients slept less than
patients with a normal BMI (patients reported less sleep in a nearly linear
relationship from the normal through the obese group); and (4) this trend of
decreasing sleep time was reversed in the extremely obese patients. According
to the authors, the study found that reduced amounts of sleep are associated
with overweight and obese status and that interventions manipulating total
sleep time could elucidate a cause-and-effect relationship between insufficient
sleep and obesity.
TARGET HEALTH excels in Regulatory Affairs
and works closely with many of its clients performing all FDA submissions.
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.
FDA Advisory Meeting on
COX-2 Inhibitors
The FDA has announced a joint public meeting
of the agency's Arthritis Advisory Committee and the Drug Safety and Risk
Management Advisory Committee to be held February 16, 17 and 18, 2005. The
committees will discuss the overall benefit-to-risk considerations (including
cardiovascular and gastrointestinal concerns) for COX-2 selective non-steroidal
anti-inflammatory drugs (NSAIDs) and related medicines. Members of the public
are encouraged to participate in this meeting. Interested persons may present
data, information or views, orally or in writing, on issues pending before the
committees. Oral presentations from the public will be scheduled between 1:00
p.m. and 3:00 p.m. on February 17. Time allotted for each presentation may be
limited. Those desiring to make formal oral presentations should register to
speak at the meeting before February 4, 2005. No registration is required for
those only planning on attending the meeting. The three-day meeting will be
held at the Hilton Washington DC North, 620 Perry Parkway, Gaithersburg, Md.
The proceedings will start at 8:00 a.m. each day. Agendas and other background
materials will be posted online no later than one business day before the
meeting. Please more information about the meeting, please contact Dr. Jules T.
Mitchel (julesmitchel@targethealth.com).
VIII. TARGET HEALTH
TARGET HEALTH INC. (www.targethealth.com) is a full service
e*CRO with fulltime staff dedicated to all aspects of drug and device
development. Areas of expertise include Regulatory Affairs, comprising, but not
limited to, IND, IDE, NDA, PMA and 510(k) submissions, execution of Clinical
Trials, Project Management, Biostatistics and Data Management, Web Trials,
utilizing Target e*CRF™, our proprietary Internet-based Clinical Trial System,
and Medical Writing. TARGET HEALTH's Pharmaceutical Advisory Dream Team (PADT)
assists companies in strategic planning from Discovery to Market Launch. Let us
help you on our next project.
TARGET HEALTH INC.
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24th Floor
New York, NY 10016
Phone: (212) 681-2100; Fax (212) 681-2105
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Dr. Jules T. Mitchel, President (julesmitchel@targethealth.com)
Ms Joyce Hays, CEO (joycehays@targethealth.com)
ANSWER TO QUIZ
1) Mark McClellan - Former FDA Commissioner,
now head of Medicare & Medicaid
2) Henry McKinnell - CEO Pfizer
3) Raymond Gilmartin - CEO Merck
4) Lester Crawford - Acting FDA Commissioner
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