(Complimentary Newsletter from Target Health Inc.)
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23 January 2006
I.
WHAT'S NEW?
American
Academy of Dermatology Annual Meeting
II. QUIZ
(Fill In The Blanks)
Diet
& Disease
III.
HISTORY OF MEDICINE
Medieval
Household Pest Control
IV. INFECTIOUS DISEASE
HIV/AIDS Study Stopped - Intermittent Therapy Was Not a Good Idea
V. NEUROLOGY
Mouse Model of Alzheimer's Disease Shows Role of Cell Division
VI. RHEUMATOLOGY
Congestive Heart Failure and Rheumatoid Arthritis
VII. EPIDEMIOLOGY
Nut Consumption and Changes in Inflammatory Biomarkers
VIII. FDA
New Program in Device Safety
IX. Target Health Inc.
American
Academy of Dermatology Annual Meeting
Target Health is
pleased to announce it will present a poster in the treatment of Head Lice
at the annual meeting of the American Academy of Dermatology in San Francisco
(March 3-6). Please let us know if you will be attending the annual meeting
and please stop by our poster. For more information about this program,
please contact Dr.
Jules T. Mitchel.
Diet & Disease
Coffee, tea,
colas, energy drinks, chocolate, and certain over-the-counter cold medicines
all contain caffeine, as do decaffeinated coffee, tea, and colas - albeit in
smaller amounts. Caffeine causes a temporary increase in 1) ___ pressure in
people who do not consume it regularly. However, research shows that even with
regular consumption, about half of all people continue to experience blood
pressure spikes. If you have high blood pressure or are at 2) ___ for it,
consider eliminating the colas, coffees, teas, etc. that contain caffeine.
Caffeine consumption of 300 milligrams per day causes 3) ___ in blood pressure
for up to several hours, particularly in people who don't normally consume it
or who do but never developed a tolerance for it. You cannot be certain whether
you are caffeine intolerant unless you undergo laboratory monitoring, so
minimizing 4) ___ intake may be the best option for people who have high blood
pressure or risk factors for high blood pressure. These risk factors include 5)
___, not 6) ___ regularly, or having 7) ___.
Answers: 1) blood; 2) risk;
3) increases; 4) caffeine; 5) overweight; 6) exercising; 7) diabetes
Medieval Household Pest
Control
A 15th century English
Leechbook (collection of medical recipes) suggests the following
"traps": 'For fleas and lice to slay them, take horsemint and strew
it in your house, and it will slay them' or 'Take the juice of rue and anoint
your body with it' or 'Take gorse and boil it in water, and sprinkle that water
about the house, and they will die. Palladius (5th century) recommended bring
fleas to a sticky end on surfaces which were often sprinkled with oil dregs.
John Gerard's Herball makes the following claims for: Fleabane (Erigeron sp.)
'burned where flies, gnats, fleas or any other venomous things are, doth drive
them away' Fleawort (Plaintains or Plantago sp.) 'some hold that the herb
strewn in the chamber where many fleas be, will drive them away, for which
cause it took the name Flea wort: but I think it is rather because the seed
does resemble a flea so much, that it is hard to discerne the one from the
other'; Willow herb (Primilaceae or Lysimachia sp.), 'it is reported that the
fume or smoke of the herbe burned doth drive away fleas and gnats and all
manner of venomous beasts'.
HIV/AIDS Study Stopped -
Intermittent Therapy Was Not a Good Idea
Target Health
is pleased to announce that Dr. Jules T. Mitchel, is again providing
consultation services to NIH in the area of HIV.
According to a report released by the National Institute of Allergy and
Infectious Diseases (NIAID), enrollment into a large international HIV/AIDS
trial comparing continuous antiretroviral therapy with episodic drug treatment
guided by levels of CD4+ cells has been stopped. Enrollment was stopped because
those patients receiving episodic therapy had twice the risk of disease
progression (the development of clinical AIDS or death), the major outcome of
the study. NIAID made the decision to halt enrollment in collaboration with the
study's Executive Committee and following a recommendation received from an
independent Data and Safety Monitoring Board (DSMB). The DSMB, charged with
regularly evaluating data and safety issues during the multi-year trial,
conducted a review of the interim study data in early January. The trial, known
as Strategies for Management of Anti-Retroviral Therapy, or SMART, was designed to determine which of
two different HIV treatment strategies would result in greater overall clinical
benefit. HIV-positive volunteers were assigned at random to either a viral
suppression strategy, in which antiretroviral therapy (ART) was taken on an
ongoing basis to suppress HIV viral load; or a drug conservation strategy, in
which ART was started only when the levels of key immune cells, called CD4+
cells, dropped below 250 cells per cubic millimeter (mm3). Volunteers in the
drug conservation group were taken off ART, with the aims of reducing drug side
effects and preserving treatment options, whenever their CD4+ cells were above
350 cells/mm3. The trial involved an international collaboration of 318
clinical sites in 33 countries. It began enrollment in January 2002 and had
successfully recruited more than 90% of its target of 6,000 participants. As of
January 11, 2006, when enrollment was stopped, 5,472 volunteers had joined the
study. At the time of the DSMB review, the average follow-up was approximately
15 months. The analysis revealed that participants on CD4+ cell-guided episodic
treatment faced more than twice the risk of disease progression relative to
participants on continuous ART. Furthermore, there was an increase in major
complications such as cardiovascular, kidney and liver diseases in the
participants on the drug conservation arm. These complications have been
associated with ART, and it was hoped that they would be seen less frequently
in those patients receiving less drug. Although the risk-to-benefit ratio of
drug conservation over the longer term remains uncertain, the DSMB recommended
that enrollment into the trial be halted in light of the findings. Upon
reviewing the results, the Executive Committee also conveyed to local study
investigators its recommendation that it would be prudent to re-initiate
therapy in ART-experienced patients in the drug conservation arm.
Mouse Model of Alzheimer's
Disease Shows Role of Cell Division
For unknown reasons, nerve
cells (neurons) affected by Alzheimer’s disease (AD), as well as many other
neurodegenerative diseases, often start to divide before they die. A new study
in mice, published in the Journal of Neuroscience (2006;26:775-784), shows
that, in animal models of AD, this abnormal cell division starts long before
amyloid plaques or other other markers of the disease appear. Cell division
occurs through a process called the cell cycle. The study compared the brains
of three different mouse models of AD to brains from normal mice, looking
specifically for markers of cell cycling. They found that, in the AD mouse
models, cell cycle-related proteins appeared in neurons 6 months before the
first amyloid plaques or disease-related immune reactions developed in the
brain. Many of the neurons also had increased numbers of chromosomes, which is
typical of cells that have begun to divide. These changes were not seen in
normal mice. The regions of the brain most affected by the neuronal cell
cycling were the cortex and the hippocampus, the same regions most affected in
AD. The cortex is important for thought and reasoning, while the hippocampus
plays a key role in learning and memory. Some parts of the brainstem also
showed evidence of cell cycling. While the cell cycling appeared to be
necessary for neurons to die, it was not an immediate cause of cell death in
the mouse models of AD. Instead, the affected neurons appeared to live for many
months in a near-functional state, with the mice showing only mild behavioral
changes during that time. This suggests that another type of cellular problem,
still unidentified, must damage the neurons in order for them to die. The
findings shed new light on the theory that the accumulation of amyloid beta in
the brain causes the neuron death in AD. Because the abnormal cell cycling
begins months before the formation of amyloid plaques, it is unlikely that the
plaques themselves trigger the disease process. However, tiny clumps made up of
several amyloid beta molecules (called micro-molecular aggregates) form before
the plaques and may trigger the disease. Since the three mouse models tested in
this study all had mutations in the gene that codes for amyloid precursor
protein, the similarity between affected brain regions in these mice and in
people with AD also supports the amyloid hypothesis. The results indicate that
the mice, which do not develop neurofibrillary tangles or the severe behavioral
symptoms of AD, are accurate models of the early cellular processes that lead
to the disease.
Congestive Heart Failure
and Rheumatoid Arthritis
Although mortality among patients with rheumatoid arthritis (RA) is higher than
in the general population, the relative contribution of comorbid diseases to
this mortality difference is not known. As a result, a study published in
Arthritis & Rheumatism (2006;54:60-67), was performed to evaluate the
contribution of congestive heart failure (CHF) and ischemic heart disease
(IHD), including myocardial infarction, to the excess mortality in patients
with RA. The study included patients who first developed between 1955 and 1995,
and an age- and gender-matched non-RA cohort. All subjects were followed up
until death, migration from the county, or until 2001. Detailed
information from the complete medical records was collected. Statistical
analyses included the person-years method, cumulative incidence, and Cox
regression modeling. Attributable risk analysis techniques were used to
estimate the number of RA deaths that would be prevented if the incidence of
CHF was the same in patients with RA and non-RA subjects. The study population
included 603 patients with RA and 603 subjects without RA. During follow-up,
the mortality rates among patients with RA and non-RA subjects were 39.0 and
29.2 per 1,000 person-years, respectively. There was a significantly higher
cumulative incidence of CHF (but not IHD) in patients with RA compared with
non-RA subjects (37.1% versus 27.7% at 30 years of followup, respectively; P
< 0.001). The risk of death associated with either CHF or IHD was not
significantly different between patients with RA and non-RA subjects. If the
risk of developing CHF was the same in patients with RA and individuals without
RA, the overall mortality rate difference between RA and non-RA hypothetically
would be reduced from 9.8 to 8.0 excess deaths per 1,000 person-years. The
authors concluded that CHF, rather than IHD, appears to be an important
contributor to the excess overall mortality among patients with RA. CHF
contributes to this excess mortality primarily through the increased incidence
of CHF in RA, rather than increased mortality associated with CHF in patients
with RA compared with non-RA subjects. Eliminating the excess risk of CHF in
patients with RA could significantly improve their survival.
Nut Consumption and Changes
in Inflammatory Biomarkers
Nuts and
seeds are rich in unsaturated fat and other nutrients that may reduce
inflammation, and frequent nut consumption is associated with lower risk of
cardiovascular disease and type 2 diabetes. As a result, a study published in
the American Journal of Epidemiology (2006;163:222-231), was performed to
examined the associations between nut and seed consumption and C-reactive
protein, interleukin-6, and fibrinogen. The study included 6,080 US
participants aged 45–84 years with adequate information on diet and biomarkers.
Nut and seed consumption was categorized as never/rare, less than once/week,
1–4 times/week, and five or more times/week. After adjustment for age, gender,
race/ethnicity, site, education, income, smoking, physical activity, use of
fish oil supplements, and other dietary factors, mean biomarker levels in
categories of increasing consumption were as follows: C-reactive protein (1.98,
1.97, 1.80, and 1.72 mg/liter); interleukin-6 (1.25, 1.24, 1.21, and 1.15
pg/ml); and fibrinogen (343, 338, 338, and 331 mg/dl) (all p's for trend <
0.01). Further adjustment for hypertension, diabetes, medication use, and lipid
levels yielded similar results. Additional adjustment for body mass index
moderately attenuated the magnitude of the associations, yielding borderline
statistical significance. Associations of nut and seed consumption with these
biomarkers were not modified by body mass index, waist:hip ratio, or
race/ethnicity. The authors concluded that frequent nut and seed consumption
was associated with lower levels of inflammatory markers, which may partially
explain the inverse association of nut consumption with cardiovascular disease
and diabetes risk.
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.
New Program in Device Safety
The FDA is launching a new program
to transform and strengthen the way it currently monitors the safety of medical
devices after they reach the market. The FDA Center for Devices and Radiological
Health's (CDRH) Postmarket Transformation Initiative should better protect the
public health by allowing the FDA to identify, analyze and act on problems more
quickly, including alerting the public sooner of potential medical device
issues.Areas in which this initiative will focus include:
- Working toward an electronic reporting system for
adverse medical device events;
- Unique ways to identify medical devices including
standardized and globally accepted names;
- Ways to improve device information in patient
records;
- Improved internal collaboration on post market safety
issues; and
- Identifying opportunities to improve the safety of
medical devices through collaborative efforts with professional
organizations and the medical device industry.
The FDA undertook this initiative after a comprehensive,
year-long internal inventory of the tools used to monitor the safety of medical
devices after they are approved. This inventory identified many areas that are
working well; however, it also identified challenges associated with medical
devices after they reach the market. To guide this process, the CDRH Postmarket
Transformation Leadership Team has been established consisting of senior level
FDA management as well as outside consultants who are experienced in device
safety and product regulation. As the first step, the team will review CDRH's
Medical Device Postmarket Safety Program report and accompanying
recommendations for possible ways to address areas that need improvement. The
CDRH Postmarket Transformation Leadership Team is expected to have
recommendations back to CDRH within approximately four months.
For more information about our expertise in Regulatory Affairs,
please contact Dr. Jules T.
Mitchel or Dr. Glen Park.
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 your next project.
TARGET HEALTH INC.
261 Madison Avenue
24th Floor
New York, NY 10016
Phone: (212) 681-2100; Fax (212) 681-2105
Target Health
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Dr. Jules T. Mitchel,
President
Ms Joyce Hays, CEO
©2006 Target Health Inc. All rights reserved