PSORIATIC ARTHRITIS NEWSLETTER NO. 113

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PSORIATIC ARTHRITIS NEWS AND VIEWS

VOLUME- 6 ISSUE- 14

November 30, 2006

PSORIATIC ARTHRITIS MEDICAL NEWS

HUGH ACETAMINOPHEN RECALL ANNOUNCED

About 11 Million Bottles of Store-Brand 500-Milligram Caplets Recalled

By Miranda Hitti WebMD Medical News - Reviewed By Louise Chang, MD

Editor’s Note: Although this is “old news†from early November, please

check your medicine shelf.

Nov. 9, 2006 -- The FDA today announced a recall of about 11 million bottles

of store-brand acetaminophen 500-milligram caplets.

Those caplets are over-the-counter drugs for pain relief and fever

reduction. They're sold by about 130 companies, including Wal-Mart, CVS, and

other

drug stores, grocery stores, and wholesalers.

The recall is due to " small metal fragments found in a small number of these

caplets, " states an FDA news release.

The fragments range in size from " microdots " to 8-millimeter pieces of wire,

according to the FDA.

The FDA and the caplets' maker, Perrigo Company of Allegan, Mich., are

investigating how those metal fragments got into the caplets.

So far, no illnesses, injuries, or consumer complaints have been reported to

the FDA or Perrigo, according to the FDA.

The FDA " believes the probability of serious adverse health consequences is

remote, " the FDA's Brodsky told reporters in a teleconference.

Brodsky is the FDA's assistant commissioner for external relations.

" However, if a consumer were to swallow an affected caplet, it could result

in minor stomach discomfort and/or possible cuts to the mouth or throat, "

Brodsky says.

Advice for Consumers

For a full list of the companies that sell store-brand 500 milligram

acetaminophen made by Perrigo, visit the FDA's web site at

www.fda.gov/oc/po/firmrecalls/perrigo/perrigocustlist.html.

The FDA's web site also lists the recalled batches of the drug. That list is

posted at www.fda.gov/oc/po/firmrecalls/perrigo/perrigobatchlist.html.

The recalled drugs have expiration dates ranging from September 2006 through

August 2009.

The FDA advises consumers who believe they have the recalled acetaminophen

to " discontinue use immediately " and call Perrigo's consumer affairs department

at (877) 546-0454 for further instructions.

People who think they may have been harmed by the affected caplets should

talk to their doctors, says Brodsky.

" We believe, at present, that this is a relatively small fraction of the

total available acetaminophen on the market, " the FDA's Throckmorton,

MD, told reporters in the teleconference. Throckmorton is the deputy director of

the FDA's Center for Drug Evaluation and Research.

Any adverse reactions to the products should be reported to the FDA's

MedWatch program, which can be reached by phone at (800) FDA-1088, by fax at

(800)

FDA-0178, or on the MedWatch web site at _www.fda.gov/medwatch_

(http://www.fda.gov/medwatch) .

Adverse reactions should also be reported by phone to Perrigo's consumer

affairs department at (877) 546-0454, says the FDA.

Investigation Under Way

According to the FDA, Perrigo told the FDA about the problem on Nov. 1.

Perrigo discovered, through its own regulatory quality-control procedures,

that their tableting equipment was wearing down prematurely, says the FDA.

The FDA says Perrigo told the FDA that 70 million caplets went through a

metal detector, resulting in the discovery of about 200 caplets containing metal

fragments ranging from " microdots " to portions of wire 8 millimeters long.

Perrigo is working with the FDA on correcting the problem.

In a Perrigo news release, the company says it bought raw materials for the

caplets from a third-party supplier. Perrigo didn't name that supplier.

Hendrickson, Perrigo's executive vice president and general manager of

Perrigo Consumer Health Care, commented on the recall in Perrigo's news

release.

" Our quality control systems noted trace amounts of metal particulate in a

very small number of these caplet products, " Hendrickson says.

" Although the frequency of occurrence is very low, the probability of health

risk is remote, and there have been no reports of injuries or illness

related to this incident, we are taking this measure to maintain the highest

possible product quality standards for our retail customers and their store

brand

consumers. "

SOURCES: News release, FDA. News release, Perrigo Company. Brodsky,

assistant commissioner for external relations, FDA. Throckmorton, MD,

deputy director, Center for Drug Evaluation and Research, FDA. Associated

Press. © 2006 WebMD Inc. All rights reserved.

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FASTEST OSTEOPORSIS DRUG IS ACTONEL

Actonel Beats Fosamax in Fewest First-Year Fractures After Menopause

By DeNoon - WebMD Medical News - Reviewed By Louise Chang, MD

Nov. 27, 2006 -- Actonel and Fosamax both prevent bone loss after menopause.

But Actonel works faster, a study by top osteoporosis experts suggests.

Actonel (made by Procter & Gamble) and Fosamax (made by Merck) are both

effective treatments for age-related osteoporosis. This kind of bone loss is a

particular problem for women after menopause.

The two drugs are members of a class of drugs known as bisphosphonates, as

is a newer drug, Roche's Boniva.

There has been some evidence that Actonel may work more quickly to prevent

fractures -- particularly the all-too-common hip and non-spine fractures that

can greatly reduce a person's quality of life.

But is this really the case?

B. Watts, MD, director of the University of Cincinnati Bone Health

and Osteoporosis Center, joined a team of internationally renowned experts in an

effort to find out.

The researchers analyzed insurance records for 12,215 postmenopausal women

who took Actonel and 21,615 women who took Fosamax for the first time. The

women were 65 and older.

The result: After a year of treatment, women taking Actonel had 43% fewer

hip fractures and 18% fewer non-spine fractures than women taking Fosamax.

" This adds to the suggestion from clinical trials that Actonel works faster

than Fosamax, " Watts tells WebMD. " We found a significantly lower rate of

fracture at hip and non-vertebral sites for patients given Actonel vs. Fosamax

at both six and 12 months.

" I am not saying one drug is better than the other -- only that Actonel

works faster, " Watts says.

The study -- sponsored by Procter & Gamble and Sanofi -- appears in the

current online issue of the journal Osteoporosis International.

Slice of Life -- but Not Proof Positive

Watts is quick to point out that the study is not a clinical trial and

therefore cannot be taken as conclusive proof.

But the study impresses Holly Thacker, MD, director of the Women's Health

Center at The Cleveland Clinic.

Thacker, who was not involved in the study, notes that Watts and colleagues

looked at the kind of women doctors see in real life. Moreover, they evaluated

the endpoint that really matters to women suffering bone loss -- actual bone

fractures.

" I tend to prescribe Actonel more often than Fosamax, so this study is

reassuring, " Thacker tells WebMD.

" We now have some excellent drugs for bone loss. In the bisphosphonate

family, I rank Actonel No. 1, with Fosamax a close second, " she says. " I rank

Boniva a distant third, because it has not yet been shown to reduce hip

fracture. "

All things being equal, Watts and Thacker would prescribe Actonel over

Fosamax.

But both of these top doctors point out that not all women are equal. Some

women may tolerate one drug better than another. Or their insurance may pay

more for one than the other.

In either case, women will get the most benefit from the drug that works

best for them.

Long-Term Treatment

Watts notes that bone-loss drugs should be taken for many years. But most

patients stop taking them after six or seven months -- greatly reducing their

potential benefit.

" When we start someone on osteoporosis treatment, we hope they will continue

taking it for years, " Watts says.

" But bone loss is a silent disease -- like high blood pressure or high

cholesterol. Until something happens, the disease doesn't make them feel bad,

and

the drug doesn't make them feel better. That is sometimes hard for people to

accept, " he says.

Thacker, too, stresses the importance of long-term treatment. Unlike Watts,

who usually begins drug treatment only when a woman has frank osteoporosis,

Thacker begins as soon as she detects bone loss.

" Once you're starting to lose bone mass, you need to be on treatment, "

Thacker says.

" First, we make sure a woman is getting enough calcium and vitamin D, "

Thacker says. " But if she is, and she's still losing bone mass, we start

treatment. It is a long-term commitment. The chances are, you will be on it for

a long

time. "

SOURCES: Silverman, S. Osteoporosis International, Online First edition.

B. Watts, MD, professor of medicine, University of Cincinnati College of

Medicine; director, University of Cincinnati Bone Health and Osteoporosis

Center. Holly Thacker, MD, director of the Women's Health Center, The Cleveland

Clinic; associate professor, The Cleveland Clinic College of Medicine, Case

Western Reserve University. © 2006 WebMD Inc. All rights reserved.

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ADVISORS ASK FDA TO APPROVE CELEBREX FOR JUVENILE RHEUMATOID ARTHRITIS By

Peggy Peck, Senior Editor, MedPage Today

ROCKVILLE, Md., Nov. 30 -- An FDA advisory panel said Wednesday that the

-2 inhibitor Celebrex (celecoxib) should be approved for treatment of pain

associated with juvenile rheumatoid arthritis.

The panel voted 15-to-one to recommend the approval, even though eight

advisers said the available data did not demonstrated that Celebrex was safe for

treating juvenile rheumatoid arthritis.

But when push came to shove, the members agreed that the benefits of the

drug outweighed its risks in rheumatoid arthritis patients ages two and older.

The advisers did, however, recommend careful monitoring of the drug, perhaps by

registry, if it is approved for this JRA indication.

Just as in adults, Celebrex demonstrated good short-term safety, said

rheumatologist Joan M.Bathon, M.D., of s Hopkins in Baltimore, a panel

member.

But long-term safety has yet to established, she said.

Pfizer, which markets Celebrex, estimated that 60,000 children in the U.S.

have JRA.

A company study indicted that Celebrex is about as effective as naproxen in

treating children, and both drugs had similar side effects.

Celebrex is the only -2 inhibitor currently on the market. Merck's

blockbuster -2 drug, Vioxx (rofecoxib), was voluntarily taken off the market

in

September 2004 when clinical trials linked the drug to increased risk of

cardiovascular events.

Bextra (valdecoxib), a -2 drug marketed by Pfizer, was withdrawn in the

first quarter of 2005 when it, too, was linked to increased risk of

cardiovascular event. © 2004-2006 MedPage Today, LLC. All Rights Reserved.

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DON'T EXPECT BIG PUSH FOR CELEBREX FOR JUVENILE ARTHRITIS

By Gardner - HealthDay Reporter

THURSDAY, Nov. 30 (HealthDay News) -- A U.S. government advisory panel's

recommendation to allow Celebrex to be used for children with juvenile

rheumatoid arthritis isn't likely to change the treatment landscape

dramatically.

More probably, the painkiller will quietly become one more option in the

array already available, doctors said.

" There will not be a mad rush to switch kids over to Celebrex, " said Dr.

Lindsey, section head of rheumatology at Ochsner Health System in Baton

Rouge, La.

" I don't think there's going to be a huge move to this drug, " added Dr.

Norman Ilowite, chief of the division of rheumatology at Montefiore Children's

Hospital in New York City. " Doctors will try this on patients with

gastrointestinal problems who are on conventional NSAIDs (nonsteroidal

anti-inflammatory

drugs). "

" We're not sure exactly what the role of this drug is going to be in the

treatment of juvenile rheumatoid arthritis, " Ilowite continued. " The biggest

issue is that there will be more choices. There's not really good evidence that

Celebrex spares side effects or is particularly effective more than other

choices, but for individualized patients it might be. "

The Food and Drug Administration panel voted 15-1 on Wednesday that the

benefits of the drug for children with juvenile rheumatoid arthritis (JRA)

outweigh the shortage of proof on its safety.

However, the panel also voted 8-7, with one abstention, that available data

doesn't demonstrate that Celebrex is safe in treating JRA and that a registry

should be established to track these young patients for 10 to 20 years.

The FDA isn't bound to follow the recommendations of its advisory panels but

typically does.

The short-term side-effect profile of Celebrex is fairly benign, experts

said.

" I don't think it's dangerous because I think the dose will be on the low

side, " Lindsey said. " The safety issues will be reasonably good. "

At issue, however, are potential long-term side effects, including

cardiovascular side effects.

Celebrex is a member of the controversial group of painkillers called -2

inhibitors, which have been linked to an increased risk of heart attack and

stroke. Two other -2s, Vioxx and Bextra, have been withdrawn from the market

because of heart-risk concerns.

Celebrex remains available to consumers, but in 2005, the FDA required that

the drug carry a " black box " warning on the possible risk of heart attack or

stroke.

The severity of this problem in children is unclear.

" Potential cardiovascular toxicity is less of an issue with children because

there aren't too many kids who get heart attacks or strokes, " Ilowite said.

" Down the line the worry is there, but it's not so much of an issue as [it is

for] patients who are elderly or who have cardiovascular problems. "

" The risk of heart disease is minimal in children, " Lindsey added. " The only

question would be long-term. If some child takes Celebrex for 15 years, that

would be more of a concern. "

Side effects will be minimized if the drug is used short-term or

intermittently, Lindsey said.

" It's not like a cure. It's just another treatment, " he said. " It will help

kids who haven't been helped by other anti-inflammatories. "

Celebrex is already being used off-label in children, said Dr. Kathleen

Haines, a pediatric rheumatologist with the ph M. Sanzari Children's

Hospital

at Hackensck University Medical Center in Hackensack, N. J.

" The sad case is that few new drugs are approved for any cause other than

antibiotics, and we do a lot of off-label prescribing because we're forced to, "

she added.

Haines, who testified at the FDA panel's hearing Wednesday, noted, " In a

sense, Celebrex has been available, at least for older kids. "

If the FDA does approves this new indication, she said, pediatricians, in

addition to rheumatologists, may feel more comfortable prescribing Celebrex even

for non-rheumatoid-arthritis conditions, such as tendonitis or sports pain.

" There are a lot of places where it might come into play once it has a

pediatric indication, " said Haines.

It's estimated that as many as 60,000 children in the United States have

JRA, which causes painful joint swelling and can affect growth and development.

SOURCES: Norman Ilowite, M.D., chief, division of rheumatology, Montefiore

Children's Hospital, and professor of pediatrics, Albert Einstein College of

Medicine, New York City; Lindsey, M.D., section head of rheumatology,

Ochsner Health System, Baton Rouge, La.; Kathleen Haines, M.D., pediatric

rheumatologist, The ph M. Sanzari Children's Hospital, Hackensack University

Medical Center, Hackensack, N.J. Copyright © 2006 ScoutNews, LLC. All

rights reserved. © 1996-2005 MedicineNet, Inc. All rights reserved. Copyright

and

Legal Disclaimer.

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SMOKING PUTS BRAKES ON JOINT INJURY REPAIR

Cigarette toxins interfere with cartilage cell growth, study finds

Nov. 20 (HealthDay News) -- Injured joints may be even slower to heal in

smokers, a new study shows.

Cigarette smoke held back the recovery of fractures and ligament injuries in

mice, according to two studies in the December issue of the Journal of

Orthopaedic Research.

In the first study, researchers at Washington University School of Medicine

in St. Louis looked at fracture healing in a group of mice exposed to

cigarette smoke 6 days a week for a month. There was also a control group of

mice

that weren't exposed to smoke.

The researchers found that fracture healing was delayed in the smoke-exposed

mice. This delay was noted in the early stages of healing and was caused by

cigarette smoke's hindrance of the development of mature cartilage cells.

While the study showed an association between cigarette smoke and cartilage

formation, the researchers said it's likely that smoking has other effects on

fracture healing and that these need to be examined in future studies.

" Clinically, if specific events can be identified, smoking cessation in

humans, even temporarily, may improve or speed the healing process after injury

and decrease the significant morbidity associated with cigarette smoking during

fracture healing, " the study authors wrote.

A second study by the same group of researchers found that exposure to

cigarette smoke slowed the healing of medial collateral ligament (MCL) injury in

mice.

The studies add to previous research that found that cigarette smoke can

affect recovery from fractures and ligament injuries. It's also been shown that

smokers have higher rates of hip fracture, fracture healing problems and bone

infection. In addition, smoking interferes with the healing of soft tissue

wounds.

The U.S. National Institute of Arthritis and Musculoskeletal and Skin

Diseases has more about smoking and bone health (_www.niams.nih.gov_

(http://www.niams.nih.gov) ). -- Preidt - SOURCE: Wiley & Sons

Inc Copyright ©

2006 ScoutNews LLC.

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LYRICA SHOWS DURABLE EFFECT IN FIBROMYALGIA

By , MedPage Today Staff Writer Reviewed by Zalman S. Agus, MD;

Emeritus Professor at the University of Pennsylvania School of Medicine.

November 16, 2006

Please note that this study suggests the effect of Lyrica (pregabalin) is

more long-lived, although not all patients will have a response and not all will

be able to tolerate the medication's side effects. The drug is not yet

approved for fibromyalgia.

This study was published as an abstract and presented orally at a

conference. These data and conclusions should be considered to be preliminary as

they

have not yet been reviewed and published in a peer-reviewed publication.

WASHINGTON, Nov. 16 -- In a majority of patients with fibromyalgia, Lyrica

(pregabalin) maintains its painkilling effect for several months, a researcher

reported here.

" This is the first study to report long-term pain relief for fibromyalgia, "

according to Crofford, M.D., of the University of Kentucky in

Lexington, speaking at the American College of Rheumatology meeting here.

Lyrica, manufactured by Pfizer, is approved for the treatment of such

conditions as diabetic neuropathy and post-herpetic neuralgia, but earlier

double-blind studies have suggested that it relieves pain associated with

fibromyalgia, as well as improving quality of sleep and reducing fatigue, Dr.

Crofford

said.

But many drugs have shown a short-term benefit in fibromyalgia, commented

Ruderman, M.D., of Northwestern in Chicago, who was not involved in the

study. " Lots of things look interesting in fibromyalgia in small studies, short

studies, but they don't really last, " he said.

It was for that reason, Dr. Crofford said, that she and colleagues undertook

a six-month, two-phase clinical trial involving 1,051 participants, most of

them women. On average, they had a pain score of 78 on a scale of 100 and had

had fibromyalgia for more than seven years.

In the first phase, lasting six weeks, all patients self-titrated to a dose

of Lyrica at which they felt comfortable, to a maximum of 600 mg/day. Patients

were classified as responders if they had at least a 50% reduction in pain

scores at their optimum dose and reported that they were " much " or " very much "

improved.

At the end of the six weeks, 663 patients (or 63%) were classified as

responders and 566 entered the 26-week, double-blind, placebo-controlled part of

the trial, Dr. Crofford said. Of those, 279 stayed on Lyrica, and 287 were

switched to placebo.

The researchers found:

One in four placebo patients reported their pain worsened within seven days

of beginning the double-blind part of the study, compared with 34 days for

those who remained on Lyrica.

The time to loss of therapeutic effect was significantly longer for Lyrica

patients, at P<0.001.

By the end of the double-blind study, 61% of placebo patients had lost

therapeutic response, compared to 32% of those getting Lyrica. The main adverse

effects were mild or moderate dizziness (36%), somnolence (22%), sinusitis,

arthralgia, and anxiety.

Dr. Crofford said that the roughly 40% of the original participants who

didn't go on to the double-blind phase dropped out for three main reasons: they

couldn't tolerate the drug, they were lost to follow-up, or they reported lack

of efficacy.

Dr. Ruderman said the study will allow physicians treating patients with the

condition to give some guidance as to how long they can expect a therapeutic

effect. Durability of response, he noted, " is an incredibly important issue "

for physicians and patients.

That said, he cautioned that the drug is not approved for fibromyalgia, " but

nothing is. "

Dr. Crofford and all co-authors disclosed a relationship with Pfizer. Three

of the four co-authors disclosed that they were Pfizer employees.

Primary source: Arthritis & Rheumatism Supplement. Crofford LJ et al. " A

Six-month, Double-blind, Placebo-controlled, Durability of Effect Study of

Pregabalin for Pain Associated With Fibromyalgia. " Arthritis & Rheumatism 2006;

54(9): © 2004-2006 MedPage Today, LLC. .

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FIBROMYALGIA PAIN IS FOR REAL

Researchers Say Chronic Pain Patients Don't Process Body's Natural Pain

Relievers

By Salynn Boyles - WebMD Medical News Reviewed By Louise Chang, MD

Nov. 30, 2006 -- There is now " overwhelming " scientific evidence showing

that fibromyalgia and related chronic pain conditions are real, but their

clinical management leaves much to be desired.

That is the conclusion of two researchers from the University of Michigan

who have studied fibromyalgia for several years.

Because there has been no obvious physiological cause for the pain disorder,

doctors still routinely dismiss fibromyalgia as being " in a patient's head. "

But after reviewing the research, E. , PhD, and J.

Clauw, MD, write that it is increasingly clear that fibromyalgia is a central

nervous system disorder and that patients experience hypersensitivity to pain.

There also appears to be a fairly strong genetic component to fibromyalgia and

related conditions.

" It is time for us to move past the rhetoric about whether these conditions

are real, and take these patients seriously as we endeavor to learn more about

the causes and most effective treatments for these disorders, " and

Clauw write in the December issue of the journal Current Pain and Headache

Reports.

Brain Imaging Studies

As many as 10 million Americans may have fibromyalgia, according to The

National Fibromyalgia Association.

The disorder is characterized by chronic pain throughout the body, but

symptoms may also include fatigue, headaches, and problems with memory and

concentration.

Brain imaging studies conducted at the University of Michigan and other

research centers in recent years show clear differences in responses to pain

stimulation among people with and without fibromyalgia.

Compared to people without the disorder, fibromyalgia patients showed

increased brain activity in response to pain.

" These studies indicate that fibromyalgia patients have abnormalities within

their central brain structures, " Clauw says.

Research by , Clauw, and colleagues also suggests that fibromyalgia

patients don't process the body's natural pain relievers as efficiently as

people without the disorder.

" We think that these may have both a heightened sensitivity to pain and this

dysfunction in their analgesic [painkilling] mechanism, " tells WebMD.

" It is not yet clear how this all fits together. "

National Fibromyalgia Association president and founder Lynne Matallana

tells WebMD that the doctors who treat fibromyalgia patients face a unique

challenge.

" This is a new paradigm for medical professionals to understand, " she says.

" It isn't a virus, or bacteria or inflammation. It isn't a tumor or something

else that you can see. It is a problem within the pain-processing center of

the central nervous system. "

Treatment Options Still Few

While the recent research has done much to improve the understanding of

fibromyalgia and related chronic pain conditions, few advances have been made in

the treatment of these disorders, says.

The use of medications such as antidepressants can help some patients with

fibromyalgia. And regular exercise seems to help many patients.

Acupuncture has been shown to reduce pain in some studies, but not others,

he adds.

Matallana says several drug companies are in the later stages of testing

several new drugs designed specifically for the treatment of fibromyalgia, which

target the central nervous system.

" We are really excited about this research, " she says.

SOURCES: , R. and Clauw, D. Current Pain and Headache Reports,

December 2006; online edition. E. , PhD, research investigator,

University of Michigan Medical Center, Ann Arbor. J. Clauw, MD,

department

of medicine, division of rheumatology, University of Michigan Medical Center,

Ann Arbor. Lynne Matallana, president and founder, National Fibromyalgia

Association. © 2006 WebMD Inc. All rights reserved.

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FOR ARTHRITIS CARDIO PROTECTION, BIOLOGICS FOUND EQUAL TO METHOTREXATE By

Crystal Phend, MedPage Today Staff Writer -Reviewed by Zalman S. Agus, MD;

Emeritus Professor at the University of Pennsylvania School of Medicine.

BOSTON, Nov. 29 -- The biologic agents used to treat rheumatoid arthritis

are no better or worse for the heart than methotrexate, according to a

case-control study.

Compared with methotrexate, biologics for RA conferred no more or less risk

of cardiovascular events, although oral glucocorticoid monotherapy increased

the odds by 50% and other cytotoxic agents raised the risk by 80%, said

H. , M.D., M.P.H., of Brigham and Women's Hospital here, and

colleagues.

Their study, reported in the December issue of Arthritis & Rheumatism,

compared stroke and heart attack rates in 3,501 primarily frail older patients,

enrolled in a state prescription drug assistance program and Medicare, who were

taking RA drugs.

Biologic agents Humira (adalimumab), Enbrel (etanercept), Remicade

(infliximab) and Kineret (anakinra) as a group carried the same risk as

methotrexate

(odds ratio 1.0, 95% confidence interval 0.5 to 1.9), which was not

significantly changed by combination with methotrexate (OR 0.8, 95% CI 0.3 to

2.0) or

with other immunosuppressive agents (OR 1.2, 95% CI 0.7 to 2.2).

Oral glucocorticoid monotherapy significantly increased cardiovascular event

risk compared with methotrexate (OR 1.5, 95% CI 1.1 to 2.1), with a similar

trend when combined with other drugs (OR 1.3, 95% CI 0.8 to 2.0).

The cytotoxic immunosuppressive agents azathioprine, cyclosporine, and Arava

(leflunomide) increased cardiovascular event risk the most of any group of

agents whether as monotherapy or in combination treatment (both OR 1.8, 95% CI

1.1 to 3.0).

The noncytotoxic agents, which included gold, Plaquenil (hydroxychloroquine)

and Azulfidine (sulfasalazine), did not significantly increase

cardiovascular event risk compared with methotrexate (OR 1.2, 95% CI 0.8 to

1.7).

Previous studies have identified cardiovascular benefits for various agents

in reducing event rates, surrogate measures and even death, but an

investigation of all available immunosuppressive agents across a broad spectrum

of

patients with RA was lacking.

So, the researchers examined cardiovascular risk for the medications

compared to methotrexate. Using RA patients not on immunosuppressive agents as

the

reference group would not have been appropriate, the authors wrote, because

those patients may have disease remission, mild disease, or no actual RA.

The study included patients with a RA diagnosis on at least two office

visits and a filled immunosuppressive medication prescription within three

months.

Among these were 946 cases who had been hospitalized for a cardiovascular

event (438 for myocardial infarction, 639 for stroke) during the approximately

two-year follow-up period.

The researchers compared each of the cases with 10 age- and sex-matched

controls with RA who had not had a cardiovascular event by the time of the

patient's index event.

Both groups were predominantly white (93% to 94%) and female (89% to 92%).

Rheumatologic care was similar between groups though cases were more likely to

have been hospitalized in the year prior to their RA diagnosis (37% versus

31%) and, as might be expected, had more cardiovascular comorbidities and

medications than the control group.

In the prescription assistance program, patients received all medications

for a copay of $6 without restrictions on the use of immunosuppressive agents.

Each medication treatment category was mutually exclusive such that " other

cytotoxic agents " included monotherapy and combination therapy but not

combinations with methotrexate, biologics or glucocorticoids.

When the investigators analyzed the event rates for myocardial infarction

and stroke separately, the results were similar to those of the composite

findings but with widely overlapping confidence intervals. Analyses looking at

glucocorticoids according to average daily dosage and cumulative dosage revealed

no gradient of cardiovascular risk.

The study was limited by lack of data on important cardiovascular risk

factors such as smoking and Framingham risk score and out-of-hospital events.

Also, there were no data on underlying RA severity. If patients with more

severe disease who were more likely to develop cardiovascular events

preferentially were channeled to the more potent methotrexate and biologic

agents,

there may have been a false bias against these medications.

" When studying the cardiovascular effects of an immunosuppressive agent, "

Dr. and colleagues wrote, " it is difficult to disentangle the effects of

the medications from the underlying [RA] and its severity. "

They noted that the increased cardiovascular risk found for the cytotoxic

agents other than methotrexate may have been due to drug-induced hypertension,

but may also reflect suboptimal control of inflammation by these agents

compared to methotrexate.

Randomized, controlled studies should be done to better understand the

effects of immunosuppressive agents on cardiovascular outcomes among patients

with

rheumatoid arthritis, the investigators concluded.

The study was supported by the Engalitcheff Arthritis Outcomes Initiative.

Other relevant grant support was provided by the Arthritis Foundation, NIH,

Merck, Pfizer, and Savient.

Primary source: Arthritis & Rheumatism - Source reference:

DH, et al " Immunosuppressive Medications and Hospitalization For

Cardiovascular Events in Patients With Rheumatoid Arthritis " Arthritis Rheum

2006; 54:3790-3798.

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not necessarily represent the views of the University of Pennsylvania School

of Medicine, MedPage Today, and the commercial supporter. Specific medicines

discussed in this activity may not yet be approved by the FDA for the use as

indicated by the writer or reviewer. Before prescribing any medication, we

advise you to review the complete prescribing information, including

indications, contraindications, warnings, precautions, and adverse effects.

Specific

patient care decisions are the responsibility of the healthcare professional

caring for the patient.

© 2004-2006 MedPage Today, LLC.

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STRESSFUL SLEEP LOSS MAY IMPAIR MEMORY

By Reinberg - HealthDay Reporter

Nov. 28 (HealthDay News) -- Stressful, sleepless nights may impair learning

and memory retention, new research suggests.

Researchers say stressed-out rats kept up for three days straight failed to

produce adequate new cells in the brain's hippocampus -- an area thought

necessary for learning and memory.

" The stressful nature of sleep deprivation exerts negative effects on the

hippocampus, " concluded a team led by Gould, a professor of psychology

at Princeton University in Princeton, N.J.

Her team published the findings in the Nov. 27 early online edition of the

Proceedings of the National Academy of Sciences.

Gould's group already knew that extended sleep deprivation is a strong

stressor for the brain. In this new study, they wondered if the stress hormone

corticosterone might play a role in sleep deprivation's effects on new brain

cell production.

In the experiment, rats were placed on a circular metal platform suspended

just above water in a plastic container. Falling asleep caused the animals to

fall into the water -- adding heightened stress to the sleep-deprivation mix.

The researchers found that after three days of this type of stressful sleep

deprivation, the rats' brains showed elevated levels of corticosterone. Higher

levels of the hormone were associated with a significant reduction in the

number of new brain cells produced in the rat's hippocampus.

To double-check that link, the researchers repeated the experiments in rats

that had had their hormone-producing adrenal glands surgically removed. In

these animals, brain-cell production continued as usual, even after similar

sleep-deprivation experiments.

These results suggested that increases in levels of the stress hormone

account for impaired cell production in sleep-deprived brains.

One expert isn't sure whether the effect seen in this study is transferable

to people, however.

" A lot of these effects may be species-specific, " said Jerry Siegel, a

professor of psychiatry at the University of California, Los Angeles. " In the

rat,

there is data indicating all sorts of dire effects from sleep deprivation

leading to death. These are not seen in humans. So, generalizing to humans is

not easy to do, " he said. " There might be a connection, but you can't be sure. "

Another expert isn't sure that the study proves that all sleep deprivation

is necessarily stressful.

" There is no doubt that the protocol used here was stressful, " said ph

D. , an associate professor of cell and neurobiology at the University of

Southern California. " However, this is not so clear with other methods of

sleep deprivation, " said.

" For instance, continuous, gentle handling of mice for six hours or so has

been reported to cause near maximal increase in sleep propensity once the

handling is terminated, " he said. " But is this stressful? In an animal

habituated

to handling, this may be the least stressful way to sleep-deprive. "

This could have a parallel in humans -- for example, the difference between

partying for two or three nights straight (less stressful) or being forced by

someone else to stay awake (very stressful).

" Conceivably, you might see an even larger number of surviving neurons if

sleep deprivation is as non-stressful as possible, " explained. " It might

be that sleep deprivation is not all that bad in humans if the associated

stress can be reduced. "

SOURCES: Jerry Siegel, Ph.D., professor, psychiatry, University of

California, Los Angeles; ph D. , Ph.D., associate professor, cell and

neurobiology, University of Southern California, Los Angeles; Nov. 27, 2006,

early

edition, Proceedings of the National Academy of Sciences Copyright © 2006

ScoutNews LLC. All rights reserved.

********************************************

LIVING WITH CHRONIC FATIGUE SYNDROME

One Patient's Story By Generoso - Staff Writer, MedicineNet.com

Reviewed by Dr. Shiel, MD, FACP, FACR

At 21 years of age, * felt like she was falling apart.

(*Name has been changed)

Once an energetic cheerleader and member of a professional dance team, full

of energy and life, gradually found herself bedridden and unable to

work. As time went on she became more confused as to why she was feeling

constantly tired.

Then one day a friend of hers, who was a nurse, asked if she had ever heard

of chronic fatigue syndrome.

“My doctor back then didn’t believe in chronic fatigue syndrome,â€

says. “It was still up in the air; people didn’t believe it existed. I think

it’

s better now, but back then it wasn’t.â€

found herself undergoing a series of tests, and when they were

finished, she was diagnosed with chronic fatigue syndrome, a disease which

inhibits

people from performing everyday activities due to severe tiredness. Although

the cause of chronic fatigue syndrome is still unknown, doctors can diagnose

it by ruling out other possible causes of fatigue.

“There was a sense of relief because finally there was a reason for all I

was experiencing,†says. “People would constantly ask what was wrong

with

me, and I felt like I was going crazy. I never guessed it could be one

particular illness that could be causing it all.â€

started on a long journey of medical tests in an effort to get better.

She went through years of disappointment, having MRIs taken, going through

blood tests and a thyroid test, and was put on a series of different

medications and herbs. She put time, money and effort into seeing naturalists,

visited

mainstream doctors, and went through a series of allergy injections in an

effort to find an answer.

For about three years she was on a strict allergy diet where she had to

exclude milk, sugar, corn and wheat from her diet, and also had to remove all

dust particles from her house.

“My diet just became more and more limited,†says. “I was basically

eating meat and salad, wheat free pasta and wheat-free, milk free cookies. My

diet was very, very plain.â€

Although she followed her diet strictly, she still felt tired. Then in 1998,

five years after her initial diagnosis with chronic fatigue syndrome, the

dizziness started.

“I have constant dizziness,†says. “When I look at things,

everything

is always moving.â€

sometimes has dizzy spells that are worse than others where she feels

off balance and has to grab onto something. Her symptoms are sporadic in that

she often can go a few days without feeling severely dizzy, but then

experiences several dizzy spells in a short amount of time.

“With chronic fatigue syndrome symptoms come and go,†says. “I also

have muscle aches, headaches, sore throats and TMJ to name a few,†she said.

“

I sleep with a night guard to help prevent my jaw from locking while I sleep,

although it still happens from time to time. My teeth will ache and I even

went a whole year unable to chew on one side of my mouth.â€

Another symptom of chronic fatigue syndrome that plagues is sleep

disturbance. She often wakes up during the night for no reason on an average of

15 to 20 times and can remain awake for hours at a time. She underwent a sleep

study to find out the cause, but was unable to come up with an answer. It

still takes her at least an hour to fall asleep at night.

also experiences problems with her joints and has elbow pain as well

as pain in her thumb joints and knee joints. Her list of symptoms goes on to

include temporary memory loss , depression, anxiety, irritability, acne, PMS,

and lightheadedness. Yet, above all, her strongest and most constant symptoms

are her fatigue and dizziness.

“The fatigue I experience isn’t just ‘being tired,’ she explains.

“Every

fiber of my being feels sick from fatigue.â€

Since was too fatigued to work, she had to move back with her parents

while going through the fight for social security and the wait for housing. It

wasn’t until 2000, at age 28, that she was able to finally live on her own

for the first time since she was 21.

“That was a great feeling, to have my own place,†says.

says one of the hardest parts of her condition was the amount of

people who didn’t believe she was actually sick.

“There were so many skeptics,†she says. “I was not only fighting to feel

better, I was constantly having to justify being sick to others because so many

people didn’t understand. Others view people with chronic fatigue syndrome

as unmotivated and lazy.â€

grew tired of putting hope into new doctors and new techniques to only

be disappointed. After numerous attempts with different medications and

diets, she decided that taking no medication and small, well-balanced foods was

the best choice for her. Her relationship with God, an understanding husband

and a daily nap is how she gets through the day.

“It helped me to just accept what it is and live with it,†says. “I

try to live each day to the fullest and not get so caught up in being sick.

It’

s important for me not to dwell on it.â€

Today is happily married with two children, which is something that

she never thought would be possible with her condition. She says her strong

Christian faith is what has made the most difference in her life.

“I really try not to think about the illness itself and how much it has

changed my life or that I’ll never be better,†says. “Some days

I’m not

able to do as much and some days I’m able to do more. There is life with

chronic fatigue syndrome. It may be different and more difficult than

originally

planned, but it still can be a full, beautiful life.â€

Editor's Note: Although no cure for chronic fatigue syndrome exists today

there is still hope for future research and development. Researchers have been

working to find a cure since it was officially accepted as a disease in 1988.

**************************************************

Good Health to All,

Jack

Newsletter Editor

_Cornishpro@..._ (mailto:Cornishpro@...)

Issue 2006- 14

11/30/06