Life

Sock's Toxicity And Drugs In RA:

Life

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Cooking dinner. Mowing the lawn. Mopping the floor. They may seem minor, but everyday tasks can take a toll on your body. And when your joints are stiff and painful from arthritis, running a household can seem like an overwhelming job. The biggest mistake many people with arthritis make is trying to do everything at once.

It's a cycle -they do too much, then they become over-fatigued or cause a flare. Once their energy is back and the pain is gone, they try to make up for lost time -and then they get fatigued again and have another flare.

The good news is that you can take many steps to make the work in and around your home easier to manage. Follow these guidelines:

Organize:By planning ahead you can organize your tasks in ways that will conserve energy. For instance, clean one area or floor at a time. If you're doing laundry in the basement, combine tasks that can be done there to avoid hikes up and down the stairs.

Ask yourself: How many tasks can I realistically accomplish in this room or on this floor without causing a flare or becoming over-fatigued?

Prioritize:Accept the fact that you won’t be able to get everything done in one day. Decide which are the most important tasks to accomplish and focus on them. Other items can wait until another time.

Ask yourself: What chores really have to be done now? And what tasks can be delayed?

Distribute:Break tasks into smaller segments that can be accomplished over a number of days. For example, carrying laundry can strain your joints. When clothes are wet, they can be heavy and hard to maneuver into the dryer.

And if your washer and dryer are in your basement, you can spend a lot of time running up and down the stairs. To ease the strain, do a load of laundry every other day instead of all in one day. Another option -set time limits for yourself. For instance, clean the closet for 30 minutes each day until the job is done.

Ask yourself: How can this job be spread over a number of days?

Alternate;Two ways to classify and alternate tasks are:
Light tasks and medium tasks. Alternate light tasks with medium tasks. If you do a heavy task, plan on taking a break after completing it and follow it up with a lighter task. This gives your joints a break and allows you to work longer.

Standing tasks and sitting tasks. If you stand up while washing the dishes, then plan on sitting down, when you can, while preparing a meal. This keeps one set of joints from taking all of the strain.

Whether you do a chore standing or sitting often is determined by habit. You may be used to folding laundry while standing by your bed, but remember that you can also do it while sitting.

Ask yourself: What order should I do these tasks in? ;Pace yourself
Remember to take regular rest breaks. This doesn't mean you have to lie down and sleep, just make sure to relax the set of joints you just used. Length of rest varies person by person -listen to your body.

Stop for a break before you're tired or hurt. Ask yourself: When will I take my breaks? Delegate;Another way to distribute work is to ask for assistance or hire someone to help you. This is especially important with strenuous activities that put stress on your joints and can cause pain and fatigue.

Family and friends are good sources for help. Don't forget that even young children can be given regular chores.

Ask yourself: Who else can do this task? Duplicate. Keep several sets of cleaning supplies distributed around the house so that you won't have to carry them far. For example, keep a toilet brush and cleanser in each bathroom.

Ask yourself: What cleaning supplies do I use in more than one room?
Here are some additional tips for functioning in and around your home. Depending upon which joints are most affected, some tips may be more helpful than others:

In the kitchen:Use electric appliances. For instance, use a food processor to do your chopping. Buy prepared foods and convenience items. For example, buy salad mix that is pre-washed and shredded.

Use scissors to open a package instead of tearing it open with your hands. Ask for groceries in a paper versus a plastic bag. You can carry it between your forearm and hip to avoid straining your hands.

Plan ahead to avoid multiple last-minute tasks when preparing a large meal. Reduce stress on your joints by placing your mixing bowl on a damp cloth in the sink while you stir. The cloth will keep the bowl from slipping, and holding the spoon like a dagger takes stress off your hands.

Use nonstick sprays, foil and disposable baking pans to make cleaning up easier. Use a cart with wheels to move heavy items from one place to another. Buy a cutting board with a gripping surface that holds food firmly as you cut.

Use a microwave whenever possible to avoid stooping at the oven. Use hot water to loosen a jar lid and pressure from your palm to open it, or use a jar opener. Buy lightweight pots, pans, bowls and dishes.

Around the house:Organize closets and cabinets so that the heavy and most frequently used objects are easy to reach -between the middle of your thigh and shoulder. Insert a dish towel in drawer or door handles to make them easier to pull open.

Leave your most frequently used items out on the counter in the kitchen and bathroom and on your dresser in the bedroom.

Limit yourself to one major cleaning task a day. Use long-handled tools for reaching.

Outside:Gather your tools together in a wheelbarrow so that you're not making several trips back and forth. Use tools that are going to minimize stress on your joints. Examples are ergonomic rakes and shovels. Tape yardsticks onto your gardening utensils so that you won't have to bend over as much to use them.

Put pipe insulation tubing around tool handles to make them easier to hold. Leave the hose in the yard instead of dragging it out of storage each time you use it. Put a chair at each end of a garden row. It will help you get up from the ground.

Do your gardening in small containers that you can keep at an accessible level or use raised beds. Weed after it rains or the garden has been watered -soft soil means less tugging.

A note from a patient: Don't do like I first,did,and waste your time and your money on too many of over-the-counter vitamins and supplements.

Make sure you get good medical care combined with exercise. And then a saying that a good friend gave to me when I was really in depression and having a hard time dealing with this, and she said to me, "Keep company with those who make you feel better." And that's what helps me. I make sure I'm around people who care. I have a wonderfully supportive family, and that's what keeps me going.

The ability for people to actually work with their physicians and take on some of the responsibility of managing their disease on their own shoulders. I know in my own experience I have regular visits with my rheumatologist and my orthopedic surgeon, but all the other time in between those visits pretty much the care is left on my shoulders.

I have really worked very hard in conjunction with my medical professionals to develop my overall plan, and I think that if people can do that and learn to cooperate their care and manage it on a day-to-day basis, then the years and decades will become much easier.

Fatigue ;Well, I think one of the things that has helped me the most is really is to pay attention to what causes the fatigue, and then be very good at scheduling your time or managing your time and plan ahead.

Don't try to take on too much, but just take on little bits at a time, building up to a bigger assignment or something. In other words, just sort of segment your time out, and that way you won't have too much to do all at one time and become overly fatigued.

It's an ongoing battle, and when you wake up in the morning and you just think, "I can't do it," it's your attitude, and you have to say, "I can." And it's just amazing once you do those sit-ups or that walk or whatever how you are able to function and never give up that hope that you can function.

Sadness is an experience that all of us feel from time to time, usually having to do with some disappointment or some loss. That will interrupt a person's mood intermittently, but gradually they get back to functioning in a normal sense.

If someone is beginning to develop a depressive illness, some of the biological things that happen are sleep begins to be interfered with, eating habits change, and interest in every-day-life diminishes. Usually the normal things that the patient is able to be involved in don’t seem as important.

They have decreased concentration, and they often feel irrationally guilty and ruminate about things. They're tearful; they're crying; they feel more irritable. And, in an extreme sense, there are people who are worried about self-destruction but yet afraid to mention that to anyone that they're close to or to their physician.

Getting support from family members and friends is very important. Often, feeling understood gratifies people so much - they feel like other people care about them. It's often very important that they discuss the frustration and the depression with their physician.

The doctor may suggest that they see someone like a psychiatrist so they can have an opportunity to really pour their heart out about what's troubling them and what they're frightened of.

The other thing that needs to be considered is the use of antidepressant medication, though not necessarily right away. This often can be quite helpful in lifting someone's mood and also can be helpful in terms of pain control even though it doesn't necessarily do anything for the underlying arthritis process.

Not everyone needs a antidepressant,it depends on their coping skills. It depends on what their previous history has been. If you have someone who has never been ill and all of a sudden has this diagnosis mentioned to them, the way that they react to it will often reflect how they've dealt with other traumas in their life.

If there is someone who has had multiple illnesses, this additional illness can often give them an overwhelming sense of "What's going to happen to me?" and a complete loss of control. People like to feel like they're in control of themselves and in control of their health. When this starts to be preyed upon, everyone feels a little bit of loss of self and somewhat of a loss of self-esteem. But we're talking about degrees here.

People living with rheumatoid arthritis have normal life stresses, as we all do, but we know that one symptom of stress is muscle tension. As these muscles in rheumatoid arthritis patients pull on the ligaments, the joints, and the tendons, they decrease mobility. This can lead to more pain, more depression, and more stress.

When a patient has an illness that's grossly interfering with their functioning, the important thing is to try and find an area where the patient can feel some gain in what's happening - so they feel like some form of control is coming back into their life.

That often helps the mood. "At least I was able to do this much today. If I practice this, maybe by next week I'll be able to do a little bit more." There's a sense of pride and self-esteem in trying. There's a sense of gaining something over the illness. I think those things are helpful. Learn to relax.

I believe stress does have an impact on my symptoms, and I try to control that by exercise and proper diet and enough rest. As a mom with two children and a very active life, I'm not working outside the home now, but do you think I have a spare moment? No. I am volunteering in their classrooms, I am involved in the PTA and I am an advocate for RA. I sing in my church choir, and my husband's going, "What about time for me?"

So, it's a very busy life, and when I do fill my days too full, I do find that I get overly tired. I do have to stop sometimes and get just a little extra rest. And when I do get overly stressed, I think that the symptom that crops up for me is that I do get a little bit tired. I don't immediately have aches and pains and swelling, but I do feel it a little bit in the fatigue department.

Perhaps you can, but I think you have to be more disciplined than most of us are willing to be. I still look back and perhaps judge my own performance and abilities, but if I had followed the strictest guidelines of "do not add more than one food, maybe add two foods a week. Wait longer periods of time between. Eat only organic food. Check what's in your vitamins for additional additives."

I mean, if you want to be so extreme, perhaps you can control it, but it takes every ounce of energy you have to try to go down that path.

And I believe now, having gone down that path (without success ), you need to be in closer communication with your doctor, and finding out what your other possibilities are by asking, "What can I be doing in conjunction with good healthy diet and exercise and vitamin regimes?" Because I don't know that I would ever have the kind of discipline to go down that strict of a path.

I think one of the points that you really have to ask yourself is when you go and look for information about any topic, you would ask somebody, "How do I do it? What's the best way?" And you would take their advice. And their advice is usually based on the fact that they've done some research, and they know what helps the majority of people.

Now, that's not to say that diet might not alone help an occasional person with this. We would love diet to work. I wouldn't have to use half the medications we use with the side effects. It would be so simple. But obviously, diet doesn't work , we wouldn't be talking about this. Everybody would be on diet. That would be the end of the question.

"Whether a good diet in addition to medical care is important, I would never argue. But as a sole therapy, I don't have any proof that it helps."

People with arthritis are frustrated. They don't want to feel bad. They don't want side effects. They're not sure what to do. So that's where you have to ask the expert. And we really don't have any proof that diet, as a single agent without anything else, does anything to stop arthritis. We wish it did, but it doesn't.

Whether a good diet in addition to medical care is important, I would never argue. But as a sole therapy, I don't have any proof that it helps except maybe in the smallest minority (people allergic to certain foods ), and I would feel bad if you went in that direction. Why don't you go in the direction of the majority?

Remember, you're not committing yourself for life. If you start to feel well, you can always stop it to see if you need it. But that's the perspective. Put it in the same perspective that you would any other decision you'd make in your life about anything else. Where would you go for information? How would you evaluate it? What would you do?

The harm with alternative therapies is not what it does to your body, but if you look across at a population study and ask, "How much time from the onset of therapy did it take you to see the doctor to get the diagnosis, and what prevented you from going to the doctor?" the number one thing that sticks out is alternative therapy.

The patients who take diet, the patients who take the copper bracelet, stay away from the doctor the longest period of time and don't get a proper diagnosis. That's the harm in strictly, alternative therapies. It doesn't get you to the correct opinion.

I'm not saying that it may not have some role in addition to other therapy,( there are many good complementary therapies that are helpful when used in conjunction with conventional therapy ) but it keeps you from the doctor. That's what the harm of these things really is. You can't reverse a deformed joint.

Facts of Life:

Using assistive devices can make performing many daily activities -such as reading a book, opening a jar or buttoning a jacket -less frustrating. Contact your pharmacy or health care professional for information on ordering these items. Many aids can also be purchased at a medical supply store.

Use thick, padded grips. Many kitchen tools are now available with thick, padded handles. You can devise your own creations by wrapping foam tubing, the kind used for pipe insulation, around all kinds of hand-held household items -from toothbrushes, hairbrushes and combs to pens, key rings and kitchen utensils.

Learn tricks for turning lids, handles and knobs. The key is leverage - the longer the handle, the less force you need. You can buy extended handles for doorknobs and stove controls, gadgets to open car doors and under-the-counter jar openers that grip a jar’s lid as you physically turn the jar.

Use aids to help you dress. These can help if you have trouble bending and reaching. Aids include shoehorns with an extension handle, devices that help you pull up hosiery, shoes you close with Velcro rather than shoelaces and tools that grip buttons and zippers. You can also have elasticized Velcro tabs sewn onto shirt cuffs or have buttons sewn on with elasticized thread. Use a walking stick or cane.

One thing to emphasize is that rheumatoid arthritis is a very complicated and varied disease, so that each individual will present different challenges. In different people there may be different parts of what's causing inflammation so that in some people it may be driven by one factor more than another.

In all likelihood it's going to be the exception rather than the rule, where physicians can use a single medication. With rheumatoid arthritis, since the immune system is so complicated, we should look at it as conducting war. We may be successful in one front and then be losing on another front, so that as in any war we have to fight it on a number of different levels, and that's why physicians may have to use combination therapies.

The anti-inflammatories are there to catch any inflammation that breaks through the primary defenses, which are the disease-modifying drugs, and doctors try to use just one, but if that doesn't work, they'll use others, and they work at different levels. So whereas Enbrel inhibits TNF, methotrexate inhibits T-cells so we can attack the immune system - not attack, but control the immune system in a lot of different ways at the same time. But doctors always try to keep it as simple as they can.

One important factor overlooked by patients in medication,and efficacy is that there is pain caused by mechanical and inflammatory forces involved. As we grow older there is a lot of mechanical pain caused by on-going degenerative forces ( degenerative osteoarthritis -secondary OA.) Our current conventional and biologic medications aren't going to eliminate that part of the complex pain equation.

Many RA patients have this so called "secondary OA" or mechanical problem. We as patients will in all probability will not be able to escape that part of pain. In other words,is pain caused by mechanical,or inflammatory forces. If it is a mechanical problem we have to attack the problem in different other ways; exercise,heat,cold,anagesics etc.

Non-steroidal anti-inflammatory drugs (NSAIDs) reduce inflammation by preventing the formation of natural inflammatory substances called prostaglandins. NSAIDs are used commonly for everything from headaches to colds to nagging pains. They are also used frequently in the treatment of rheumatoid arthritis (RA), to alleviate joint pain and swelling.

While NSAIDs can be effective against RA, they have a number of side effects, including potentially serious side effects such as bleeding stomach ulcers, kidney damage, liver damage and decreased blood cell production. While rare, these side effects can be severe. In particular, bleeding stomach ulcers can be an emergency, life-threatening complication of NSAID use.

Several risk factors for developing a bleeding ulcer while taking an NSAID medication have been identified. Of these risk factors, a previous episode of ulcer bleeding presents a particularly high risk. Since patients with RA are often prescribed NSAID medications for many years, they often develop a bleeding ulcer at some time, and thus are at high risk for a second bleeding ulcer.

To decrease rates of bleeding ulcers in patients taking traditional NSAIDs, ulcer-preventing and ulcer-treating medications such as misoprostol or the “proton pump inhibitors (PPI’s)” have been used.

The new subclass of NSAIDs target specific prostaglandin-producing enzymes (called COX-2). In patients with RA, clinical trials have shown a lower rate of bleeding ulcers for these new COX-2 NSAIDs relative to the “non-selective” NSAIDs .

However, the safety of these COX-2 NSAIDs for high-risk patients with a previous episode of bleeding ulcer remained unknown. To address this issue, a group of investigators studied the safety of a COX-2 NSAID compared to traditional NSAID plus anti-ulcer therapy in high-risk arthritis patients. They published their results in a recent issue of the New England Journal of Medicine.

In this prospective, randomized, double blind trial, researchers identified 290 arthritis patients who had recently experienced an episode of bleeding ulcer.

They then randomly treated these patients with either celocoxib (Celebrex®), a COX-2 NSAID, or diclofenac (Voltaren ®), a non-selective NSAID plus the anti-ulcer therapy omeprazole (Losec®), a proton pump inhibitor (PPI). These patients were followed for six months and assessed for recurrent bleeding ulcer as well as arthritis activity.

These researchers found that the treatment group which received the COX-2 NSAID (celocoxib) had lower but statistically similar rates of bleeding ulcer compared with the non-selective NSAID (dicofenac) plus PPI (omeprazole) (4.9% vs. 6.4%).

Both treatment protocols demonstrated similar effectiveness in relief of arthritis symptoms.

From their results, these investigators conclude that treatment with a COX-2 selective NSAID was as effective as treatment with a non-selective NSAID plus an anti-ulcer PPI medication from a bleeding ulcer standpoint. They also noted that while these treatments show similar safety profiles, the rates of recurrent bleeding ulcer in both group were high (approximately 5% in 6 months); thus, neither treatment strategy completely prevents this serious medical event.

In addition, both groups demonstrated similar rates of side effects on the kidney, suggesting no additional benefit from the COX-2 selective NSAID.

Overall, this study provides RA patients and their physicians with important information regarding options for continued NSAID treatment after an episode of bleeding ulcer. In addition, this study again underscores the importance of careful administration of these medications in RA therapy.

Notes: Valdecoxib (Bextra )is an oral drug that belongs to the family of drugs called nonsteroidal anti-inflammatory drugs (NSAIDs). NSAIDs are used primarily to treat pain and arthritis. Other NSAIDs include aspirin and aspirin-related drugs, ibuprofen (Motrin), indomethacin (indocin), naproxen (Naprosyn), diclofenac (Voltaren), sulindac (Clinoril), ketoprofen (Orudis), etc.

Valdecoxib works by altering the production of prostaglandins, chemicals manufactured by the body that promote the inflammation of arthritis and cause the pain, swelling and tenderness of arthritic joints. Valdecoxib, like the newer NSAIDs celecoxib (Celebrex) and rofecoxib (Vioxx), blocks one of the enzymes that makes prostaglandins (cyclooxygenase 2), resulting in lower concentrations of prostaglandins.

As a consequence, pain, swelling and tenderness of joints due to arthritis are reduced. Valdecoxib (like celecoxib and rofecoxib) differs from most other NSAIDs in that it causes less inflammation and ulceration of the stomach and intestine (at least with short-term treatment) and does not interfere with the clotting of blood.

PRESCRIPTION: Yes GENERIC AVAILABLE: No PREPARATIONS: Oblong white tablets containing 10 or 20mg of valdecoxib. STORAGE: Valdecoxib tablets should be stored at room temperature, 59-86 °F (15-30 °C).

PRESCRIBED FOR: Valdecoxib is used for the relief of pain, fever, swelling, and tenderness caused by osteoarthritis and rheumatoid arthritis, but it does not prevent the destruction of joints by the arthritis. Valdecoxib also is approved for the relief of pain of menstrual cramps (primary dysmenorrhea).

DOSING: For osteoarthritis or rheumatoid arthritis, the usual approved dose of valdecoxib is 10 mg once daily. For dysmenorrhea, the dose is 20 mg twice daily. Valdecoxib may be taken with or without food.

DRUG INTERACTIONS: NSAIDs can reduce the actions of diuretics such as furosemide (Lasix) and hydrochlorothiazide (Hydrodiuril) in some patients and lead to retention of water.

Aspirin has repeatedly been shown to be protective against cardiovascular disease. Results of an in-vivo study showed an interaction between aspirin and ibuprofen on platelet function.

No such interaction was reported with rofecoxib, paracetamol, or diclofenac. The researchers suggested that treatment with ibuprofen in patients with increased cardiovascular risk may limit the cardioprotective effects of aspirin.

They postulated that patients with known cardiovascular disease (myocardial infarction, angina, stroke or transient ischaemic attack, and peripheral vascular disease) who take low-dose aspirin and ibuprofen might have increased risk of cardiovascular mortality.

Aspirin reduces the secondary incidence of stroke, myocardial infarction, and vascular death by about a quarter, an effect similar to that of statins. However, some patients on aspirin will have a second or subsequent heart attack or stroke and the phenomenon of "aspirin resistance" seems to have caught the attention of both the professional and mass media in a way that statin resistance has not.

Aspirin irreversibly inhibits cyclo-oxygenase (COX) by acetylation of a serine residue in the body. COX catalyses the transformation of arachidonic acid to the unstable prostaglandin (PG) intermediate PGH2, and thromboxane synthase (Tx) subsequently acts on PGH2 to form TxA2, a vasoconstrictor and platelet agonist. COX has two isoforms and only COX-1 is expressed in mature human platelets.

COX-2 is upregulated by inflammatory cytokines and mitogens and seems to be the dominant source of prostaglandins in inflammation and cancer. A variant of COX-1, "COX-3" has been detected in canine brain. However, the functional importance of this isoform remains to be determined.

The irreversible nature of COX inhibition by aspirin explains the cumulative inhibition of TxA2 generation by platelets seen when low doses of aspirin are administered chronically.

Overview analysis of indirect comparisons in clinical trials indicates that the reduction in the incidence of vascular events in high-risk patients (19% ) with high doses of aspirin (500-1500 mg a day) does not exceed that attained (32% ) with lower doses (75-150 mg a day).

Thus, although aspirin is anti-inflammatory due to inhibition of COX-2 at higher doses, inhibition of platelet COX-1 at low doses is sufficient to explain the cardioprotection observed in clinical trials.

Unlike aspirin, NSAIDs, such as ibuprofen and diclofenac, are reversible inhibitors of COX, competing with the lipid substrate arachdonic acid for access to the active site at the upper end of a deep hydrophobic channel in the core of the dimeric enzyme. The anucleate platelet is a functional discriminant between the different modes of action of aspirin and NSAIDs.

First, the capacity to regenerate COX de novo after exposure to aspirin is nonexistent (or extremely low) in platelets by contrast with other tissues, where recovery of PG formation due to resynthesis of the enzyme occurs within hours.

Second, the rapid decline in COX inhibition with NSAIDs between doses has a pronounced effect on platelet function. There is a non-linear relation between inhibition of platelet TxA2 generation and inhibition of TxA2-dependent platelet aggregation, requiring greater than 95% inhibition of TxA2 generation to influence function.

This degree of inhibition is rarely (if ever) sustained throughout the typical NSAID dosing interval.

Thus, NSAIDs would not be expected to be cardioprotective like aspirin. Controlled prospective trials of adequate size that address this issue have not been reported, while epidemiological analyses have provided conflicting answers.

Aspirin and NSAIDs are among the most commonly consumed drugs. The prescription market for NSAIDs in the USA is estimated at US$7·75 billion yearly, roughly three-quarters of that number accounted for by COX-2 inhibitors.

The over-the-counter market for NSAIDs is roughly US$2 billion annually, of which aspirin accounts for about 20%. It seems likely that many patients are taking both aspirin and NSAIDs chronically.

However, the distinct modes of COX inhibition by NSAIDs and aspirin provide the basis for a pharmacodynamic interaction, because competitive inhibition of the active site by an NSAID may impede access of aspirin to its target.

This is illustrated by shuffling the order of administration of aspirin and ibuprofen, the NSAID most commonly consumed in the USA. If 81 mg of aspirin is followed 2 h later by 400 mg ibuprofen to attain steady-state effects in volunteers, maximum inhibition of platelet TxA2 generation and consequent inhibition of platelet aggregation is sustained for 24 h after dosing.

However, if the drug order is switched, the pharmacodynamic effect of aspirin is prevented, enzyme function is reversibly inhibited, and platelet aggregation declines by about 60% after 6 h. Furthermore, if ibuprofen 400 mg is administered three times a day (a typical dosing regimen), sufficient NSAID remains from the evening dose to cause the interaction even when aspirin is given before ibuprofen the next morning.

What are the clinical implications of these observations? There are no data from controlled clinical trials that address this issue. Using the Tennessee Medicaid database, Ray et all failed to detect a cardioprotective benefit from prescribed NSAIDs (181 441 NSAID users, 181 441 controls) and also observed that the odds ratio for serious coronary heart disease in patients taking aspirin was increased in patients prescribed ibuprofen chronically and in those prescribed more than 1800 mg ibuprofen a day.

These investigators did not observe a similar interaction with naproxen. More recently, Kimmel and colleagues, in a case-control study (909 cases, 3030 controls) of prescribed and over-the-counter medications based on a telephone survey, found that consumption of a range of NSAIDs was associated with a reduced odds ratio of a first myocardial infarction , but this apparent benefit disappeared in those also taking aspirin.

Thus two studies, which differed in their conclusions about the cardioprotective effects of NSAIDs, both detected evidence of an NSAID-aspirin interaction.

The study has several limitations: the number of participants studied was quite small; they did not study the effect of cyclo-oxygenase 2 inhibitors; and they did not adjust for severity of cardiovascular disease, doses of individual NSAIDs, smoking, or body-mass index. Some or all these factors could be confounders.

Although the findings are not conclusive, they lend support to the hypothesis that treatment with a combination of ibuprofen and aspirin given for secondary prevention may be deleterious, possibly by antagonising the cardioprotective effects of aspirin in patients with established cardiovascular disease.