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Sock's Toxicity And Drugs In RA:
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Arava: Patients with RA often have other serious medical conditions and receive several drugs in their treatment regimen that could be toxic to the liver. Therefore,it is difficult to identify definitively a specific cause for severe liver injury.
"Many other factors  could be involved in these causes,but we cannot completely exclude a casual relationship to Leflunomide at this time", says Dr. Jean Bourgeion,VP of Scientific Affairs at Aventis Pharma.
"Thats why we urge patients experiencing symptoms such as nausea, unusual tiredness vomiting, stomach pain or swelling,  jaundice,or dark urine report these to their doctors at once." In view of this new information. Aventis has posted its product and patient monograph on its Web site at    
Malvern,PA--8/15/01-- Centocor,Inc. announced today it is updating the prescribing information for Remicade (infliximab), a biologic drug used in the treatment of RA and Crohn's disease.
Developed with the FDA,the revised label instructs that patients should be evaluated for latent TB with a TB skin test in reference to current ATSCDCP guidelines,and that treatment for latent TB should be initiated prior to therapy with Remicade.
In addition,the revised label strengthens the warnings about the risk of serious infections in general,and has drawn attention to this important safety information through a boxed warning. "The very mechanism of action that makes TNF-blocking agents effective is believed to be the reason why these therapeutics may increase the risk of infection, including the reactivation of latent TB", said E. William St.Clair.Duke University Medical Centre.
Morever a patient information leaflet will be sent to all prescribing physicians to assist in educating patients on the benefits and risks of Remicade treatment.
Remicade has a good risk-benefit ratio. As of June 30,2001 more than 170,000 patients world-wide have been treated with Remicade in commercial environment with 84 cases of TB reported from post-marketing surveillance and clinical trials of Remicade
The new label also addresses the risk of opportunistic infections  including histoplasmosis,listeriosis and pneumocystis. With respect to the risk for histoplasmosis infection,the revised labeling instructs that the benefits and risks of Remicade therapy should be carefully considered for patients in an area where histoplasmosis is endemic.
The vast majority of TB cases (52) occurred in Europe,where latent TB is more prevelant--20 U.S. cases--12 in other parts of the world. Among the 84 cases,14 were fatal. Most of the cases of TB reported in association with Remicade have occurred within the first 3 to 6 months of treatment,a pattern consistent with reactivation of latent--or dormant -TB,rather than a newly acquired infection.
Enbrel (etanercept) has issued similar revised warnings on labels--re infections.

Understanding why a drug is prescribed improves your knowledge about the drug and the condition for which it prescribes. This promotes adherence to treatment. Knowing how it works provides rationale for its use in treatment of a certain disease. This also provides adherence to treatment. It's also important to know what a drug's side effects are so it can be recognized,prevented and updated or discontinued when it occurs. It is also important to know the expected  results and how long it will take to see the intended results.

Peapack,NJ--8/22/01-- In response to an article published in the 8/22-29 issue of the JAMA which hypothesizes an increased cardiovascular risk with Cox-2 specific inhibitors, Pharmacia and Merk (Vioxx) strongly support the cardiovascular safety profile of their medications.
The article in JAMA is not based upon any new clinical study. The companies believe it is essential to exercise extreme caution in drawing any conclusions from this type of analysis. Furthermore,it is inconsitent with the factual,clinical experiences encountered in actual practise with the medications.
The cardiovascular safety profile of Celebrex was carefully considered at the February 7,2001 FDA Arthritis Advisory Committee meeting which concluded that celebrex demonstrated no increased cardiovascular risk in comparison to NSAIDs studied.
However,this JAMA article presents an additional analysis comparing the annual rates of heart attacks for all paintents in CLASS (Celecoxib Long-term Arthritis Safety Study)with a meta analysis. This analysis is misleading since the authors compared all patients in CLASS,in which 22 % of those patients were taking low dose aspirin for cardioprotection,to a group not taking aspirin.
A more appropiate analysis is to examine the 78% of patients in CLASS who were not taking aspirin. In fact,in CLASS for non-aspirin users the annualized rate of heart attacks was 0.33 %-- 60% lower than the incidence reported for all patients by the authors This rate was compariable to the combined NSAID comparators.
Additionally,the authors of this JAMA article acknowledged that their analysis had several limitations. It is based upon different studies with different protocols,it examined different patients populations with different cardiovascular  risk factors,and it involved various study drug comparators and use of concomitant medication.
Celebrex should not be taken by patients who have aspirin-sensitive asthma or allergic reaction to aspirin or other arthritis medication or certain sulfa drugs called sulfonamides,or who are in their third trimester of pregnancy. As with all NSAIDs it should be used with caution in patients with fluid retension,or heart failure. In clinicl studies the most common side effects were dyspepsia,diarrhea and abdominal pain,which were mild to moderate. there have been infrequent post-marketing reports of increases in prothrombin time,sometimes associated with bleeding events,predominantly in the elderly. Anticoagulant activity should be monitored when therapy with Celebrex is initiated or changed in patients taking Warfarin,particularily in the first few days.

The U.S. Food and Drug Adminisration (FDA) and Pharmacia are advising health care professionals in the U.S. about new warnings and information in the product labeling of the drug Bextra (valdecoxib), a drug approved for treatment of osteoarthritis, rheumatoid arthritis and dysmenorrhea (menstrual pain).
According to the FDA, the labeling is being updated with new warnings following postmarketing reports of serious adverse effects including life-threatening risks related to skin reactions -- including Stevens Johnson Syndrome, and anaphylactoid reactions (serious allergic reactions). In addition, the labeling will state that the drug is contraindicated -- not to be used -- in patients allergic to sulfa containing products.
On November 13, 2002, Pharmacia, the manufacturer of Bextra sent letters to health care professionals advising them of postmarketing reports and new warnings that will be included in the drug label. Since the firm began marketing the drug in March of 2002, cases of the serious skin and hypersensitivity reactions have been reported. These included cases of Stevens Johnson syndrome, toxic epidermal necrolysis, exfoliative dermatitis and erythema multiforme. Although these adverse events are rare, some of these patients required hospitalization. Based on these reports, FDA has approved labeling changes for Bextra that include a warning for serious skin reactions. As these reactions can be life threatening, people who start Bextra and experience a rash should discontinue the drug immediately.
Health care professionals are encouraged to report any unexpected adverse or serious events associated with the use of Bextra directly to Pharmacia Corporation.

Warnings From Health Canada:
Most strong pain medicines last only about four hours. Oxycontin gives a steady 12-hour release and has fewer side effects,but to addicts who chew the pill or crush and snort or inject the powder. OxyContin produces a quick,   herion-like high that can kill. Since 1998,OxyContin and oxycodone,the narcotics active ingrediant,have been linked to more than 100 deaths nationwide.
The drug's maker,Purdue Pharma,pulled it's strongest dosage off the market in May and issued tamperproof prescription pads, but pharmacies are still being robbed for the drug. OxyContin is still being abused One pharmacy in St. Albans,Vt., stopped stocking the painkiller after thieves broke in four times this summer looking for OxyContin. "The problem is not with the is with our society", said Dr. Gladstone McDowell of the Grant Pain Management Centre in Columbus.
Acetaminophen has an excellent track record and benefit-versus-risk ratio. Currently,acetaminophen is a first-line choice for pain and fever in a variety of patients,including children,pregnant women,the elderly and those with osteoarthritis (ACR/recommends for OA). In 1966,researchers learned that acetaminophen can cause liver damage when taken in overdose.
Recent medical literature reviews report that liver problems in those using acetaminophen are rare and can be explained. In some cases,there was gross overdosing-- >10 g(10,000 mg) per day. In other cases,the culprit was alcoholism or a pre-existing liver disease.
An individual's genetric makeup can also account for a variation in response. To reduce the risk of the rare side effect of liver damage,it's important to keep within the maximum doseage range per dose and per day (up to 4,000 mg or 4 g daily).
All acetaminophen products have the suggested number of tablets per dose and per day on the container. One researcher said people tend to take too little acetaminophen (not enoughh to get the best benefit) rather than too much. Currently there is a large clinical trial in progress coducted by NAIM in the U.S.A. in reference to kidney damage.
Health Canada is advising Canadians that specific lots of zirconia ceramic femoral head hip replacement devices manufactured by Saint Gobian Advanced Ceramics Desmarquest  of France are being recalled by Canadian distributors due to a high rate of failure in the implants.
It is important to note,that not all patients who have these zircona ceramic fenoral heads made after 1998 will fail. In Canada of the approximately 20,00 implants done of this type less than 5% are made of this material.
Health Canada is informing hospitals and orthopaedic surgeons to inform patients of the recall. The recall is being done in other countries,including the U.S. There will be continued monitoring of the recall by Health Canada.
The defect in the identified lots is in the femoral head,which is the ball portion of the ball-and-socket joint that makes up the zircona ceramic device. This appears to be the result of a change mde in the manufacturing process. According to information received so far, the failure tends to between 13 to 27 months after implantation.
Shared epitope levels of HLA-DRB1 genes are increased in both young-and elderly-onset RA patients researchers report. However,HLA-DRB1*04 alleles are underrepresented in elderly-onset compared with young-onset RA, suggesting a lesser importance of these genes in RA susceptibility in elderly patients.
Investigators from France in Montpellier,France--Federation de Rhumatologie, the Laboratoire d'Immunologie.obtained these results from studying the clinical,biological and HLA-DRB1 typing characteristics. in the two group of patients. there were 262 young onset (60 years or younger at the time of onset) and 60 elderly-onset patients compared with 40.1 % for normal controls.
No significant differences were found for separate disease related alleles between the two groups,but when HLA-DRB1*04 alles were evaluated as a group,the reserchers found these alleles were underrepresented in the elderly onset compared with the young onset group (37% VS. 52%). Biological characteristics and extra-articular manifestations were similar between the two groups.
A number of autoimmune diseases have been linked to one or more alleles of the major histocompatibility complex (MHC). In 1970,investigators noted that RA patients of nothern European origin exhibited an increased prevalence of the MHC Class II gene, DR4,compared to control subjects. In southern European patients with RA,DR1 was the predominant HLA haplotype.
Only specific subtypes of DR4 and DR1 were associated with development (or severity) of RA,however. For example,the specific DR4 subtypes DRB1* 0401 ( Dw4),DRB1*0404 and *0408 (Dw14) and DRB1*0405 (Dw15) appeared to convey susceptibility to development of RA,while subtypes (e.g.. DRB1*0402 (Dw10) and DRB1*0403 (Dw13) did not.
This led to the search for a common sequence among the different HLA DRB1 alleles that were associated with RA---DR4 susceptibility explanation--(some highly paid and uninformed medical trained "experts" on the web are unaware of some basic facts ).

This item was recently,widely published,mainly through the news media, I believe it may not be bad as it sounds,(partly known) but it is included as a awareness guide, (news) no comment,at this point in time. How large was the study,by whom,and what type of people where involved in the study ? The study it seems was done on people already having bleeding ulcers.
Background: The widespread use of NSAIDs (nonsteroidal antiinflammatory drugs) among older people has resulted in a large number of persons at risk for ulcers. The COX-2 inhibitors such as Celebrex and Vioxx  were introduced in the hope that they would ease the pain of arthritis but not cause ulcers.

The Study: Two treatments were compared in people already afflicted with arthritis and a bleeding ulcer. Treatment (1) was the COX-2 inhibitor celecoxib (Celebrex) and treatment (2) was the combination of the common painkiller diclofenac (Voltaren, Cataflam) + the proton-pump inhibitor omeprazole  (Prilosec). The rates of recurrent ulcer bleeding during 6 months of follow-up were appreciable and similar in the two groups.

Expert Comment: "....neither (treatment) regimen provided a good or even acceptable level of protection from recurrent ulcer bleeding." (David Y. Graham, MD, editorial, The New England Journal of Medicine)--one man's opinion at this time (there was previous studies done and published in the JAMA journal,therefore we remain cautious,until more,in depth,studies,is published. The JAMA study was comparing apples to oranges and did not disclose the full story,until later.

There is no good evidence that glucosamine up to 1500 mg per day will cause diabetes in humans. In rats given very high intravenous doses of glucosamine continuously, resistance to insulin developed. However, rats and  humans are different and the method of administration of the glucosamine in the rats is certainly not the way it is taken by humans.
Furthermore, glucosamine is different from the sugar, glucose. Even if it were the same, 1500 mg of glucose is not a large amount of sugar (1 serving of a soft drink, for example, may contain more than 20,000 mg of glucose). Some people with diabetes have noticed a rise in their blood sugars while taking glucosamine, but many others have not. A definitive answer about the relationship of glucosamine and diabetes is not available at present but so far the proof is slim . More long-term studies and observation are needed.
I would recommend weight control, dietary measures and regular exercise as being more important for the control and prevention of diabetes at this time. If someone has risk factors for diabetes, then it might be possible to reduce the daily dose of glucosamine while maintaining the chondroitin at the same dose. In diabetic persons taking glucosamine, the blood sugars and Hb A-1-C could be followed closer.
Diabetic cheiroarthropathy causes tightness of the skin and limited mobility of the hands but it is not painful. If there is pain, it may be due to tendonitis of the flexor tendons of the hands, reflex sympathetic dystrophy, diabetic neuropathy or some form of arthritis. It is associated with either type I or type II diabetes and correlates with the duration of the diabetes, elevation of the hemoglobin A1C and cigarette smoking. Treatment includes better control of the blood sugars, physiotherapy, occupational therapy and no smoking.
The rotator cuff tendonitis, calcification and bursitis refer to the soft tissue structures around the shoulder rather than to arthritis in the shoulder joint. Periarthritis of the shoulder is an overall name for such problems and is commoner in people with diabetes. Treatment includes trying different nonsteroidal anti-inflammatory drugs (NSAIDs), cortisone injections (which may cause a transient rise in the blood sugars) and physiotherapy.
In addition, it appears that you have an inflammatory arthritis that is possibly due to rheumatoid arthritis. Gout should be ruled out as it can be associated with diabetes. If indeed the diagnosis is rheumatoid arthritis, you may require aggressive combination therapy with agents such as gold injections, methotrexate, sulfasalazine, infliximab or etanercept and leflunomide.
Minocycline needs about 3 to 6 months to work and can be used in combination with most of these other agents,but others are preferable. Oral corticosteroids like prednisone should be avoided because they worsen diabetes. NSAIDs need to be limited by controlling the arthritis with these other agents because NSAIDs can have negative effects on blood pressure and kidneys in diabetics. Glucosamine may raise the blood sugar in diabetics. Physiotherapy and pain killers may help the pain as well.  
This may help someone who reads about iron deficiecy anemia or "anemia" in general;Oral iron supplements are not generally associated with worsening joint pains in any type of arthritis. However, intravenous infusions of iron are. In some patients with rheumatoid arthritis or ankylosing spondylitis, involved joints may flare-up 24-48 hours after an infusion of intravenous iron. Rarely, persons without any arthritis may get transient joint symptoms after intravenous iron therapy.
One might try different iron preparations: ferrous ascorbate (eg. Ascofer), ferrous fumarate (eg. Palafer), ferrous gluconate, ferrous sulfate (eg. Slow Fe which is absorbed slowly and Fer-in-sol which is liquid). Check with a health food store about other iron preparations.

If still a problem, eat foods containing iron eg. liver, oysters and other shellfish, kidney, heart, lean red meat, turkey and chicken, fish like tuna and salmon, lima  and dried beans, dried fruit like prunes, whole grain bread, iron-enriched cereal, egg yolks and dark green vegetables. Also take vitamin C to enhance the iron absorption from your gastrointestinal system.
However, it is most important to find the cause of the low iron. The commonest causes are bleeding from the upper and lower gastrointestinal tract and from the uterus. Unusual bleeding from the vagina is fairly obvious and should be investigated by a gynecologist. Bleeding from the gut may not be obvious. It should be investigated by a gastroenterologist. Gastroscopy (looking into the esophagus, stomach and duodenum with a special tube and light source) and colonoscopy (looking into the large bowel) may be necessary.
Nonsteroidal anti-inflammatory drugs used for arthritis are a common cause of occult bleeding from stomach erosions, stomach and duodenal ulcers and small intestinal ulcers. There are often no other symptoms except for the iron deficiecy anemia. Once the cause of the iron loss is found, it will be treated so that iron supplements are no longer necessary.