Characterized by chronic widespread joint and muscle pain,fibromyalgia is a syndrome of unknown etiology. The AmericanCollege of Rheumatology's classification criteria for fibromyalgiainclude diffuse soft tissue pain of at least 3 months' duration andpain on palpation in at least 11 of 18 paired tender points.Symptoms are often exacerbated by exertion, stress, lack of sleep,and weather changes. Fibromyalgia is primarily a diagnosis ofexclusion, established only after other causes of joint or musclepain are ruled out. The initial workup for patients who present withwidespread musculoskeletal pain should include a complete bloodcount, erythrocyte sedimentation rate, liver function tests, hepatitisC antibody, calcium, and thyrotropin. The musculoskeletal system,the neuroendocrine system, and the central nervous system, particularlythe limbic system, appear to play major roles in the pathogenesisof fibromyalgia. The goal in treating fibromyalgia is todecrease pain and to increase function without promotingpolypharmacy. Brief interdisciplinary programs have been shownto improve subjective pain. Fibromyalgia is a complex syndromeassociated with significant impairment on quality of life and functionand substantial financial costs. Once the diagnosis is made,providers should aim to increase patients' function and minimizepain. This can be accomplished through nonpharmacological andpharmacological interventions. With proper management, the rateof disability appears to be significantly reduced.

Fibromyalgia is a syndrome of unknown etiologycharacterized by chronic widespread joint andmuscle pain. Fibromyalgia was previouslyreferred to as 

 in Europe referring to regional pain syndromesassociated with profound fatigue and sleep disturbance.Fibromyalgia affects approximately 6 million people inthe United States,

 or up to 6% of the patients seen ingeneral medical practices.

 Patients are usually diagnosedbetween the ages of 20 and 50 years, but the incidencerises with age so that, by age 80, approximately8% of adults meet the classification criteria establishedby the American College of Rheumatology.

 The ratio ofwomen to men with fibromyalgia varies between 9:1

 showed that patientswith fibromyalgia have approximately 10 outpatientclinic visits per year, 1 hospitalization per 3 years, andmore than $2000 per year in medical costs. Anotherprospective study

 showed that total annual costs forfibromyalgia patients were close to $6000, comparedwith $2500 for typical patients. Six percent of thesecosts were attributable to fibromyalgia-specific claims.However, there may have been other hidden costs relatedto disability from fibromyalgia. This study alsoshowed that, for every dollar spent on fibromyalgia-specificclaims, the employer spent $57 to $143 on additionaldirect and indirect costs.

The American College of Rheumatology's criteria forfibromyalgia include diffuse soft tissue pain of at least 3months' duration and pain on palpation in at least 11 of18 paired tender points.

 These criteria are approximately88% sensitive and 81% specific for the diagnosisof fibromyalgia. Symptoms are often exacerbated byexertion, stress, lack of sleep, and weather changes. Inhalf of all patients, symptoms appear after a flu-like illnessor after physical or emotional trauma.

Approximately 30% of patients with fibromyalgia arediagnosed as having concurrent depression or anxietydisorders (

The main challenge in evaluating patients with suspectedfibromyalgia is that there is no gold standard testfor diagnosis. It is primarily a diagnosis of exclusion,established only after other causes of joint or muscle painare ruled out. The initial workup for patients who presentwith widespread musculoskeletal pain should include acomplete blood count, erythrocyte sedimentation rate,liver function tests, hepatitis C antibody, calcium, andthyrotropin. Some experts recommend that patients withsuspected fibromyalgia have a limited amount of testingbefore assigning the diagnosis. The clinician should keepin mind that an antinuclear antibody is often of low yieldwhen other features of systemic lupus erythematosus orother antinuclear antibody—associated diseases areabsent. In addition, false-positive results are common. Inone series, 10% of patients with fibromyalgia had a positiveantinuclear antibody.

 Up to 30% of healthy womenmay test positive as well.

 Similarly, imaging tests andneurophysiological studies are not recommended as initialscreening tests.

In most cases, the patient's history can distinguishfibromyalgia from other systemic illnesses. However,fibromyalgia often coexists with and has a tendency tomimic other illnesses. Estimates of its concomitancewith systemic lupus erythematosus range as high as45%. In one study

 of patients with lupus, 22% of thepatients also met criteria for fibromyalgia. Thesepatients had no difference in the measures of theirlupus activity. However, they experienced greater disabilityassociated with their illnesses. Twelve percentof patients with rheumatoid arthritis and 7% of patientswith osteoarthritis meet the criteria for fibromyalgia.

Twenty-five to 50% of patients with fibromyalgia haveRaynaud phenomenon or have symptoms consistentwith sicca syndrome.

 Patients with fibromyalgia mayinitially be misdiagnosed as having seronegativespondyloarthropathies, such as ankylosing spondylitis,because they share the common complaints of neck,spine, and back pain. However, in the absence of otherinflammatory disease, patients with fibromyalgia havenormal erythrocyte sedimentation rates and normalfindings on radiographic studies. In older adults, thesyndrome is most commonly confused with polymyalgiarheumatica, which typically presents with persistentsevere morning stiffness in the shoulders, pelvis,and torso. The erythrocyte sedimentation rate will beelevated in 80% to 90% of patients with polymyalgiarheumatica, and its symptoms respond to low-dose systemiccorticosteroids. Fibromyalgia symptoms do notrespond to corticosteroids,

 consistent with the noninflammatorynature of this disorder. However, patientswith polymyalgia rheumatica who are tapered off corticosteroidstoo rapidly can occasionally develop symptomssimilar to those of fibromyalgia. Most patientswith chronic fatigue syndrome meet the criteria forfibromyalgia, and 70% of fibromyalgia patients meetcriteria for chronic fatigue syndrome.

In nonrheumatic illnesses, patients may present withsymptoms similar to fibromyalgia. Hypothyroidism canpresent with muscle pain similar to fibromyalgia.

Patients with hepatitis C have a higher prevalence offibromyalgia.

 Research suggests that Lyme disease canalso trigger fibromyalgia.

 patients withfibromyalgia had a greater number of desaturations perhour of sleep compared with healthy control subjects.Those patients complaining of daytime hypersomnolencehad a higher number of tender points, about twiceas many arousals per hour, and lower sleep efficiencycompared with the other patients.

In terms of psychiatric morbidity, an estimated 30%of patients with fibromyalgia will have depression oranxiety at some point during their lifetime. One study

found that 40% of patients with fibromyalgia haddepression, compared with 29% of patients withrheumatoid arthritis. The likelihood of depression inpatients with musculoskeletal complaints was highest inpatients with nonarticular diseases such as fibromyalgiaor myofascial pain syndrome.

 Fibromyalgia patientsdemonstrate higher levels of anxiety and depressionthan healthy control groups.

 This may exacerbate ortrigger their somatic complaints. However, according tosome investigations, measures of depression, anxiety,and stress are comparable in patients with fibromyalgiaand patients with other chronic medical conditions.

Therefore, patients with fibromyalgia may exhibit signsand symptoms of anxiety and depression, and theircomplaints should not be attributed to psychological illnessalone.

The musculoskeletal system, the neuroendocrinesystem, and the central nervous system, particularly thelimbic system, appear to play major roles in the pathogenesisof fibromyalgia.

Many soft tissue injuries are thought to follow chronicmuscle-tendon overload and muscle fiber "microtrauma."Continual vibration or muscle twisting along withrepetitive muscle movements over time can lead tomuscle spasm and nerve irritation. In fibromyalgiapatients, it has been postulated that there is an inabilityto relax the shoulder flexor muscles between isokineticmuscle contractions.

 This, over time, could leadto muscular pain.

 suggest that patients with fibromyalgiahave abnormalities in muscle energy metabolism andmuscle tissue oxygenation. For example, in fibromyalgiapatients, biopsy specimens of tender areas of the trapeziusmuscle contain more ragged red fibers and fewerhigh-energy phosphate compounds than specimens ofnontender muscles in these patients.

 Some musclebiopsies of the tissue surrounding tender points haveshown structural changes described as "moth-eatenfibers," mitochondrial changes, and type II atrophy,indicating dysfunction in the muscle microcirculation.

Together, these data may support the hypothesis thatlocal tissue hypoxia contributes to the pain associatedwith fibromyalgia. However, it is not clear whether thesemuscle changes are a cause or an effect of fibromyalgia.The fact that local treatment of tender points is generallyineffective suggests 1 of 2 possibilities: eitherfibromyalgia is a systemic disease rather than an aggregateof localized muscle disturbances, or we simply donot have effective local therapies.

Other more recent investigations show that there areno differences between fibromyalgia patients and sedentarycontrols in terms of adenosine triphosphate levels,lactate levels, muscle tension, hypoxia, or intracellularpH.

 Results demonstrate that measures of musclefunction such as force generation and lactate productionduring exercise, and muscle pain after exertion, aresimilar between women with fibromyalgia and healthysedentary female control patients.

 This suggests thatthe cause of fibromyalgia symptoms is unlikely to be apathologic abnormality of the muscle itself.

The neuroendocrine dysfunction in fibromyalgiainvolves the hypothalamic-pituitary-adrenal axis, thehypothalamic-pituitary-thyroid axis, the growth hormoneaxis, and the locus caeruleus—norepinephrinesympathetic nervous system. With respect to the hypothalamic-pituitary-adrenal axis, some findings suggestthat fibromyalgia patients may have low adrenal responsiveness.

 showed that in these patients,when corticotrophin-releasing hormone is releasedfrom the hypothalamus, there is a disproportionatelyhigh level of corticotropin released from the pituitary inresponse and an unexpectedly small amount of cortisolthat are eventually released by the adrenal glands intothe bloodstream. This suggests that these patients mayhave a blunting of the normal stress response and maynot react appropriately to events such as infection orphysical or emotional trauma.

However, these same patients, when injected withsynthetic corticotropin, showed a similar increase intheir cortisol levels compared with healthy control subjects.

 This shows that adrenal tissue in fibromyalgiapatients may have a differing sensitivity to exogenousversus endogenous corticotropin. Therefore, perhapsthese patients have a blunted response to endogenouscorticotropin due to a downregulation of receptors, asmight be found in settings of chronic stress, rather thantrue adrenal insufficiency.

Multiple studies have shown that fibromyalgiapatients have elevated cortisol levels with a flatteneddiurnal pattern

 and lack of suppression by dexamethasone.

 Results have shown that patients withdepression also have elevated levels of corticotropin andcortisol, with a flattening of the diurnal pattern.

Investigations of the hypothalamic-pituitary-thyroidaxis in fibromyalgia patients suggest that, when thyrotropin-releasing hormone is released, thyrotropin, triiodothyronine,and thyroxine are secreted, but to alesser degree than expected.

 These data imply thatthere is some pituitary dysfunction in these patients,perhaps related to a dampened stress response.

It is also thought that sleep disorders may induceneuroendocrine dysfunction, which, in turn, promotesdisease development. During stage 4 sleep, the bodyproduces most of its growth hormone. In patients withfibromyalgia, stage 4 sleep is often disrupted.

 Althoughfactors such as weight and age were not controlled for,the patients who were studied appeared to have adecreased level of somatomedin C, the precursor togrowth hormone.

 It has been suggested that this relativegrowth hormone deficiency may account forpoor healing of muscle microtrauma, thereby contributingto nociceptive input.

 It has been shownthat patients with fibromyalgia have increased levelsof corticotropin

 and that corticotropin increases thesecretion of somatostatin in the hypothalamus.

 Somatostatinis one of the hormones that is able to inhibitgrowth hormone via the hypothalamic-pituitary portalsystem.

 This may also contribute to the relativegrowth hormone deficiency in fibromyalgia patients.Approximately 30% of patients with fibromyalgia havegrowth factor deficiency if defined by low insulin-likegrowth factor 1 levels.

 However, these low levels maybe more common than clinically significant growth hormone.

 showed impaired reactivity ofthe hypothalamic-pituitary axis in one third of thepatients with fibromyalgia, but did not show the presenceof severe growth hormone deficiency. Somepatients have experienced pain relief with injections ofsubcutaneous growth hormone versus placebo.

Fibromyalgia patients often exhibit allodynia, a phenomenonwhereby formerly innocuous stimuli becomepainful. One showed that fibromyalgia patients have significantlyhigher scores than controls on an index ofsensory discrimination for various mechanical stimuliat tender and control points. This is consistent with thetheory that they receive increased neural input to stimulirelative to controls. Weigent et al

 showed that thethresholds for detecting stimuli were similar betweenfibromyalgia patients and healthy controls. However,the points at which heat, electrical stimulation, andpressure became painful were different. Regional bloodflow investigations using functional magnetic resonanceimaging showed that, when the patients had similar subjectivediscomfort, they had the same level of blood flowto the corresponding regions of their brains.

 For thesame amount of pressure applied, however, thefibromyalgia patients experienced greater discomfortand increased regional blood flow and neurological activationthan healthy controls.

Fibromyalgia patients generally have a greater sensitivityto stimuli diffusely, suggesting that there may be acentral or a peripheral nervous system disturbance.This theory is supported by the fact that patients have2 to 3 times normal levels of substance P, a pain modulator,in their cerebrospinal fluid.

 Stress may potentiatethe nociceptive effects of substance P in fibromyalgiaby stimulating nerve growth factor. Fibromyalgiapatients may have an increased amount of this factorin their cerebrospinal fluid.

 This, in turn, may promoteperipheral nerve growth and abnormal pain perception.These patients' cerebrospinal fluid alsocontains elevated levels of calcitonin gene—relatedpeptide and dynorphin A, which normally increaseafter injury. Although there are multiple potentialexplanations for this change, one possibility is thatthere may have been an insult to the nervous systemin fibromyalgia patients.

Serotonin is a neurotransmitter in the spinal cordthat inhibits the transmission of pain. It is derived from&#955;-tryptophan, an amino acid that appears to bedecreased in the cerebrospinal fluid of patients withfibromyalgia.

Research by the National Cardiology Institute ofMexico has suggested that dysautonomia is frequent inpatients with fibromyalgia.

 They found that the sympatheticnervous system is persistently hyperactive atbaseline, but hypoactive in response to stress.

The goal in treating fibromyalgia is to decrease painand to increase function without promoting polypharmacy.Brief interdisciplinary programs have beenshown to improve subjective pain. A high pretreatmentlevel of impairment was significantly associated with abetter response to treatment.

Critical elements in developing a self-managementprogram for patients are improving self-efficacy, physicaltraining, and cognitive-behavioral techniques.

 In investigationsof patients with rheumatoid arthritis, changesin self-efficacy were shown to significantly predictchanges in pain, depression, and health status, regardlessof changes in medical regimens.

 Self-efficacy ispromoted by mastery, modeling, social persuasion, andphysiological feedback. To develop mastery, patientsmust have the chance to practice skills until they areable to succeed at them and use incremental successesas positive reinforcement for their continued efforts.Finally, physiological feedback such as pain scales mayhelp patients visualize marginal improvements.

Cognitive strategies that emphasize restructuring ofnegative thoughts and catastrophic generalizationsabout pain are powerful ways to cope with fibromyalgiapain and fatigue.

Patients with fibromyalgia may be aerobically unfit

because of inactivity due to pain. Unaccustomed exercisemay exacerbate the pain and lead to delayed-onsetmuscle soreness in the short run. Despite this, controlledtrials of exercise demonstrate that people withfibromyalgia can increase their levels of physical fitness,with associated decreases in pain.

 Bicycling, walking,and water aerobics are among the best-toleratedexercises. Perhaps this is because aerobic exerciseincreases the body's production of endogenous opioids.These powerful endorphins act through the limbic systemto decrease pain and to induce the euphoria commonlyknown as runner's high. It has not been shown,however, that endorphin levels are decreased infibromyalgia patients. Also, exercise facilitates sleep.Because sleep dysfunction compounds the symptoms offibromyalgia, restoring sleep could disrupt the cycle inwhich increased pain leads to decreased sleep, whichthen results in increasing pain and disability. In addition,aerobic exercise increases oxygenation and circulationto muscle tissue.

 Exercise can also havepsychologically beneficial effects, such as promoting asense of well-being and a sense of accomplishment.Randomized controlled trials have shown that exerciseimproves mood and decreases disability in patients withfibromyalgia.

 Therefore, patients should be encouragedto perform aerobic exercise at least 3 times a week.Flexibility training alone can improve symptoms, but toa lesser extent.

 A systematic review of randomizedcontrolled trials of nonpharmacological interventions infibromyalgia between 1980 and 2000 did not providestrong evidence for any single treatment.

 However, itshowed moderate support for aerobic exercise as a therapeuticintervention.

Almost all patients with fibromyalgia have sleep dysfunctioncharacterized by light unrefreshing sleep.

Tricyclic antidepressants may be helpful as a form oftreatment, perhaps because they improve sleep andmay reduce morning stiffness.

 They may also act byinhibiting serotonin and norepinephrine reuptake,thereby suppressing polysynaptic neuronal discharge.

A randomized controlled trial of low-dose amitriptylinehydrochloride and naproxen sodium showed thatpatients improve with tricyclic antidepressants in termsof pain, sleep difficulties, fatigue on awakening, andtender point score.

 Nonsteroidal anti-inflammatorydrugs may have an additive effect,

 although theireffect may be analgesic rather than anti-inflammatory.Fluoxetine hydrochloride may improve symptoms ofdepression and fatigue, but has not been shown todecrease the number of tender points.

 Amitriptylineand fluoxetine may work better in combination thaneither one alone.

 Trazodone hydrochloride has alsobeen shown to be effective, perhaps because it increasesthe duration of stage 3 and stage 4 sleep and decreasesthe alpha-delta sleep abnormality common infibromyalgia.

 Zolpidem tartrate does not appear toimprove the pain of fibromyalgia, but may improvesleep and daytime energy.

 Cyclobenzaprinehydrochloride may decrease the severity of pain andimprove the quality of sleep in fibromyalgia patients,but it does not appear to alleviate the fatigue or morningstiffness.

 Opioids may be helpful in treatingfibromyalgia pain, but may be habit-forming, toleragenic,and associated with adverse effects such as constipation,sedation, and nausea.

Transcutaneous electrical nerve stimulation, lasertreatment, and acupuncture appear to have limited painefficacy. Although there are no controlled trials demonstratingbenefit, 1% lidocaine hydrochloride injections,botulinum toxin injections, and dry needling are sometimesoffered to patients with fibromyalgia.

 Despite asuggestion of relative growth hormone deficiency in personswith fibromyalgia and reports of improvementafter receiving injections of growth hormone, adverseeffects, frequent injections, and cost have dampenedenthusiasm for this approach.

Relaxation strategies for the relief of muscle tensionand anxiety are also effective.

 Electromyograms withfeedback exercises and hypnosis are therapeutic modalitiesthat are being investigated.

Treatment of concomitant conditions may improvesymptoms of fibromyalgia. For example, fibromyalgiamay be particularly difficult to treat when untreateddepression, anxiety, or sleep apnea is also present.

Follow-up of patients with fibromyalgia after 14 yearsshows that patients may have minor change in theirsymptoms, but do not develop progressive disabilityfrom the disease.

 Remissions are rare after many yearsof disease, but may occur in the first year or 2, especiallyin milder community-based settings. One study

of ambulatory patients showed that 47% no longer fulfilledthe American College of Rheumatology's criteriafor fibromyalgia syndrome. Remissions were identifiedin 24.2% of patients. Therefore, patients who are basedin the community may have a good outcome. Thirty-fivepercent of patients who are able to be managed bytheir primary care physicians experience resolution ofsymptoms after 2 years.

 suggested that most fibromyalgia patients showimprovement in terms of overall status, pain, fatigue,and function at 40 months. The only predictors forfavorable outcome in this study were younger age andless sleep disturbance. However, it appears that patientssent to referral centers generally have no change intheir pain, fatigue, sleep disturbance, anxiety, ordepression symptoms after 8 years.

Problems that may interfere with the employment ofpatients with fibromyalgia include difficulty in performingrepetitive motor tasks, prolonged sitting or standing,loss of mental acuity, anxiety about poor performance,and workplace stressors.

 used computerizedworkstations in simulated work environments tophysically stress the shoulders, spines, wrists, andelbows of fibromyalgia patients, patients with rheumatoidarthritis, and healthy controls. Patients withfibromyalgia could only perform 59% of the work performedby their healthy counterparts, compared withpatients with rheumatoid arthritis, who could perform62% of that workload.

Disability secondary to chronic pain appears toresult from a combination of patients' past experiences,self-esteem, motivation, psychological distress, fatigue,ethnocultural background, education, income, andpotential financial compensation.

 Disability in chronicpain does not appear to be related to the severity ofthe pain.

 Thirty percent of patients with fibromyalgiaare disabled, compared with 2% of the general population.

 Patients with other forms of chronic pain have adisability rate of approximately 10%.

Fibromyalgia is a complex syndrome associated withsignificant impairment on quality of life and functionand substantial financial costs. Although its cause is notwell understood, it is clear that interdisciplinaryapproaches to its management are probably the mostbeneficial. Therefore, once the diagnosis is made,providers should aim to increase patients' function andminimize their pain complaints. This can be accomplishedthrough different nonpharmacological and pharmacologicalinterventions. With proper management,the rate of disability appears to be significantly reduced.

From the Spaulding Rehabilitation Hospital, Harvard Medical School (DEN), and BethIsrael Deaconess Medical Center (RHS), Boston, Mass.

Address correspondence to: Devi E. Nampiaparampil, MD, Spaulding RehabilitationHospital, Department of Physical Medicine and Rehabilitation, 125 Nashua Street,Boston, MA 02114. E-mail: dnampiaparampil@partners.org.

 A lesson on lumbago: its lessons and analogues. 

 What can rehabilitation interventions achieve in patients with primaryfibromyalgia? 

3. Wolfe F, Ross K, Anderson J, Russell IJ, Hebert L.

 The prevalence and characteristicsof fibromyalgia in the general population. 

Articles

CLINICAL

A Review of Fibromyalgia

 To assess the appropriateness of nonsteroidal antiinflammatorydrug (NSAID) use relative to recent osteoarthritistreatment guidelines from the Second Canadian ConsensusConference.

 Observational study of self-reported practice in acohort of physicians from the Canadian Osteoarthritis Rx(CANOAR) study.

 Ontario primary care physicians wererecruited from the top 10% of NSAID prescribers based on thenumber of NSAID prescriptions filled per year. Physicians wereasked to record office visits on a 1-page data collection form fromNovember 2000 to December 2001.

 Of 1400 physicians invited, 185 were enrolled and 119registered office visits. Data were analyzed for the first visits of5459 patients for whom a prescribed NSAID was identified, ofwhom 60% were female and 46% were older than 65 years.Coxibs were prescribed for 56% of study patients and were morecommonly used by those with recent gastrointestinal (GI) events(85%), those receiving warfarin sodium therapy (79%), and thosewith congestive heart failure (68%). Coxib use increased withincreasing global assessment of OA severity, but not patient age.Overall, 58% of prescriptions were considered appropriate givenpatient GI risk factors.

 Most coxib and NSAID prescriptions were consistentwith the guidelines, but there was considerable underuse ofcoxibs in at-risk patients and some overuse of coxibs and of gastroprotectiveagents with NSAIDs in patients with no identified GIrisk factors. Increased recognition of relationships between patientage and NSAID-related GI risk would likely promote more appropriateuse of traditional NSAIDs, coxibs, and gastroprotectiveagents in osteoarthritis patients.

Osteoarthritis (OA) is a joint disease characterizedby degenerative changes in the articularcartilage and progressive joint deterioration. Itis the most common type of joint disease and is a majorcause of disability.

 In Western countries, radiographicevidence of OA is present in most individuals by 65years of age and in about 80% of those older than 75years.

 In Canada, an estimated 4 million individuals 15years and older experienced arthritic disorders in 2000,and the direct and indirect costs of these diseases in1998 were estimated to be at least Can$4.4 billion.

Osteoarthritis is expected to account for about half ofthese costs.

Osteoarthritis typically presents as pain involving 1or several joints. The primary goal of treatment is torelieve pain, thereby improving function and quality oflife. Treatment guidelines in Canada

 recommend nonsteroidal anti-inflammatorydrugs (NSAIDs) as second-line treatment (after acetaminophen)for mild OA and as first-line treatment formoderate-to-severe OA.

Canadian guidelines further recommend that, inpatients at high risk for upper gastrointestinal (GI)adverse events, the use of traditional NSAIDs should beaccompanied by prophylaxis with misoprostol or a protonpump inhibitor.

 Risk factors include a history ofpeptic ulcer disease, GI bleeding, cardiovascular disease,and aged 65 years or older.

Alternatively, the use of coxib NSAIDs (cyclooxygenase-2—specific inhibitors) as first-line treatment forhigh-risk patients is also recommended by Canadianguidelines.

 Large clinical trials have demonstratedthat these drugs have efficacy similar to that of traditional(non-coxib) NSAIDs

 Although coxibs are not medicallycontraindicated for low-risk patients, economic modelssuggest that they may not be cost effective in thisgroup.

The Canadian Osteoarthritis Rx (CANOAR) studywas designed to characterize OA patients in Ontario forwhom primary care physicians prescribed NSAIDs. Thisarticle examines the use of NSAIDs in this study cohortin relation to recommendations for their appropriateuse as published in the Second Canadian ConsensusConference arthritis treatment guidelines.

The CANOAR study was an observational study of acohort of primary care physicians with high-volumeNSAID prescribing practices. The objective was todetermine the clinical circumstances under whichNSAIDs were prescribed for OA patients in routine clinicalpractice. The study took place in Ontario, aprovince of 11 million people under a single healthcaresystem.

Before conducting the study, a steering committeewas formed with 2 primary care physicians, 3 rheumatologists,a biostatistician, a health economist, the chiefexecutive officer of The Arthritis Society, and a patientwith OA. The committee met to review and modify aninitial draft protocol and data collection form. A reviewof the modified protocol by 4 rheumatologists, 4 epidemiologists,and 2 health economists further focusedthe study design.

One-page clinical encounter data forms using anonymoussequential patient identifiers were designed andpilot-tested in collaboration with 7 primary care physicians.The form recorded patient demographics, locationof principal OA joint involvement, global physicianand patient assessments, concomitant medical problems,history of clinically significant GI events, currentdrugs, and previous use of and current recommendationsfor OA therapies and gastroprotective agents(GPAs). The form allowed identification of the followingGI risk factors listed in the Second Canadian ConsensusConference guidelines: history of a clinically significantGI event, advanced age (aged 65-74 years was scored as1 risk factor, while age &#8805; 75 years was scored as 2 riskfactors), current and continuing use of warfarin sodium,current and continuing use of corticosteroids, hypertension,congestive heart failure, renal insufficiency,and hepatic insufficiency. Renal risk factors recordedwere renal insufficiency, hypertension, congestive heartfailure, hepatic insufficiency, and concomitant antihypertensivedrugs.

The forms were designed to be usable as part of theroutines of normal clinical practice. Seven pilot physicianstested the protocol by enrolling 10 patients andprovided final assessments and recommendations aboutoffice procedures for patient enrollment and consent,data form completion, and data transmission to thedata center by toll-free, never-busy facsimile. The pilotphysicians also provided estimates of required perpatient time, for inclusion in the physician recruitmentletter.

After receiving ethics review board approval, theCANOAR study proceeded with physician recruitment.Of the 12 000 primary care physicians in Ontario, 1400of the top NSAID prescribers, based on the number ofNSAID prescriptions filled in 2000, were identified from aphysician list sourced from the IMS Health Canada aggregatedprescriber-level database. These physicians wereinvited by letter to participate. Each participating physicianwas asked to record up to 130 office visits, includingfollow-up visits, of successive patients for whom theydecided to prescribe an NSAID or a coxib (new or renewal)for OA. Participants were not provided with theSecond Canadian Consensus Conference guidelines aspart of the study protocol and were not told that theirresults would be compared with guidelines. Physicianswere reimbursed Can$20 per completed form.

Although a diagnosis of OA is a determinant of eligibilityfor coxib coverage by the Ontario Drug BenefitsProgram, which provides basic drug coverage to allOntario citizens 65 years and older, the program doesnot specify OA diagnostic criteria.

 The phrase "workingdiagnosis of OA" was therefore used on the dataform to avoid telling participating physicians how todiagnose OA. Patients were included in the study if theyhad a working diagnosis of OA by the treating primarycare physician, received a prescription for an NSAID ora coxib as part of routine care on the first study visit,and gave consent for the use of their anonymous datafor aggregate analyses.

Completed data forms were sent by toll-free facsimileto the data center. Standardized data managementprotocols for paperless and semiautomated processesadapted to the specific needs of the study were used toaggregate and process the data into a relational database.The Goodman-Kruskal &#947; statistic was used as ameasure of ordinal association. All statistical comparisonswere 2-tailed, with 

 < .05 considered statisticallysignificant.

Of the 1400 physicians invited, 185 agreed to participateand were enrolled. It was not possible to examinewhether characteristics of participants differed fromthose of nonparticipants, because the aggregated prescriberlist was not ranked and did not preserve prescribingdata or other individual characteristics. Datacollection continued during 14 months, from November2000 to December 2001, with 119 (64% of thoseenrolled) of the physicians registering 8846 office visitsof 5947 OA patients in the study (the number ofpatients with 2, 3, and >3 visits were 1034, 431, and280, respectively). Data were analyzed for the first visitsof the 5459 patients for whom a prescribed NSAIDwas identified.

Of the 5459 OA patients for whom data were analyzed,60% were female and 46% were older than 65years. All residents of Ontario 65 years and older havelimited public drug coverage through the Ontario DrugBenefits Program. In this study, 57% of patients youngerthan 65 years and 19% of patients 65 years or older hadprivate drug coverage.

A large number of patients had other concomitantconditions. The most common comorbidities werehypertension (34%) and coronaryartery disease (12%). A clinicallysignificant GI event hadbeen experienced by 8% ofpatients. More than a third (34%)of patients were receiving concomitantantihypertensive therapy,and 17% were receivinglow-dose aspirin (the study protocoldid not specify a thresholddose because physicians mayhave differed in their operationaldefinitions of low-dose aspirinfor cardiovascular protection).

At the time of the first studyvisit, 20% of patients werealready receiving a GPA.Acetaminophen had previouslybeen tried by 61% of patients fortheir OA symptoms, and 49%had tried 1 or more NSAIDs(

). Five percent ofpatients had tried 3 or more NSAIDs. Of the 5459patients, 1145 (21%) were receiving NSAIDs for thefirst time at their first CANOAR study visit.

Nonsteroidal Anti-inflammatoryDrug Prescribing Patterns

Coxibs were prescribed at 56% of visits in this studycohort, evenly divided between rofecoxib and celecoxib(

). Diclofenac, meloxicam, naproxen, andibuprofen were less commonly recommended. Fortypatients (0.7%) received aspirin prescriptionsat the study visit, andbecause it was unclear whether theywere for OA therapy, these prescriptionsare not included in Figure 2.

Coxib use was higher in certainhigh-risk patient subgroups. Amongthe 26 patients who had experiencedclinically significant GI events in theprevious 60 days, 85% were prescribedcoxibs (

), while 74%of the 214 patients whose GI eventshad occurred within the last 10 yearsreceived coxibs. Most (79%) of the 72patients receiving warfarin therapyand most (68%) of the 163 patientswith congestive heart failure werealso prescribed coxibs. However, thepercentage (57%) of patients withhypertension who were prescribedcoxibs was similar to that (56%)among all patients, and coxib use did not vary withpatient age (Goodman-Kruskal &#947; = 0.07, SE = 0.02, 

 =.60; data not shown). Although it appeared that coxibswere prescribed more commonly as the number of GIand renal risk factors increased (

), these trendswere not statistically significant (

 = .21,respectively). However, the results suggested a thresholdeffect, with higher coxib use for patients with 4 ormore risk factors than for those with 3 or fewer. A posthoc analysis in which risk factor categories were pooledconfirmed that this difference was significant (GI andrenal risk factors, 

 < .001 for both; Fisher exact test).Coxib use increased significantly with increasing globalpain assessments (physician and patient assessments,

Gastroprotective Agent Prescribing Patterns

Gastroprotective agents were coprescribed with anNSAID at 31% of visits. The most common reason givenfor prescribing a GPA was NSAID GI prophylaxis (39%).Other reasons included dyspepsia (19%), gastroesophagealreflux disease (25%), and a history of ulcer(8%). Misoprostol was the most commonly prescribedGPA, usually in the form of a combination pill ofdiclofenac and misoprostol, while H2 antagonists (eg,ranitidine) and proton pump inhibitors (eg, omeprazole)were also used, although less often (

). Patientsreceiving non-coxib NSAIDs were more likely toreceive GPAs than were coxib patients (45% vs 21%).

Gastroprotective agent coprescriptions were morecommonly given to patients with a higher number ofGI risk factors (Goodman-Kruskal &#947; = &#8722;0.20, SE =0.04; 

). The percentageof patients who werecoprescribed a GPA with theirNSAID was 25% for patients youngerthan 65 years, 34% for those aged 65to 69 years, 39% for those aged 70 to74 years, 39% for those aged 75 to 79years, and 45% for those older than79 years.

Acetaminophen had been triedpreviously by 61% of study patients.The prevalence of its previous useincreased with increasing patientage and the number of GI and renalrisk factors (

 < .001 for all). In addition,previous acetaminophen usewas more common among patientswith higher patient and physicianglobal assessments of OA severity (

Most coxib prescriptions were for patients with 1 ormore GI risk factors, but a large percentage (39%) werefor patients with no identified risk factors and could beconsidered to be less cost effective (

). Most(56%) prescriptions for a traditional NSAID alone werefor patients with at least 1 GI risk factor, for whom aGPA coprescription or a coxib would be recommended.Of 1081 prescriptions for traditional NSAIDs plusGPAs, 31% went to patients with no identified risk factors.Physicians did not indicate a reason for prescribinga GPA in 40% of prescriptions for traditionalNSAIDs plus GPAs, so these cases were excluded fromthe analysis of appropriate prescribing. In 98% of theseexcluded cases, the prescription wasfor the NSAID and GPA combinationpill Arthrotec (diclofenac sodiumand misoprostol). Somephysicians who prescribedArthrotec may not have consideredthat they were actively prescribinga GPA, which may explain the highrate of nonresponse to this question.This problem was addressedby also excluding from the analysisof appropriate prescribing all 236Arthrotec prescriptions for which areason for prescribing a GPA wasgiven. Of the remaining 413 prescriptionsfor traditional NSAIDsplus GPAs, 73% went topatients with 1 or moreidentified risk factors andwere counted as appropriate.The other 27% went topatients with no identifiedrisk factors. Of these prescriptions,63% were prescribedfor NSAID GIprophylaxis only and werecounted as inappropriate,while the remainder wereprescribed for other reasons(30%) or for NSAID GI prophylaxisand other reasons(6%) and were counted asappropriate. Therefore, 83%of prescriptions for traditionalNSAIDs plus GPAswere considered appropriate.

For patients with no identified GI risk factors, 33% ofnonexcluded prescriptions were considered appropriate,whereas for those with 1 or more risk factors, 74%were considered appropriate. Overall, 58% of nonexcludedprescriptions were considered to be appropriategiven patient GI risk factors. If the analysis was restrictedfurther to exclude prescriptions for traditionalNSAIDs plus GPAs in which the GPA was prescribed forreasons other than GI prophylaxis alone, 32% of prescriptionsfor patients with no identified GI risk factors,73% of those for patients with 1 or more risk factors, and56% overall were considered appropriate.

Treatment guidelines in the United States,

 stress the importance of tailoring OAtreatment to individual patient needs. Patient age andthe presence of comorbidities should be important factorsin treatment selection. The 2000 Second CanadianConsensus Conference guidelines

 that were availablewhen this study was conducted are a relevant benchmarkfor prescribing practice at the time. Although subsequentlypublished guidelines

 have refined thecriteria for appropriate coxib, NSAID, and GPA prescription, they identify the same risk factors as did theSecond Canadian Consensus Conference and agree onselection of a coxib or an NSAID plus GPA for at-riskpatients. On the basis of the Second Canadian ConsensusConference guidelines, 42% of prescriptions inthe CANOAR study were inappropriate given patient GIrisk factors. There was underuse of coxibs and ofNSAIDs plus GPAs for patients with 1 or more risk factorsand overuse of these options for patients with noidentified risk factors. The percentage of prescriptionsdeemed appropriate was higher for coxibs than for traditionalNSAIDs alone (61% vs 44%) but lower than that(83%) for traditional NSAIDs plus GPAs. Greater appropriateuse of traditional NSAIDs in combination withGPAs than of coxibs may reflect the fact that coxibswere a new prescribing option when this study wasconducted.

All guidelines recommend acetaminophen as a firstlineagent, primarily because of its GI safety. In accordwith guidelines, most patients in this Ontario cohorthad previously tried acetaminophen, particularly olderpatients, those with multiple risk factors, and thosewith severe OA.

Bleeding, upper GI ulcers, and perforation occur inapproximately 1% of patients treated with non-coxibNSAIDs for 3 to 6 months.

 Among patients treated for1 year, 2% to 4% are affected. These events are costlyand can lead to reduced compliance and decreasedquality of life.

 Recent clinical trial evidence foundthat, compared with acetaminophen alone, NSAIDs incombination with a GPA produced significantly greaterimprovements in pain scores for patients with moderateOA.

 In our study, GPAs were prescribed at 31% ofvisits, and 39% of these prescriptions were for NSAIDGI prophylaxis. In addition, GPA prescriptionsincreased with the number of GI risk factors. Forpatients with the same number of GI risk factors, thosereceiving coxibs had a somewhat lower rate of GPAcoprescription compared with those receiving traditionalNSAIDs, often for reasons other than NSAID GIprophylaxis. In general practice, GPAs are commonlyand appropriately prescribed to treat conditions suchas gastroesophageal reflux disease and dyspepsia.

DRUG SAFETY

Appropriateness of NSAID and Coxib Prescribing for Patients With Osteoarthritis by Primary Care Physicians in Ontario: Results From the CANOAR Study

 To determine whether an intervention designed toinform and guide patients in choosing a primary care provider(PCP) could increase satisfaction and trust.

 A randomized controlled trial conducted at the SantaClara Medical Center of the Kaiser Permanente Medical CareProgram in Northern California.

 Patients needing a PCP were randomlyassigned to Informed Choice (provider-level information offered),Guided Choice (PCP names provided based on the similarity ofpatients' and practitioners' patient-centered beliefs, and patientsthen chose), or Usual Care. One year later, mailed questionnairesasked about patients' trust and satisfaction, perceptions of thechoice process, and trust and satisfaction with Kaiser Permanente.More than 5000 adult patients were linked with a PCP as part ofthe project, and completed surveys were returned by 2437patients.

 Neither intervention arm generated better matches onpatient-practitioner beliefs than Usual Care; however, trust and satisfactionwere higher among Guided Choice patients. Across studyarms, patient-practitioner belief discrepancy showed a consistentpositive association with trust, satisfaction, and attitudes towardKaiser Permanente.

 The discrepancy between patient and practitionerbeliefs about care is an important determinant of trust and satisfaction,and involving patients in the selection of their PCP can havean independent positive effect. It should be possible to build on theexperience of this project to develop programs that better matchpatients and practitioners within managed care plans.

People in almost 50 million US households selectedor changed to a new physician in a recent 2-year period.

 In finding a new physician, patientsprefer to select rather than be assigned, and those whochoose are more satisfied, trusting, and likely to adhereto recommendations.

 Most people rely on the recommendationsof friends, family, or coworkers. However,those who desire information from their health planstypically indicate that they "pick blindly" from listsprovided to them, and many patients attribute the findingof a clinician with whom they were comfortable togood luck.

Patients vary in the kinds of practitioner informationto which they would like access,

: descriptors and characteristics (eg,sex, medical school, and years in practice), convenienceand logistics (eg, location, hours, and wait forappointments), expertise and qualifications (eg, training,number of procedures performed, and malpracticesuits), and relationship and bedside manner (eg, compassion,communication skills, and practice style).Although expertise and qualifications were the characteristicsthat patients mentioned most often as important,finding a physician who shared a similar ideologyand had good communication skills was deemed bymany as at least as important.

A review of 40 commercial (eg, WebMD and bestdoctors.com) and organization-specific (eg, CIGNA, Pacificare,and Boston Medical Center) Web sites that containedprovider-specific information indicated that the availableinformation varied considerably.

 For instance,physician location was contained in 92.5% of Web sites,specialty in 87.5%, medical school in 62.5%, and boardcertification in 55.0%. Information on physicians' philosophyof providing care was available in only 3 (7.5%)of the sites reviewed.

Although few sources provide information on practitionerbeliefs about care, several studies

 havedemonstrated that the extent to which patients andpractitioners hold similar or comparable beliefs is associatedwith satisfaction and trust. In these studies,patients and their physicians completed identical versionsof the Patient-Practitioner Orientation Scale(PPOS), a validated instrument that measures thedegree to which each holds patient-centered beliefsabout the sharing of power and information. Building onthese findings, this article presents the results of aprospective randomized trial in which patients wereguided in their choice of a practitioner based on theirbeliefs about care.

It was hypothesized that providing patients with abasis for choosing a primary care provider (PCP) basedon beliefs about care in the Guided Choice arm wouldresult in physician-patient pairs who were in greateragreement than those who had not received such information.Moreover, it was expected that the greaterbelief similarity found in Guided Choice would result ingreater patient trust and satisfaction.

The funding agencies for this project played no rolein any aspect of its design or in the collection, analysis,or interpretation of the data, and they made no requirementsof approval of the finished manuscript. TheKaiser Foundation Research Institute InstitutionalReview Board approved the study.

The site for the study was the Department ofMedicine at the Santa Clara Medical Center of theKaiser Permanente (KP) Medical Care Program inNorthern California, a large group-model health maintenanceorganization. At the time the study began,there were approximately 162 000 members and 80adult medicine PCPs on staff at the Santa ClaraMedical Center. Of these PCPs, 52 completed thePPOS and were linked with at least 1 patient throughthe intervention.

Any adult member 30 or older who was not linked toa PCP in the automated health plan database was eligiblefor the study, although only one family membercould participate. Patients were selected from recentlyenrolled members who did not have a PCP, ongoingmembers who did not have a PCP listed, and patients of2 PCPs with large panels who had retired shortly beforethe initiation of the study. Within each of these sources,patients were randomly assigned to 1 of 2 intervention(choice) arms or to the Usual Care arm. Further detailsof the selection and randomization processes have beenpreviously published.

All patients in the 2 intervention arms were contactedby mail at the outset of the study and were encouragedto contact the center to obtain a new PCP viatelephone or a Web site set up especially for this project.The Web site had a set of simple instructions forselecting a PCP, and patients who used the telephonereached a research assistant who led them through thesame procedure.

 Patients in this arm were offeredprovider-specific information on all available PCPs,which included sex, age, practitioner type (physician ornurse practitioner), medical office location, race or ethnicity,languages spoken, medical school attended, areasof clinical interest, areas of personal interest or hobbies,and openness to alternative medicine. A recent photographwas also available for those who used the Internet.

 Patients in this arm had available tothem all the information of Informed Choice patients,but their selection process involved an additional element:they were given a list of PCPs whose beliefs aboutthe sharing of power and information were closest totheirs. To accomplish this, before the project began, allavailable PCPs were asked to complete a 9-item sub-scaleof the PPOS. All Guided Choice patients responded toidentical items as part of the selection process, and theiranswers were computer scored immediately (scorerange, 9-54, with a higher score indicating greaterpatient-centeredness). Patients were then offered a listof 2 to 5 PCPs whose scores were most similar (theywere told that these practitioners had a "communicationstyle" that most closely matched theirs).

The algorithm for recommending practitioners providedthe names of at least the 2 best matches, definedas the lowest absolute difference between the patient'sand the practitioner's scores. Up to 5 practitioners'names were offered if the absolute difference betweenthe patient's and the practitioner's PPOS scores waswithin 5 points. Guided Choice patients were notrequired or pressured to select one of the indicated practitionersand were encouraged to explore additionalinformation (the same information available to InformedChoice patients) about any PCP with an open panel.

Patients in the Usual Care arm, which served as abaseline or control group, consisted of new and ongoingmembers who were not identified as part of the panel ofa specific PCP. They were contacted by mail and wereencouraged to call the medical center's patient servicesdepartment to obtain a PCP. Patient services staff didnot have access to any systematic information aboutpractitioners and were instructed not to offer unsolicitedinformation, although they were courteous inanswering practitioner-relevant questions. In theabsence of a stated preference, patients were linked toan available PCP by whatever nonsystematic mechanismswere typically used at that center.

Usual Care patients whose PCP had just retiredreceived a letter from the health plan informing them oftheir PCP's retirement and assigning them to a newPCP. Although this method of assignment was morerestrictive than that used for the other Usual Carepatients, the 2 methods of pairing patients and practitioners(which were combined for purposes of analysis)were low choice and low information and were standardprocedure (ie, usual care) at that center for connectingpatients with PCPs. All patients were surveyed by mailto assess outcomes approximately 1 year after theirlinkage with a PCP.

There were 10 944 patients deemed eligible for thestudy. Of these, 5059 (46.2%) were linked with a PCPduring the study, 44.0% in the combined choice armsand 51.0% in the control arm. For the survey, we sampled3884 patients, which excluded half of the UsualCare arm patients of retiring physicians who had beenassigned a new PCP by mail (done to save survey costs)and more than 500 patients who had died, left thehealth plan, or for whom accurate contact informationwas unavailable. After 3 waves of mailing and 1 telephonereminder, we received completed surveys from2437 patients, a response rate of 62.7%. This wasreduced by 269 respondents who had selected a PCPwho practiced at a different site, 144 patients who indicatedthat the listed practitioner had never been theirPCP, and 15 people who had left KP. All baseline analysesof patients are based on these 2009 patients whohad been randomized to 1 of the 3 arms. However,because we did not have PPOS scores for both membersof some patient-practitioner pairs, analyses that investigatedpatient-practitioner belief similarity are based on1766 patients (

The following information was obtained via questionnaire:

Personal and Demographic Characteristics.

 Thisincluded information such as sex, age, education,ethnicity, marital status, and current state ofhealth.

November 2004 - Part 1

A Review of Fibromyalgia

Appropriateness of NSAID and Coxib Prescribing for Patients With Osteoarthritis by Primary Care Physicians in Ontario: Results From the CANOAR Study

Matching Patients and Practitioners Based on Beliefs About Care: Results of a Randomized Controlled Trial

Systematic Reviews for Evidence-based Management: How to Find Them and What to Do With Them

A Randomized Study to Decrease the Use of Potentially Inappropriate Medications Among Community-dwelling Older Adults in a Southeastern Managed Care Organization

COX-2 Inhibitor Use After Vioxx: Careful Balance or End of the Rope?

Measuring Patient Safety in Ambulatory Care: Potential for Identifying Medical Group Drug"Drug Interaction Rates Using Claims Data

Correspondence regarding, "Potential Application of the National Kidney Foundation's Chronic Kidney Disease Guidelines in a Managed Care Setting"

Identifying Controlled Substance Patterns of Utilization Requiring Evaluation Using Administrative Claims Data