OBJECTIVE:To investigate the risk of radiographic knee osteoarthritis (OA) and lumbar spondylosis associated with occupational activity in elderly Japanese subjects using the large-scale population-based cohort of the Research on Osteoarthritis Against Disability (ROAD) study.METHODS:From the baseline survey of the ROAD study, 1,471 participants age > or =50 years (531 men and 940 women) living in mountainous and seacoast communities were analyzed. Information collected included a lifetime occupational history and details of specific work place physical activities. Radiographic severity at the knee and lumbar spine was determined by the Kellgren/Lawrence (K/L) grading system.RESULTS:The prevalence of K/L grade > or =2 knee OA and lumbar spondylosis among agricultural, forestry, and fishery workers was significantly higher than among clerical workers and technical experts in the overall population. For occupational activities, sitting on a chair had a significant inverse association with K/L grade > or =2 knee OA and lumbar spondylosis. Standing, walking, climbing, and heavy lifting were associated with K/L grade > or =2 knee OA, but were not associated with K/L grade > or =2 lumbar spondylosis. Kneeling and squatting were associated with K/L grade > or =3 knee OA.CONCLUSION:This cross-sectional study using a population-based cohort suggests that sitting on a chair is a significant protective factor against both radiographic knee OA and lumbar spondylosis in Japanese subjects. An occupational activity that includes heavy lifting appears to have a greater effect on knee OA than on lumbar spondylosis.
OBJECTIVE:To estimate the prevalence of systemic sclerosis (SSc) using population-based administrative data, and to assess the sensitivity of case ascertainment approaches.METHODS:We ascertained SSc cases from Quebec physician billing and hospitalization databases (covering approximately 7.5 million individuals). Three case definition algorithms were compared, and statistical methods accounting for imperfect case ascertainment were used to estimate SSc prevalence and case ascertainment sensitivity. A hierarchical Bayesian latent class regression model that accounted for possible between-test dependence conditional on disease status estimated the effect of patient characteristics on SSc prevalence and the sensitivity of the 3 ascertainment algorithms.RESULTS:Accounting for error inherent in both the billing and the hospitalization data, we estimated SSc prevalence in 2003 at 74.4 cases per 100,000 women (95% credible interval [95% CrI] 69.3-79.7) and 13.3 cases per 100,000 men (95% CrI 11.1-16.1). Prevalence was higher for older individuals, particularly in urban women (161.2 cases per 100,000, 95% CrI 148.6-175.0). Prevalence was lowest in young men (in rural areas, as low as 2.8 cases per 100,000, 95% CrI 1.4-4.8). In general, no single algorithm was very sensitive, with point estimates for sensitivity ranging from 20-73%.CONCLUSION:We found marked differences in SSc prevalence according to age, sex, and region. In general, no single case ascertainment approach was very sensitive for SSc. Therefore, using data from multiple sources, with adjustment for the imperfect nature of each, is an important strategy in population-based studies of SSc and similar conditions.
OBJECTIVE:To determine the factors associated with increased levels of fatigue over the course of the disease in systemic lupus erythematosus (SLE) patients from LUpus in MInorities: NAture versus nurture, a longitudinal multiethnic cohort.METHODS:Patients with SLE (according to the American College of Rheumatology revised and updated criteria) age >/=16 years with a disease duration </=5 years at entry into the cohort, and of Hispanic (Texan or Puerto Rican), African American, or Caucasian ethnicity were studied. The association between socioeconomic/demographic characteristics, health behaviors, behavioral and psychological, functional and clinical characteristics, and fatigue was examined using generalized estimating equations to account for the longitudinal nature of the data.RESULTS:A total of 515 patients ( approximately 91% female) contributed 2,609 visits to these analyses. Of these patients, 93 (18.1%) were Texan-Hispanic, 101 (19.6%) were Puerto Rican-Hispanic, 169 (32.8%) were African Americans, and 152 (29.5%) were Caucasian. The mean +/- SD patient age and followup time were 37.2 +/- 12.6 years and 4.7 +/- 3.2 years, respectively. Variables associated with increased levels of fatigue in the multivariable analyses were Caucasian ethnicity, the presence of constitutional symptoms (fever, weight loss), and higher levels of pain, abnormal illness-related behaviors, and helplessness (P values between 0.0018 and <0.0001).CONCLUSION:The presence of pain, abnormal illness-related behaviors, helplessness, and constitutional manifestations were associated with increased levels of fatigue. However, SLE-specific measures, such as disease activity and damage, were not. Interventions aimed at decreasing fatigue need to take into account these findings.
Objective. To determine the effectiveness of an intervention Tool Kit of arthritis self-management materials to be sent once through the mail, and to describe the populations reached.Methods. Spanish speakers (n = 335), non-Hispanic English-speaking African Americans (n = 156), and other non-Hispanic English speakers (n = 404) were recruited separately and randomized within each of the 3 ethnic/racial categories to immediately receive the intervention Tool Kit (n = 458) or to a 4-month wait-list control status (n = 463). At the end of 4 months, controls were sent the Tool Kit. All subjects were followed in a longitudinal study for 9 months. Self-administered measures included health status, health behavior, arthritis self-efficacy, medical care utilization, and demographic variables. Using analyses of covariance and t-tests, analyses were conducted for all participants and for Spanish- and English-language groups.Results. At 4 months, comparing all intervention subjects with randomized wait-list controls, there were significant (P < 0.01) benefits in all outcomes except medical care utilization and self-rated health. The results were maintained at 9 months compared with baseline. On average, the Tool Kit reached persons ages 50-56 years with 12-15 years of schooling. There were few differences between English- and Spanish-language participants in either the effectiveness or reach variables.Conclusion. A mailed Arthritis Self-Management Tool Kit proved effective in improving health status, health behavior, and self-efficacy variables for up to 9 months. It also reached younger persons in both English- and Spanish-language groups and Spanish speakers with higher education levels than previous studies of the small-group Arthritis Self-Management Program.
The patient was a 58-year-old woman with left eye ptosis and vision loss. The patient had a history of Wegener's granulomatosis (WG) first diagnosed in 1995, 13 years before her presentation with the current illness. Her WG had been characterized by a migratory, pauciarticular arthritis; leukocytoclastic vasculitis of the skin; elbow nodules caused by cutaneous extravascular necrotizing granulomata (Churg-Strauss granulomas) (Figure 1); biopsy-proven pauci-immune glomerulonephritis; and necrotizing pulmonary vasculitis. The patient had been treated virtually continuously between 1995 and 2008 with a variety of agents, including several courses of high-dose glucocorticoids, oral cyclophosphamide, and azathioprine. Churg-Strauss granulomas. Cutaneous extravascular necrotizing granulomas are present on the patient's elbows (A), and knee (B) 4 months before presentation. The patient presented to the Rheumatology Clinic with symptoms for 2 weeks of impaired vision in her left eye and drooping of the left eyelid. In addition, the patient noted that she had had frequent low-grade migraine headaches for at least 6 months. The headaches had worsened over the 2 weeks that preceded her clinic visit and were accompanied by nausea, vomiting, and pain in the region of her left cheek. The headaches were cyclical in nature, worsening one day but subsiding the next. The patient believed that each headache cycle was accompanied by worsening of vision in the left eye and more severe drooping of her left upper eyelid. The patient denied any history of migraine headaches. The patient had had 2 similar episodes of vision loss in the left eye within 6 months of her presentation. On both occasions, she had presented with amaurosis fugax and vision loss in the left eye. She had been admitted to an outside hospital, undergone magnetic resonance imaging (MRI) studies that had been read as negative, and received the diagnosis of optic neuropathy secondary to WG. During both hospital admissions, the patient had been treated with methylprednisolone 1 gm/day for 3 days, with resolution of her headaches and subjective improvement in her vision. One month after her second admission for ocular dysfunction, the patient was evaluated as an outpatient by the Neuro-ophthalmology Service at our hospital. At that time, the patient was found to have normal afferent visual fields in both eyes except for a residual inferior arcuate scotoma in the left eye. WG had been diagnosed when the patient was age 45 years. Her most recent disease flare before the presumed optic neuropathy had occurred 2 years before presentation, at which time she had developed pulmonary infiltrates and undergone a lung biopsy that showed necrotizing, granulomatous inflammation. Over the previous 13 years, she had been treated with combinations of prednisone, azathioprine, and cyclophosphamide. She had no history of glucose intolerance. At the time of her hospitalization, she was receiving prednisone 10 mg/day. In addition, 3 months before admission she had undergone a course of treatment with rituximab (2 1-gm infusions separated by 2 weeks). This treatment had led to the depletion of circulating B cells. The patient was receiving trimethoprim/sulfamethoxazole as prophylaxis against Pneumocystis jiroveci pneumonia. The patient's family history was negative for rheumatic diseases, cancer, and ophthalmologic problems. She was receiving disability at the time of admission but had previously worked in social services, delivering meals to the elderly. She lived with her husband and had no children. She had an 18 pack-year smoking history and smoked approximately 10 cigarettes per day. She rarely drank alcohol. Her travel history was remarkable for a trip to Florida 10 months earlier, but otherwise she had traveled little outside of New England. The patient reported sinus congestion on the left side that was worse at night. She denied any bloody noses or nasal crusting, ocular erythema, oral ulcers, fevers, chills, neck stiffness, photophobia, hearing changes, cough, rhinorrhea, sore throat, or weakness. Upon admission to the floor, the patient had a temperature of 97.0°F. Her pulse was 108/minute and her blood pressure was 135/79 mm Hg. She was breathing at a rate of 20/minute and her oxygen saturation was 92% on room air. She was a thin woman who appeared older than her stated age. She had an obvious left ptosis. There was no tenderness over her frontal or maxillary sinuses and no neck stiffness. Her dentition was normal. The tympanic membranes and hearing were normal. No cervical or supraclavicular adenopathy was present. Examination of her heart revealed a normal S1 and S2 with no murmurs, rubs, or gallops. Her lungs were clear and her abdomen soft, without hepatosplenomegaly or masses. The radial and pedal artery pulses were normal. She had thin, fragile skin but no rash. The previous Churg-Strauss granulomas over the elbows and knees were not evident. Upon neurologic examination, the patient's pupils were both 4.5 mm in dim light, but the left pupil was poorly reactive and demonstrated an afferent pupillary defect. In addition to her left ptosis, the patient had severely impaired elevation, depression, abduction, and adduction of the ipsilateral eye, consistent with paresis of the left oculomotor (III), trochlear (IV), and abducens (VI) cranial nerves. Facial sensation was intact, with the exception of slightly impaired sensation in the distribution of the ophthalmic division of the left trigeminal nerve (V1). The patient was only able to detect the movement of large objects in the peripheral visual field of the left eye. The visual acuity and ocular movements of the right eye were normal, as was the remainder of the neurologic examination. The patient's erythrocyte sedimentation rate was 86 mm/hour (normal value <20) and her serum C-reactive protein level was 37.6 mg/liter (normal value <8.0). The serum creatinine and hematocrit levels were 1.1 mg/dl and 34.5%, respectively. The peripheral white blood cell count was 9,500/mm3. Other laboratory results are shown in Table 1. Flow cytometry was performed to assess the status of her B cells. Computed tomography (CT) scans of the brain, sinuses, and chest were performed. The brain and sinus CT scans demonstrated complete opacification of the left maxillary sinus with signs of chronic inflammatory changes (Figure 2A). The Otolaryngology Service performed a rigid fiberoptic examination that revealed no evidence of a bacterial or fungal infection in the nose. The left middle meatus was swabbed for cultures, which were negative for bacteria and fungi. A chest CT scan revealed multiple cavitary and non-cavitary lesions in all lung lobes, some with surrounding “ground glass” opacity (Figure 2B). A, Computed tomography (CT) scan of the sinuses shows complete opacification of the left maxillary sinus and signs of chronic inflammatory change. B, CT scan of the chest shows multiple cavitary and non-cavitary lesions in all lung lobes, some with surrounding “ground glass” opacity. MRI and MR venogram studies showed patent cavernous sinuses, but the tentorial and falcine dura had increased fluid-attenuated inversion recovery signal and enhanced abnormally following gadolinium administration (Figure 3). There was also a subtle signal abnormality in the left orbital apex (Figure 4). A lumbar puncture was performed. The cerebrospinal fluid (CSF) protein level was 61 mg/dl (normal range 15–45). Tubes 1 and 2 had 12 and 9 white blood cells, respectively, with a lymphocytic predominance. There were no red blood cells in the CSF. Coronal view of a T1-weighted magnetic resonance imaging study of the brain reveals increased fluid-attenuated inversion recovery signal in the falx. Subtle signal within the apex of the cavernous sinus. A serum assay for antineutrophil cytoplasmic antibodies (ANCAs) was positive by indirect immunofluorescence. An enzyme immunoassay for antibodies directed against proteinase 3 was positive at 326 units (normal value <20). This had increased from 102 units only 1 month before her admission. Antibodies to myeloperoxidase were negative, as was an assay for antibodies to Borrelia burgdorferi, a rapid plasma reagin assay, and blood cultures. A 58-year-old woman with a history of WG and 2 prior episodes of glucocorticoid-responsive left optic neuropathy presented with headaches, a central scotoma of the left eye, and cranial nerve dysfunction involving the left third, fourth, fifth, and sixth nerves. She had a lymphocytic pleocytosis in her CSF and multiple abnormalities on imaging studies of her sinuses, lungs, and meninges. The patient's left eye vision loss and cranial nerve abnormalities were consistent with localization of the lesion to the orbital apex (Figure 5). She was diagnosed as having an orbital apex syndrome. Orbital apex syndromes are constellations of neurologic findings that result from dysfunction of the optic, oculomotor, and abducens nerves, as well as involvement of the ophthalmic division of the trigeminal nerve. Some patients also have involvement of the vascular supply and drainage of the posterior orbital regions, the sympathetic innervation of the orbit, and the sensory nerves that supply the forehead. Orbital apex syndromes result from a variety of pathologic processes that lead to crowding or infiltration of the structures within the orbital apex. The cavernous sinus and orbital apex, with the location of the inflammatory lesion indicated. (Figure courtesy of Dr. John Stone.) The major diagnostic considerations for an orbital apex syndrome in an immunosuppressed patient are an opportunistic infection, a neoplasm, thrombosis of the cavernous sinus, or a space-occupying lesion of some other type (Table 2). We consider each of these major diagnostic possibilities in turn. Infections are common and potentially life-threatening complications of the treatment of WG. Indeed, infectious complications of therapy are now more likely to lead to death in this disorder than WG is itself (1). It is therefore essential to consider a broad differential of infectious etiologies and to approach the patient with a thoughtful diagnostic evaluation before initiating any immunosuppressive treatment. This patient's chronic course of WG and the consequent need for years of immunosuppression placed her at particular risk for an opportunistic infection. Moreover, damage to her sinuses and lungs from previous periods of active WG had created potential sites at which opportunistic microbes might thrive. The proximity of the maxillary sinus to the orbital apex was consistent with the spread of infection into the cavernous sinus from a focus within the sinuses. Cavitary pulmonary lesions are among the classic lung findings in WG but are also highly typical of a number of mycobacterial and fungal infections. Organisms commonly involved in cavernous sinus infections include Mucormycosis, Aspergillus, Mycobacterium tuberculosis, Staphylococcus aureus, Streptococcus pneumoniae, Actinomyces, Treponema pallidum, herpes zoster, gram-negative bacilli, and anaerobes (2). Many patients with fungal rhinosinusitis are immunocompromised or have diabetes mellitus as an underlying risk factor. As an example, diabetes mellitus is a notorious predisposing condition for Mucormycosis infections. However, patients do not have to be overtly immunocompromised in order to develop a serious rhinosinusitis infection. The condition known as allergic fungal rhinosinusitis is a chronic disorder that can develop in immunocompetent individuals (3, 4). The lymphocytic pleocytosis and the meningeal enhancement on the MRI findings were concerning for the possibility of an infection in the orbital apex that had extended into the CSF. Our patient had negative sinus cultures and a negative rapid plasma reagin test result. In addition, her sinuses had been visualized by the Otolaryngology Service, which deemed the likelihood of infection low. Moreover, the patient's sinus imaging was also not consistent with an acute, invasive sinusitis. Nasopharyngeal cancer, lymphoma, pituitary adenoma, meningioma, and metastatic disease can all cause an orbital apex syndrome (2). Our patient had been treated intensively with cyclophosphamide and azathioprine, both of which are associated with secondary malignancies (5). Her previous hospital admissions for optic neuropathy might have been caused by a secondary malignancy that had regressed following high-dose glucocorticoid treatment. A lymphoma would be particularly likely to partially respond to such therapy. However, her brain CT scan did not demonstrate any mass lesions, and flow cytometry of her CSF was negative. A septic cavernous sinus thrombosis can occur in the setting of periorbital infections, leading to an orbital apex syndrome. An aseptic cavernous sinus thrombosis can also occur in the setting of idiopathic inflammation. Patients with WG are known to be at risk for venous thrombotic events, but these events are typically deep venous thromboses of the legs, frequently complicated by pulmonary emboli (6). Cavernous sinus thrombosis, in contrast, is not a complication that is common to WG. The patient's negative MR venogram result significantly decreased the possibility of this complication (7). WG can be associated with a host of ocular and orbital complications. These include inflammatory masses within the orbit, episcleritis, conjunctivitis, granulomatous inflammation of the tarsal conjunctivae, scleritis, peripheral ulcerative keratitis, uveitis, retinitis, retinal vascular disease, optic neuropathy, and oculomotor cranial neuropathy (8-13). Optic neuropathy, which had been diagnosed in our patient within 6 months of her admission, has been reported to occur in patients with WG in multiple case reports and pathology reviews (8, 14, 15-18). The optic neuropathy in patients with WG generally occurs either in isolation or with cranial nerve palsies, meningeal involvement, or ocular manifestations that extended to other portions of the eye. Three mechanisms leading to optic neuropathy in WG have been described: compression of the optic nerve from an inflammatory mass within the orbit, granulomatous inflammation of the optic nerve itself, and anterior ischemic optic neuropathy from vascular compromise of the posterior ciliary artery. The last mechanism is analogous to the most common pathway through which patients with giant cell arteritis lose vision. It was conceivable that our patient's orbital apex syndrome had been caused by WG-associated inflammation within her orbital apex, manifested by the very subtle signal observed on her MRI finding (Figure 4). This lesion, too small to be detected as a mass lesion on her brain CT scan, was situated as such that it could have accounted for all of the patient's cranial nerve lesions. WG can also cause chronic meningitis that is identical to that with which our patient presented: headache, low-grade lymphocytic pleocytosis, and meningeal enhancement upon MRI (19). In addition, cavitary pulmonary lesions and sinus disease are consistent with (although not diagnostic of) WG. Therefore, WG was a viable explanation for the patient's lymphocytic pleocytosis, dural enhancement, pulmonary cavitary lesions, and maxillary sinusitis, as well as her orbital apex syndrome (20, 21). One point arguing against WG as a cause of our patient's illness was the fact that she had been treated aggressively for this condition and had been treated with rituximab, an agent designed to deplete B cells, only 3 months earlier. Preliminary investigations of rituximab for the treatment of WG have been encouraging (22, 23), and the results of a randomized trial are awaited (Specks U: unpublished observations). Flow cytometry on the patient's peripheral blood indicated that she was still B cell depleted. Despite this, her serum ANCA titer had increased over the 1 month before admission. Infections, malignancies, cavernous sinus thrombosis, and WG were all carefully considered in this patient's differential diagnosis. The patient had had no fevers during either the 2 weeks since the recurrence of her ocular symptoms or over the 6 months that had preceded her presentation. This fact argued against infection, even though her glucocorticoids and other immunosuppressive therapies might have masked systemic signs of an infection. The 2 previous episodes of vision loss also argued against infection, as did the benign findings by the Otolaryngology Service upon examination of the patient's nose and sinuses. However, complete reassurance about an infection in this setting was not possible without surgical exploration of the cavernous sinus. Similar considerations held for malignancies that could have caused this problem. Cavernous sinus thrombosis appeared to be excluded with a reasonable degree of certainty by the negative MR venogram result (7). On the other hand, several features compellingly argued for WG as the cause of the patient's presentation. First, the 2 previous responses of her vision loss to high doses of glucocorticoids had not led to dissemination of the process, as one might anticipate in the setting of an infection. Furthermore, the patient had findings on her chest CT scan that were consistent with newly active disease in her lungs. Finally, her ANCA titer had risen significantly (despite the absence of peripheral B cells). In view of these considerations and the significant potential morbidity associated with performing a biopsy of the orbital apex region, the decision was made to treat the patient empirically for WG. The patient received 1 gm of methylprednisolone intravenously each day for 3 consecutive days, and was then discharged receiving prednisone 60 mg daily. Her headaches resolved completely and she recovered full extraocular muscle function, including resolution of her ptosis. However, the central scotoma remained unchanged. Followup visual fields testing 4 months after discharge showed a persistent central visual field defect of the affected eye. WG is an ANCA-associated necrotizing granulomatous disease that classically involves medium and small vessels. In the classic, disseminated form of the disease, both the renal and pulmonary vascular beds are involved. However, WG is a remarkably protean disorder that can present with neurologic, musculoskeletal, dermatologic, gastrointestinal, urologic, cardiac, or ophthalmologic symptoms. Among the multiple ocular complications of WG, orbital apex syndrome has been described (8, 12, 13). The rheumatologist should consider an orbital apex syndrome when a patient presents with deep, aching orbital pain, diplopia, conjunctival injection, proptosis, loss of vision, ocular motor dysfunction, or combinations of these features. In severe orbital apex syndromes, the patient presents with full ptosis, a dilated pupil, and a numb eye that does not move in any direction. Such a presentation localizes the lesion to the apex of the orbit adjacent to the carotid artery and cavernous sinus, the region through which cranial nerves II, III, IV, VI, and V1 course (Figure 5). More subtle presentations are challenging and are often missed. For instance, mild ptosis and diplopia in a patient with some orbital pain or the occurrence of a Horner's syndrome in a patient with an abducens neuropathy also suggests an orbital apical localization. In WG, orbital apex syndromes probably stem from a primary granulomatous process that is akin to the process leading to orbital pseudotumors. Alternatively, an orbital apex syndrome could result from the extension of inflammation that originates within a paranasal sinus. The timing of the patient's presentation with regard to her rituximab therapy is worthy of comment. She developed her full-blown orbital apex syndrome only 3 months after undergoing B cell depletion therapy with rituximab, and she remained B cell depleted at the time of her presentation. Perhaps paradoxically, however, her serum proteinase 3 ANCA assay actually indicated an increase in her ANCA titer at presentation compared with her titer at the time of the first rituximab infusion. These facts underscore some important points about the emerging potential role of rituximab therapy in WG. Although peripheral B cells are depleted by therapies directed against CD20, long-lived plasma cells (which do not bear CD20 on their surfaces) can continue to produce ANCA through stimuli that remain poorly understood. If rituximab proves to be effective in WG, the mechanism of its efficacy will require further elucidation (24). In addition, as our case illustrates, if rituximab is effective for some patients with WG, it is not likely to be effective in all patients. Additional studies will be required to understand the most appropriate clinical settings in which to employ B cell depletion as a treatment strategy. Orbital apex syndrome caused by Wegener's granulomatosis. All authors were involved in drafting the article or revising it critically for important intellectual content, and all authors approved the final version to be published. Dr. Stone had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis. Study conception and design. Cooley, Pless, Stone. Acquisition of data. Cooley, Pless, Stone. Analysis and interpretation of data. Cooley, Pless, Stone.
OBJECTIVE:To assess whether the risk of incident systemic lupus erythematosus (SLE) is associated with the use of combined oral contraceptives (COCs), because studies of the link between exogenous hormonal exposure and the risk of SLE have produced conflicting results.METHODS:We conducted a population-based nested case-control study among women ages 18-45 years, using the UK's General Practice Research Database. All incident cases of SLE from 1994-2004 (n = 786) were identified in the database and matched with up to 10 controls (n = 7,817) among women without SLE at the time of the case's diagnosis.RESULTS:The adjusted rate ratio (RR) of incident SLE associated with any use of COC was 1.19 (95% confidence interval [95% CI] 0.98-1.45), whereas with current use it was 1.54 (95% CI 1.15-2.07). The rate was particularly increased in current users who had only recently started COC use (RR 2.52, 95% CI 1.14-5.57) compared with longer-term current users (RR 1.45, 95% CI 1.06-1.99). The risk appeared to be particularly elevated with current exposure to first- or second-generation contraceptives (RR 1.65, 95% CI 1.20-2.26), and increasing with the dose of ethinyl estradiol (RR 1.42, 1.63, and 2.92 for < or =30 microg, 31-49 microg, and 50 microg, respectively).CONCLUSION:The use of COCs is associated with an increased risk of SLE. This risk is particularly elevated in women who recently started contraceptive use, suggesting an acute effect in a small subgroup of susceptible women.
OBJECTIVE:To examine the impact of distraction on the retention of rehearsed information in patients with fibromyalgia syndrome (FMS).METHODS:Data refer to the neurocognitive examination of 134 patients (91 with FMS and 43 control subjects) presenting with memory loss. Four neurocognitive measures free of distraction, along with 2 measures with added distraction, were completed. Differences in the retention of rehearsed and unrehearsed information with a source of distraction present were calculated.RESULTS:Patients with FMS showed normal cognitive functioning on verbal memory tests free of distraction. Adding a source of distraction caused unrefreshed information to be lost at a disproportionate rate in patients with FMS. Over 87% of patients with FMS scored in the impaired range on a task of unrehearsed verbal memory. Adding a source of distraction to well-rehearsed information produced a normal rate of recall in FMS.CONCLUSION:Rehearsal mechanisms are intact in patients with FMS and play beneficial roles in managing interference from a source of distraction. In the absence of rehearsal, a source of distraction added to unrefreshed information signals a remarkable level of cognitive deficit in FMS that goes undetected by conventionally relied-upon neurocognitive measures. We present a theory to promote understanding of the cognitive deficit of people with FMS based on reduced speed of lexical activation and poor recall after distraction.
OBJECTIVE:A number of studies (all n <200) have assessed health-related quality of life (HRQOL) in patients with systemic sclerosis (SSc), but no systematic review of the effect of SSc on HRQOL has been done. The objective of this study was to systematically review the literature on HRQOL in SSc measured using the Medical Outcomes Trust Short Form 36 (SF-36). METHODS:A comprehensive search was conducted in August 2007 using Medline, CINAHL, and EMBase to identify original research studies reporting SF-36 scores of SSc patients. Selected studies were reviewed and characteristics of the study samples and SF-36 data were extracted. Bayesian meta-analysis and meta-regression were performed to obtain pooled estimates of SF-36 physical component summary (PCS) and mental component summary (MCS) scores for all patients as well as by limited and diffuse disease status. RESULTS:Twelve data sets with a total of 1,127 SSc patients were included in the systematic review. HRQOL was impaired in patients with SSc, with pooled SF-36 PCS scores being more than 1 SD below the general population (38.3; 95% credible interval [95% CI] 35.2, 41.5) and pooled SF-36 MCS scores being approximately 0.5 SDs below the general population (46.6; 95% CI 44.2, 49.1). SF-36 PCS scores were 3.5 points (95% CI -1.0, 8.0) lower in patients with diffuse compared with limited disease. CONCLUSION:This study provides robust evidence of the presence and magnitude of impairment in HRQOL in patients with SSc. Although the impairment appears greater in physical health, mental health impairment is also reported.
OBJECTIVE:To conduct a systematic review of the quality and content of the psychometric evidence relating to 4 shoulder disability scales: the Disabilities of the Arm, Shoulder, and Hand (DASH) questionnaire, the Shoulder Pain and Disability Index (SPADI), the American Shoulder and Elbow Surgeons (ASES) score, and the Simple Shoulder Test (SST). METHODS:We conducted a structured search using 3 databases (Medline, CINAHL, EMBase). In total, 71 published primary studies were analyzed. A pair of raters conducted data extraction and critical appraisal using structured tools. A descriptive synthesis was performed. RESULTS:Quality ratings of 55% of the studies reviewed reached a level of > or =75%. Most studies suggest that all 4 questionnaires have excellent reliability (intraclass correlation coefficient > or =0.90). The 4 questionnaires are strongly correlated (r >0.70) with each other and with a number of similar indices, and the questionnaires were able to differentiate between different populations and disability levels. The minimal detectable change (MDC) is approximately 9.4 for the ASES, 10.5 for the DASH, and 18 for the SPADI; the minimal clinically important difference (MCID) is approximately 6.4 for the ASES and 10.2 for the DASH, and ranges between 8 and 13 for the SPADI. MDC and MCID have not been defined for the SST. CONCLUSION:The psychometric properties of the ASES, DASH, and SPADI have been shown to be acceptable for clinical use. Conversely, some properties of the SST still need be evaluated, particularly the absolute errors of measurement. Overall, validation studies have focused on less clinically relevant properties (construct validity or group reliability) than estimates of MDC and MCID.
Objective. To assess the impact of certolizumab pegol (CZP), a novel PEGylated anti-tumor necrosis factor, in combination with methotrexate (MTX) on productivity outside and within the home, and on participation in family, social, and leisure activities in adult patients with rheumatoid arthritis (RA).Methods. The efficacy and safety of CZP (200 mg and 400 mg) plus MTX were assessed in 2 phase III, multicenter, double-blind, placebo-controlled trials (Rheumatoid Arthritis Prevention of Structural Damage [RAPID] 1 and RAPID 2). The novel, validated, RA-specific Work Productivity Survey (WPS-RA) was used to assess work place and home productivity. WPS-RA responses were collected at baseline and every 4 weeks until withdrawal/study completion.Results. At baseline, 41.6% and 39.8% of subjects were employed outside the home in RAPID 1 and RAPID 2, respectively. Compared with placebo plus MTX, CZP plus MTX significantly reduced work absenteeism and presenteeism among patients working outside the home. Significant reductions in number of household days lost, household days with productivity reduced by >= 50%, and days lost due to RA for participation in family, social, and leisure activities were reported by patients in active treatment relative to placebo plus MTX. Improvements in all measures were observed with CZP plus MTX as early as week 4, and maintained until the study end (12 months in RAPID 1, 6 months in RAPID 2). Findings were consistent with clinical improvements with CZP plus MTX in both trials.Conclusion. CZP plus MTX improved productivity outside and within the home and resulted in more participation in social activities compared with placebo plus MTX. These observations suggest that considerable indirect cost gains might be achieved with this therapeutic agent in RA.
OBJECTIVE:The association between hyperuricemia and cardiovascular events has been documented in high-risk groups, but is still undetermined in general populations, especially Chinese. This study assessed the temporal association between serum uric acid level, hyperuricemia, and cardiovascular mortality.METHODS:A prospective cohort study of 41,879 men and 48,514 women ages > or = 35 years was conducted using data from the MJ Health Screening Centers in Taiwan. Mortality from all causes, total cardiovascular disease (CVD), ischemic stroke, congestive heart failure, hypertensive disease, and coronary heart disease were compared according to increasing serum uric acid levels.RESULTS:A total of 1,151 (21.2%) events of 5,427 total deaths were ascribed to CVD (mean followup 8.2 years). Hazard ratios (HRs) for hyperuricemia (serum uric acid level >7 mg/dl) were estimated with Cox regression model after adjusting for age, sex, body mass index, cholesterol, triglycerides, diabetes, hypertension, heavy cigarette smoking, and frequent alcohol consumption. In all patients, HRs were 1.16 (P < 0.001) for all-cause mortality, 1.39 (P < 0.001) for total CVD, and 1.35 (P = 0.02) for ischemic stroke. In subgroup analysis, the HRs for cardiovascular risk remained significant in patients with hypertension (1.44, P < 0.001) and in patients with diabetes (1.64, P < 0.001). In addition, in a low metabolic risk subgroup, the HRs for all-cause mortality and total cardiovascular morbidity were 1.24 (P = 0.02) and 1.48 (P = 0.16), respectively.CONCLUSION:Hyperuricemia was an independent risk factor of mortality from all causes, total CVD, and ischemic stroke in the Taiwanese general population, in high-risk groups, and potentially in low-risk groups.
OBJECTIVE:To determine the risk of tuberculosis (TB) among a cohort of patients with rheumatoid arthritis (RA) in Quebec and assess whether this risk is associated with exposure to nonbiologic disease-modifying antirheumatic drugs (DMARDs).METHODS:We studied a cohort of patients with RA identified from the Quebec provincial physician billing and hospitalization databases for 1980-2003. TB incidence rates were determined for the period 1992-2003 and compared with the general population, standardized for age and sex using the standardized incidence ratio (SIR). Conditional logistic regression was used in a nested case-control analysis to estimate the rate ratio (RR) of TB related to nonbiologic DMARD exposure during the year before the index date.RESULTS:Of the 24,282 patients with RA in the cohort, 50 cases of TB were identified. The standardized incidence rate was 45.8 cases per 100,000 person-years compared with 4.2 cases per 100,000 person-years in the general population of Quebec (SIR 10.9, 95% confidence interval [95% CI] 7.9-15.0). The adjusted RR of TB was 2.4 (95% CI 1.1-5.4) with corticosteroid use and 3.0 (95% CI 1.6-5.8) with nonbiologic DMARD use.CONCLUSION:The age- and sex-standardized incidence rate of TB in RA patients is 10 times that of the general population. At least some of this risk may be related to nonbiologic DMARD and corticosteroid therapies. Our data support the role of TB screening before initiation of any immunosuppressive therapy.
OBJECTIVE:Digital ulcerations are one of the most frequent manifestations of microangiopathy in patients with systemic sclerosis (SSc; scleroderma). The early detection of SSc patients who are at high risk to develop digital ulcers could allow a preventive treatment of these complications with reduction of morbidity and social costs. The aim of our study was to develop a capillaroscopic skin ulcer risk index (CSURI) that can predict the onset of new digital ulcers by using nailfold videocapillaroscopy (NVC) in patients with SSc.METHODS:We performed NVC in 120 consecutive unselected patients with SSc (13 men, 107 women, mean +/- SD age 56.1 +/- 13.4 years, mean +/- SD SSc duration 44.7 +/- 60.7 months) to assess the total number of capillaries in the distal row (N), maximum loop diameter (D), number of megacapillaries (M), and the M:N ratio.RESULTS:Within 3 months since NVC examination, 35 of 120 patients experienced digital ulcers. A significant association between ischemic lesions and the M:N ratio, N, and D was observed; the combination of these parameters allowed us to develop the CSURI, which is characterized by the formula D x M:N(2). A receiver operating characteristic curve analysis showed an area under the curve of 0.926 for ulcer appearance, with specificity and sensitivity of 85.9% and 94.3%, respectively, at the cutoff value of 2.94. Interestingly, 33 of 35 patients with new skin ulcers had a CSURI >2.94, but only 2 of 35 had a CSURI < or =2.94.CONCLUSION:The proposed CSURI may represent a novel tool with the ability to predict the development of digital ulcers in patients with scleroderma.
OBJECTIVE:To develop and validate a composite disease activity score for juvenile idiopathic arthritis (JIA), the Juvenile Arthritis Disease Activity Score (JADAS).METHODS:The JADAS includes 4 measures: physician global assessment of disease activity, parent/patient global assessment of well-being, active joint count, and erythrocyte sedimentation rate. These variables are part of the American College of Rheumatology (ACR) Pediatric 30 (Pedi 30), Pedi 50, and Pedi 70 criteria for improvement. Validation analyses were conducted on >4,500 patients and included assessment of construct validity, discriminant validity, and responsiveness to change. Three versions of the JADAS were tested based on 71-joint (range 0-101), 27-joint (range 0-57), or 10-joint (range 0-40) counts. Statistical performances of the JADAS were compared with those of 2 rheumatoid arthritis composite scores, the Disease Activity Score in 28 joints (DAS28) and the Clinical Disease Activity Index (CDAI).RESULTS:The JADAS demonstrated good construct validity, yielding strong correlations with JIA activity measures not included in the score and moderate correlations with the Childhood Health Assessment Questionnaire. Correlations obtained for the 3 JADAS versions were comparable, but superior to those yielded by the DAS28 and CDAI. The area under the curve of the JADAS predicted long-term disease outcome, measured as radiographic progression over 3 years. In 2 clinical trials, the JADAS discriminated well between ACR Pedi 30, Pedi 50, and Pedi 70 response and revealed strong responsiveness to clinical change.CONCLUSION:The JADAS was found to be a valid instrument for assessment of disease activity in JIA and is potentially applicable in standard clinical care, observational studies, and clinical trials.
OBJECTIVE As populations age and the prevalence of hip osteoarthritis (OA) increases, health care providers must manage increasing demands for services. Evidence regarding the progression of hip OA can assist health care practitioners in determining expected patient prognosis and planning care. This systematic review of prospective cohort studies examines prognostic variables in patients with hip OA. METHODS Articles were selected following a comprehensive search of Medline, EMBase, CINAHL, and Allied and Complementary Medicine from database inception to October 2008 and hand searches of the reference lists of retrieved articles. Inclusion criteria involved 1) estimates of the association between prognostic variables and progression of OA, 2) prospective cohort design, 3) patients diagnosed with hip OA based on established criteria, 4) at least 1 year of followup, and 5) access to the full published text. Two independent reviewers assessed the methodologic quality of each study and the association between prognostic variables and OA progression. RESULTS Eighteen articles met the inclusion criteria; 17 were considered to be of high quality. Strong evidence of progression was associated with age, joint space width at entry, femoral head migration, femoral osteophytes, bony sclerosis, Kellgren/Lawrence hip grade 3, baseline hip pain, and Lequesne index score > or =10. Strong evidence of no association with progression was associated with acetabular osteophytes. Evidence was weak or inconclusive regarding associations between various other radiographic or clinical variables, molecular biomarkers, or use of nonsteroidal inflammatory drugs. CONCLUSION Overall, few variables were found to be strongly associated with the progression of hip OA, and a variety of other variables were weakly predictive of outcome.
Objective. Selection of flare as the primary outcome variable in systemic lupus erythematosus (SLE) clinical trials fails to capture patients with persistently active disease (PAD). We sought to elucidate the frequency and determinants of flare and PAD.Methods. Prospectively collected data from the Toronto Lupus Cohort were used to determine the incidence of flare and PAD in 2004 and 2005. Flare was defined as an increase in SLE Disease Activity Index 2000 update (SLEDAI-2K) score of >= 4 from the previous visit. PAD was defined as a SLEDAI-2K score of >= 4, excluding serology alone, on >= 2 consecutive visits. Data from 1, 2, and 3 years prior were used to model flare and PAD in 2004. Model properties were tested for prediction of flare and PAD in 2005.Results. One-third of the patients had >= 1 flare, whereas nearly half experienced PAD in a given year. Nearly 60% of the patients had episodes of flare or PAD per year. At least 25% of patients had PAD without achieving the definition of flare. In the best-fitting model, predictors of PAD in 2004 were SLEDAI-2K score at the start of the outcome interval and prior cutaneous or musculoskeletal disease activity. This model gave 79% correct prediction of PAD in 2005. In contrast, flare prediction models performed poorly.Conclusion. Persistent activity is a common disease state in SLE and should be an outcome variable in SLE clinical trials. Our PAD prediction model may aid prognostication and selection of patients for inclusion in clinical trials.
