Diuretic use,increased serum urate levels,and risk of incident gout in a population‐based study of adults with hypertension: The Atherosclerosis Risk in Communities cohort study

Objective

To quantify the role of diuretic use in gout development in an adult population with hypertension.

Methods

The Atherosclerosis Risk in Communities study, a prospective population‐based cohort from 4 US communities, consisted of 4 visits over a 9‐year period. Participants were included in this analysis if they answered a query about gout, were free of gout at baseline, and had hypertension (defined as taking medication to treat hypertension or having blood pressure of ≥140/90 mm Hg). Trained interviewers recorded use of antihypertensive drugs. Incident gout was defined as self‐reported onset of gout after baseline. Using a time‐dependent Cox proportional hazards model, we estimated hazard ratios (HRs; with 95% confidence intervals [95% CIs]) for incident gout by time‐varying diuretic use, both adjusted for confounders and tested for mediation by serum urate level.

Results

There were 5,789 participants with hypertension; 37% were treated with a diuretic. Use of any diuretic (HR 1.48 [95% CI 1.11, 1.98]), a thiazide diuretic (HR 1.44 [95% CI 1.00, 2.10]), or a loop diuretic (HR 2.31 [95% CI 1.36, 3.91]) was associated with incident gout as compared with not using any diuretic, not using a thiazide diuretic, or not using a loop diuretic, respectively. After adjusting for serum urate level, the association between diuretic use and gout was null. Use of antihypertensive medication other than diuretic agents was associated with decreased gout risk (adjusted HR 0.64 [95% CI 0.49, 0.86]) compared to untreated hypertension. The longitudinal change in serum urate levels was 0.72 mg/dl (95% CI 0.57, 0.87) higher in those who began treatment with a diuretic than in those who did not (P < 0.001).

Conclusion

Thiazide and loop diuretics were associated with increased gout risk, an association mediated by a change in serum urate levels.

     

High incidence of potentially virus‐induced malignancies in systemic lupus erythematosus: A long‐term followup study in a Danish cohort

Objective

Patients with systemic lupus erythematosus (SLE) seem to experience an increased prevalence of oncogenic virus infections. The aim of the present study was to investigate whether SLE patients have an increased risk of virus‐associated malignancies, defined as malignancies potentially caused by virus infection.

Methods

A hospital‐based cohort of 576 SLE patients was linked to the Danish Cancer Registry. The cohort was followed up for malignancies from the date of SLE diagnosis, and standardized incidence ratios (SIRs) were calculated for various forms of cancer.

Results

The median duration of followup was 13.2 years. Compared to the general population, the patients experienced an increased overall risk of cancer (SIR 1.6 [95% confidence interval (95% CI)] 1.2–2.0). We observed an increased risk of virus‐associated cancers combined (SIR 2.9 [95% CI 2.0–4.1]). Among human papillomavirus (HPV)–associated malignant and premalignant conditions, high risk was found for anal cancer (SIR 26.9 [95% CI 8.7–83.4]), vaginal/vulvar cancer (SIR 9.1 [95% CI 2.3–36.5]), epithelial dysplasia/carcinoma in situ of the uterine cervix (SIR 1.8 [95% CI 1.2–2.7]), and nonmelanoma skin cancer (SIR 2.0 [95% CI 1.2–3.6]). Increased SIRs were also found for other potentially virus‐induced cancer types (liver cancer SIR 9.9 [95% CI 2.5–39.8], bladder cancer SIR 3.6 [95% CI 1.4–9.7], and non‐Hodgkin's lymphoma SIR 5.0 [95% CI 1.9–13.3]).

Conclusion

The patients in this SLE cohort experienced an increased risk of HPV‐associated tumors and other potentially virus‐induced cancers during long‐term followup. Our findings call for clinical alertness to oncogenic virus infections in SLE patients.

     

Autoimmune diseases in women with Turner's Syndrome

Objective

In terms of number of X chromosomes, women with Turner's syndrome cytogenetically resemble men. An increased risk of autoimmune diseases has been observed among women with Turner's syndrome. This study was undertaken to investigate whether the autoimmune disease profile in women with Turner's syndrome is characterized by diseases with a female or male predominance.

Methods

Using the Danish Cytogenetic Central Register, the Danish National Patient Register, and the Danish Civil Registration System, we estimated relative risk of 46 different autoimmune diseases in a cohort of 798 Danish women with Turner's syndrome followed up for 12,461 person‐years between 1980 and 2004. Standardized incidence ratios (SIRs) of first hospitalization for autoimmune disease and 95% confidence intervals (95% CIs) were used as measures of relative risk.

Results

The overall risk of autoimmune disease among women with Turner's syndrome was twice that among Danish women in general (SIR 2.1 [95% CI 1.6–2.7]). For autoimmune diseases with a female predominance, the SIR among women with Turner's syndrome was 1.7 (95% CI 1.2–2.4), whereas the SIR for autoimmune diseases with a male predominance among these women was 3.9 (95% CI 2.5–5.8). Associations were strongest for Hashimoto thyroiditis (SIR 14.6 [95% CI 6.7–27.1]), a strongly female‐predominant condition, and type 1 diabetes mellitus (SIR 4.1 [95% CI 2.5–6.3]).

Conclusion

Women with Turner's syndrome are at excess risk of autoimmune diseases, notably autoimmune diseases characterized by male predominance.

     

Propensity‐adjusted association of methotrexate with overall survival in rheumatoid arthritis

Objective

While medications used to treat rheumatoid arthritis (RA) may affect survival in RA, few studies take into account the propensity for medication use, which may reflect selection bias in treatment allocation in survival models. We undertook this study to examine the relationship between methotrexate (MTX) use and mortality in RA, after controlling for individual propensity scores for MTX use.

Methods

We studied 5,626 RA patients prospectively for 25 years to determine the risk of death associated with MTX use, modeled in time‐varying Cox regression models. We used the random forest method to generate individual propensity scores for MTX use at study entry and during followup in a time‐varying manner; these scores were included in the multivariate model. We also investigated whether selective discontinuation of MTX immediately prior to death altered the risk of mortality, and we examined the association of duration of MTX use with survival.

Results

During followup, 666 patients (12%) died. MTX use was associated with reduced risk of death (adjusted hazard ratio 0.30 [95% confidence interval 0.09–1.03]). Selective MTX cessation immediately before death did not account for the protective association of MTX use with mortality. Only MTX use for >1 year was associated with lower risks of mortality, but associations were not stronger with longer durations of use.

Conclusion

MTX use was associated with a 70% reduction in mortality in RA.

     

Epidemiology of gout in women: Fifty‐two–year followup of a prospective cohort

Objective

Despite the recent doubling of the incidence of gout among women and its substantial prevalence particularly in the aging female population, the risk factors for gout among women remain unknown. We undertook this study to evaluate purported risk factors for incident gout among women and to compare them with those among men.

Methods

Using prospective data from the Framingham Heart Study, we examined over a 52‐year period (1950–2002) the relationship between purported risk factors and the incidence of gout in 2,476 women and 1,951 men.

Results

We documented 304 incident cases of gout, 104 of them among women. The incidence rates of gout for women per 1,000 person‐years according to serum uric acid levels of <5.0, 5.0–5.9, 6.0–6.9, 7.0–7.9, and ≥8.0 mg/dl were 0.8, 2.5, 4.2, 13.1, and 27.3, respectively (P for trend < 0.0001). The magnitude of this association was lower than that among men (P for interaction = 0.0002). Multivariate relative risks conferred by increasing age (per 5 years), obesity (body mass index ≥30 kg/m²), alcohol intake (≥7 ounces of pure alcohol/week), hypertension, and diuretic use were 1.24, 2.74, 3.10, 1.82, and 2.39, respectively (all P < 0.05), for women.

Conclusion

These prospective data with long‐term followup provide evidence that higher levels of serum uric acid increase the risk of gout in a graded manner among women, but the rate of increase is lower than that among men. Increasing age, obesity, alcohol consumption, hypertension, and diuretic use were associated with the risk of incident gout among women.

     

Treatment for rheumatoid arthritis and the risk of hospitalization for pneumonia: Associations with prednisone,disease‐modifying antirheumatic drugs,and anti–tumor necrosis factor therapy

Objective

Pneumonia is a major cause of mortality and morbidity in rheumatoid arthritis (RA). This study was undertaken to determine the rate and predictors of hospitalization for pneumonia and the extent to which specific RA treatments increase pneumonia risk.

Methods

RA patients (n = 16,788) were assessed semiannually for 3.5 years. Pneumonia was confirmed by medical records or detailed patient interview. Covariates included RA severity measures, diabetes, pulmonary disease, and myocardial infarction. Cox proportional hazards regression was used to determine the multivariable risk associated with RA treatments.

Results

After adjustment for covariates, prednisone use increased the risk of pneumonia hospitalization (hazard ratio [HR] 1.7 [95% confidence interval 1.5–2.0]), including a dose‐related increase in risk (≤5mg/day HR 1.4 [95% confidence interval 1.1–1.6], >5–10 mg/day HR 2.1 [95% confidence interval 1.7–2.7], >10 mg/day HR 2.3 [95% confidence interval 1.6–3.2]). Leflunomide also increased the risk (HR 1.2 [95% confidence interval 1.0–1.5]). HRs for etanercept (0.8 [95% confidence interval 0.6–110]) and sulfasalazine (0.7 [95% confidence interval 0.5–1.0]) did not reflect an increased risk of pneumonia. HRs for infliximab, adalimumab, and methotrexate were not significantly different from zero.

Conclusion

There is a dose‐related relationship between prednisone use and pneumonia risk in RA. No increase in risk was found for anti–tumor necrosis factor therapy or methotrexate. These data call into question the belief that low‐dose prednisone is safe. Because corticosteroid use is common in RA, the results of this study suggest that prednisone exposure may have important public health consequences.

     

Prevalence of gout and hyperuricemia in the US general population: The National Health and Nutrition Examination Survey 2007–2008

Objective

To estimate the prevalence of gout and hyperuricemia based on the latest nationally representative sample of US men and women (National Health and Nutrition Examination Survey [NHANES] 2007–2008).

Methods

Using data from 5,707 participants in NHANES 2007–2008, we estimated the prevalence of gout and hyperuricemia. During home interviews for NHANES 2007–2008, all participants were asked about a history of health professional– or physician‐diagnosed gout. Our primary definition of hyperuricemia was a serum urate level of >7.0 mg/dl for men and >5.7 mg/dl for women. We explored potential secular trends in these estimates and their possible explanations by comparing them with estimates based on 18,825 participants in NHANES‐III (1988–1994).

Results

The prevalence of gout among US adults in 2007–2008 was 3.9% (8.3 million individuals). The prevalence among men was 5.9% (6.1 million), and the prevalence among women was 2.0% (2.2 million). The mean serum urate levels were 6.14 mg/dl among men and 4.87 mg/dl among women, corresponding to hyperuricemia prevalences of 21.2% and 21.6%, respectively. These estimates were higher than those in NHANES‐III, with differences of 1.2% in the prevalence of gout (95% confidence interval [95% CI] 0.6, 1.9), 0.15 mg/dl in the serum urate level (95% CI 0.07, 0.24), and 3.2% in the prevalence of hyperuricemia (95% CI 1.2, 5.2). These differences were substantially attenuated after adjusting for body mass index and/or hypertension.

Conclusion

These findings from nationally representative samples of US adults suggest that the prevalence of both gout and hyperuricemia remains substantial and may have increased over the past 2 decades, which is likely related to increasing frequencies of adiposity and hypertension.

     

Opposing effects of HLA–DRB1*13 alleles on the risk of developing anti–citrullinated protein antibody–positive and anti–citrullinated protein antibody–negative rheumatoid arthritis

Objective

The effect of non–shared epitope HLA–DRB1 alleles on rheumatoid arthritis (RA) is poorly understood. This study was undertaken to investigate the effects of several HLA–DRB1 alleles, independent of the shared epitope, on the risk of developing anti–citrullinated protein antibody (ACPA)–positive or ACPA‐negative RA in a large case–control study.

Methods

HLA typing for the DRB1 gene was performed in 1,352 patients with RA and 922 controls from the Swedish Epidemiological Investigation of Rheumatoid Arthritis study. Relative risks (RRs) and 95% confidence intervals (95% CIs) were calculated.

Results

DRB1*13 was found to protect against ACPA‐positive RA when stratifying for the shared epitope and using a dominant genetic model (RR 0.41 [95% CI 0.26–0.64]). Furthermore, DRB1*13 neutralized the effect of the shared epitope in ACPA‐positive RA (RR 3.91 [95% CI 3.04–5.02] in patients who had the shared epitope but not DRB1*13, and RR 1.22 [95% CI 0.81–1.83] in patients with both the shared epitope and DRB1*13, as compared with patients negative for both the shared epitope and DRB1*13). However, we did not replicate the previous published risk of ACPA‐negative RA conferred by DRB1*03 when a dominant genetic model was used (RR 1.29 [95% CI 0.91–1.82]). Similarly, no significant effect of DRB1*03 on RR for ACPA‐negative RA was seen using the recessive genetic model (RR 1.18 [95% CI 0.6–2.4]). In contrast, the combination of DRB1*03 and DRB1*13 was significantly associated with increased risk of developing ACPA‐negative RA (RR 2.07 [95% CI 1.17–3.67]).

Conclusion

Our findings indicate that the DRB1*13 allele plays a dual role in the development of RA, by protecting against ACPA‐positive RA but, in combination with DRB1*03, increasing the risk of ACPA‐negative RA.

     

Incidence of physician‐diagnosed osteoarthritis among active duty United States military service members

Objective

To examine the incidence of osteoarthritis and the influence of demographic and occupational factors associated with this condition among active duty US service members between 1999 and 2008.

Methods

To determine the total number of incident cases of osteoarthritis, the Defense Medical Surveillance System (DMSS) was queried by sex, race, age, branch of military service, and rank using code 715 of the International Classification of Diseases, Ninth Revision, Clinical Modification. Multivariable Poisson regression analysis was used to estimate incidence rates, rate ratios, and 95% confidence intervals (95% CIs) for osteoarthritis per 1,000 person‐years.

Results

A total of 108,266 incident cases of osteoarthritis were documented in the DMSS within a population that experienced 13,768,885 person‐years at risk of disease during the study period. The overall unadjusted incidence rate among all active duty US service members during the study period was 7.86 cases per 1,000 person‐years. Significant demographic and occupational risk factors for osteoarthritis included sex, age, race, branch of service, and rank (P < 0.001). Women experienced an adjusted incidence rate for osteoarthritis that was nearly 20% higher than that for men (rate ratio 1.19 [95% CI 1.17–1.21]). Service members ages ≥40 years experienced an adjusted incidence rate for osteoarthritis that was ∼19 times higher than that for those ages <20 years (rate ratio 18.61 [95% CI 17.57–19.57]). Black service members experienced significantly higher incidence rates of osteoarthritis than those in the white and “other” race categories.

Conclusion

Rates of osteoarthritis were significantly higher in military populations than in comparable age groups in the general population.

     

Mortality outcomes in pediatric rheumatology in the US

Objective

To describe mortality rates, causes of death, and potential mortality risk factors in pediatric rheumatic diseases in the US.

Methods

We used the Indianapolis Pediatric Rheumatology Disease Registry, which includes 49,023 patients from 62 centers who were newly diagnosed between 1992 and 2001. Identifiers were matched with the Social Security Death Index censored for March 2005. Deaths were confirmed by death certificates, referring physicians, and medical records. Causes of death were derived by chart review or from the death certificate. Standardized mortality ratios (SMRs) and 95% confidence intervals (95% CIs) were determined.

Results

After excluding patients with malignancy, 110 deaths among 48,885 patients (0.23%) were confirmed. Patients had been followed up for a mean ± SD of 7.9 ± 2.7 years. The SMR of the entire cohort was significantly decreased (0.65 [95% CI 0.53–0.78]), with differences in patients followed up for ≥9 years. The SMR was significantly greater for systemic lupus erythematosus (3.06 [95% CI 1.78–4.90]) and dermatomyositis (2.64 [95% CI 0.86–6.17]) but not for systemic juvenile rheumatoid arthritis (1.8 [95% CI 0.66–3.92]). The SMR was significantly decreased in pain syndromes (0.41 [95% CI 0.21–0.72]). Causes of death were related to the rheumatic diagnosis (including complications) in 39 patients (35%), treatment complications in 11 (10%), non‐natural causes in 25 (23%), background disease in 23 (21%), and were unknown in 12 patients (11%). Rheumatic diagnoses, age at diagnosis, sex, and early use of systemic steroids and methotrexate were significantly associated with the risk of death.

Conclusion

Our findings indicate that the overall mortality rate for pediatric rheumatic diseases was not increased. Even for the diseases and conditions associated with increased mortality, mortality rates were significantly lower than those reported in previous studies.

     

Responsiveness of self‐report and therapist‐rated upper extremity structural impairment and functional outcome measures in early rheumatoid arthritis

Objective

To provide a responsiveness analysis of the self‐report and therapist‐rated upper extremity functional outcome measures used in a rehabilitation trial.

Methods

A variety of commonly used therapist‐assessed and self‐report structural impairment and functional outcome measures were compared for the ability to detect and measure change in wrist and hand status in an early rheumatoid arthritis population over 12 months. Responsiveness was measured using the standardized response mean (SRM) and effect size (ES).

Results

The most responsive measures were the Michigan Hand Outcomes Questionnaire (SRM 0.49 [95% confidence interval (95% CI) 0.27, 0.72], ES = 0.37 [95% CI 0.21, 0.54]), dominant metacarpophalangeal joint ulnar deviation (SRM 0.46 [95% CI 0.27, 0.65], ES = 0.58 [95% CI 0.34, 0.82]), and mean power handgrip test (SRM 0.45 [95% CI 0.26, 0.64], ES = 0.32 [95% CI 0.18, 0.45]) The least responsive measure was the Health Assessment Questionnaire (SRM ?0.12 [95% CI ?0.31, 0.08], ES = ?0.08 [95% CI ?0.21, 0.05]).

Conclusion

Over 12 months, there was substantial variation in wrist and hand outcome measures to detect change over time in an early RA population. Careful consideration is required to choose the most appropriate measure that can detect change.

     

Frequency of varus and valgus thrust and factors associated with thrust presence in persons with or at higher risk of developing knee osteoarthritis

Objective

Varus thrust observed during gait has been shown to be associated with a 4‐fold increase in the risk of medial knee osteoarthritis (OA) progression. Valgus thrust is believed to be less common than varus thrust; the prevalence of each is uncertain. Racial differences in risk factors may help explain variations in the natural history of knee OA. We undertook this study to determine the frequency of varus and valgus thrust in African Americans and Caucasians and to identify factors associated with thrust presence.

Methods

The Osteoarthritis Initiative cohort includes men and women who have knee OA or are at increased risk of developing it. Trained examiners assessed thrust presence by gait observation. Logistic regression with generalized estimating equations was used to identify factors associated with thrust presence, and odds ratios (ORs) with 95% confidence intervals (95% CIs) were calculated.

Results

Compared with Caucasians, African Americans had lower odds of varus thrust, controlling for age, sex, body mass index (BMI), injury, surgery, disease severity, strength, pain, and alignment in persons without knee OA (adjusted OR 0.50 [95% CI 0.36, 0.72]) and in those with knee OA (adjusted OR 0.46 [95% CI 0.34, 0.61]). Also independently associated with varus thrust were age, sex, BMI, disease severity, strength, and alignment. The odds of valgus thrust were greater for African Americans than for Caucasians in persons without knee OA (adjusted OR 1.69 [95% CI 1.02, 2.80]) and in those with knee OA (adjusted OR 1.98 [95% CI 1.35, 2.91]). Also independently associated with valgus thrust were disease severity and malalignment.

Conclusion

Compared with Caucasians, African Americans had lower odds of varus thrust and greater odds of valgus thrust. These findings may help explain the difference between these groups in the pattern of OA involvement at the knee.

     

Does hand osteoarthritis predict future hip or knee osteoarthritis?

Objective

To evaluate the risk of future hip or knee osteoarthritis (OA) in subjects with hand OA at baseline and to evaluate whether the concurrent presence of hand OA, other risk factors for OA, or an OA biomarker (type II collagen C‐telopeptide degradation product [CTX‐II]) further increases the risk.

Methods

Radiographs of the hands (baseline) and the hips and knees (baseline and 6.6 years later) were obtained in a randomly selected subset of participants in the Rotterdam Study who were ages 55 years and older. Radiographs were scored for the presence of OA using the Kellgren/Lawrence (K/L) system. A total of 1,235 subjects without OA of the hip/knee (K/L score 0–1) at baseline were included in the study. CTX‐II levels were measured at baseline. The independent risk of future hip/knee OA in subjects with hand OA at baseline was assessed by logistic regression, as stratified for age, sex, body mass index, family history of OA, and heavy workload.

Results

Overall 12.1% of the participants (19.7% of those with hand OA versus 10.0% of those without) developed hip or knee OA (odds ratio [OR] 2.1 [95% confidence interval (95% CI) 1.3–3.1]). Subjects with hand OA had an increased risk of future hip OA (OR 3.0 [95% CI 1.6–5.4]), which was further increased in those with a family history of OA. Subjects with hand OA had an OR of 1.6 [95% CI 1.0–2.8) for the future development of knee OA, which was further increased in those who were overweight. Concurrent hand OA and high levels of CTX‐II further increased the risk of having hip or knee OA at followup (OR 4.2 [95% CI 2.3–7.8]).

Conclusion

The presence of hand OA at baseline showed an increased risk of future hip/knee OA (higher for hip OA than for knee OA). The concurrent presence of hand OA and other OA risk factors or high CTX‐II levels further increased the risk of future hip/knee OA.

     

Do rheumatoid arthritis and lymphoma share risk factors?: A comparison of lymphoma and cancer risks before and after diagnosis of rheumatoid arthritis

Objective

Patients with rheumatoid arthritis (RA), in particular those with the most severe disease, are at increased risk of developing malignant lymphoma. Whether this increase is entirely a consequence of the RA disease and/or its treatment or is reflective of shared susceptibility to the two diseases remains unclear. We undertook this study to assess whether patients with RA are already at increased risk of lymphoma or of other cancers before the diagnosis of RA, and if the relative risk increases with time since RA diagnosis.

Methods

Patients with incident RA (symptom duration <1 year) (n = 6,745) registered in the Swedish Early Arthritis Registry from 1997 through 2006 were identified. For each patient, 5 general population controls were randomly matched by sex, age, marital status, and residence (n = 33,657). For all study subjects, inclusion in the nationwide Swedish Cancer Register in 1958–2006 was determined. Relative risks (RRs) (with 95% confidence intervals [95% CIs]) of lymphoma and of cancer overall, before and after diagnosis of RA, were estimated using conditional logistic regression and Cox regression, respectively.

Results

Before diagnosis of RA, there was no observed increase in the risk of lymphoma (RR [odds ratio] 0.67 [95% CI 0.37–1.23]) or other cancers (RR 0.78 [95% CI 0.70–0.88]). During the first 10 years following diagnosis of RA, the overall RR (hazard ratio) of lymphoma development was 1.75 (95 % CI 1.04–2.96).

Conclusion

These findings indicate that overall, a history of cancer, including lymphoma, does not increase the risk of subsequent RA development. Shared susceptibility to RA and lymphoma may thus be of limited importance. In contrast, increased lymphoma risks were observed within the first decade following RA diagnosis.

     

Are common symptoms in childhood associated with chronic widespread body pain in adulthood?: Results from the 1958 british birth cohort study

Objective

Studies have shown that common symptoms in childhood predict the onset of chronic widespread pain in the short term. However, it is unknown whether this association persists into adulthood. The aim of the current study was to examine, prospectively, whether children with common symptoms experience an increased risk of chronic widespread pain as adults.

Methods

Information on vomiting/bilious attacks, abdominal pain, and headaches/migraine was collected on 10,453 7‐year‐old children, by maternal report. Similar data were gathered when the children were ages 11 years and 16 years. Body pain at age 45 years was assessed by postal questionnaire. Poisson regression was used to examine chronic widespread pain in relation to childhood symptom reporting.

Results

Of the 10,453 subjects on whom data were obtained when they were children, 7,470 participated at age 45 years (71.5%). Children with multiple symptoms at age 7 years experienced a 50% increased risk of chronic widespread pain (relative risk 1.5 [95% confidence interval 1.03, 2.3]). This relationship persisted after adjustment for sex, recent psychological distress, and childhood and current socioeconomic status, and after excluding children with major illnesses that might have explained early symptom reporting. A similar relationship with symptoms at ages 11 and 16 years was observed, although this was not associated with additional risk compared with that found with the presence of symptoms at age 7 years. However, despite a modest increase in risk, the presence of multiple symptoms at early ages was uncommon (<1.5%), and therefore, the associated population attributable risk was low (<1%).

Conclusion

Multiple common symptoms in childhood are associated with an increased risk of chronic widespread pain in adulthood. However, the magnitude of this increased risk is modest, and reports of multiple symptoms in childhood are uncommon. Thus the “early pain pathway” phenomenon is applicable only to a small proportion of individuals with chronic widespread pain.

     

Occurrence of antineutrophil cytoplasmic antibodies and associated vasculitis in patients with hyperthyroidism treated with antithyroid drugs: A long‐term followup study

Objective

To test whether antineutrophil cytoplasmic antibodies (ANCA) and ANCA‐associated vasculitis (AAV) are not only induced during treatment with antithyroid drugs, but can also become evident when medication has been ceased, possibly after years.

Methods

Patients who visited our hospital for the treatment of hyperthyroidism were included (n = 207). Treatment consisted of antithyroid medications, radioactive iodide, thyroidectomy, or a combination of these treatment options. Patients were retested 3–6 years later to evaluate long‐term effects of antithyroid drugs. Patients were tested for the presence of ANCA and, if positive, evaluated for the presence of AAV.

Results

Of 209 patients with hyperthyroidism, 12 patients (6%) were positive for myeloperoxidase‐ (MPO‐), proteinase 3‐, or human leukocyte elastase‐ANCA. Seventy‐seven of 209 patients were retested; 1 patient who had not been treated with antithyroid drugs had developed MPO‐ANCA. In 3 of 6 patients previously positive, ANCA could still be detected. The presence of ANCA was highly associated with treatment with antithyroid drugs (odds ratio 11.8 [95% confidence interval 1.5–93.3]). Of 13 patients with a positive ANCA result on enzyme‐linked immunosorbent assay, AAV with glomerulonephritis was diagnosed in 4 (31%).

Conclusion

The presence of ANCA with or without vasculitis is associated with previous treatment with antithyroid drugs, possibly after years.

     

The influence of age at symptom onset and length of followup on mortality in patients with recent‐onset inflammatory polyarthritis

Objective

To investigate the influence of age at symptom onset and length of followup on mortality in patients with recent‐onset inflammatory polyarthritis (IP), and to examine predictors of mortality in relation to disease duration.

Methods

From 1990 to 1994, patients with recent‐onset IP were registered with the Norfolk Arthritis Register (NOAR) and followed up prospectively. Standardized mortality ratios (SMRs) were calculated for all‐cause and cardiovascular disease (CVD) mortality and for those who were younger than age 55 years at disease onset and for the first 5 and 10 years of followup. Cox proportional hazards models were developed to assess predictors of early and later mortality.

Results

Of 1,098 patients, 224 (20%) had died by the end of 2004. All‐cause and CVD mortality were increased in rheumatoid factor (RF)–positive patients and in this subgroup, CVD mortality was increased at both early and later followup (SMR 5‐year followup 1.93 [95% confidence interval 1.08–3.19]; SMR 10‐year followup 2.00 [95% confidence interval 1.37–2.80]). CVD mortality was highest in seropositive patients <55 years of age at disease onset (SMR 5.58 [95% confidence interval 2.24–11.50]). In multivariate models, age at onset, male sex, RF positivity, Health Assessment Questionnaire score ≥1.5, and nodules were predictors of early and later mortality.

Conclusion

Patients with IP had higher rates of CVD mortality throughout the followup period studied, and this was highest in seropositive patients who were <55 years of age at symptom onset. This subgroup deserves particular attention in terms of disease and risk factor modification. Nodules were independent predictors of CVD mortality, suggesting that extraarticular/vascular inflammation identifies patients at particularly high CVD risk.

     

Treatment of fibromyalgia with cyclobenzaprine: A meta‐analysis

Objective

To systematically review the effectiveness of cyclobenzaprine in the treatment of fibromyalgia.

Methods

Articles describing randomized, placebo‐controlled trials of cyclobenzaprine in people with fibromyalgia were obtained from Medline, EMBase, Psyclit, the Cochrane Library, and Federal Research in Progress Database. Unpublished literature and bibliographies were also reviewed. Outcomes, including global improvement, treatment effects on pain, fatigue, sleep, and tender points over time, were abstracted.

Results

Five randomized, placebo‐controlled trials were identified. The odds ratio for global improvement with therapy was 3.0 (95% confidence interval [95% CI] 1.6–5.6) with a pooled risk difference of 0.21 (95% CI 0.09–0.34), which calculates to 4.8 (95% CI 3.0–11) individuals needing treatment for 1 patient to experience symptom improvement. Pain improved early on, but there was no improvement in fatigue or tender points at any time.

Conclusion

Cyclobenzaprine‐treated patients were 3 times as likely to report overall improvement and to report moderate reductions in individual symptoms, particularly sleep.

     

Baseline levels of c‐reactive protein and prediction of death from cardiovascular disease in patients with inflammatory polyarthritis : A ten‐year followup study of a primary care–based inception cohort

Objective

To test the hypothesis that the C‐reactive protein (CRP) concentration at baseline is an independent predictor of death from cardiovascular disease (CVD) in newly diagnosed patients with inflammatory polyarthritis (IP).

Methods

Patients with IP (n = 506) who were recruited from the Norfolk Arthritis Register between 1990 and 1992 were followed up to the end of 2001, and complete data on mortality were obtained. At baseline, subjects underwent a structured interview and joint examination and completed a Health Assessment Questionnaire (HAQ). Blood was obtained and analyzed for rheumatoid factor (RF) and CRP concentration. Cox regression was used to calculate hazards ratios (HRs) for risk of death from CVD.

Results

The median followup was 10.1 years (interquartile range 9.3–10.8). There were 104 deaths, 40 of which were the result of CVD. Elevated CRP levels (≥5 mg/liter) predicted death from CVD in univariate analyses: HR 3.9 (95% confidence interval [95% CI] 1.2–13.4) for men, and HR 4.22 (95% CI 1.4–12.6) for women. After adjusting for age and sex, the CVD mortality association was strongest in the subgroup of patients who were RF positive at baseline (adjusted HR 7.4 [95% CI 1.7–32.2]). Multivariate analysis revealed that elevated CRP levels remained a significant independent predictor of death from CVD, even after adjusting for age, sex, smoking status, HAQ score, RF positivity, and swollen joint counts (HR 3.3 [95% CI 1.4–7.6]).

Conclusion

The CRP concentration at baseline is an important predictor of subsequent death from CVD in patients with new‐onset IP and is independent of other indicators of disease severity. This supports the theory that CRP may play a direct role in the pathogenesis of CVD.