Close association of herpes zoster reactivation and systemic lupus erythematosus (SLE) diagnosis: case-control study of patients with SLE or noninflammatory nusculoskeletal disorders

OBJECTIVE: To investigate the prevalence of infections, particularly the frequency of shingles and the timing of varicella zoster virus (VZV) reactivation, and antibiotic use, vaccinations, and joint trauma prior to and at diagnosis of systemic lupus erythematosus (SLE). METHODS: We sent questionnaires to patients with SLE (n = 93) and controls with noninflammatory musculoskeletal disorders (MSK; n = 353) including osteoarthritis, fibromyalgia, and tendonitis. We matched SLE patients to controls for sex (up to 1:3). RESULTS: The response rate in SLE was 66% and in controls 69% (p < 0.53). Four of 61 SLE patients and 12 of 173 controls were men. The mean disease duration in the SLE group was 8 +/- 1 years compared to 10 +/- 1 years in controls (p < 0.23). SLE patients were significantly younger than controls (mean age of SLE patients 49 +/- 2 vs 57 +/- 1 years for controls; p < 0.0004), and results were adjusted for age. A significantly higher proportion of SLE participants had a history of VZV (shingles) (19% vs 7%, respectively; OR 2.98, p < 0.003), whereas rubella was reported less in SLE (23% vs 42%; OR 0.43, p < 0.03). VZV infections were clustered just prior to or after diagnosis in SLE but were more widely spaced temporally in the controls (1 +/- 4.5 years after the diagnosis of SLE vs -14.7 +/- 4 years before the diagnosis of noninflammatory MSK disorder; p < 0.003). Diagnosis of shingles was observed in 6 of 11 SLE patients within +/- 2 years of SLE diagnosis, whereas only 2 of 15 controls had shingles within +/- 2 years of diagnosis (OR 7.2, p < 0.03). Only 2 patients with SLE were taking immunosuppressive drugs or steroids at time of shingles, so immunosuppressive therapy was not usually concomitant at time of VZV reactivation. Common infections (respiratory, urinary tract, ear, and eye) in the SLE group exceeded controls, but not significantly (23% vs 9%; OR 2.98, p < 0.06) and SLE patients were more likely to have been vaccinated since 18 years of age with any type of vaccine (69% vs 51%; OR 2.21, p < 0.04). SLE patients were less likely than controls to report joint trauma within one year prior to their diagnosis (25% vs 40%; OR 0.49, p < 0.04). There were no differences with respect to streptococcal throat infection (p < 0.96), diarrhea/vomiting (p < 0.84), rash with fever (p < 0.07), parvovirus infection (p < 0.16), infection after surgery (p < 0.58), respiratory tract infection (p < 0.71), or ear (p < 0.09) and eye infection (p < 0.68) one year prior to diagnosis. A higher proportion of SLE patients had a history of urinary tract infections (46% vs 25%), but this was not significant (p < 0.17), nor was it significant one year prior to diagnosis (p < 0.63). Overall, the likelihood of having any infection one year prior to diagnosis was not significantly higher in the SLE group (p < 0.56). There were no differences one year prior to diagnosis in travel history (p < 0.69), hospitalizations (p < 0.47), use of antibiotics (p < 0.54), history of rheumatic fever, positive TB skin test, or hepatitis A, B or C infection. CONCLUSION: Varicella reactivation as shingles is increased in patients with SLE and clusters around diagnosis. Vaccinations are increased in those with SLE compared to controls. Common infections are not significantly increased in SLE patients prior to onset of symptoms. We cannot determine if VZV infections are causally associated with SLE in some people, are from an abnormal immune system response due to the lupus itself or from the use of steroids or other immunosuppressive drugs to control the disease, or are spurious.     

Direct medical costs and their predictors in patients with rheumatoid arthritis: a three-year study of 7,527 patients

OBJECTIVE: To estimate total direct medical costs in persons with rheumatoid arthritis (RA) and to characterize predictors of these costs. METHODS: Patients (n = 7,527) participating in a longitudinal study of outcome in RA completed 25,050 semiannual questionnaires from January 1999 through December 2001. From these we determined direct medical care costs converted to 2001 US dollars using the consumer price index. We used generalized estimating equations to examine potential predictors of the costs. Monte Carlo simulations and sensitivity analyses were performed to evaluate the varying prevalence and cost of biologic therapy. RESULTS: The mean total annual direct medical care cost in 2001 for a patient with RA was 9,519 US dollars. Drug costs were 6,324 US dollars (66% of the total), while hospitalization costs were only 1,573 US dollars (17%). Approximately 25% of patients received biologic therapy. The mean total annual direct cost for patients receiving biologic agents was 19,016 US dollars per year, while the cost for those not receiving biologic therapy was 6,164 US dollars. RA patients who were in the worst quartile of functional status, as measured by the Health Assessment Questionnaire, experienced direct medical costs for the subsequent year that were 5,022 US dollars more than the costs incurred by those in the best quartile. Physical status as determined by the Short Form 36 physical component scale had a similar large effect on RA costs, as did comorbidity. Medical insurance type played a more limited role. However, those without insurance had substantially lower service utilization and costs, and health maintenance organization patients had lower drug costs and total medical costs. Increased years of education, increased income, and majority ethnic status were all associated with increased drug costs but not hospitalization costs. Costs in all categories decreased after age 65 years. CONCLUSION: Estimates of direct medical costs for patients with RA are substantially higher than cost estimates before the biologic therapy era, and costs are now driven predominantly by the cost of drugs, primarily biologic agents. RA patients with poor function continue to incur substantially higher costs, as do those with comorbid conditions, and sociodemographic characteristics also play an important role in determination of costs.     

Abortive base-excision repair of radiation-induced clustered DNA lesions in Escherichia coli

It has been postulated that ionizing radiation produces a unique form of cellular DNA damage called "clustered damages" or "multiply damaged sites". Here, we show that clustered DNA damages are indeed formed in Escherichia coli by ionizing radiation and are converted to lethal double-strand breaks during attempted base-excision repair. In wild-type cells possessing the oxidative DNA glycosylases that cleave DNA at repairable single damages, double-strand breaks are formed at radiation-induced clusters during postirradiation incubation and also in a dose-dependent fashion. E. coli mutants lacking these enzymes do not form double-strand breaks postirradiation and are substantially more radioresistant than wild-type cells. Furthermore, overproduction of one of the oxidative DNA glycosylases in mutant cells confers a radiosensitive phenotype and an increase in the number of double-strand breaks. Thus, the effect of the oxidative DNA glycosylases in potentiating DNA damage must be considered when estimating radiation risk.     

Maternal Health Literacy Progression Among Rural Perinatal Women

This research examined changes in maternal health literacy progression among 106 low income, high risk, rural perinatal African American and White women who received home visits by Registered Nurse Case Managers through the Enterprise Community Healthy Start Program. Maternal health literacy progression would enable women to better address intermediate factors in their lives that impacted birth outcomes, and ultimately infant mortality (Lu and Halfon in Mater Child Health J 7(1):13–30, 2003; Sharma et al. in J Natl Med Assoc 86(11):857–860, 1994). The Life Skills Progression Instrument (LSP) (Wollesen and Peifer, in Life skills progression. An outcome and intervention planning instrument for use with families at risk. Paul H. Brookes Publishing Co., Baltimore, 2006) measured changes in behaviors that represented intermediate factors in birth outcomes. Maternal Health Care Literacy (LSP/M-HCL) was a woman’s use of information, critical thinking and health care services; Maternal Self Care Literacy (LSP/M-SCL) was a woman’s management of personal and child health at home (Smith and Moore in Health literacy and depression in the context of home visitation. Mater Child Health J, 2011). Adequacy was set at a score of (≥4). Among 106 women in the study initial scores were inadequate (<4) on LSP/M-HCL (83 %), and on LSP/M-SCL (30 %). Significant positive changes were noted in maternal health literacy progression from the initial prenatal assessment to the first (p < .01) postpartum assessment and to the final (p < .01) postpartum assessment using McNemar’s test of gain scores. Numeric comparison of first and last gain scores indicated women’s scores progressed (LSP/M-HCL; p < .0001) and (LSP/M-SCL; p < .0001). Elevated depression scores were most frequent among women with <4 LSP/M-HCL and/or <4 LSP/M-SCL. Visit notes indicated lack or loss of relationship with the father of the baby and intimate partner discord contributed to higher depression scores.