Driving Ability and Safety in Rheumatoid Arthritis: A Systematic Review.

OBJECTIVE: To identify whether rheumatoid arthritis (RA) is associated with driving ability and/or the use of assistive devices or modifications to improve driving ability. METHODS: We conducted a systematic literature review following Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines of RA and driving ability/adaptations by searching multiple databases from inception to April 2018. Eligible studies were original articles in the English language that had quantitative data regarding the study objective and at least 5 RA patients. Similar outcomes were extracted across studies and grouped into categories for review. RESULTS: Our search yielded 1,935 potential reports, of which 22 fulfilled eligibility criteria, totaling 6,285 RA patients. The prevalence of driving issues in RA was highly variable among the studies. Some of the shared themes addressed in these publications included RA in association with rates of motor vehicle crashes, self-reported driving difficulty, inability to drive, use of driving adaptations, use of assistance by other people for transport, and difficulty with general transportation. CONCLUSION: Despite variability among individual reports, driving difficulties and the use of driving adaptations are relatively common in individuals with RA. Given the central importance of automobile driving for the quality of life of RA patients, further investigations of driving ability and potential driving adaptations that can help overcome barriers to safe driving are needed.

Physical activity measured using wearable activity tracking devices associated with gout flares.

OBJECTIVE: To determine the feasibility and validity of using wearable activity trackers to test associations between gout flares with physical activity and sleep. METHODS: Participants with physician-diagnosed gout, hyperuricemia (≥ 6.8 mg/dl), current smartphone use, and ≥ 2 self-reported flares in the previous 6 months were enrolled. Physical activity, heart rate, and sleep data were obtained from wearable activity trackers (Fitbit Charge HR2). Daily compliance was defined by the availability of sufficiently complete activity data at least 80% of the day. Associations of weekly gout flares with sleep and activity were measured by comparing flare-related values to average sleep and steps per day. We used mixed linear models to account for repeated observations. RESULTS: Forty-four participants enrolled; 33 met the criteria for minimal wear time and flare reporting, with activity tracker data available for 60.5% of all total study days. Mean ± SD age was 48.8 ± 14.9 years; 85% were men; 15% were black; 88% were on allopurinol or febuxostat, and 30% reported ≥ 6 flares in the prior 6 months. Activity trackers captured 204 (38%) person-weeks with flares and 340 (62%) person-weeks without flares. Mean ± SD daily step count was significantly lower (p < 0.0001) during weeks with gout flares (5900 ± 4071) than during non-flare periods (6972 ± 5214); sleep however did not differ. CONCLUSION: The pattern of wear in this study illustrates reasonable feasibility of using such devices in future arthritis research. The use of these devices to passively measure changes in physical activity patterns may provide an estimate of gout flare occurrence and duration. TRIAL REGISTRATION: NCT, NCT02855437 . Registered 4 August 2016.

Extraction of Rheumatoid Arthritis Disease Activity Measures From Electronic Health Records Using Automated Processing Algorithms.

OBJECTIVE: The accurate and efficient collection and documentation of disease activity measures (DAMs) is critical to improve clinical care and outcomes research in rheumatoid arthritis (RA). This study evaluated the performance of an automated process to extract DAMs from medical notes in the electronic health record (EHR). METHODS: An automated text processing system was developed to extract the Disease Activity Score for 28 joints (DAS28) and its clinical and laboratory elements from the Veterans Affairs EHR for patients enrolled in the Veterans Affairs Rheumatoid Arthritis (VARA) registry. After automated text processing derivation, data accuracy was assessed by comparing the automated text processing system and manual extraction with gold standard chart review in a separate validation phase. RESULTS: In the validation phase, 1569 notes from 596 patients at 3 sites were evaluated, with 75 (6%) notes detected only by automated text processing, 85 (5%) detected only by manual extraction, and 1408 (90%) detected by both methods. The accuracy of automated text processing ranged from 90.7% to 96.7% and the accuracy of manual extraction ranged from 91.3% to 95.0% for the different clinical and laboratory elements. The accuracy of the two methods to calculate the DAS28 was 78.1% for automated text processing and 78.3% for manual extraction. CONCLUSION: The automated text processing approach is highly efficient and performed as well as the manual extraction approach. This advance has the potential for significant improvements in the collection, documentation, and extraction of these data to support clinical practice and outcomes research relevant to RA as well as the potential for broader application to other health conditions.

Comparison of an interactive voice response system and smartphone application in the identification of gout flares.

OBJECTIVE: To examine the feasibility, preference, and satisfaction of an interactive voice response (IVR) system versus a customized smartphone application (StudyBuddy) to capture gout flares METHODS: In this 24-week prospective, randomized, crossover, open-label pilot study, 44 gout patients were randomized to IVR vs. StudyBuddy and were crossed over to the other technology after 12 weeks. Flares were reported via weekly (and later daily) scheduled StudyBuddy or IVR queries. Feasibility was ascertained via response rate to scheduled queries. At 12 and 24 weeks, participants completed preference/satisfaction surveys. Preference and satisfaction were assessed using dichotomous or ordinal questions. Sensitivity was assessed by the frequency of flare reporting with each approach. RESULTS: Thirty-eight of 44 participants completed the study. Among completers, feasibility was similar for IVR (81%) and StudyBuddy (80%). Conversely, most (74%) preferred StudyBuddy. Measures of satisfaction (ease of use, preference over in-person clinic visits, and willingness for future use) were similar between the IVR and StudyBuddy; however, more participants deemed the StudyBuddy as convenient (95% vs. 73%, P = 0.01) and less disruptive (97% vs. 82%, P = 0.03). Although the per patient number of weeks in flare was not significantly different (mean 3.4 vs. 2.6 weeks/patient, P = 0.15), the StudyBuddy captured more of the total flare weeks (35%) than IVR (27%, P = 0.02). CONCLUSION: A smartphone application and IVR demonstrated similar feasibility but overall sensitivity to capture gout flares and participant preference were greater for the smartphone application. Participant preference for the smartphone application appeared to relate to perceptions of greater convenience and lower disruption. TRIAL REGISTRATION: NCT, NCT02855437 . Registered 4 August 2016.

Allopurinol Dose Escalation and Mortality Among Patients With Gout: A National Propensity-Matched Cohort Study.

OBJECTIVE: Observational data suggest that hyperuricemia and gout are associated with increased mortality, while allopurinol use is associated with reduced mortality. In addition, the protective effect of allopurinol may be dose dependent. The aim of the current study was to determine whether allopurinol dose escalation is associated with cause-specific mortality in patients with gout. METHODS: In this 10-year observational, active-comparator study of US Veterans with gout who initiated treatment with allopurinol, propensity score matching, Cox proportional hazards models, and competing risks regression analyses were used to assess differences in cause-specific mortality between patients whose allopurinol dose was escalated (dose escalators) and those whose allopurinol dose was not escalated or was reduced (non-escalators) over a 2-year period. RESULTS: Among the 6,428 dose escalators and 6,428 matched non-escalators, there were 2,867 deaths during the observation period (40.4 deaths per 1,000 person-years). Dose escalators experienced an increase in all-cause mortality (hazard ratio [HR] 1.08, 95% confidence interval [95% CI] 1.01-1.17), with the effect sizes being similar for incidence of cardiovascular-related deaths (HR 1.08, 95% CI 0.97-1.21) and cancer-related deaths (HR 1.06, 95% CI 0.88-1.27), although neither reached statistical significance. Dose escalation to achieve the goal of lowering the serum urate (SU) level to <6.0 mg/dl was infrequent. At 2 years, 10% of dose escalators were receiving a final daily dose of >300 mg and 31% had achieved the SU goal. In a sensitivity analysis limited to dose escalators achieving the SU goal, there was a nonsignificant reduction of 7% in the hazard of cardiovascular-related mortality (HR 0.93, 95% CI 0.76-1.14). CONCLUSION: This is the largest study to date to investigate the effects of allopurinol use on mortality and is the first to use a rigorous active-comparator design. Dose escalation was associated with a small (<10%) increase in all-cause mortality, thus showing that a strategy of allopurinol dose escalation, which in current real-life practice is characterized by limited dose increases, is unlikely to improve the survival of patients with gout.

Utilization of Care Outside the Veterans Affairs Health Care System by US Veterans With Rheumatoid Arthritis.

OBJECTIVE: Many veterans enrolled in Veterans Affairs (VA) health care systems also receive care through other health care systems. Both VA and non-VA health care use must therefore be considered when conducting research in this population. This study characterized dual-care utilization in veterans with rheumatoid arthritis (RA) and explored associations with RA disease activity. METHODS: Through a questionnaire mailed to RA patients at 3 VA sites, veterans reported medical services by non-VA primary care and subspecialty providers, comorbidities, non-VA medications, and hospitalizations. Disease Activity Score in 28 joints (DAS28) and Multidimensional Health Assessment Questionnaire (MD-HAQ) scores were recorded during VA clinic visits, and respondent groups were compared. RESULTS: Of the 510 participants surveyed, 318 (62%) responded. Respondents were older (ages 69 versus 66 years; P = 0.006), more likely nonsmokers (80% versus 67%; P = 0.001), and had lower disease activity (DAS28 3.3 versus 3.8; P < 0.001, MD-HAQ 0.8 versus 0.9; P = 0.01) than nonrespondents (n = 192 [38%]). The respondents with a non-VA provider (n = 130 [41%]) were older (71 versus 68 years; P = 0.001) and had more education (14 versus 13 years; P = 0.021) than nondual-care users. Only 6% of respondents reported having a non-VA rheumatologist, with 2% receiving a non-VA prescribed biologic agent or disease-modifying antirheumatic drug. CONCLUSION: In this study, VA beneficiaries with RA had lower dual-care utilization than previously reported for the general VA population, with few patients receiving dual rheumatology care or non-VA RA medications. This survey suggests that most US veterans with RA who access VA care use the VA as their primary source of arthritis care.

Periodontitis and Porphyromonas gingivalis in patients with rheumatoid arthritis.

OBJECTIVE: To examine the degree to which shared risk factors explain the relationship of periodontitis (PD) to rheumatoid arthritis (RA) and to determine the associations of PD and Porphyromonas gingivalis with pathologic and clinical features of RA. METHODS: Patients with RA (n = 287) and patients with osteoarthritis as disease controls (n = 330) underwent a standardized periodontal examination. The HLA-DRB1 status of all participants was imputed using single-nucleotide polymorphisms from the extended major histocompatibility complex. Circulating anti-P gingivalis antibodies were measured using an enzyme-linked immunosorbent assay, and subgingival plaque was assessed for the presence of P gingivalis using polymerase chain reaction (PCR). Associations of PD with RA were examined using multivariable regression. RESULTS: Presence of PD was more common in patients with RA and patients with anti-citrullinated protein antibody (ACPA)-positive RA (n = 240; determined using the anti-cyclic citrullinated peptide 2 [anti-CCP-2] test) than in controls (35% and 37%, respectively, versus 26%; P = 0.022 and P = 0.006, respectively). There were no differences between RA patients and controls in the levels of anti-P gingivalis or the frequency of P gingivalis positivity by PCR. The anti-P gingivalis findings showed a weak, but statistically significant, association with the findings for both anti-CCP-2 (r = 0.14, P = 0.022) and rheumatoid factor (RF) (r = 0.19, P = 0.001). Presence of PD was associated with increased swollen joint counts (P = 0.004), greater disease activity according to the 28-joint Disease Activity Score using C-reactive protein level (P = 0.045), and higher total Sharp scores of radiographic damage (P = 0.015), as well as with the presence and levels of anti-CCP-2 (P = 0.011) and RF (P < 0.001). The expression levels of select ACPAs (including antibodies to citrullinated filaggrin) were higher in patients with subgingival P gingivalis and in those with higher levels of anti-P gingivalis antibodies, irrespective of smoking status. Associations of PD with established seropositive RA were independent of all covariates examined, including evidence of P gingivalis infection. CONCLUSION: Both PD and P gingivalis appear to shape the autoreactivity of RA. In addition, these results demonstrate an independent relationship between PD and established seropositive RA.

Prospective study of survival outcomes in Non-Hodgkin's lymphoma patients with rheumatoid arthritis.

PURPOSE: Although preliminary studies suggest that non-Hodgkin's lymphoma (NHL) complicating rheumatoid arthritis (RA) may be a clinically distinct entity compared with that occurring in the general population, studies examining the impact of antecedent RA on survival are limited. In this prospective study, we examined the association of RA with survival in patients with NHL. PATIENTS AND METHODS: Using two large lymphoma registries, we identified patients with evidence of RA preceding NHL. Survival in RA patients was compared with that of controls using proportional hazards regression, adjusting for the effects of age, sex, lymphoma diagnosis-to-treatment lag time, calendar year, International Prognostic Index score, and NHL grade. RESULTS: The frequency of NHL subtypes was similar in RA patients (n = 65) and controls (n = 1,530). Compared with controls, RA patients with NHL had similar overall survival (hazard ratio [HR] = 0.95; 95% CI, 0.70 to 1.30) but were at lower risk of lymphoma progression or relapse (HR = 0.41; 95% CI, 0.25 to 0.68) or death related to lymphoma or its treatment (HR = 0.60; 95% CI, 0.37 to 0.98), but were more than twice as likely to die from causes unrelated to lymphoma (HR = 2.16; 95% CI, 1.33 to 3.50). CONCLUSION: RA is associated with improved NHL-related outcomes, including a 40% reduced risk of death occurring as a result of lymphoma or its treatment and approximately a 60% lower risk of lymphoma relapse or progression compared with non-RA controls. However, the survival advantage gained in RA from the acquisition of lymphomas with favorable prognoses is negated through an increased mortality from other comorbid conditions.

Primary cutaneous melanoma: surgical management and other treatment options.

The incidence of primary cutaneous melanoma continues to increase and is a growing public health problem. By virtue of its metastatic potential, melanoma accounts for most of the deaths from cutaneous malignancies. Management of cutaneous melanoma has undergone a paradigm shift in recent years. Clinical studies have furthered our understanding of the biology of this disease and have changed the standards of care. Specifically, sentinel node biopsy and interferon as the first effective postsurgical therapy have had a significant impact on the treatment of patients with melanoma. Surgery remains the primary treatment modality for cutaneous melanoma. An adequate excision of the primary lesion accomplishes durable local control and is curative for patients without micrometastatic disease. Although the extent of surgical resection has decreased in recent years, the standard treatment for primary cutaneous melanoma remains wide surgical excision with histologically negative margins. The extent of excision is based on the theory that the incidence and radial extent of local recurrences can be predicted by specific primary tumor histopathologic characteristics. Tumor thickness and ulceration are the most important histologic features associated with prognosis and are the basis for the current recommendations for surgical treatment of the primary tumor. The extent of surgical therapy for primary melanoma is an area of ongoing debate. No clinical trial has shown a survival disadvantage for narrow versus wide excision regimens for melanoma of any thickness. Ongoing clinical trials will determine the relationship between the extent of surgical therapy for the primary tumor and the outcomes of recurrence and survival in patients with melanoma.