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Objective: To evaluate the incidence rates of mycobacterial infections in silicosis patients with systemic autoimmune rheumatic disease (ARD). Methods: This was a retrospective cohort of silicosis patients between January of 1999 and December of 2023. We compared the incidence of tuberculosis and nontuberculous mycobacterial disease (NTM) in patients with silicosis with and without ARD. We also compared the tuberculosis incidence in the overall cohort with general Brazilian population estimates. Results: The study comprised 369 silicosis patients, of whom 35 (9.5%) had ARD. Having ARD did not affect the cumulative incidence of mycobacterial diseases. The risk of tuberculosis was higher in the cohort when compared with that in the adult Brazilian male population (age-adjusted incidence rate ratio = 20.46; 95% CI 14.89-28.13). Conclusions: In this cohort of patients with silicosis, ARD was not associated with the incidence of mycobacterial diseases. [ABSTRACT FROM AUTHOR]

Rheumatoid arthritis (RA) is an autoimmune inflammatory and heterogeneous disease that affects several systems, especially the joints. Among the extra-articular manifestations of RA, pleuropulmonary involvement occurs frequently, with different presentations, potentially in all anatomic thoracic compartments, and may determine high morbidity and mortality. The most common pleuropulmonary manifestations in patients with RA include interstitial lung disease (ILD), pleural disease, pulmonary arterial hypertension, rheumatoid lung nodules, airway disease (bronchiectasis and bronchiolitis), and lymphadenopathy. Pulmonary hypertension and ILD are the manifestations with the greatest negative impact in prognosis. HRCT of the chest is essential in the evaluation of patients with RA with respiratory symptoms, especially those with higher risk factors for ILD, such as male gender, smoking, older age, high levels of rheumatoid factor, or positive anti-cyclic citrullinated peptide antibody results. Additionally, other etiologies that may determine tomographic pleuropulmonary manifestations in patients with RA are infections, neoplasms, and drug-induced lung disease. In these scenarios, clinical presentation is heterogeneous, varying from being asymptomatic to having progressive respiratory failure. Knowledge on the potential etiologies causing tomographic pleuropulmonary manifestations in patients with RA coupled with proper clinical reasoning is crucial to diagnose and treat these patients. [ABSTRACT FROM AUTHOR]

To present recent evidence on the prevalence, incidence, costs, activity limitations, and work limitations of common conditions requiring rehabilitation. Medline (PubMed), SCOPUS, Web of Science, and the gray literature were searched for relevant articles about amputation, osteoarthritis, rheumatoid arthritis, back pain, multiple sclerosis, spinal cord injury, stroke, and traumatic brain injury. Relevant articles (N=106) were included. Two investigators independently reviewed articles and selected relevant articles for inclusion. Quality grading was performed using the Methodological Evaluation of Observational Research Checklist and Newcastle-Ottawa Quality Assessment Form. The prevalence of back pain in the past 3 months was 33.9% among community-dwelling adults, and patients with back pain contribute $365 billion in all-cause medical costs. Osteoarthritis is the next most prevalent condition (approximately 10.4%), and patients with this condition contribute $460 billion in all-cause medical costs. These 2 conditions are the most prevalent and costly (medically) of the illnesses explored in this study. Stroke follows these conditions in both prevalence (2.5%-3.7%) and medical costs ($28 billion). Other conditions may have a lower prevalence but are associated with relatively higher per capita effects. Consistent with previous findings, back pain and osteoarthritis are the most prevalent conditions with high aggregate medical costs. By contrast, other conditions have a lower prevalence or cost but relatively higher per capita costs and effects on activity and work. The data are extremely heterogeneous, which makes anything beyond broad comparisons challenging. Additional information is needed to determine the relative impact of each condition. [ABSTRACT FROM AUTHOR]

The purpose of this study was to assess the clinical feasibility and effectiveness of manual mobilization of the hands of patients with rheumatoid arthritis (RA). A total of 320 individual hand joints were evaluated after recruiting an experimental research group of 12 participants with RA and, for clinical comparability, 8 participants with hand osteoarthritis (OA). One hand per participant was randomized to receive weekly low-grade (I-II) Kaltenborn manual mobilization, using passive sustained stretch of the metacarpophalangeal (MCP) joints II to V by licensed manual therapists. After 2 weeks, the randomized treated hand was crossed over to control (untreated) during weeks 3 to 4 and vice versa. Final assessment was at 2 months, which was 1 month after the last treatment at week 4. Primary hand outcomes included pain by visual analog scale, tender or swollen joint count, and presence of Doppler signal or synovial fluid and radiographic joint space by musculoskeletal ultrasound. In the RA group, both the initially randomized treated hand and the contralateral hand improved significantly from baseline to crossover to follow-up at 2 months (pain outcomes and Doppler signal, P <.050; synovial fluid and MCP joint space, P ≤.001). Hand pain and MCP joint space also improved significantly in OA. There were no dropouts or reported adverse events in either the RA or OA group. In this study, manual mobilization of the hands of patients with RA was shown to be feasible, safe, and effective to integrate into specialized healthcare. [ABSTRACT FROM AUTHOR]

Copyright of Radiologia Brasileira is the property of Radiologia Brasileira and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Background: A number of studies have suggested a bidirectional relationship of periodontitis with rheumatoid arthritis (RA) and type 2 diabetes mellitus (T2DM). However, the genetic factors that underlie these relationships have not been elucidated.Methods: We conducted a multicenter case-control study that included 185 patients with RA and chronic periodontitis (CP), 149 patients with T2DM and CP, 251 patients with CP, and 130 systemically and periodontally healthy controls from a cohort of Japanese adults to assess the shared genetic risk factors for RA and CP as well as for T2DM and CP. A total of 17 candidate single nucleotide polymorphisms (SNPs) associated with RA, T2DM, and CP were genotyped.Results: Multiple logistic regression analyses revealed that the KCNQ1 rs2237892 was significantly associated with comorbidity of RA and CP (P = 0.005) after adjustment for age, sex, and smoking status. The carriers of the T allele among patients with RA and CP showed significantly higher disease activity scores including 28 joints using C-reactive protein values than the non-carriers (P = 0.02), although the age, female percentage, and smoking status were comparable. Other SNPs were not associated with comorbidity of RA and CP, T2DM and CP, or susceptibility to CP.Conclusion: The results of the present pilot study suggest for the first time that the KCNQ1 rs2237892 may constitute a shared genetic risk factor for RA and CP, but not for T2DM and CP in Japanese adults. [ABSTRACT FROM AUTHOR]

Background: This study evaluates periodontal conditions and microbiologic findings and their influence on rheumatologic disease parameters in patients with rheumatoid arthritis (RA).Methods: One hundred and sixty-eight patients with RA were included. A healthy control group (HC, n = 168) was composed according to age, sex, and smoking habits. Rheumatologic data (duration of illness, Disease Activity Score 28, rheumatic factor [RF], anti-cyclic citrullinated peptide [aCCP], medications) were extracted from patients' records. Dental examination included: 1) dental findings (decayed, missing, and/or filled adult teeth [DMF-T] index); 2) gingival inflammation (papillary bleeding index [PBI]); and 3) periodontal status (probing depth [PD], attachment loss [AL]). Periodontal condition was classified as healthy/mild, moderate, or severe periodontitis. Subgingival biofilm was analyzed regarding 11 periodontopathogenic bacteria. Statistical analyses included: 1) Kolmogorov-Smirnov test; 2) Mann-Whitney U test; 3) Pearson χ2 test; 4) Kruskal-Wallis test; and 5) regression analysis; level of significance α = 5%.Results: Mean DMF-T was significantly higher in patients with RA (19.3 ± 4.8) than in HC group (16.9 ± 5.8), especially owing to number of missing teeth (RA = 6.0 ± 5.4, HC = 3.1 ± 3.3; P <0.01). Patients with RA had a significantly higher proportion of increased PD (P <0.01) and AL compared with HC group (P <0.01). Moderate to severe periodontitis was noted in 98% of patients with RA and 82% of the HC group (P <0.01). RF-positive patients with RA suffered from worse periodontal conditions than RF-negative patients (P = 0.01). Age, PBI, and presence of Treponema denticola (P <0.03) are related to periodontal condition in patients with RA. Although not statistically significant, Porphyromonas gingivalis and Fusobacterium nucleatum occur in higher concentrations more often in aCCP-positive patients with RA (P = 0.06).Conclusions: Patients with RA had worse periodontal conditions than HC participants. Although a trend for higher F. nucleatum and P. gingivalis concentrations in aCCP-positive patients with RA was found, importance of periodontal pathogenic bacteria and rheumatoid parameters in the interrelationship between periodontitis and RA remains unclear. [ABSTRACT FROM AUTHOR]

Background: Recent consensus emphasizes the importance of studying individuals at risk for rheumatoid arthritis (pre-RA) and those with early RA (eRA). Periodontal tissues have been recently evaluated, but these studies are limited. To evaluate the periodontal condition, immunoglobulin (Ig)G subclasses against Porphyromonas gingivalis in individuals with pre-RA and eRA were compared with controls to establish an association between periodontal infection markers and rheumatic activity.Methods: Rheumatologic and periodontal condition was evaluated in 119 individuals with pre-RA, 48 patients with eRA, and matched controls. P. gingivalis IgG1 and IgG2 were analyzed. C-reactive protein, erythrocyte sedimentation rate (ESR), rheumatoid factor, anticitrullinated protein antibodies (ACPAs), and RA activity were measured. The groups were compared with McNemar test and paired t-test. Conditional logistic regression was performed for pre-RA confounders, and χ(2) test was used to evaluate periodontal variables and RA activity indices.Results: Pre-RA individuals showed significantly higher levels of plaque index (P = 0.01) and bleeding on probing (P = 0.03) and higher severity of periodontal disease (P = 0.02). Periodontitis was associated with pre-RA (odds ratio, 3.39; 95% confidence interval, 1.64 to 7.01) but not with eRA. In pre-RA, P. gingivalis-specific IgG2 was associated with ACPAs (P = 0.049) and disease severity visual analog scale (P = 0.03). In eRA, IgG2 against P. gingivalis was associated with ESR (P = 0.046) and ACPAs (P = 0.04). P. gingivalis was associated with ACPAs (P = 0.04).Conclusions: This study shows that individuals with pre-RA have significant inflammatory periodontal involvement. There was a significant association between IgG against P. gingivalis and ACPAs in pre-RA and markers of RA activity in individuals with eRA. [ABSTRACT FROM AUTHOR]

Copyright of Brazilian Journal of Pulmonology / Jornal Brasileiro de Pneumologia is the property of Sociedade Brasileira de Pneumologia e Tisiologia and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Background: Periodontopathic bacteria have been implicated as contributory to the etiology of rheumatoid arthritis (RA). Anticyclic citrullinated peptide (CCP) antibodies and rheumatoid factor (RF) were shown to be associated with RA. This study examines whether serum levels of antibodies to periodontopathic bacteria may affect clinical and laboratory profiles of RA. Methods: The study participants consisted of 80 patients with RA, and 38 age-, sex-, smoking status-, and periodontal condition-balanced healthy controls. After periodontal and rheumatologic examination, serum levels of immunoglobulin G (lgG) antibodies to Porphyromonasgingivalis (Pg), Prevotella intermedia, Aggregatibacter actinomycetemcomitans (Aa) (previously Actinobacillus actinomycetemcomitans), and Eikenella corrodens (Ec) and those of anti-CCP antibodies and RF were determined by an enzyme-linked immunosorbent assay. Results: Patients with RA showed significantly higher levels of anti-Pg and anti-CCP antibodies than controls (P = 0.04 and P<0.0001 ). In contrast, IgG responses to Aa and Ec in patients with RA were significantly lower than those in controls (P <0.0001 and P= 0.0001 ). Multiple logistic regression analysis revealed a significant association of anti-Pg and anti-Aa IgG responses with RA, after adjustment for age, sex, and smoking (P = 0.005 and P= 0.02). Anti-Pg titer displayed a significant correlation with RF levels, probing depth, and clinical attachment level (P= 0.03, P= 0.03, and P= 0.02). Conclusion: These results suggest that serum levels of anti- Pg IgG antibodies were associated with RA, and might affect serum levels of RF and periodontal condition in patients with RA. [ABSTRACT FROM AUTHOR]

Background: A limited number of studies suggest a prevalence of periodontal pathogens in patients with rheumatoid arthritis (RA); however, results are inconsistent. The aim of this study is to investigate clinical periodontal and microbiologic parameters in patients with RA. Methods: Sixty-six patients with RA, aged 49.5 ± 8.4 years, participated in the study. The periodontal classification was assessed with the periodontal screening index (PSR/PSI) allocated to the following parameters: 1) healthy; 2) gingivitis (PSR/PSI score 0 to 2, maximum one sextant score; 3) moderate periodontitis (> 1 sextant PSR/PSI score 3, maximum one sextant score; or, 4) severe periodontitis (>1 sextant PSR/PSI score 4). Pool samples were taken for microbiologic (polymerase chain reaction) analysis for the presence of 11 periodontal pathogens. Statistical analysis was by non-parametric analysis of covariance. Results: No patients were periodontally healthy: 24 patients were classified as having gingivitis; 18 patients had moderate periodontitis; 23 patients had severe periodontitis; and one patient was toothless. For most patients, Fusobacterium nucleatum (98%), Eikenella corrodens (91%), and Parvimonas micra (previously Peptostreptococcus micros; 88%) were above the detection threshold. Strong periodontal pathogens were less frequently detected: Aggregatibacter actinomycetemcomitans (previously Actinobacillus actinomycetemcomitans, 16%); Porphyromonas gingivalis (58%); and Tannerella forsythia (previously T. forsythensis, 78%). Statistical analysis showed no significant influence of rheumatic factor (P= 0.33) on periodontal classification and on microbiologic parameters (P>0.05). Only smoking showed a significant influence (P = 0.0004) on the periodontal classification and in the case of E. corrodens (P= 0.02). Conclusions: Most patients with RA in this study showed moderate-to-severe periodontitis and the presence of periodontal pathogens. No association was found between rheumatic factor on periodontal classification and microbiologic parameters. [ABSTRACT FROM AUTHOR]

Abstract: Smulders E, van Lankveld W, Eggermont F, Duysens J, Weerdesteyn V. Step performance in persons with rheumatoid arthritis: a case-control study. Objective: To investigate factors that could lead to falls in patients with rheumatoid arthritis (RA). Design: Case-control study. Setting: Hospital. Participants: Patients with RA (n=15) and age- and sex-matched controls (n=15; mean ± SD age, 60.5±7.1y). Interventions: Not applicable. Main Outcome Measures: Performance of participants on a step task. Furthermore, manual performance was assessed, as well as questionnaires for balance confidence, fear of falling, and activity level. Results: Patients with RA showed nonsignificantly increased RTs (time to anticipatory postural adjustment and foot lift) and significantly increased movement times (MTs). Push-off force and step velocity were significantly lower in patients with RA. During a manual task, delayed RTs and MTs were seen. Moreover, lower levels of balance confidence and more fear of falling were reported in patients with RA. There were no differences in activity levels. Conclusions: When performing a quick step, patients with RA show delayed MT and step velocity and decreased push off. Because quick stepping often is used to avoid falls, the increase in step execution time might have undesirable consequences. Furthermore, patients with RA have lower balance confidence and more fear of falling than healthy controls; these factors also contribute to higher fall risk. [Copyright &y& Elsevier]

Background: Rheumatoid arthritis (RA) and periodontitis are common chronic inflammatory conditions and share many pathologic features. A similar profile of cytokines is involved in the pathogenesis of the two diseases. The relationship between the disease activity of RA and the periodontal condition remains unclear. This study examines whether the disease activity of RA affects serum cytokine and periodontal profiles. Methods: The study subjects consisted of 84 Japanese adults with RA and 22 race-matched control individuals. After periodontal and rheumatologic examination, the disease activity of RA was determined with the Disease Activity Score including 28 joints using C-reactive protein (DAS28-CRP). Serum levels of cytokines including interleukin (IL)-β, IL-6, IL-12, IL-12 p40, IL-18, and tumor necrosis factor-α (TNF-(α) were determined by an enzyme-linked immunosorbent assay. High-sensitive CRP was also measured with a latex particle-enhanced nephelometric method. Results: Of 84 patients with RA, 28 and 56 patients exhibited low and moderate to high disease activity, respectively. Serum levels of IL-6, TNF-α and CRP were significantly different between the two groups (P<0.05). Additionally, a significant correlation was observed between DAS28-CRP and percentage of sites with bleeding on probing (BOP) (P= 0.008) and between serum TNF-α levels and percentage of sites with BOP (P= 0.01) in 56 patients with RA with moderate to high activity. Conclusion: These results suggest that the disease activity of RA correlated with serum levels of IL-6, TNF-α, and CRP, and it might influence BOP in the patients with moderate to high disease activity. [ABSTRACT FROM AUTHOR]

Abstract: Chiari-Grisar C, Koller U, Stamm TA, Wanivenhaus A, Trieb K. Performance of the Disabilities of the Arm, Shoulder and Hand Outcome Questionnaire and the Moberg Picking Up Test in patients with finger joint arthroplasty. Objective: To compare the performance of the Disabilities of the Arm, Shoulder and Hand Outcome (DASH) Questionnaire and the Moberg Picking Up Test (MPUT) with other outcome measurement tools in assessing both hand function and aspects of general health in finger joint arthroplasty in patients with rheumatoid arthritis (RA). Design: Case series, with an average follow-up duration of 104.9 months. Setting: Orthopedic outpatient clinic at a university hospital. Participants: Of 64 consecutive patients (21 dead, 6 lost to follow-up), 37 patients with 140 spacers in 107 metacarpophalangeal and 33 proximal interphalangeal joints of 51 hands were evaluated. Interventions: Not applicable. Main Outcome Measures: Hand function tests and general health measures. Results: The DASH correlated with both hand function (Health Assessment Questionnaire: r=.72, P<.01; MPUT: r=0.6, P<.01) and general health (Medical Outcomes Study 36-Item Short-Form Health Survey subscales: r range, −.73 to −.31; P range, <.001 to <.05). The MPUT was a suitable tool for precision grip testing. Conclusions: The DASH has the advantage of being self-administered and assesses both functional and health aspects. It can be recommended as an instrument for a routine clinical follow-up for patients with hand surgery and RA. Additional tests should be applied when detailed information is needed. [Copyright &y& Elsevier]

The authors discuss the relationship between periodontitis and rheumatoid arthritis (RA). They mention the inflammatory nature of both diseases, the imbalance of proinflammatory and anti-inflammatory cytokines that may be a cause for both diseases, and the need to screen RA patients for periodontal issues with extra care.

Abstract: Häkkinen A, Neva MH, Kauppi M, Hannonen P, Ylinen J, Mäkinen H, Jäppinen I, Sokka T. Decreased muscle strength and mobility of the neck in patients with rheumatoid arthritis and atlantoaxial disorders. Objective: To compare neck muscle strength and mobility of the cervical spine in rheumatoid arthritis (RA) patients with and without atlantoaxial (AA) disorders (anterior atlantoaxial subluxation [AAS], AA impaction). Design: Clinical cross-sectional study. Setting: Outpatient rheumatology and rehabilitation clinics in a Finnish hospital. Participants: Patients with RA (N=124; mean age ± standard deviation, 62±y) on a waiting list for orthopedic surgery. Thirty (24%) patients presented with AA disorders (16 with anterior AAS, 8 with AA impaction, 6 with a combination of anterior AAS and AA impaction). Interventions: Not applicable. Main Outcome Measures: Neck function was measured by isometric neck strength and mobility tests, neck pain by a visual analog scale, erosion of the hands and feet by radiography, and the patients’ function by the Health Assessment Questionnaire (HAQ). Results: Maximal neck muscle strength against flexion, extension, and rotation was lower in patients with AA disorders compared with the other patients in both women (P=.012) and men (P=.017). Mobility was lowest in the AA impaction group in all measured directions (P<.001). Peripheral erosive disease was more frequent in the group with AA disorders. They also had longer disease duration and were more disabled (HAQ) than the other patients. Conclusions: Neck muscle strength is significantly decreased in patients with AA disorders. Mobility of the cervical spine is most limited in patients with AA impaction, but can be normal in cases with solitary anterior AAS. [Copyright &y& Elsevier]

: Rationale and ObjectivesThe authors'' purpose was to investigate the reliability of a personal computer (PC)–based display system compared with a workstation in the evaluation of rheumatoid arthritis on computed radiographs of the hands.: Materials and MethodsTwo radiologists on two occasions independently scored randomized computed radiographs of individual joints of the hands from 23 patients with rheumatoid arthritis and 14 control subjects. Each joint was scored from 0 (definitely normal) to 30 (severe disease) for each of four variables: soft-tissue swelling, osteopenia, erosions, and joint space narrowing. The observations were replicated on a picture archiving and communication system workstation and a PC. Intraobserver and interobserver reliability were calculated, as was the difference in scores between the two systems. The null hypothesis was that there was no difference between the workstation and the PC.: ResultsThe intraobserver reliability for normal versus abnormal joints was 73% with the workstation and 79% with the PC. The intraobserver reliability for workstation versus PC was 83%. There was moderate interreader reliability for both platforms (average κ statistic, 0.46 [workstation] vs 0.45 [PC]). Small differences in scores between platforms are probably due mostly to the ordinal nature of the scoring system.: ConclusionFor evaluating computed radiographs of the hands in early rheumatoid arthritis, a PC-based system provides results similar to those obtained with a workstation, at considerably reduced cost. [Copyright &y& Elsevier]

Background: This investigation was designed to determine and compare the distribution pattern of anti-neutrophil cytoplasmic antibodies (ANCA) in patients with systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA) in the presence or absence of periodontal disease. Methods: Sera of 30 patients with SLE and 30 with RA were tested for ANCA utilizing an indirect enzyme immunosorbent assay (ELISA) directed to a neutrophil granular extract and 6 neutrophil granule proteins. A control group of 20 healthy individuals showing neither evidence of periodontal disease nor systemic compromise was also included in this study. Results: For RA, the number of ANCA-positive sera was very low but was evenly distributed among patients with and without periodontitis. Conversely, a high number of ANCA-positive sera in SLE was found mostly in individuals presenting periodontal compromise. A statistically significant association between ANCA and periodontitis in SLE patients was found (P <0.005, chi square test). Conclusions: A marked difference in the number and distribution of ANCA with respect to periodontitis between RA and SLE was found. Hyperresponsiveness of B cells and polyclonal B activation to periodontopathic bacteria in SLE might be accountable for the high numbers of ANCA and the close association observed between those autoantibodies and periodontitis in SLE. [ABSTRACT FROM AUTHOR]

Background: Rheumatoid arthritis flares have a profound effect on patients, causing pain and disability. However, flares often occur between regularly scheduled health care provider visits and are, therefore, difficult to monitor and manage. We sought to develop a mobile phone app combined with a population management system to help track RA flares between visits. Objective: The objective of this study is to implement the mobile app plus the population management system to monitor rheumatoid arthritis disease activity between scheduled health care provider visits over a period of 6 months. Methods: This is a randomized controlled trial that lasts for 6 months for each participant. We aim to recruit 190 patients, randomized 50:50 to the intervention group versus the control group. The intervention group will be assigned the mobile app and be prompted to answer daily questionnaires sent to their mobile devices. Both groups will be assigned a population manager, who will communicate with the participants via telephone at 6 weeks and 18 weeks. The population manager will also communicate with the participants in the intervention group if their responses indicate a sustained increase in rheumatoid arthritis disease activity. To assess patient satisfaction, the primary outcomes will be scores on the Treatment Satisfaction Questionnaire for Medication as well as the Perceived Efficacy in Patient-Physician Interactions questionnaire at 6 months. To determine the effect of the mobile app on rheumatoid arthritis disease activity, the primary outcome will be the Clinical Disease Activity Index at 6 months. Results: The trial started in November 2016, and an estimated 2.5 years will be necessary to complete the study. Study results are expected to be published by the end of 2019. Conclusions: The completion of this study will provide important data regarding the following: (1) the assessment of validated outcome measures to assess rheumatoid arthritis disease activity with a mobile app between routinely scheduled health care provider visits, (2) patient engagement in monitoring their condition, and (3) communication between patients and health care providers through the population management system. Trial Registration: ClinicalTrials.gov NCT02822521, http://clinicaltrials.gov/ct2/show/NCT02822521 (Archived by WebCite at http://www.webcitation.org/6xed3kGPd) [ABSTRACT FROM AUTHOR]