Tanezumab for the treatment of osteoarthritis pain.

Tanezumab is a novel humanized IgG2 monoclonal antibody that works by selectively targeting, binding to and inhibiting nerve growth factor (NGF). NGF is upregulated in response to injury and inflammation, and preclinical data indicate it plays a role in pain signaling by inducing peripheral and central sensitization. Tanezumab potentially reduces sensitization and pain by blocking the interaction between NGF and the tropomyosin receptor kinase A (TrkA), and it has been studied extensively for the treatment of pain in patients with osteoarthritis (OA). In 2017, tanezumab was granted fast track designation in the U.S. for the treatment of chronic pain in patients with OA, as well as for the treatment of chronic low-back pain. This review discusses the mechanism of action, preclinical data and phase I, II and III studies of efficacy and safety of tanezumab in patients with OA.

Recurrent strokes and memory loss in a patient with triple-positive antiphospholipid antibody syndrome.

Antiphospholipid syndrome may cause recurrent thromboembolic events of the microvasculature, arteries and veins. It is also characterised by a range of neurological and psychiatric dysfunctions, as well as complications during pregnancy. Patients with triple-positive antiphospholipid syndrome have persistently elevated levels of lupus anticoagulant (LA), anti-beta-2-glycoprotein I (B2GPI) and anticardiolipin antibodies (aCL). These patients also have a higher risk of initial or recurrent thrombosis.We report the case of a 36-year-old man who was presented with progressive memory loss and recurrent stroke. He had persistently elevated antiphospholipid antibody titres (LA, aCL-immunoglobulin G and B2GPI antibodies). These features persisted while the patient was receiving low-dose aspirin (LDA), 81mg daily. Vitamin K antagonist (VKA); warfarin, with the international normalised ratio (INR) maintained at 2-3 was then added to his treatment regimen. The VKA dose was maintained at - a higher therapeutic INR while LDA administration was continued to achieve resolution of the patient's symptoms.

Janus Kinase Inhibitors and Risk of Venous Thromboembolism: A Systematic Review and Meta-analysis.

OBJECTIVE: To assess the risk of venous thromboembolism (VTE) in patients treated with Janus kinase (JAK) inhibitors in clinical trials. PATIENTS AND METHODS: We performed a literature search of Ovid MEDLINE and ePub Ahead of Print, In-Process & Other Non-Indexed Citations, and Daily; Ovid EMBASE; Ovid Cochrane Central Register of Controlled Trials; Ovid Cochrane Database of Systematic Reviews; and Scopus, from inception to December 4, 2019, for randomized, placebo-controlled trials with JAK inhibitors as an intervention and reported adverse events. Odds ratio with 95% CI was calculated to estimate the VTE risk using a random effects model. Two independent reviewers screened and extracted data. The GRADE (Grading of Recommendations Assessment, Development and Evaluation) approach was used to assess certainty in estimated VTE risk. RESULTS: We included 29 trials (13,910 patients). No statistically significant association was found between use of JAK inhibitors and risk of VTE (odds ratio, 0.91; 95% CI, 0.57 to 1.47; P=.70; I2=0; low certainty because of serious imprecision). Results using Bayesian analysis were consistent with those of the primary analysis. Results of stratified and meta-regression analyses suggested no interaction by dose of drug, indication for treatment, or length of follow-up. CONCLUSION: We found insufficient evidence to support an increased risk of JAK inhibitor-associated VTE based on currently available data.

Medical overuse of therapies and diagnostics in rheumatology.

Medical overuse leads to a burden on healthcare costs and potentially is harmful to patients. We wanted to address medical overuse in musculoskeletal disease and rheumatology. We performed a systemic literature review from PubMed and Embase to study medical overuse. On the initial screen, 1499 studies were identified, 839 of them were related to medical overuse. Out of these, 52 were related to overuse in musculoskeletal diseases. Finally, 20 articles were chosen for this systemic review that reported overuse in rheumatology. The article identifies issues with overtesting, including the use of dual-energy X-ray absorptiometry to screen for osteoporosis in women younger than 65 years old and the use of magnetic resonance imaging to evaluate for osteoarthritis. Studies related to overtreatment reported over-prescription of vitamin D supplements resulting in vitamin D toxicity and increased risk of inappropriate prescriptions in patients with osteoarthritis and rheumatoid arthritis. Overtreating osteoporosis was reported after industry-sponsored education. Articles describing methods to reduce overuse included a study showing the reduction of unnecessary dual-energy X-ray absorptiometry scans after the introduction of the Choosing Wisely Campaign. Our findings suggest that there is some evidence that overtesting and overtreatment may be present in the field of rheumatology. This review aims to highlight this and help rheumatologists to be aware of overuse practices and provide appropriate evidence-based healthcare.

Health-related risk behaviors among myocardial infarction survivors in the United States: A propensity score matched study.

BACKGROUND: According to the American College of Cardiology/the American Heart Association (ACC/AHA) recommendations, health-related risk behaviors for secondary prevention of myocardial infarction (MI) are critical to determine. OBJECTIVE: This study aimed to compare health-related risk behaviors between MI survivors and propensity-score-matched non-MI controls using nationally representative data. METHODS: This cross-sectional, matched case-control study used publicly available Behavioral Risk Factor Surveillance System (BRFSS) 2017 data. Older adults with MI were propensity-score-matched to their non-MI controls. The 10 dependent variables included body mass index (BMI), smoking status, heavy alcohol consumption, influenza vaccine, length of time since last routine and cholesterol checkup, alcohol consumption, fruit and vegetable consumption, and physical activity. Chi-square tests and binomial logistic regression were used to examine the health-related risk behaviors differences between MI survivors and propensity-score-matched non-MI controls. RESULTS: The final study sample consisted of 18,021 MI survivors and 54,063 non-MI controls after propensity score matching. Multivariable logistic regression analysis showed significant differences between MI survivors and matched non-MI controls in terms of cholesterol checkup, smoking status, and alcohol consumption. For example, multivariate analysis of health-related risk behaviors showed MI survivors were more likely to be smokers (AOR = 1.46, 95% CI: 1.28-1.68). CONCLUSION: Based on this national survey of adults, MI survivors were more likely to be smokers but less likely to consume alcohol compared to their propensity-score-matched controls. Moreover, MI survivors were more likely to have their cholesterol checkup within the past 2 years compared to matched non-MI controls. Although lower alcohol consumption and greater chances of cholesterol checkups are reassuring health-related behaviors, interventions are needed to minimize the chances of smoking in this population.

The Influence of Depression on Health Care Expenditures Among Adults with Spondylosis, Intervertebral Disc Disorders, and Other Back Problems in the United States.

BACKGROUND: Back pain is a very prevalent complaint, affecting two-thirds of the US population, and it accounts for $100 billion annually in health care expenditures. The occurrence of depression has been reported in existing literature among patients with back pain, but there is limited information regarding health care expenditures among patients with back pain and concurrent depression. OBJECTIVE: To assess excess total and subtypes of health care expenditures among adults with spondylosis, intervertebral disc disorders, and other back problems who reported having depression compared with those without depression in the United States. METHODS: We utilized a cross-sectional design, pooling Medical Expenditure Panel Survey data from 2010-2012. The eligible study sample included adults (age ≥18 years) who reported positive health care expenditure. Total and subtypes of health care expenditures constituted the dependent variable. Ordinary least squares (OLS) regressions on logged expenditures were performed. Four models were developed to assess influence of demographics, functional ability, and concurrent diagnoses on health care expenditures. RESULTS: A total of 6,739 adults with spondylosis, intervertebral disc disorders, and other back problems were assessed, 20.2% (N = 1,316) of whom had concurrent depression. Adults with concurrent depression had significantly higher total health care expenditures ($13,153) compared with the nondepression group ($7,477, P < 0.001). Outpatient and prescription expenditures showed similar findings. After adjusting for demographics, functional disabilities, and comorbidities, excess cost remained higher in the group reporting concurrent depression (46%). CONCLUSIONS: This study demonstrates that the presence of depression in adults with spondylosis, intervertebral disc disorders, and other back problems is associated with greater economic burden. These findings remained consistent after adjusting for all independent sets of variables. The study's findings suggest that interventions resulting in better management of depression have the potential to significantly reduce the economic burden in this population.

Risk of Infections and Cancer in Patients With Rheumatologic Diseases Receiving Interleukin Inhibitors: A Systematic Review and Meta-analysis.

Importance: The safety profile of interleukin (IL) inhibitors is not well established. Objective: To assess the risk of serious infections, opportunistic infections, and cancer in patients with rheumatologic diseases treated with IL inhibitors. Data Sources: Ovid MEDLINE and Epub Ahead of Print, In-Process & Other Non-Indexed Citations; Ovid MEDLINE Daily; Ovid Embase; Ovid Cochrane Central Register of Controlled Trials; Ovid Cochrane Database of Systematic Reviews; and Scopus were searched (inception to November 30, 2018). Study Selection: Randomized, placebo-controlled trials that evaluated IL inhibitor therapies in rheumatic diseases and reported safety data were included in the analyses. Data Extraction and Synthesis: This systematic review is reported according to the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) statement. Two investigators independently extracted study data and assessed risk of bias and certainty in the evidence. Fixed-effects meta-analysis was conducted to pool odds ratios (ORs) for serious infections, opportunistic infections, and cancers for IL inhibitors vs placebo. Main Outcomes and Measures: The outcomes of interest were the number of serious infections, opportunistic infections, and cancers in individuals receiving IL inhibitor therapies compared with placebo. Results: In this meta-analysis, 74 studies comprising 29 214 patients (24 236 patients for serious infections, 9998 for opportunistic infections, and 21 065 for cancer [number of patients overlaps for each outcome]) were included. Patients receiving IL inhibitors had a higher risk of serious infections (OR, 1.97; 95% CI, 1.58-2.44; P < .001, I2 = 0%; high certainty), opportunistic infections (OR, 2.35; 95% CI, 1.09-5.05; P = .03, I2 = 0%; moderate certainty), and cancer (OR, 1.52; 95% CI, 1.05-2.19; P = .03, I2 = 11%; moderate certainty). Conclusions and Relevance: The risk of serious infections, opportunistic infections, and cancer appears to be increased in patients with rheumatologic diseases who are treated with IL inhibitors compared with placebo.

Healthcare expenditures among community-dwelling adults with thyroid cancer in the United States: A propensity score matched analysis.

OBJECTIVE: This study assessed the excess healthcare expenditures and factors associated with it among community-dwelling adults with thyroid cancer compared to non-cancer controls in the United States. METHOD: A retrospective, cross-sectional, matched case-control study design was used by pooling multiple years of Medical Expenditure Panel Survey (MEPS) data (2002-2012). The eligible study sample comprised of adults (age ≥18 years), who were alive during the calendar year and reported positive healthcare expenditure. The case group consisted of adults with thyroid cancer only while the control group consisted of adults who did not have any form of cancer. Total and subtypes of mean annual healthcare expenditures comprised the main study outcome. We also calculated the total and subtypes of out-of-pocket (OOP) expenditures as well as OOP as a percentage of household income. Ordinary Least Square (OLS) regressions on log-transformed expenditures were conducted to elucidate the influence of different factors on healthcare expenditures among adults with thyroid cancer. RESULTS: The yearly average total healthcare expenditures among adults with thyroid cancer was significantly higher compared to propensity score matched controls ($9,585 vs. $5,830, p < 0.001). Similar observations were found in terms of inpatient, and outpatient expenditures. Functional status as well as comorbid conditions were significantly associated with excess expenditures. The yearly average total OOP expenditure for adults with thyroid cancer was significantly higher compared to matched controls ($1,425 vs. $974, p < 0.001), with major differences observed in inpatient OOP ($178 vs. $24, p = 0.003), outpatient OOP ($435vs. $256, p < 0.001), and prescription OOP ($554 vs. $423, p < 0.001) expenditures. There was a significant (p < 0.001) difference between the average OOP as a percentage of household income between adults with thyroid cancer (Mean: 7.54%, S.E: 1.52%) and matched controls (Mean: 5.80%, S.E: 0.47%). CONCLUSIONS: Our findings suggest that holistic care approach could be helpful to significantly reduce the economic burden in this population. Viable strategies such as limits on OOP costs are required to minimize this high OOP burden among cancer survivors and their families.

Management of asymptomatic coccidioidomycosis in patients with rheumatic diseases.

Coccidioidomycosis is an endemic fungal infection common in the southwestern United States. Some rheumatology clinics periodically screen patients with coccidioidal serology, resulting in the identification of patients who are serologically positive but without clinical symptoms. The management of such patients is unclear. A retrospective study was conducted between 2007 and 2015 at two arthritis centers in Tucson, Arizona. The asymptomatic patients were identified who were receiving disease-modifying antirheumatic agents and had a positive coccidioidal serology. Serological testing including IgM and IgG was performed by enzyme immunoassay (EIA), immunodiffusion (IDTP and IDCF), or complement fixation. Out of 71 patients who were identified with positive coccidioidal serologies, 19 were asymptomatic. 18/19 patients continued antirheumatic therapy, 13 without interruption. 13/19 patients received no antifungal treatment, including 10 who remained on antirheumatic treatment. The other six were started on fluconazole, ranging from 8 to 73 months (median 30.5 months). After a median follow-up of 43 months, no patient developed clinically active coccidioidomycosis. Overall, 14 had only a positive EIA serological test. These results suggest that continued antirheumatic therapy is safe in asymptomatic patients with positive coccidioidal serological tests and that routine implementation of antifungal treatment may not always be warranted. The findings also raise concern regarding the utility of routine serological testing of asymptomatic patients residing in the coccidioidal endemic area, mainly using the EIA test.

The 100 top-cited publications in psoriatic arthritis: a bibliometric analysis.

BACKGROUND: Citation analysis is a quantitative, bibliometric method that analyzes the frequency and pattern of citations in any given scientific discipline. Over the last two decades, the study of psoriatic arthritis has undergone substantial progress, which has enhanced our ability to assess and treat the disease, and yet an updated citation analysis that reflects these advances is lacking. OBJECTIVE: To highlight the scientific progress in psoriatic arthritis by identifying and analyzing the 100 top-cited psoriatic arthritis articles from the last 40 years. METHODS: Publications on psoriatic arthritis were identified using the Scopus citation database and Web of Science. No date range limits were applied. Data on the 100 top-cited publications were extracted and analyzed. RESULTS: Of the 100 top-cited publications, the median number of citations per publication was 265.9. Articles originated from 29 different countries. Publication dates ranged from 1973 to 2014. The majority (n = 88) were published after 1994, and the greatest number of highly cited psoriatic arthritis publications were reported between 2001 and 2007 (n = 36). Journals with the highest number of top-cited articles included Arthritis and Rheumatology (formerly Arthritis and Rheumatism) (n = 26), followed by Annals of Rheumatic Diseases (n = 21) and Journal of Rheumatology (n = 11). The top six journals with the most highly cited psoriatic arthritis articles were rheumatology journals, with the exception of the Journal of American Academy of Dermatology, a dermatology-based periodical. General medical journals published only nine of the 100 top citations. Impact factors ranged from 2.133 to 44.002, with a mean impact factor of 9.103. There were five authors with 10 or more highly cited psoriatic arthritis publications and 30 authors with five or more of the top publications. Subgroup analysis of the top 25 articles included nine randomized clinical trials, nine observational studies, five reviews, and two guideline statements. Additional subgroup analysis identified the top five hallmark trials in the field. Key publications provided data on classification criteria, disease prevalence, patterns of clinical and radiographic presentation, disease outcomes, associated cardiovascular disease risk, immunologic features and HLA associations, and efficacy and therapeutic benefit of TNFα inihbitors, interleukin-12/23 antagonists, and sulfasalazine. CONCLUSIONS: The study of psoriatic arthritis is rapidly evolving. This bibliometric analysis delineates the landmark publications in psoriatic arthritis that have defined innovative therapeutic modalities and provided critical reviews, guidelines, and other key studies, which highlight the important progress made in the field.

Psoriasis and Psoriatic Spectrum Disease: A Primer for the Primary Care Physician.

Psoriasis is a chronic, immune-mediated disorder that affects approximately 7.5 million people in the United States. Individuals with psoriasis may develop cutaneous, articular, and systemic manifestations, which are a source of significant morbidity and a heightened risk of mortality, and may adversely impact patient-reported quality of life measures. Psoriasis is now recognized as a risk factor for cardiovascular disease, metabolic syndrome, peripheral vascular disease, inflammatory bowel disease, certain malignancies, and chronic renal disease. Therefore, it has become increasingly relevant that primary care physicians have a basic working knowledge and an understanding of fundamental management principles of psoriasis. This review highlights the salient clinical features of psoriasis and psoriatic spectrum disease, emphasizing key updates with respect to systemic disease and associated conditions, and briefly outlines a therapeutic algorithm for the primary care physician.

Disease Milestones through Bibliometric Analysis of the Top 100 Cited Articles in Multiple Myeloma.

Multiple myeloma (MM) accounts for 1.6% of all cancers and 5%-10% of all hematologic malignancies in the United States (US). Despite marked progress in disease management, it remains incurable with high rates of relapse. We conducted a bibliographic analysis on the Web of Science (WOS) from July 25, 2017 and July 29, 2017. Among the top 100 most-cited articles (1901-2012), the most cited article received 2404 citations and least cited article received 336 citations. Forty-four of 100 articles were published in journals with impact factors greater than 20. We observed that over the years, the focus of research has shifted from diagnosis, staging, and pathogenesis to better treatment outcomes. A subgroup analysis of the top 100 cited articles published in the last five years (2012-2017) demonstrated that several landmark studies, which will likely change the landscape of treating multiple myeloma, were not included in the top 100 list. Interestingly, most of these articles were focused on novel therapeutic agents. This bibliographic analysis provides a list of the 100 top-cited articles in multiple myeloma along with the captivating comprehension of the history and development in various aspects of disease processes. The landscape of this disease is rapidly evolving, and bibliometric studies such as the one presented provide a valuable tool that can highlight the important transitions in the field.

Health Behaviors among Stroke Survivors in the United States: A Propensity Score-Matched Study.

GOAL: The American Heart Association/American Stroke Association has specific recommendations for secondary stroke prevention. The aim of this study was to compare health behaviors engagement between stroke survivors and propensity score-matched controls. METHODS: We conducted a retrospective, cross-sectional, matched case-control study using data from the 2015 Behavioral Risk Factor Surveillance System (BRFSS) survey. We included older adults aged 50 or older who participated in the 2015 BRFSS survey and completed the interview. Each case was matched to 3 controls (1:3) based on propensity scores to increase the power of the analyses. Stroke survivors were compared with controls on their physical activity, smoking, alcohol use, body mass index (BMI), last flu immunization, last physical checkup, last blood cholesterol check, heavy drinking, and vegetable and fruit consumption. We used binomial logistic regression to assess health behaviors among stroke survivors compared with controls. RESULTS: The final study sample consisted of 13,249 stroke survivors and 39,747 controls without stroke after propensity score matching. Multivariable analyses revealed that there were significant differences between stroke survivors and matched controls in terms of BMI, physical activity, smoking status, alcohol consumption, and vegetable and fruit consumption. For example, stroke survivors were 51% more likely to be smokers (adjusted odds ratio [AOR] 1.51, 95% confidence interval [CI], 1.32-1.73) and 14% less likely to consume alcohol (AOR .86, 95% CI .78-.95). CONCLUSION: Findings from our study indicate that compared with propensity score-matched controls, stroke survivors engage in poorer health behaviors with the exception of alcohol consumption.

Role of one, two and three doses of high-dose chemotherapy with autologous transplantation in the treatment of high-risk or relapsed testicular cancer: a systematic review.

Approximately 20-30% of patients with metastatic germ cell cancers (GCCs) can develop relapsed or refractory (RR) disease, about 40-50% of patients who relapse after salvage chemotherapy may reach long-term remission. The goal of this review was to identify patients who appear to benefit from high-dose chemotherapy (HDCT) and autologous stem cell transplant (ASCT). To access this, we performed a systematic medical literature review to evaluate the effectiveness of HDCT in the frontline setting, as well as in patients with RR testicular cancer. We searched databases for interventional clinical studies and identified 5883 studies. We selected 49 studies for inclusion, which included a total of 5985 patients. Seventeen studies reported results of newly diagnosed poor-risk GCC patients and 32 studies reported results of RR patients. For newly diagnosed patients with poor prognostic predictors, a risk adjusted strategy using unfavorable tumor marker decline with initial standard chemotherapy regimen and upfront HDCT demonstrated improved outcomes. Our data suggest a minimum of two HDCT cycles with ASCT should be standard of care for patients with RR GCC. Failure of HDCT results in a poor prognosis with only 10% of patients achieving lasting remission with salvage therapy.