Objectives Hydroxychloroquine (HCQ) is a key therapy in systemic lupus erythematosus (SLE). Medication non-adherence is reported in up to 80% of lupus patients and results in increased morbidity, mortality, and health care utilization. HCQ levels are a sensitive and reliable method to assess medication adherence. Our study evaluated the role of HCQ level measurement in routine clinical care and its association with disease activity in a predominantly Hispanic population. Methods SLE patients from the Columbia University Lupus cohort treated with HCQ for ≥ 6 months and reporting medication adherence were included. HCQ levels were measured by whole blood high performance liquid chromatography. Non-adherence was defined as an HCQ level <500 ng/ml. The association between HCQ levels and disease activity measured by Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K) was evaluated. Results One hundred and eight patients were enrolled; the median age was 38 years, 91% were female, and 63% were Hispanic. The median SLEDAI-2K was 4.3 (0–20). Forty-one percent of patients had an HCQ level <500 ng/ml consistent with non-adherence, of which 19% had undetectable levels. A higher SLEDAI-2K score was associated with low HCQ levels ( p = 0.003). This association remained significant after adjusting for depression ( p = 0.0007). Conclusion HCQ levels < 500 ng/ml were associated with higher disease activity and accounted for 32% of the SLEDAI-2K variability. HCQ blood measurement is a simple and reliable method to evaluate medication adherence in SLE. Reasons for non-adherence (levels < 500 ng/ml) should be further explored and addressed.

Despite improvements in technique and technology for total knee arthroplasty (TKA), anterior knee pain impacts patient outcomes and satisfaction. Addressing the prosthetic and surgical technique related causes of pain after TKA, specifically as it relates to anterior knee pain, can aid surgeons in addressing these issues with their patients. Design features of the femoral and patellar components which have been reported as pain generators include: Improper femoral as well as patellar component sizing or designs that result in patellofemoral stuffing; a shortened trochlear groove distance from the flange to the intercondylar box; and then surgical technique related issues resulting in: Lateral patellar facet syndrome; overstuffed patella/ flange combination; asymmetric patellar resurfacing, improper transverse plane component rotation resulting in patellar subluxation/tilt. Any design consideration that allows impingement of extensor mechanism anatomical elements has the possibility of impacting outcome by becoming a pain generator. As the number of TKA procedures continues to increase, it is increasingly critical to develop improved, evidence based prostheses that maximize function and patient satisfaction while minimizing pain and other complications. MINIREVIEWSSubmit a

Asians as a group comprise > 60% the world’s population. There is an incredible amount of diversity in Asian and admixed populations that has not been addressed in a pharmacogenetic context. The known pharmacogenetic differences in Asian subgroups generally represent previously known variants that are present at much lower or higher frequencies in Asians compared with other populations. In this review we summarize the main drugs and known genes that appear to have differences in their pharmacogenetic properties in certain Asian populations. Evidence‐based guidelines and summary statistics from the US Food and Drug Administration and the Clinical Pharmacogenetics Implementation Consortium were analyzed for ethnic differences in outcomes. Implicated drugs included commonly prescribed drugs such as warfarin, clopidogrel, carbamazepine, and allopurinol. The majority of these associations are due to Asians more commonly being poor metabolizers of cytochrome P450 (CYP) 2C19 and carriers of the human leukocyte antigen (HLA)‐B*15:02 allele. The relative risk increase was shown to vary between genes and drugs, but could be > 100‐fold higher in Asians. Specifically, there was a 172‐fold increased risk of Stevens‒Johnson syndrome and toxic epidermal necrolysis with carbamazepine use among HLA‐B*15:02 carriers. The effects ranged from relatively benign reactions such as reduced drug efficacy to severe cutaneous skin reactions. These reactions are severe and prevalent enough to warrant pharmacogenetic testing and appropriate changes in dose and medication choice for at‐risk populations. Further studies should be done on Asian cohorts to more fully understand pharmacogenetic variants in these populations and to clarify how such differences may influence drug response.

The LFA-REAL provides a reliable surrogate for more complicated disease activity measures when used by lupus clinical investigators or clinicians.

Belimumab (Benlysta) is a fully-humanized monoclonal antibody that inhibits B-lymphocyte stimulator (also known as B cell activating factor) and was approved by the U.S. Federal Drug Administration and European Medicines Evaluation Agency for treatment in adults with autoantibody-positive systemic lupus erythematosus (SLE). Rituximab (Rituxan) is a chimeric anti-CD20 monoclonal antibody targeting B lymphocytes. This review discusses the key findings of the phase III trials in adults with SLE and of real-world use of belimumab and rituximab in the care of both adult and pediatric SLE patients. It highlights the safety profile of belimumab and rituximab and gives insight into the consideration of these therapies for specific SLE disease states. It concludes with a discussion of the current clinical trials investigating B cell therapies in specific SLE disease states and a look to the future, with ongoing clinical trials.

Objective In the era of powerful immunosuppression, opportunistic infections are an increasing concern in systemic lupus erythematosus. One of the best-studied opportunistic infections is Pneumocystis pneumonia; however, the prevalence of Pneumocystis pneumonia in systemic lupus erythematosus is not clearly defined. This study evaluates the prevalence of Pneumocystis pneumonia in hospitalized systemic lupus erythematosus patients, with a focus on validating the Pneumocystis pneumonia and systemic lupus erythematosus diagnoses with clinical information. Methods This retrospective cohort study evaluates the prevalence of Pneumocystis pneumonia in all systemic lupus erythematosus patients treated at Columbia University Medical Center-New York Presbyterian Hospital between January 2000 and September 2014, using electronic medical record data. Patients with human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS) and patients with renal transplants (including both early and late post-transplant patients) represented immunocompromised control groups. Patients with systemic lupus erythematosus, Pneumocystis pneumonia, HIV/AIDS, or renal transplant were identified using diagnostic codes from the International Classification of Diseases, Ninth Revision (ICD-9). Results Out of 2013 hospitalized systemic lupus erythematosus patients, nine had presumed Pneumocystis pneumonia, yielding a low prevalence of Pneumocystis pneumonia in systemic lupus erythematosus of 0.45%. Three of the nine Pneumocystis pneumonia cases were patients with concomitant systemic lupus erythematosus and HIV/AIDS. Only one of these nine cases was histologically confirmed as Pneumocystis pneumonia, in a patient with concomitant systemic lupus erythematosus and HIV/AIDS and a CD4 count of 13 cells/mm. The prevalence of Pneumocystis pneumonia in renal transplant patients and HIV/AIDS patients was 0.61% and 5.98%, respectively. Conclusion Given the reported high rate of adverse effects to trimethoprim-sulfamethoxazole in systemic lupus erythematosus and the low prevalence of Pneumocystis pneumonia in hospitalized systemic lupus erythematosus patients, our data do not substantiate the need for Pneumocystis pneumonia prophylaxis in systemic lupus erythematosus patients, except in those with concurrent HIV/AIDS.

Background/Objective: An increasing prevalence of total knee arthroplasty (TKA) procedures among the adolescent population makes it critical to establish a greater understanding of the patient and hospital demographics of this population. The purpose of this study is to compare inpatient demographics between the adolescent and adult populations as well as assess patient and hospital demographics at which adolescent TKA procedures are performed. Methods: Kids' Inpatient Database (KID) and Nationwide Inpatient Sample (NIS) database were used to retrieve data for all TKA patients under 20 years and over the age of 65, respectively. Variables analyzed included patient age, gender, ethnicity, primary diagnosis, length of stay, primary payer status, total hospital charges, complication rates, and hospital status. Results: The study found a significant increase in procedure frequency (156 to 448), complication rates (3.51% to 17.61%), and total charges ($38,776 to $128,811) for adolescent TKA patients. Some trends in demographics and outcomes for adolescent TKAs differed from their adult counterparts, as the primary diagnosis, hospital status, gender, and payer status. Additionally, the number of procedures, complication rates, length of stay, and charges were all significantly higher in adolescent than in adult TKAs. Conclusions: Although the TKA procedure rates are rising in the adolescent population, the lack of available demographic information limits the efficacy of the procedure in the younger population, presenting a challenge for health-care providers. Further studies should focus on whether epidemiological disparities, which have been noted in adults, also exist in the adolescent patient population.

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