Assessing single joints in arthritis clinical trials

Endpoints and outcome measurements to detect changes in joint structure for the assessment of single joints are needed to enable rheumatology clinical trials of therapies targeting preservation of joint structure, especially via locally applied therapies. While the assessment of certain aspects of single joint inflammation and function is accepted in the evaluation of osteoarthritis (OA) using the WOMAC, it tends to be limited to the knee and hip. The advent of therapies that are directed toward a single joint in inflammatory arthritis, including intraarticular cytokine antagonists and gene therapeutics, requires reliable measures to assess change over time in single joints and the clinical meaningfulness of such change. Traditionally, clinical trials for inflammatory arthritis have used composite response indices such as American College of Rheumatology response or improvement in Disease Activity Score as outcomes based on multiple joint clinical measures, acute phase reactants, and functional status. However, it is not known whether these will appropriately detect changes referable to single joint intervention. This Special Interest Group was developed to bring together interested individuals to identify and evaluate outcome measurements for single joints. The knee was the initial focus, as clinical, radiographic, and functional assessments have been well developed for knee OA. A PubMed English language review was conducted before OMERACT 8, evaluating existing clinical instruments in the context of the OMERACT filter. At OMERACT 8, the group developed a research agenda to perform additional validation studies of clinical and functional indices, imaging, synovial histopathology, and soluble biomarkers.     

Differentiation of amphetamine/methamphetamine and other cross-immunoreactive sympathomimetic amines in urine samples by serial dilution testing

BACKGROUND: Immunoassay-based screening for amphetamines has a variable positive predictive value (PPV) for detecting amphetamine abuse. The lack of immunoassay specificity necessitates confirmatory testing by gas chromatography-mass spectrometry (GC/MS), but the technical complexity and expense of GC/MS limit its availability. Physicians may make decisions regarding patient disposition based on unverified results. In this study we assessed the utility of using dose-response properties to distinguish urine samples containing amphetamines from samples containing cross-immunoreactive species. METHODS: Urine was supplemented with known concentrations of amphetamine, methamphetamine, methylenedioxymethamphetamine (MDMA), or pseudoephedrine. Using a series of dilutions, we determined the maximum change in rate over the fractional change in concentration for each compound in the Emit II amphetamine/methamphetamine immunoassay. Patient urine samples that screened positive for amphetamines were diluted 1:1, 1:10, and 1:20, and maximum slope estimates within the dynamic assay range were determined. An optimal slope cutoff that differentiated samples containing (meth)amphetamine from those containing cross-reacting species was determined by ROC analysis. RESULTS: The slope of the dose response was largest for amphetamine and methamphetamine, followed by MDMA and pseudoephedrine. The optimum slope cutoff for identifying patient specimens containing (meth)amphetamine was 320 (sensitivity, 96%; specificity, 90%; PPV, 92%). High concentrations of less reactive compounds may mask low concentrations of amphetamines. CONCLUSIONS: Use of the slope of the dose-response relationship in patient urine specimens can enhance the PPV of presumptive positive immunoassay results but does not exclude the presence of low amphetamine concentrations in samples containing high concentrations of cross-reactive species.     

Birth equity on the front lines: Impact of a community-based doula program in Brooklyn,NY

Background

We assessed whether participation in Healthy Start Brooklyn's By My Side Birth Support Program—a maternal-health program providing community-based doula support during pregnancy, labor and delivery, and the early postpartum period—was associated with improved birth outcomes. By My Side takes a strength-based approach that aligns with the doula principles of respecting the client's autonomy, providing culturally appropriate care without judgment or conditions, and promoting informed decision making.

Methods

Using a matched cohort design, birth certificate records for By My Side participants from 2010 through 2017 (n = 603) were each matched to three controls who also lived in the program area (n = 1809). Controls were matched on maternal age, race/ethnicity, education level, and trimester of prenatal-care initiation, using the simple random sampling method. The sample was restricted to singleton births. The odds of preterm birth, low birthweight, and cesarean birth were estimated, using conditional logistic regression.

Results

By My Side participants had lower odds of having a preterm birth (5.6% vs 11.9%, P < .0001) or a low-birthweight baby (5.8% vs 9.7%, P = .0031) than controls. There was no statistically significant difference in the odds of cesarean delivery.

Conclusion

Participation in the By My Side Birth Support Program was associated with lower odds of preterm birth and low birthweight for participants, who were predominantly Black and Hispanic. Investing in doula services is an important way to address birth inequities among higher risk populations such as birthing people of color and those living in poverty. It could also help shape a new vision of the maternal-health system, placing the needs and well-being of birthing people at the center.     

Health status response of rheumatoid arthritis to treatment with DAB486IL-2

Objective . To examine and compare health status and disease activity changes in patients with rheumatoid arthritis (RA) in a clinical trial of the biologic agent DAB₄₈₆IL-2. Methods . Data on 45 patients with RA who were enrolled in a multicourse, double-blind trial, consisting of a first, placebo-controlled, course followed by open-label treatment with the active agent to a total of 3 active courses, were examined for evidence of improvement in health status (measured using the 5 components of the Arthritis Impact Measurement Scales 2 [AIMS2]) and disease activity (measured using standard clinical measures and erythrocyte sedimentation rate). Results . Over a single course of treatment, DAB₄₈₆IL-2-treated patients showed significant improvement relative to placebo-treated patients on the symptom and social components of AIMS2 and in patient's assessment of disease activity. With subsequent open-label courses of treatment with DAB₄₈₆IL-2, all 5 AIMS2 health status components and the disease activity measures of tender and swollen joint counts, grip strength, and the observer and patient assessments showed steady and generally parallel improvement. Conclusion . Short-term health status effects of this biologic agent were detected using the AIMS2.