Impact of T-cell costimulation modulation in patients with undifferentiated inflammatory arthritis or very early rheumatoid arthritis: a clinical and imaging study of abatacept (the ADJUST trial)

Several agents provide treatment for established rheumatoid arthritis (RA), but a crucial therapeutic goal is to delay/prevent progression of undifferentiated arthritis (UA) or very early RA

Randomized Clinical Trial Design to Assess Abatacept in Resistant Nephrotic Syndrome

Introduction: Treatment-resistant nephrotic syndrome is a rare form of glomerular disease that occurs in children and adults. No Food and Drug Administration−approved treatments consistently achieve remission of proteinuria and preservation of kidney function. CD80 (B7-1) can be expressed on injured podocytes, and administration of abatacept (modified CTLA4-Ig based on a natural ligand to CD80) has been associated with sustained normalization of urinary protein excretion and maintenance of glomerular filtration rate in experimental and clinical settings. Methods: In this report, we describe the rationale for and design of a randomized, placebo-controlled, clinical trial of abatacept in patients with treatment-resistant nephrotic syndrome caused by focal segmental glomerulosclerosis or minimal change disease. The design is a hybrid of a parallel-group and crossover design (switchover) with the primary objectives assessed in the first period of the study and the secondary objectives assessed using data from both periods. All participants will receive the active agent in 1 of the periods. The duration of treatment will be 4 months per period. Results: The primary outcome will be improvement in nephrotic-range proteinuria to subnephrotic range, that is, reduction from baseline to 4 months in urine protein:creatinine ratio ≥ 50% and to a level < 3. The projected sample size is 90 patients, which has 80% power to detect a treatment difference of 28%. Conclusion: This study advances efforts to validate CD80 as a therapeutic target for treatment-resistant nephrotic syndrome, and implements a precision medicine-based approach to this serious kidney condition in which the selection of a therapeutic agent is guided by the underlying disease mechanism operating in individual patients

A Geologically Based Indoor-Radon Potential Map of Kentucky

We combined 71,930 short-term (median duration 4 days) home radon test results with 1:24,000-scale bedrock geologic map coverage of Kentucky to produce a statewide geologically based indoor-radon potential map. The test results were positively skewed with a mean of 266 Bq/m3, median of 122 Bq/m3, and 75th percentile of 289 Bq/m3. We identified 106 formations with ≥10 test results. Analysis of results from 20 predominantly monolithologic formations showed indoor-radon concentrations to be positively skewed on a formation-by-formation basis, with a proportional relationship between sample means and standard deviations. Limestone (median 170 Bq/m3) and dolostone (median 130 Bq/m3) tended to have higher indoor-radon concentrations than siltstones and sandstones (median 67 Bq/m3) or unlithified surficial deposits (median 63 Bq/m3). Individual shales had median values ranging from 67 to 189 Bq/m3; the median value for all shale values was 85 Bq/m3. Percentages of values falling above the U.S. Environmental Protection Agency (EPA) action level of 148 Bq/m3 were sandstone and siltstone: 24%, unlithified clastic: 21%, dolostone: 46%, limestone: 55%, and shale: 34%. Mississippian limestones, Ordovician limestones, and Devonian black shales had the highest indoor-radon potential values in Kentucky. Indoor-radon test mean values for the selected formations were also weakly, but statistically significantly, correlated with mean aeroradiometric uranium concentrations. To produce a map useful to nonspecialists, we classified each of the 106 formations into five radon-geologic classes on the basis of their 75th percentile radon concentrations. The statewide map is freely available through an interactive internet map service

Psychogenic tremors

We diagnosed 24 patients, 9 men and 15 women ranging in age from 15 to 78 years, with clinically established or documented psychogenic tremors. Clinical presentations were unique, with complex tremors (often resting, postural, and kinetic), unusual temporal profiles (abrupt onset with a variable course), absence of other neurologic signs, inconsistent and incongruous symptomatology, selective disability with ability to perform some functions despite severe tremors, distractibility that lessens or abolishes tremor, atypical tremorgraphic recordings with changing amplitude and frequency, unusual handwriting and drawing specimens, presence of multiple undiagnosed somatizations, unresponsiveness to all treatments, absence of documented disease by laboratory or radiographic tests, presence of psychiatric disease, spontaneous remissions, or recovery with psychotherapy. We present criteria for the diagnosis of psychogenic tremor.</jats:p