Improved pain, physical functioning and health status in patients with rheumatoid arthritis treated with CP-690,550, an orally active Janus kinase (JAK) inhibitor: results from a randomised, double-blind, placebo-controlled trial.

OBJECTIVES: To determine the efficacy of CP-690,550 in improving pain, function and health status in patients with moderate to severe active rheumatoid arthritis (RA) and an inadequate response to methotrexate or a tumour necrosis factor alpha inhibitor. METHODS: Patients were randomised equally to placebo, CP-690,550 5, 15 or 30 mg twice daily for 6 weeks, with 6 weeks' follow-up. The patient's assessment of arthritis pain (pain), patient's assessment of disease activity, Health Assessment Questionnaire-Disability Index (HAQ-DI) and Short Form-36 (SF-36) were recorded. RESULTS: At week 6, significantly more patients in the CP-690,550 5, 15 and 30 mg twice-daily groups experienced a 50% improvement in pain compared with placebo (44%, 66%, 78% and 14%, respectively), clinically meaningful reductions in HAQ-DI (> or =0.3 units) (57%, 75%, 76% and 36%, respectively) and clinically meaningful improvements in SF-36 domains and physical and mental components. CONCLUSIONS: CP-690,550 was efficacious in improving the pain, function and health status of patients with RA, from week 1 to week 6.

Responsiveness of the Acne-Specific Quality of Life Questionnaire (Acne-QoL) to treatment for acne vulgaris in placebo-controlled clinical trials.

The Acne-Specific Quality of Life Questionnaire (Acne-QoL) was developed to measure the impact of facial acne across four dimensions of patient quality of life. The main objective of the current study was to evaluate the responsiveness of this instrument. Secondarily, this study provided an opportunity to extend the developer's psychometric validation. The Acne-QoL was utilized in two randomized, double-blind, placebo-controlled studies of the efficacy of Estrostep (norethindrone acetate/ethinyl estradiol) in the treatment of facial acne; a total of 296 Estrostep and 295 placebo patients were evaluated. The Acne-QoL was completed at the beginning, middle (cycle 3), and end (cycle 6) of the 6-month treatment period. The responsiveness of the Acne-QoL was demonstrated through its ability to detect both small (baseline to mid-study) and moderate (baseline to study end) treatment advantages for Estrostep patients. Confirmatory factor analysis supported the subscale structure, and internal consistency estimates were excellent. Convergent and discriminant validity were supported by correlations between Acne-QoL scores and clinical measures that were both in the direction and relative magnitude hypothesized. Finally, item response theory analyses confirmed that each item is highly related to its subscale's latent construct and that each subscale is sensitive across a broad range of the underlying continuum. The results of this evaluation confirm that the Acne-QoL is responsive, internally consistent, and valid.

Compliance from self-reported versus pharmacy claims data with metered-dose inhalers.

OBJECTIVE: To determine how well self-reported compliance with metered-dose inhalers (MDIs) agrees with compliance determined from pharmacy claims data. Additional analyses were conducted to establish phychmetric properties of the questionnaire. METHODS: A cross-sectional survey was performed of all adult enrollees with asthma of a managed care organization. The overall return rate was 63.4% (696/1098). Patents with persistent asthma and at least one prescription claim for a controller MDI during the four months preceding the survey were included. Pharmacy claims data were used to calculate a compliance ratio. Self-reported compliance was based on a four-item questionnaire. The primary end points were the percent-agreement and the overall correlation between the two measures. The questionnaire's internal reliability and construct validity were assessed using Cronbach's alpha and Pearson's correlations, respectively. Mean item response scores for compliant patients were compared with scores of noncompliant patients using the Student's t-test. RESULTS: One hundred questionnaire respondents met the study criteria. The mean +/- SD compliance ratio was 0.52+/-0.27, the mean +/- SD self-reported compliance score was 4.07+/-1.0. The overall percent agreement and correlation between self-reported compliance score and the compliance ratio were 75.5% and r = 0.348 (p = 0.01), respectively. The percent agreement was highest (85%) when noncompliant patients (by compliance ratio <0.8) reported being noncompliant (questionnaire score <5). Cronbach's alpha was 0.86. CONCLUSIONS: This study demonstrated a moderate correlation between self-reported asthma compliance and the compliance ratio determined using claims data. The questionnaire may be useful as a screening tool to detect noncompliant behavior in populations or individual patients with asthma.

Ductal carcinoma in situ of the breast: correlation of pathologic and mammographic features with extent of disease.

Optimal treatment of ductal carcinoma in situ (DCIS) of the breast requires an improved understanding of its pathologic extent and propensity for local recurrence. This study was performed to analyze mammographic and pathologic features of DCIS that might predict the extent of disease within the breast and facilitate treatment selection between lumpectomy alone, lumpectomy and radiotherapy, and mastectomy. At our institution, 60 cases of DCIS were diagnosed in 59 patients from June 1985 to February 1995 and form the basis of this retrospective study. Demographic and treatment-related information was obtained from hospital and tumor registry records. Mammograms were reviewed and size estimates of the abnormalities were determined. Pathologic slides from all cases were reviewed and classified according to size group, focality, nuclear grade, necrosis, and histologic subtype. DNA ploidy status and proliferation indices were available for 28 patients. Pathologically, 43 (72%) cases were < 15 mm, 14 (23%) were 16 to 40 mm, and 3 (5%) were > 40 mm. Five (8%) of the lesions were multicentric, 28 (47%) focal, and 27 (45%) multifocal. Thirty-three (55%) patients were treated by mastectomy, 16 (27%) by lumpectomy alone, and 11 (18%) by lumpectomy and radiation therapy. Mammographic size, histologic grade, presence or absence of necrosis, histologic subtype, DNA ploidy, and proliferative index were compared with pathologic size and focality by chi 2 analysis. Mammographic size correlated significantly with pathologic size (chi 2 = 11.3; P = 0.02) but underestimated the extent of disease in 9 cases. Although focality correlated significantly with pathologic size (chi 2 = 15.8; P = 0.003), the remaining histopathologic features did not significantly correlate with pathologic size or focality. Histopathologic features, including DNA studies, do not reliably predict the pathologic extent of DCIS, but mammographic size and focality do significantly correlate with pathologic size. Nevertheless, most cases of DCIS are small focal or multifocal lesions that are amenable to breast conservation approaches; further studies are needed to determine the appropriate use of lumpectomy, radiation therapy, and mastectomy in the treatment of DCIS.

Differential phase contrast and magneto-optic edge detection.

Magneto-optic (MO) edge detection is an alternative readout method for MO data storage systems. I show the equivalence of MO edge detection and the standard phase-detection methods of scanning optical microscopy but with the detected quantity depending primarily on spatial variations in the ellipticity rather than the phase of the reflected light. In particular, the equivalence of MO edge detection with a split detector and differential-phase-contrast detection is proven by a general theory of the optical imaging process and the symmetries in the system. The MO edge-detection signal results from variations in the phase of the light along the detection branches, these phase variations depending primarily on the ellipticity of the reflected light. This method of analysis gives not only a simple explanation of the detection techniques but allows the experience gained in scanning optical microscopy to be applied to MO edge detection.

Structure of the globular protein vicilin revealed by scanning tunnelling microscopy.

Scanning tunnelling microscopy (s.t.m.) has been used to study the structure of the non-crystalline globular protein vicilin. Molecules were deposited on amorphous carbon substrates and imaged both in air and in vacuo without additional sample preparation. Current-voltage plots of an individual protein molecule are also reported. The s.t.m. images are compared with conventional transmission electron micrographs and with a model of vicilin based on small-angle synchrotron X-ray scattering data.

Age, chronic obstructive pulmonary disease, and Innovar induced ventilatory depression during regional anesthesia.

The effect of Innovar on ventilatory response to CO2 was studied in 35 patients undergoing peripheral surgery with regional anesthesia. The dosage schedule (per 70 kg body weight) was 2 ml intramuscularly, prior to the block, and 1 ml intravenously, after the block. The decrease in mean CO2 response slope (15 percent decrease from control 30 minutes after the first dose) was not statistically significant. Control slope varied inversely with age (r = 0.41, p less than 0.05), and (in 22 patients) directly with the FEV1/FVC ratio (r = 0.54, p less than 0.02) and with the combined variables (FEV1/FVC)/age (r = 0.58, p less than 0.01). Depression of CO2 response slope following Innovar did not vary with age or FEV1. We conclude that, in otherwise normal patients, these doses of innovar cause only minor depression of ventilatory response to CO2. However, in those patients who already have a depressed response (the elderly and those with a decreased FEV1/FVC ratio), this additional depression occasionally may be clinically important.