Movement Disorder Society-sponsored revision of the Unified Parkinson's Disease Rating Scale (MDS-UPDRS): Process, format, and clinimetric testing plan.

This article presents the revision process, major innovations, and clinimetric testing program for the Movement Disorder Society (MDS)-sponsored revision of the Unified Parkinson's Disease Rating Scale (UPDRS), known as the MDS-UPDRS. The UPDRS is the most widely used scale for the clinical study of Parkinson's disease (PD). The MDS previously organized a critique of the UPDRS, which cited many strengths, but recommended revision of the scale to accommodate new advances and to resolve problematic areas. An MDS-UPDRS committee prepared the revision using the recommendations of the published critique of the scale. Subcommittees developed new material that was reviewed by the entire committee. A 1-day face-to-face committee meeting was organized to resolve areas of debate and to arrive at a working draft ready for clinimetric testing. The MDS-UPDRS retains the UPDRS structure of four parts with a total summed score, but the parts have been modified to provide a section that integrates nonmotor elements of PD: I, Nonmotor Experiences of Daily Living; II, Motor Experiences of Daily Living; III, Motor Examination; and IV, Motor Complications. All items have five response options with uniform anchors of 0 = normal, 1 = slight, 2 = mild, 3 = moderate, and 4 = severe. Several questions in Part I and all of Part II are written as a patient/caregiver questionnaire, so that the total rater time should remain approximately 30 minutes. Detailed instructions for testing and data acquisition accompany the MDS-UPDRS in order to increase uniform usage. Multiple language editions are planned. A three-part clinimetric program will provide testing of reliability, validity, and responsiveness to interventions. Although the MDS-UPDRS will not be published until it has successfully passed clinimetric testing, explanation of the process, key changes, and clinimetric programs allow clinicians and researchers to understand and participate in the revision process.     

Efficacy of a patient-training videotape on motor fluctuations for on-off diaries in parkinson's disease

Patient on-off diaries are used in clinical trials, but a method to assure agreement between patient and examiner has never been developed. We tested whether a patient-teaching tape increased the rate of agreement between patient diary ratings and simultaneous neurologic assessment by a trained professional. A total of 32 consecutive patients who had Parkinson's disease with motor fluctuations independently completed a 4-h on-off diary (nine ratings) at the same time as an examiner. Those with <80% agreement with the examiner (n = 20) were randomized to view either a training tape that showed motor fluctuations (experimental group) or another videotape of general patient educational material (control group). All patients then underwent the same 4-h assessment of motor fluctuations. To test for long-term retention, they returned 1 month later and, without reviewing the videotape, underwent a final 4-h correlation assessment. After the training tape, the experimental group showed significant improvement, whereas the control group showed no improvement. Furthermore, another month later, the improvement in the experimental group was retained. Based on these findings, we suggest that future clinical trials assessing motor fluctuations incorporate this tape into their basic methodology.     

Lipid screening in HIV-infected veterans

BACKGROUND: Lipid screening is recommended for patients taking protease inhibitors (PIs). METHODS: We examined data from the Veterans Administration Immunology Case Registry to assess lipid screening among HIV-infected veterans who received PIs for at least 6 consecutive months during 1999 and 2001. We estimated crude and adjusted associations between lipid screening and patient characteristics (age, gender, HIV exposure, and race/ethnicity), comorbidities (AIDS, cardiovascular disease, diabetes, hypertension, smoking, and hyperlipidemia), and facility characteristics (urban location, case management, guidelines, and quality improvement programs). RESULTS: Among 4065 patients on PIs, clinicians screened 2395 (59%) for lipids within 6 months of initiating treatment. Adjusting for patient characteristics, comorbidities, facility traits, and clustering, lipid screening was more common among patients who were cared for in urban areas (relative risk [RR] = 1.3, confidence limits: 1.0-1.5), diabetic (RR = 1.2, confidence limits: 1.1-1.3), or previously hyperlipidemic (RR = 1.4, confidence limits: 1.3-1.5) and less common among patients with a history of intravenous drug use (IVDU) (RR = 0.90, confidence limits: 0.79-1.0) or unknown HIV risk (RR = 0.85, confidence limits: 0.75-0.95). CONCLUSIONS: Six in 10 patients taking PIs receive lipid screening within 6 months of PI use. Systemic interventions to improve overall HIV quality of care should also address lipid screening, particularly among patients with unknown or IVDU HIV risk and those cared for in nonurban areas.     

An orthotopic metastatic prostate cancer model in SCID mice via grafting of a transplantable human prostate tumor line

Metastasis is the major cause of prostate cancer deaths and there is a need for clinically relevant in vivo models allowing elucidation of molecular and cellular mechanisms underlying metastatic behavior. Here we describe the development of a new in vivo model system for metastatic prostate cancer. Pieces of prostate cancer tissue from a patient were grafted in testosterone-supplemented male NOD-SCID mice at the subrenal capsule graft site permitting high tumor take rates. After five serial transplantations, the tumor tissues were grafted into mouse prostates. Resulting tumors and suspected metastatic lesions were subjected to histopathological and immunohistochemical analysis. Samples of metastatic tissue were regrafted in mouse anterior prostates and their growth and spread examined, leading to isolation from lymph nodes of a metastatic subline, PCa1-met. Orthotopic grafting of PCa1-met tissue in 47 hosts led in all cases to metastases to multiple organs (lymph nodes, lung, liver, kidney, spleen and, notably, bone). Histopathological analysis showed strong similarity between orthotopic grafts and their metastases. The latter were of human origin as indicated by immunostaining using antibodies against human mitochondria, androgen receptor, prostate-specific antigen and Ki-67. Spectral karyotyping showed few chromosomal alterations in the PCa1-met subline. This study indicates that transplantable subrenal capsule xenografts of human prostate cancer tissue in NOD-SCID mice can, as distinct from primary cancer tissue, be successfully grown in the orthotopic site. Orthotopic xenografts of the transplantable tumor lines and metastatic sublines can be used for studying various aspects of metastatic prostate cancer, including metastasis to bone.     

Genetic testing for inherited eye conditions in over 6,000 individuals through the eyeGENE network

Genetic testing in a multisite clinical trial network for inherited eye conditions is described in this retrospective review of data collected through eyeGENE®, the National Ophthalmic Disease Genotyping and Phenotyping Network. Participants in eyeGENE were enrolled through a network of clinical providers throughout the United States and Canada. Blood samples and clinical data were collected to establish a phenotype:genotype database, biorepository, and patient registry. Data and samples are available for research use, and participants are provided results of clinical genetic testing. eyeGENE utilized a unique, distributed clinical trial design to enroll 6,403 participants from 5,385 families diagnosed with over 30 different inherited eye conditions. The most common diagnoses given for participants were retinitis pigmentosa (RP), Stargardt disease, and choroideremia. Pathogenic variants were most frequently reported in ABCA4 (37%), USH2A (7%), RPGR (6%), CHM (5%), and PRPH2 (3%). Among the 5,552 participants with genetic testing, at least one pathogenic or likely pathogenic variant was observed in 3,448 participants (62.1%), and variants of uncertain significance in 1,712 participants (30.8%). Ten genes represent 68% of all pathogenic and likely pathogenic variants in eyeGENE. Cross‐referencing current gene therapy clinical trials, over a thousand participants may be eligible, based on pathogenic variants in genes targeted by those therapies. This article is the first summary of genetic testing from thousands of participants tested through eyeGENE, including reports from 5,552 individuals. eyeGENE provides a launching point for inherited eye research, connects researchers with potential future study participants, and provides a valuable resource to the vision community.