A Narrative Review of Patient-reported Outcomes in Overactive Bladder: What is the Way of the Future?

CONTEXT: Debate exists on overactive bladder (OAB) treatment-response assessment in clinical trials and the nature and shortcomings of the different endpoints used in OAB clinical research. OBJECTIVE: To evaluate current evidence and tools that measure OAB treatment response in clinical trials and to inform the development of a new multidimensional patient-reported outcome (PRO) that could be used as a primary endpoint in OAB trials. EVIDENCE ACQUISITION: We conducted a narrative review of OAB literature available in the PubMed database published between January 1, 2004 and June 30, 2015. Eighty articles were selected for full text review. EVIDENCE SYNTHESIS: The assessment of treatment outcomes in OAB is challenging due to the heterogeneity of symptoms and reliance on PROs. OAB studies report a high level of placebo effect and the placebo response is poorly understood. We found significant correlations between PRO measures and bladder diaries. There is evidence of several issues with the bladder diary: burden, over/underestimation, recall period, and lack of validation. Trials for other conditions-interstitial cystitis, benign prostatic hyperplasia, headache, and restless legs syndrome-have used symptom scales rather than diaries to measure treatment outcomes and some now incorporate PRO measures as primary, coprimary, and secondary endpoints. The International Consultation on Incontinence Research Society recommends evaluation of satisfaction, symptoms, health-related quality of life, and adverse events. CONCLUSIONS: There is strong evidence of the shortcomings in current approaches to measuring OAB outcomes in clinical trials and recognition that a new simpler approach which incorporates symptom and health-related quality of life assessment could provide a more comprehensive, standardized approach to OAB assessment. PATIENT SUMMARY: Overactive bladder is a urinary syndrome. Individuals experience different symptoms to varying degrees, which poses difficulties in accurately measuring the effect of treatment. This review found evidence and recommendations that propose a simpler but more comprehensive way to measure treatment outcomes.

Two-quadrant area structure function analysis for optical surface characterization.

This paper describes the use of the area structure function (SF) for the specification and characterization of optical surfaces. A two-quadrant area SF is introduced because the one-quadrant area SF does not completely describe surfaces with certain asymmetries. Area SF calculations of simulation data and of a diamond turned surface are shown and compared to area power spectral density (PSD) and area autocorrelation function (ACF) representations. The direct relationship between SF, PSD, and ACF for a stationary surface does not apply to non-stationary surfaces typical of optics with figure errors.

Precision engineering: an evolutionary perspective.

Precision engineering is a relatively new name for a technology with roots going back over a thousand years; those roots span astronomy, metrology, fundamental standards, manufacturing and money-making (literally). Throughout that history, precision engineers have created links across disparate disciplines to generate innovative responses to society's needs and wants. This review combines historical and technological perspectives to illuminate precision engineering's current character and directions. It first provides us a working definition of precision engineering and then reviews the subject's roots. Examples will be given showing the contributions of the technology to society, while simultaneously showing the creative tension between the technological convergence that spurs new directions and the vertical disintegration that optimizes manufacturing economics.

Further qualification of a therapeutic responder index for patients with chronic low back pain.

OBJECTIVE: Previously, a preliminary patient responder index (RI) in chronic low back pain (CLBP) was developed and validated in 5 placebo-controlled clinical trials. The resulting RI was a > 30% improvement in CLBP and patient global assessment (PGA), and no worsening (< 20%) in the Roland Morris Disability Questionnaire (RMDQ) total score. Our objective was to provide further characterization of the preliminary RI in a trial with an active control. METHODS: Data from a 6-week randomized, double-blind study of celecoxib compared to tramadol hydrochloride was analyzed to determine differences by treatment group on the CLBP RI and its components, to compare the CLBP RI with each of its individual components, and to reanalyze the original cutoff points for the responder criteria. RESULTS: Of the celecoxib arm, 50.7%, and of the tramadol hydrochloride arm, 43.7% were classified as responders under the CLBP RI (p = 0.043). The PGA is the most important component in the RI (45% of the sample failed to reach the > 30% improvement criteria on the PGA compared to 34% on the low back pain visual analog scale and only 11% on the RMDQ. The agreement among the CLBP RI with each of its 3 components was largest for the PGA component (κ coefficient 0.849) and smallest for the RMDQ component (κ coefficient 0.207). CONCLUSION: The RI appears to be particularly sensitive to the cutoff point used for improvement in the PGA component. Further testing of the index in trials with other active comparators is required to gain a fuller understanding of its performance.

Clinical implications of the implementation of advanced treatment planning algorithms for thoracic treatments.

BACKGROUND AND PURPOSE: Radiotherapy treatment planning algorithms continue to develop and current planning systems typically offer simpler, but faster, algorithms, which may be 2, 2.5 or 3D in modelling scatter, but which do not model electron transport (type a) and more accurate algorithms which aim to be fully 3D, i.e. which model 3D scatter and also model electron transport (type b). A range of comparative planning studies and experiments indicate that the main situation where the changes are significant between the two types of algorithm is where lung tissue is involved. However, more generally, interface areas between materials of different electron density and composition are expected to show differences between the two types of algorithms. These are likely to pose potentially significant clinical consequences when a centre changes from using older simpler algorithms to more accurate fully 3D ones and require careful consideration. MATERIALS AND METHODS: Some modelling is presented using the different type algorithms for a recently available novel design of linear accelerator treatment head, as part of the commissioning of that machine and in preparing for a change in TPS algorithm. The TPS data are compared to measurements and to Monte Carlo calculations. RESULTS AND DISCUSSION: The results add to the evidence of other studies that 3D planning techniques and type b dose calculation algorithms lead to systematic changes in computation and delivery of radiotherapy dose and in dose distributions, as compared to simpler methods, and that these changes are more pronounced in treatments involving lung tissue. The type b algorithms agree well with Monte Carlo modelling. CONCLUSIONS: Careful analysis of the changes is required before adopting new algorithms into clinical treatment planning practice. Discussion is needed between physicists and oncologists to fully understand the effects and potential consequences. These include changes in delivered dose to the reference point, to coverage of the PTV and to the dose distribution and also to dosimetric parameters used to constrain toxicity for lung, e.g. V20, and other tissues. There are consequences for assessment of dose-effect relationships and of parameters used in treatment planning decisions and this is an opportune time to re-evaluate this information.

Novel orphanin FQ/nociceptin transcripts are expressed in human immune cells.

The opioid-like receptor (NOP) is widely expressed throughout the human immune system. Here, we report that human peripheral blood lymphocytes (PBLs) express transcripts encoding the NOP receptor agonist, orphanin FQ/nociceptin (OFQ/N). OFQ/N transcripts in resting PBLs were restricted to CD19+B cells and contained a novel 5' exon (ImEx2b), replacing exons 1 and 2 found in neuronal transcripts. Translation of ImEx2b-containing transcripts resulted in truncated OFQ/N precursors lacking a classical signal peptide. Mitogen activation of PBLs dramatically up-regulated neuronal-like transcripts, predominantly in CD3+T cells. Overall, this suggests different promoters direct specific OFQ/N transcript expression in immune cells.