Identifying the clinical domains of fibromyalgia: Contributions from clinician and patient delphi exercises

Objective In evaluating the effectiveness of fibromyalgia (FM) therapies, it is important to assess the impact of those therapies on the full array of domains considered important by both clinicians and patients. The objective of this research was to identify and prioritize the key clinically relevant and important domains impacted by FM that should be evaluated by outcome assessment instruments used in FM clinical trials, and to approach consensus among clinicians and patients on the priority of those domains to be assessed in clinical care and research. Methods Group consensus was achieved using the Delphi method, a structured process of consensus building via questionnaires together with systematic and controlled opinion feedback. The Delphi exercises involved 23 clinicians with expertise in FM and 100 patients with FM as defined by American College of Rheumatology criteria. Results The Delphi exercise revealed that the domains ranked most highly by patients were similar to the domain rankings by clinicians. Pain was consistently ranked highest by both panels. Fatigue, impact on sleep, health-related quality of life, comorbid depression, and cognitive difficulty were also ranked highly. Stiffness was ranked highly by patients but not clinicians. In contrast, side effects was important to clinicians but was not identified as important in the patient Delphi exercise. Conclusion The clinician and patient Delphi exercises identified and ranked key domains that need to be assessed in FM research. Based on these results, a conceptual framework for measuring patient-reported outcomes is proposed.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/60452/1/23826_ftp.pd

Development of responder definitions for fibromyalgia clinical trials

Objective To develop responder definitions for fibromyalgia (FM) clinical trials using key symptom and function domains. Methods Twenty‐four candidate responder definitions were developed by expert consensus and were evaluated in 12 randomized, placebo‐controlled trials of 4 medications for the treatment of FM. For each definition, the treatment effects of the medication compared with placebo were analyzed using Cochran‐Mantel‐Haenszel tests or chi‐square tests. A meta‐analysis of the pooled results for the 4 medications established risk ratios to determine the definitions that best favored medication over placebo. Results Two definitions performed best in the analyses. Both definitions included ≥30% reduction in pain and ≥10% improvement in physical function. The definitions differed in that one (≥30% improvement in FM [FM30] short version) included ≥30% improvement in sleep or fatigue, and the other (FM30 long version) required ≥30% improvement in 2 of the following symptoms: sleep, fatigue, depression, anxiety, or cognition. In the analysis of both versions, the response rate was ≥15% for each medication and was significantly greater compared with placebo. The risk ratio favoring drug over placebo in the pooled analysis for FM30 version 3 (short version) was 1.50 (95% confidence interval [95% CI] 1.24–1.82; P ≤ 0.0001); the risk ratio for FM30 version 6 (long version) was 1.60 (95% CI 1.31–1.96; P ≤ 0.00001). Conclusion Among the 24 responder definitions tested, 2 were identified as most sensitive in identifying response to treatment. The identification of responder definitions for FM clinical trials that include assessments of key symptom and function domains may improve the sensitivity of clinical trials to identify meaningful improvements, leading to improved management of FM.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/90281/1/33360_ftp.pd

Measures of fibromyalgia: Fibromyalgia Impact Questionnaire (FIQ), Brief Pain Inventory (BPI), Multidimensional Fatigue Inventory (MFI‐20), Medical Outcomes Study (MOS) Sleep Scale, and Multiple Ability Self‐Report Questionnaire (MASQ)

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/88107/1/20531_ftp.pd

Characterizing a Shallow Groundwater System beneath Irrigated Sugarcane with Electrical Resistivity and Radon (222Rn), Puunene, Hawai

In this study, we use a combination of electrical resistivity profiling and radon (222Rn) measurements to characterize a shallow groundwater system beneath the last remaining, largescale sugarcane plantation on Maui, Hawaii. Hawaiian Commercial & Sugar Company has continuously operated a sugarcane plantation on the western flank of Haleakala Volcano since 1878. The sugarcane is irrigated with a combination of surface water brought through tunnels from the wetter, eastern flank of Haleakala Volcano and groundwater from wells within the plantation. To assess the flow of irrigation water through the shallow subsurface, we collected a representative topo-sequence of four 2-D resistivity profiles that sample different topographic and hydrologic settings within the plantation. The profiles show a down-slope-thickening (0 to 20 m), surficial low-resistivity (10-200 Ohm-m) layer extending from the upslope limit of irrigated sugarcane to the lowest elevations of the plantation. At a canal crossing, the low resistivity layer thickens and is less resistive upslope of the canal. Beneath a reservoir at midelevation, the layer thickens to 20 m and curves down slope beneath the reservoir and up to the base of the field beyond. At the base of the slope, the low resistivity layer is 20-m thick below both fields and a second reservoir. An increase in radon concentration in the down-flow direction within the canal system at one location suggests groundwater infiltration into the canal. We attribute the low-resistivity layer to irrigation water that has infiltrated below the root zone and leaked from canals and reservoirs within the plantation. The water flows down slope to the base of the slope and there flows vertically, recharging the basal aquifer. We suggest that seepage from the canals and reservoirs is in part controlled by the local pressure head within the shallow flow system

Estimation of minimum clinically important difference for pain in fibromyalgia

Objective To estimate the minimum clinically important difference (MCID) for several pain measures obtained from the Brief Pain Inventory (BPI) for patients with fibromyalgia. Methods Data were pooled across 12‐week treatment periods from 4 randomized, double‐blind, placebo‐controlled studies designed to evaluate the safety and efficacy of duloxetine for the treatment of fibromyalgia. Each study enrolled subjects with American College of Rheumatology–defined fibromyalgia who presented with moderate to severe pain. The MCIDs for the BPI average pain item score and the BPI severity score (the mean of the BPI pain scale values: right now, average, least, and worst) were estimated by anchoring against the Patient's Global Impressions of Improvement scale. Results The anchor‐based MCIDs for the BPI average pain item and severity scores were 2.1 and 2.2 points, respectively. These MCIDs correspond to 32.3% and 34.2% reductions from baseline in scores. Conclusion In these analyses, the MCIDs for several pain measures obtained from the BPI were similar (∼2 points) and corresponded to a 30–35% improvement from baseline to end point. These findings may be beneficial for use in designing clinical trials in which the BPI is used to evaluate improvements in pain severity.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/87063/1/20449_ftp.pd

Computing covariant vectors, Lyapunov vectors, Oseledets vectors, and dichotomy projectors: a comparative numerical study

Covariant vectors, Lyapunov vectors, or Oseledets vectors are increasingly being used for a variety of model analyses in areas such as partial differential equations, nonautonomous differentiable dynamical systems, and random dynamical systems. These vectors identify spatially varying directions of specific asymptotic growth rates and obey equivariance principles. In recent years new computational methods for approximating Oseledets vectors have been developed, motivated by increasing model complexity and greater demands for accuracy. In this numerical study we introduce two new approaches based on singular value decomposition and exponential dichotomies and comparatively review and improve two recent popular approaches of Ginelli et al. (2007) and Wolfe and Samelson (2007). We compare the performance of the four approaches via three case studies with very different dynamics in terms of symmetry, spectral separation, and dimension. We also investigate which methods perform well with limited data

No sex scandals please, we're French: French attitudes towards politicians' public and private conduct

The notion of distinct ‘public’ and ‘private’ spheres underpins much normative and practical engagement with political misconduct. What is less clear is whether citizens draw distinctions between misdemeanours in the ‘public’ and ‘private’ spheres, and whether they judge these in systematically different ways. This paper explores attitudes to political misconduct in France. French citizens are often said to be particularly relaxed about politicians’ private affairs, but there has been little empirical evidence for this proposition. Drawing on original survey data, this paper demonstrates clearly that French citizens draw a sharp distinction between politicians’ public and private transgressions, and are more tolerant of the latter