PURPOSE:To assess the association of severity of ocular discomfort with measures of quality of life among patients with moderate to severe dry eye disease (DED).
METHODS:This is a prospective, ...observational, cohort study within a randomized clinical trial. Patients (N = 535) in the Dry Eye Assessment and Management study with moderate to severe DED completed the Ocular Surface Disease Index on DED symptoms, the SF-36 on quality of life, and the Brief Ocular Discomfort Inventory questionnaire and had a comprehensive ophthalmic assessment by a study-certified clinician. The ocular discomfort on average over the past week was scored on an 11-point scale (0 for no discomfort and 10 for discomfort as bad as you can imagine).
RESULTS:The average ocular discomfort scores for patients ranged from 0 to 10, with a mean of 4.28. Discomfort scores did not vary with demographic characteristics, signs of DED, self-reported depression, or self-reported nonocular pain conditions. Ocular discomfort scores did correlate moderately to strongly with total Ocular Surface Disease Index scores (Spearman correlation coefficient, rs, 0.47–0.67) and with measures of interference with activities of daily living general activity level, mood, walking ability, ability for normal work, relations with other people, sleep, and enjoyment of life (rs = 0.39–0.65).
CONCLUSIONS:Among patients in the Dry Eye Assessment and Management study, worse ocular discomfort was associated with worse overall DED symptoms and interfered to a greater degree with activities of daily living. Ocular discomfort is an important part of the assessment of patients with DED.
Several brain regions have been implicated in human painful experiences, but none have been proven to be specific to pain. We exploited arterial spin-labeling quantitative perfusion imaging and a ...newly developed procedure to identify a specific role for the dorsal posterior insula (dpIns) in pain. Tract tracing studies in animals identify a similar region as fundamental to nociception, which suggests the dpIns is its human homolog and, as such, a potential therapeutic target.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SBMB, UILJ, UKNU, UL, UM, UPUK
Missing data in clinical trials can have a major effect on the validity of the inferences that can be drawn from the trial. This article reviews methods for preventing missing data and, failing that, ...dealing with data that are missing.
Background
Missing data have seriously compromised inferences from clinical trials, yet the topic has received little attention in the clinical-trial community.
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Existing regulatory guidances
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on the design, conduct, and analysis of clinical trials have little specific advice on how to address the problem of missing data. A recent National Research Council (NRC) report
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on the topic seeks to address this gap, and this article summarizes some of the main findings and recommendations of that report. The authors of this article served on the panel that prepared the report.
Missing data have seriously compromised inferences from clinical trials.
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For example, . . .
An essential component of the interpretation of results of randomized clinical trials of treatments for chronic pain involves the determination of their clinical importance or meaningfulness. This ...involves two distinct processes—interpreting the clinical importance of individual patient improvements and the clinical importance of group differences—which are frequently misunderstood. In this article, we first describe the essential differences between the interpretation of the clinical importance of patient improvements and of group differences. We then discuss the factors to consider when evaluating the clinical importance of group differences, which include the results of responder analyses of the primary outcome measure, the treatment effect size compared to available therapies, analyses of secondary efficacy endpoints, the safety and tolerability of treatment, the rapidity of onset and durability of the treatment benefit, convenience, cost, limitations of existing treatments, and other factors. The clinical importance of individual patient improvements can be determined by assessing what patients themselves consider meaningful improvement using well-described methods. In contrast, the clinical meaningfulness of group differences must be determined by a multi-factorial evaluation of the benefits and risks of the treatment and of other available treatments for the condition in light of the primary goals of therapy. Such determinations must be conducted on a case-by-case basis, and are ideally informed by patients and their significant others, clinicians, researchers, statisticians, and representatives of society at large.
It is well known that pain is a significant contributor to a lower level of quality of life (QOL) in both humans and animals. Models of the domains that constitute QOL generally include a combination ...of emotional function, social function, spiritual function, physical function, and health status, including pain 1. Which of these domains is most affected by a painful process is dependent on many things, including patient-specific factors, social–situational factors, and societal–cultural factors.
The objective of the present research was to develop a single measure of the major symptoms of both neuropathic and non-neuropathic pain that can be used in studies of epidemiology, natural history, ...pathophysiologic mechanisms, and treatment response. We expanded and revised the Short-form McGill Pain Questionnaire1Copyright: SF-MPQ, R. Melzack; SF-MPQ-2, R. Melzack and the Initiative on Methods, Measurement, and Pain Assessment in Clinical Trials (IMMPACT).1 (SF-MPQ) pain descriptors by adding symptoms relevant to neuropathic pain and by modifying the response format to a 0–10 numerical rating scale to provide increased responsiveness in longitudinal studies and clinical trials. The reliability, validity, and subscale structure of the revised SF-MPQ (SF-MPQ-21) were examined in responses from 882 individuals with diverse chronic pain syndromes and in 226 patients with painful diabetic peripheral neuropathy who participated in a randomized clinical trial. The data suggest that the SF-MPQ-2 has excellent reliability and validity, and the results of both exploratory and confirmatory factor analyses provided support for four readily interpretable subscales—continuous pain, intermittent pain, predominantly neuropathic pain, and affective descriptors. These results provide a basis for use of the SF-MPQ-2 in future clinical research, including clinical trials of treatments for neuropathic and non-neuropathic pain conditions.
Abstract Background: The measurement of spasticity as a symptom of neurologic disease is an area of growing interest. Clinician-rated measures of spasticity purport to be objective but do not measure ...the patient's experience and may not be sensitive to changes that are meaningful to the patient. In a patient with clinical spasticity, the best judge of the perceived severity of the symptom is the patient. Objectives: The aim of this study was to assess the validity and reliability, and determine the clinical importance, of change on a 0–10 numeric rating scale (NRS) as a patient-rated measure of the perceived severity of spasticity. Methods: Using data from a large,randomized,doubleblind, placebo-controlled study of an endocannabinoid system modulator in patients with multiple sclerosis-related spasticity, we evaluated the test-retest reliability and comparison-based validity of a patient-reported 0-10 NRS measure of spasticity severity with the Ashworth Scale and Spasm Frequency Scale. We estimated the level of change from baseline on the 0–10 NRS spasticity scale that constituted a clinically important difference (CID) and a minimal CID (MCID) as anchored to the patient's global impression of change (PGIC). Results: Data from a total of 189 patients were included in this assessment (114 women, 75 men; mean age, 49.1 years). The test-retest reliability analysis found an interclass correlation coefficient of 0.83 ( P < 0.001) between 2 measures of the 0–10 NRS spasticity scores recorded over a 7- to 14-day period before randomization. A significant correlation was found between change on 0–10 NRS and change in the Spasm Frequency Scale ( r = 0.63; P < 0.001), and a moderate correlation was found between the change on 0–10 NRS and the PGIC ( r = 0.47; P < 0.001). A reduction of ∼30% in the spasticity 0–10 NRS score best represented the CID and a change of 18% the MCID. Conclusions: The measurement of the symptom of spasticity using a patient-rated 0-10 NRS was found to be both reliable and valid. The definitions of CID and MCID will facilitate the use of appropriate responder analyses and help clinicians interpret the significance of future results.
Pain is a ubiquitous phenomenon, but the experience of pain varies considerably from person to person. Advances in understanding of the growing number of pathophysiologic mechanisms that underlie the ...generation of pain and the influence of the brain on the experience of pain led to the investigation of numerous compounds for treating pain. Improved knowledge of the subjective nature of pain, the variations in the measurement of pain, the mind-body placebo effect and the impact of differences in the conduct of a clinical trial on the outcome have changed approaches to design and implement studies. Careful consideration of how these concepts affect the choice of study population, the randomization and blinding process, the measurement and collection of data, and the analysis and interpretation of results should improve the quality of clinical trials for potential pain therapies.
Celotno besedilo
Dostopno za:
DOBA, IJS, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
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