Biology and therapy of fibromyalgia. Evidence-based biomarkers for fibromyalgia syndrome

Researchers studying fibromyalgia strive to identify objective, measurable biomarkers that may identify susceptible individuals, may facilitate diagnosis, or that parallel activity of the disease. Candidate objective measures range from sophisticated functional neuroimaging to office-ready measures of the pressure pain threshold. A systematic literature review was completed to assess highly investigated, objective measures used in fibromyalgia studies. To date, only experimental pain testing has been shown to coincide with improvements in clinical status in a longitudinal study. Concerted efforts to systematically evaluate additional objective measures in research trials will be vital for ongoing progress in outcome research and translation into clinical practice.     

Religious Coping with Chronic Pain

This study examined the role of religious and nonreligious cognitive-behavioral coping in a sample of 61 chronic pain patients from a midwestern pain clinic. Participants described their chronic pain and indicated their use of religious and nonreligious cognitive-behavioral coping strategies. Results supported a multidimensional conceptualization of religious coping that includes both positive and negative strategies. Positive religious coping strategies were associated significantly with positive affect and religious outcome after statistically controlling for demographic variables. In contrast, measures of negative religious coping strategies were not associated significantly with outcome variables. Several significant associations also were found between nonreligious cognitive-behavioral coping strategies and outcome variables. The results underscore the need for further research concerning the contributions of religious coping in adjustment to chronic pain. Practitioners of applied psychophysiology should assess their chronic pain patients' religious appraisals and religious coping as another important stress management strategy.     

One hundred years ago: How to be happy though a doctor

ObjectivesTo assess the growth of quality of life measures and to examine the availability of measures across specialties.DesignSystematic searches of electronic databases to identify developmental and evaluative work relating to health outcome measures assessed by patients.Results3921 reports that described the development and evaluation of patient assessed measures met the inclusion criteria. Of those that were classifiable, 1819 (46%) were disease or population specific, 865 (22%) were generic, 690 (18%) were dimension specific, 409 (10%) were utility, and 62 (1%) were individualised measures. During 1990-9 the number of new reports of development and evaluation rose from 144 to 650 per year. Reports of disease specific measures rose exponentially. Over 30% of evaluations were in cancer, rheumatology and musculoskeletal disorders, and older people''s health. The generic measures—SF-36, sickness impact profile, and Nottingham health profile—accounted for 612 (16%) reports.ConclusionsIn some specialties there are numerous measures of quality of life and little standardisation. Primary research through the concurrent evaluation of measures and secondary research through structured reviews of measures are prerequisites for standardisation. Recommendations for the selection of patient assessed measures of health outcome are needed.

What is already known on this topic

Quality of life measures are increasingly used for measuring health outcomes in evaluative researchThere is little standardisation in the use of such measures within clinical trials

What this study adds

There has been exponential growth in reports relating to the development and evaluation of quality of life measuresThe number of reports varies considerably according to the health problem     

Teleconference versus Face-to-Face Scientific Peer Review of Grant Application: Effects on Review Outcomes

Teleconferencing as a setting for scientific peer review is an attractive option for funding agencies, given the substantial environmental and cost savings. Despite this, there is a paucity of published data validating teleconference-based peer review compared to the face-to-face process.Our aim was to conduct a retrospective analysis of scientific peer review data to investigate whether review setting has an effect on review process and outcome measures.We analyzed reviewer scoring data from a research program that had recently modified the review setting from face-to-face to a teleconference format with minimal changes to the overall review procedures. This analysis included approximately 1600 applications over a 4-year period: two years of face-to-face panel meetings compared to two years of teleconference meetings. The average overall scientific merit scores, score distribution, standard deviations and reviewer inter-rater reliability statistics were measured, as well as reviewer demographics and length of time discussing applications.The data indicate that few differences are evident between face-to-face and teleconference settings with regard to average overall scientific merit score, scoring distribution, standard deviation, reviewer demographics or inter-rater reliability. However, some difference was found in the discussion time.These findings suggest that most review outcome measures are unaffected by review setting, which would support the trend of using teleconference reviews rather than face-to-face meetings. However, further studies are needed to assess any correlations among discussion time, application funding and the productivity of funded research projects.     

Evaluating Outcomes Used in Cardiothoracic Surgery Interventional Research: A Systematic Review of Reviews to Develop a Core Outcome Set

Background

When planning clinical trials, it is a key element to choose appropriate outcomes that ensure the comparability of effects of interventions in ways that minimise bias. We hypothesise that outcome measures in cardiothoracic surgical trials are inconsistent and without standard. Therefore, comparing the relative effectiveness of interventions across studies is problematic. We surmise that cardiothoracic research has focused habitually on the identification of risk factors and on the reduction of adverse outcomes with less consideration of factors that contribute to well being and positive health outcomes (salutogenesis).

Methods and Findings

We conducted a systematic review of reviews to determine both the type and number of outcomes reported in current cardiothoracic surgery interventional research, in order to identify a list of potential outcomes for a minimum core outcome set (COS). Special focus was placed on outcomes that emphasise salutogenesis. We interpreted salutogenic outcomes as those relating to optimum and/or positive health and well being. We searched Issue 7 (July 2014) of the Cochrane Database of Systematic Reviews. Systematic reviews of randomised trials on non-minimal-invasive off- or on-pump cardiothoracic surgery (elective and emergency, excluding transplants) investigating pre-, intra- or postsurgical interventions related to the outcome of the procedure were eligible for inclusion. We excluded protocols and withdrawn systematic reviews. Two review authors extracted outcome data independently. Unique lists of salutogenically and non-salutogenically focused outcomes were established. 15 systematic reviews involving 371 randomized trials and 58,253 patients were included in this review. Applied definitions of single and composite endpoints varied significantly, and patient-centred, salutogenically focused outcomes were seldom reported. One third of included reviews did not assess patient-centred outcomes at all; all other reviews were unable to perform meta-analyses due to an absence of data or heterogeneity in outcome measures. This compares to 36 non-salutogenically focused outcome domains representing 121 individual non-salutogenically focused outcomes, whereof 50% were assessed only once. Measures of mortality, cerebrovascular complications and hospitalisation were reported most frequently. Two reviews chose a composite endpoint as primary outcome. Pooled analysis of composite endpoints was not possible, as the required data was not reported per patient in all components.

Conclusion

In cardiothoracic surgical trials, choice and definition of non-salutogenically focused single and composite outcomes are inconsistent. There is an absence of patient centred, salutogenically focused outcome parameters in cardiac trials. We recommend the development of a core outcome set of salutogenically focused and non-salutogenically focused outcomes for cardiothoracic surgical research.     

Importance of behavioral manipulations and measures in rat models of brain damage and brain repair

The relevance of careful behavioral measures and manipulations in animal research on neural plasticity and brain damage has become increasingly clear. Recent research in adult rats indicates that an understanding of neural restructuring after brain damage requires an understanding of how it is influenced by postinjury behavioral experiences. Other research indicates that optimizing pharmacological and other treatments for brain damage may require their combination with rehabilitative training. Assessing the efficacy of a treatment approach in animal models requires the use of sensitive behavioral measures of functional outcome. In research on restorative plasticity after brain damage, procedures for handling and housing rats should promote the quality of behavioral measures and manipulations.     

Performance based objective outcome measures and spinal manipulation

This paper provides a general overview of performance based outcome measures used in an attempt to objectively measure the ramifications of spinal manipulation. While not a systematic or exhaustive review it serves to categorize, and provide insight into the background, successes and shortcomings of measurement techniques used. The outcome measures are drawn from the full spectrum of approaches to research and are broken down into the following sections: (1) biomechanically constrained motor performance measures, (2) neurologically constrained performance measures and (3) perceptual, perceptual motor, and complex task constrained performance measures. The paper concludes with some future research directions to enhance the understanding of the impact of spinal manipulation, and how to objectively measure its mechanical and physiological effects on the human system.     

Assessment of breast aesthetics

A good aesthetic outcome is an important endpoint of breast cancer treatment. Subjective ratings, direct physical measurements, measurements on photographs, and assessment by three-dimensional imaging are reviewed and future directions in aesthetic outcome measurements are discussed. Qualitative, subjective scales have frequently been used to assess aesthetic outcomes following breast cancer treatment. However, none of these scales has achieved widespread use because they are typically vague and have low intraobserver and interobserver agreement. Anthropometry is not routinely performed because conducting the large studies needed to validate anthropometric measures (i.e., studies in which several observers measure the same subjects multiple times) is impractical. Quantitative measures based on digital/digitized photographs have yielded acceptable results but have some limitations. Three-dimensional imaging has the potential to enable consistent, objective assessment of breast appearance, including properties (e.g., volume) that are not available from two-dimensional images. However, further work is needed to define three-dimensional measures of aesthetic properties and how they should be interpreted.     

Biobehavioral Intervention for Older Adults Coping with Essential Tremor

Four questions were addressed: (a) does biobehavioral intervention result in within-session reduction of tremor severity; (b) do relaxation and electromyographic (EMG) biofeedback training produce differential effects; (c) do within-session treatment effects generalize to daily performance; and (d) are reductions in tremor severity maintained at follow-up assessment? Three adults, ages 51, 77, and 83, each with a diagnosis of essential tremor (ET), and a long standing history of tremor of the hands uncontrolled by medication, took part. A repeated pre–post-training single-case experimental design embedded within a sequential A–B–C–D design was used; in addition, 1 participant received a return to the B phase. Outcome measures included within-session clinical and self-ratings of tremor severity, surface electromyography (sEMG) of forearm muscles, and daily self-ratings of tremor at home. Tremor was measured while participants engaged in eating or drinking tasks. The Behavioral Relaxation Scale (BRS) served as a process measure to assess relaxation proficiency. Clinical ratings of tremor and the BRS had high interobserver agreement. Visual inspection and statistical tests of single-case data were used to evaluate outcomes. Each participant showed significant within-session improvements on various measures of tremor and improvement during intervention as compared to baseline phases. There were no clear-cut differences between relaxation and biofeedback phases. Improvements declined somewhat at a 12-week follow-up. Relationships among measures of tremor are discussed. Biobehavioral interventions hold promise for older adults coping with ET. Further research is needed using an array of biobehavioral measures to assess intervention outcome.     

Effects of Kinect-based virtual reality game training on upper extremity motor recovery in chronic stroke

Background: Therapeutic benefits of Kinect-based virtual reality (VR) game training in rehabilitation encourage its use to improve motor function.

Objective: To assess the effects of Kinect-based VR training on motor recovery of the upper extremity and functional outcomes in patients with chronic stroke.

Methods: In this randomized controlled trial, group A received 20 sessions of physical therapy (PT)?+?20 sessions of Kinect-based VR training and group B received only 20 sessions of PT. Clinical outcome measures were assessed at baseline and at the end of the treatments. Primary outcome measures that assess stroke patients’ motor function included upper extremity (UE) Fugl-Meyer Assessment (FMA). Secondary outcome measures were Brunnstrom Recovery Stages (BRS), Modified Ashworth Scale (MAS), Box and Block test (BBT), Motricity index (MI), and active range of motion (AROM) measurement.

Results: Statistically significant improvements in game scores (p?p?Conclusions: To conclude, our results suggest that the adjunct use of Kinect-based VR training may contribute to the improvement of UE motor function and AROM in chronic stroke patients. Further studies with a larger number of subjects with longer follow-up periods are needed to establish its effectiveness in neurorehabilitation.     

Patient-reported outcome measures in plastic surgery: use and interpretation in evidence-based medicine

Understanding patients' perceptions of surgical results and their impacts on quality of life is of primary importance in plastic surgery, as procedures are largely performed to improve either appearance or function. Patient-reported outcome measures are questionnaires specifically designed to quantify aspects of health-related quality of life from the patient's perspective. This article presents an overview of patient-reported outcome measures. It also aims to provide plastic surgeons with the necessary critical appraisal skills to interpret and apply evidence from patient-reported outcomes research in their own clinical practice.     

The impact of culturally competent diabetes care interventions for improving diabetes-related outcomes in ethnic minority groups: a systematic review

Diabet. Med. 29, 1237-1252 (2012) ABSTRACT: Aim To examine the evidence on culturally competent interventions tailored to the needs of people with diabetes from ethnic minority groups. Methods MEDLINE (NHS Evidence), CINAHL and reference lists of retrieved papers were searched from inception to September 2011; two National Health Service specialist libraries were also searched. Google, Cochrane and DARE databases were interrogated and experts consulted. Studies were included if they reported primary research on the impact of culturally competent interventions on outcome measures of any ethnic minority group with diabetes. Paper selection and appraisal were conducted independently by two reviewers. The heterogeneity of the studies required narrative analysis. A novel culturally competent assessment tool was used to systematically assess the cultural competency of each intervention. Results Three hundred and twenty papers were retrieved and 11 included. Study designs varied with a diverse range of service providers. Of the interventions, 64% were found to be highly culturally competent (scoring 90-100%) and 36% moderately culturally competent (70-89%). Data were collected from 2616 participants on 22 patient-reported outcome measures. A consistent finding from 10 of the studies was that any structured intervention, tailored to ethnic minority groups by integrating elements of culture, language, religion and health literacy skills, produced a positive impact on a range of patient-important outcomes. Conclusions Benefits in using culturally competent interventions with ethnic minority groups with diabetes were identified. The majority of interventions described as culturally competent were confirmed as so, when assessed using the culturally competent assessment tool. Further good quality research is required to determine effectiveness and cost-effectiveness of culturally competent interventions to influence diabetes service commissioners.     

Satisfaction of the uncertainty principle in cancer clinical trials: retrospective cohort analysis

Objective To assess whether publicly funded adult cancer trials satisfy the uncertainty principle, which states that physicians should enrol a patient in a trial only if they are substantially uncertain which of the treatments in the trial is most appropriate for the patient. This principle is violated if trials systematically favour either the experimental or the standard treatment.Design Retrospective cohort study of completed cancer trials, with randomisation as the unit of analysis.Setting Two cooperative research groups in the United States.Studies included 93 phase III randomised trials (103 randomisations) that completed recruitment of patients between 1981 and 1995.Main outcome measures Whether the randomisation favoured the experimental treatment, the standard treatment, or neither treatment; effect size (outcome of the experimental treatment compared with outcome of the standard treatment) for each randomisation.Results Three randomisations (3%) favoured the standard treatment, 70 (68%) found no significant difference between treatments, and 30 (29%) favoured the experimental treatment. The average effect size was 1.20 (95% confidence interval 1.13 to 1.28), reflecting a slight advantage for the experimental treatment.Conclusions In cooperative group trials in adults with cancer, there is a measurable average improvement in disease control associated with assignment to the experimental rather than the standard arm. However, the heterogeneity of outcomes and the small magnitude of the advantage suggest that, as a group, these trials satisfy the uncertainty principle.     

Documenting the Efficacy of Virtual RealityExposure with Psychophysiological andInformation Processing Measures

Many outcome studies have been conducted to assess the efficacy of virtual reality in the treatment of specific phobias. However, most studies used self-report data. The addition of objective measures of arousal and information processing mechanisms would be a valuable contribution in order to validate the usefulness of virtual reality in the treatment of anxiety disorders. The goal of this study was to document the impact of virtual reality exposure (VRE) on cardiac response and automatic processing of threatening stimuli. Twenty-eight adults suffering from arachnophobia were assessed and received an exposure-based treatment using virtual reality. General outcome and specific processes measures included a battery of standardized questionnaires, a pictorial emotional Stroop task, a behavioral avoidance test and a measure of participants’ inter-beat intervals (IBI) while they were looking at a live tarantula. Assessment was conducted before and after treatment. Repeated measures ANOVAs revealed that therapy had a positive impact on questionnaire data, as well as on the behavioral avoidance test. Analyses made on the pictorial Stroop task showed that information processing of spider-related stimuli changed after treatment, which also indicates therapeutic success. Psychophysiological data also showed a positive change after treatment, suggesting a decrease in anxiety. In sum, VRE led to significant therapeutic improvements on objective measures as well as on self-report instruments.     

New trends in assessing the outcomes of mental health interventions

Assessing the outcomes of interventions in mental health care is both important and challenging. The aim of this paper is to advance the field of outcomes research by proposing a taxonomy of the decisions that clinicians and researchers need to consider when evaluating outcomes. Our taxonomy has eight components, framed as decisions: Whose outcome will be considered? Which scientific stage is being investigated? What outcome domain(s) matter? What level of assessment will be used? Will clinical and/or recovery outcomes be assessed? Whose perspective will be considered? Will deficits and/or strengths be the focus? Will invariant or individualized measures be preferred? We propose a future focus on understanding what matters most to people using mental health services, and on the use of measures rated by service users as the primary approach to evaluating outcome.     

Wearable Sensor Use for Assessing Standing Balance and Walking Stability in People with Parkinson’s Disease: A Systematic Review

Background

Postural instability and gait disability threaten the independence and well-being of people with Parkinson’s disease and increase the risk of falls and fall-related injuries. Prospective research has shown that commonly-used clinical assessments of balance and walking lack the sensitivity to accurately and consistently identify those people with Parkinson’s disease who are at a higher risk of falling. Wearable sensors provide a portable and affordable alternative for researchers and clinicians who are seeking to objectively assess movements and falls risk in the clinical setting. However, no consensus currently exists on the optimal placements for sensors and the best outcome measures to use for assessing standing balance and walking stability in Parkinson’s disease patients. Hence, this systematic review aimed to examine the available literature to establish the best sensor types, locations and outcomes to assess standing balance and walking stability in this population.

Methods

Papers listed in three electronic databases were searched by title and abstract to identify articles measuring standing balance or walking stability with any kind of wearable sensor among adults diagnosed with PD. To be eligible for inclusion, papers were required to be full-text articles published in English between January 1994 and December 2014 that assessed measures of standing balance or walking stability with wearable sensors in people with PD. Articles were excluded if they; i) did not use any form of wearable sensor to measure variables associated with standing balance or walking stability; ii) did not include a control group or control condition; iii) were an abstract and/or included in the proceedings of a conference; or iv) were a review article or case study. The targeted search of the three electronic databases identified 340 articles that were potentially eligible for inclusion, but following title, abstract and full-text review only 26 articles were deemed to meet the inclusion criteria. Included articles were assessed for methodological quality and relevant data from the papers were extracted and synthesized.

Results

Quality assessment of these included articles indicated that 31% were of low methodological quality, while 58% were of moderate methodological quality and 11% were of high methodological quality. All studies adopted a cross-sectional design and used a variety of sensor types and outcome measures to assess standing balance or walking stability in people with Parkinson’s disease. Despite the typically low to moderate methodological quality, 81% of the studies reported differences in sensor-based measures of standing balance or walking stability between different groups of Parkinson’s disease patients and/or healthy controls.

Conclusion

These data support the use of wearable sensors for detecting differences in standing balance and walking stability between people with PD and controls. Further high-quality research is needed to better understand the utility of wearable sensors for the early identification of Parkinson’s disease symptoms and for assessing falls risk in this population.

PROSPERO Registration

CRD42014010838     

The use of actigraphy in the monitoring of methylphenidate versus placebo in ADHD: a meta-analysis

Attention-deficit/hyperactivity disorder (ADHD) is the most common neurobehavioral disorder of childhood. There is an increasing need to find objective measures and markers of the disorder in order to assess the efficacy of the therapy and to improve follow-up strategies. Actigraphy is an objective method for recording motor activity and sleep parameters using small, computerized, watch-like devices worn on the body, and it has been used in many clinical trials to assess methylphenidate efficacy and adverse effects in ADHD. Our article aim is to systematically review and perform a meta-analysis of the current evidence on the role of actigraphy in both the detection of changes in activity and in sleep patterns in randomized clinical trials that compared methylphenidate against placebo in the treatment of ADHD. A comprehensive literature search of PubMed/MEDLINE, Scopus, Embase, Cochrane Library, CINHAL and PsycINFO databases was carried out to find randomized clinical trials comparing methylphenidate versus placebo in children with ADHD, using actigraphic measures as an outcome. No start date limit was used and the search was updated until June 2013. The primary outcome measures were ‘total sleep time’ and daytime ‘activity mean’. As secondary outcomes, we analyzed ‘sleep onset latency’, ‘sleep efficiency’ and ‘wake after sleep onset’. Eight articles comprising 393 patients were included in the analysis. Children with ADHD using MPH compared to placebo have a significant difference of a large effect with a diminishing value in the activity mean. For the total sleep time, we found a significant and large effect in the decrease in sleep in MPH group. This study shows that MPH may effectively reduce mean activity in ADHD children, but it may negatively affect total sleep time.     

Discrimination ability of prediction models for ordinal outcomes: Relationships between existing measures and a new measure

In this paper, we focus on measures to evaluate discrimination of prediction models for ordinal outcomes. We review existing extensions of the dichotomous c‐index—which is equivalent to the area under the receiver operating characteristic (ROC) curve—suggest a new measure, and study their relationships. The volume under the ROC surface (VUS) scores sets of cases including one case from each outcome category. VUS considers sets as either correctly or incorrectly ordered by the model. All other existing measures assess pairs of cases. We propose an ordinal c‐index (ORC) that is set‐based but, contrary to VUS, scores sets more gradually by indicating the closeness of the model‐based ordering to the perfect ordering. As a result, the ORC does not decrease rapidly as the number of outcome categories increases. It turns out that the ORC can be rewritten as the average of pairwise c‐indexes. Hence, the ORC has both a set‐ and pair‐based interpretation. There are several relationships between the existing measures, leading to only two types of existing measures: a prevalence‐weighted average of pairwise c‐indexes and the VUS. Our suggested measure ORC positions itself in between as it is set‐based but turns out to equal an unweighted average of pairwise c‐indexes. The measures are demonstrated through a case study on the prediction of six‐month outcome after traumatic brain injury. In conclusion, the set‐based nature and graded scoring system make the ORC an attractive measure with a simple interpretation, together with its prevalence‐independence that is a natural property of a discrimination measure.     

Binary regression: Total gain in positive and negative predictive values

Models that predict disease incidence or disease recurrence are attractive for clinicians as well as for patients. The usefulness of a risk prediction model is linked to the two questions whether the observed outcome is confirmed by the prediction and whether the risk prediction is accurate in predicting the future outcome, respectively. The first phrasing of the question is linked to considering sensitivity and specificity and the latter to the positive and negative predictive values. We present the measures of standardized total gain in positive and negative predictive values dealing with the performance or accuracy of the prediction model for a binary outcome. Both measures provide a useful tool for assessing the performance or accuracy of a set of predictor variables for the prediction of a binary outcome. This concept is a tool for evaluating the optimal prediction model in future research.     

Clinical outcomes and outcome measurement tools reported in randomised controlled trials of treatment for snakebite envenoming: A systematic review

BackgroundSnakebite is a priority neglected tropical disease and causes a range of complications that vary depending on the snake species. Randomised clinical trials have used varied outcome measures that do not allow results to be compared or combined. In accordance with the Core Outcomes Measurements in Effectiveness Trials (COMET) initiative, this systematic review aims to support the development of a globally relevant core outcome set for snakebite.MethodsAll randomised controlled trials, secondary analyses of randomised controlled trials and study protocols investigating the efficacy of therapeutics for human snakebite envenoming were eligible for inclusion. Study screening and data extraction were conducted in duplicate by two independent reviewers. All primary and secondary outcome measures were extracted and compiled, as were adverse event outcome measures. Similar outcome measures were grouped into domains. The study was prospectively registered with PROSPERO: CRD42020196160.ResultsThis systematic review included 43 randomised controlled trials, two secondary analyses and 13 study protocols. A total of 382 outcome measures were extracted and, after duplicates were merged, there were 153 unique outcomes. The most frequently used outcome domain (‘venom antigenaemia’) was included in less than one third of the studies. The unique outcomes were classified into 60 outcome domains. Patient-centred outcomes were used in only three of the studies.DiscussionSignificant heterogeneity in outcome measures exists in snakebite clinical trials. Consensus is needed to select outcome measures that are valid, reliable, patient-centred and feasible. The results of this systematic review strongly support the development of a core outcome set for use in snakebite clinical trials.