Tools for Assessing Outcomes in Studies of Chronic Cough: CHEST Guideline and Expert Panel Report

BACKGROUND: Since the publication of the 2006 American College of Chest Physicians (CHEST) cough guidelines, a variety of tools has been developed or further refined for assessing cough. The purpose of the present committee was to evaluate instruments used by investigators performing clinical research on chronic cough. The specific aims were to (1) assess the performance of tools designed to measure cough frequency, severity, and impact in adults, adolescents, and children with chronic cough and (2) make recommendations or suggestions related to these findings.

METHODS: By following the CHEST methodologic guidelines, the CHEST Expert Cough Panel based its recommendations and suggestions on a recently published comparative effectiveness review commissioned by the US Agency for Healthcare Research and Quality, a corresponding summary published in CHEST, and an updated systematic review through November 2013. Recommendations or suggestions based on these data were discussed, graded, and voted on during a meeting of the Expert Cough Panel.

RESULTS: We recommend for adults, adolescents (≥ 14 years of age), and children complaining of chronic cough that validated and reliable health-related quality-of-life (QoL) questionnaires be used as the measurement of choice to assess the impact of cough, such as the Leicester Cough Questionnaire and the Cough-Specific Quality-of-Life Questionnaire in adult and adolescent patients and the Parent Cough-Specific Quality of Life Questionnaire in children. We recommend acoustic cough counting to assess cough frequency but not cough severity. Limited data exist regarding the performance of visual analog scales, numeric rating scales, and tussigenic challenges.

CONCLUSIONS: Validated and reliable cough-specific health-related QoL questionnaires are recommended as the measurement of choice to assess the impact of cough on patients. How they compare is yet to be determined. When used, the reporting of cough severity by visual analog or numeric rating scales should be standardized. Previously validated QoL questionnaires or other cough assessments should not be modified unless the new version has been shown to be reliable and valid. Finally, in research settings, tussigenic challenges play a role in understanding mechanisms of cough.

Methodologies for the Development of the Management of Cough: CHEST Guideline and Expert Panel Report

BACKGROUND: This series of guidance documents on cough, which will be published over time, is a hybrid of two processes: (1) evidence-based guidelines and (2) trustworthy consensus statements based on a robust and transparent process.

METHODS: The CHEST Guidelines Oversight Committee selected a nonconflicted Panel Chair and jointly assembled an international panel of experts in each clinical area with few, if any, conflicts of interest. PICO (population, intervention, comparator, outcome)-based key questions and parameters of eligibility were developed for each clinical topic to inform the comprehensive literature search. Existing guidelines, systematic reviews, and primary studies were assessed for relevance and quality. Data elements were extracted into evidence tables and synthesized to provide summary statistics. These, in turn, are presented to support the evidence-based graded recommendations. A highly structured consensus-based Delphi approach was used to provide expert advice on all guidance statements. Transparency of process was documented.

RESULTS: Evidence-based guideline recommendations and consensus-based suggestions were carefully crafted to provide direction to health-care providers and investigators who treat and/or study patients with cough. Manuscripts and tables summarize the evidence in each clinical area supporting the recommendations and suggestions.

CONCLUSIONS: The resulting guidance statements are based on a rigorous methodology and transparency of process. Unless otherwise stated, the recommendations and suggestions meet the guidelines for trustworthiness developed by the Institute of Medicine and can be applied with confidence by physicians, nurses, other health-care providers, investigators, and patients.

Somatic Cough Syndrome (Previously Referred to as Psychogenic Cough) and Tic Cough (Previously Referred to as Habit Cough) in Adults and Children: CHEST Guideline and Expert Panel Report

BACKGROUND: We conducted a systematic review on the management of psychogenic cough, habit cough, and tic cough to update the recommendations and suggestions of the 2006 guideline on this topic.

METHODS: We followed the American College of Chest Physicians (CHEST) methodologic guidelines and the Grading of Recommendations, Assessment, Development, and Evaluation framework. The Expert Cough Panel based their recommendations on data from the systematic review, patients' values and preferences, and the clinical context. Final grading was reached by consensus according to Delphi methodology.

RESULTS: The results of the systematic review revealed only low-quality evidence to support how to define or diagnose psychogenic or habit cough with no validated diagnostic criteria. With respect to treatment, low-quality evidence allowed the committee to only suggest therapy for children believed to have psychogenic cough. Such therapy might consist of nonpharmacologic trials of hypnosis or suggestion therapy, or combinations of reassurance, counseling, and referral to a psychologist, psychotherapy, and appropriate psychotropic medications. Based on multiple resources and contemporary psychologic, psychiatric, and neurologic criteria (Diagnostic and Statistical Manual of Mental Disorders, 5th edition and tic disorder guidelines), the committee suggests that the terms psychogenic and habit cough are out of date and inaccurate.

CONCLUSIONS: Compared with the 2006 CHEST Cough Guidelines, the major change in suggestions is that the terms psychogenic and habit cough be abandoned in favor of somatic cough syndrome and tic cough, respectively, even though the evidence to do so at this time is of low quality.

Treatment of Unexplained Chronic Cough: CHEST Guideline and Expert Panel Report

Background: Unexplained chronic cough (UCC) causes significant quality of life impairment. There is a need to identify effective assessment and treatment approaches for UCC.

Methods: This systematic review of randomized controlled clinical trials asked: What is the efficacy of treatment compared to usual care on cough severity, cough frequency, and cough-related quality of life in patients with unexplained chronic cough (UCC)? Studies of adults and adolescents >12 years with a chronic cough of >8 weeks duration that was unexplained after systematic investigation and treatment were included and assessed for relevance and quality. Based upon the systematic review, guideline suggestions were developed and voted upon using CHEST organization methodology.

Results: 11 RCTs and 5 systematic reviews were included. The 11 RCTs reported data on 570 participants with chronic cough who received a variety of interventions. Study quality was high in 10 RCTs. The studies used a variety of descriptors and assessments to identify unexplained chronic cough. While gabapentin and morphine showed positive effects on cough-related quality of life, only gabapentin was supported as a treatment recommendation. Studies of inhaled corticosteroids (ICS) suffered from intervention fidelity bias, and when this was addressed, ICS were not found to be effective for UCC. Esomeprazole was not effective for UCC without features of gastroesophageal acid reflux. Studies addressing non-acid gastroesophageal reflux were not identified. A multimodality speech pathology intervention improved cough severity.

Conclusions: The evidence supporting the diagnosis and management of UCC is limited. UCC requires further study to establish agreed terminology and the optimal methods of investigation using established criteria for intervention fidelity. Speech pathology based cough suppression is suggested as a treatment option for UCC. This guideline presents suggestions for diagnosis and treatment based on the best available evidence and identifies gaps in our knowledge and areas for future research.

Assessment of Intervention Fidelity and Recommendations for Researchers Conducting Studies on the Diagnosis and Treatment of Chronic Cough in the Adult: CHEST Guideline and Expert Panel Report

BACKGROUND: Successful management of chronic cough has varied in the primary research studies in the reported literature. One of the potential reasons relates to a lack of intervention fidelity to the core elements of the diagnostic and/or therapeutic interventions that were meant to be used by the investigators.

METHODS: We conducted a systematic review to summarize the evidence supporting intervention fidelity as an important methodologic consideration in assessing the effectiveness of clinical practice guidelines used for the diagnosis and management of chronic cough. We developed and used a tool to assess for five areas of intervention fidelity. Medline (PubMed), Scopus, and the Cochrane Database of Systematic Reviews were searched from January 1998 to May 2014. Guideline recommendations and suggestions for those conducting research using guidelines or protocols to diagnose and manage chronic cough in the adult were developed and voted upon using CHEST Organization methodology.

RESULTS: A total of 23 studies (17 uncontrolled prospective observational, two randomized controlled, and four retrospective observational) met our inclusion criteria. These articles included 3,636 patients. Data could not be pooled for meta-analysis because of heterogeneity. Findings related to the five areas of intervention fidelity included three areas primarily related to the provider and two primarily related to the patients. In the area of study design, 11 of 23 studies appeared to be underpinned by a single guideline/protocol; for training of providers, two of 23 studies reported training, and zero of 23 reported the use of an intervention manual; and for the area of delivery of treatment, when assessing the treatment of gastroesophageal reflux disease, three of 23 studies appeared consistent with the most recent guideline/protocol referenced by the authors. For receipt of treatment, zero of 23 studies mentioned measuring concordance of patient-interventionist understanding of the treatment recommended, and zero of 23 mentioned measuring enactment of treatment, with three of 23 measuring side effects and two of 23 measuring adherence. The overall average intervention fidelity score for all 23 studies was poor (20.74 out of 48).

CONCLUSIONS: Only low-quality evidence supports that intervention fidelity strategies were used when conducting primary research in diagnosing and managing chronic cough in adults. This supports the contention that some of the variability in the reporting of patients with unexplained or unresolved chronic cough may be due to lack of intervention fidelity. By following the recommendations and suggestions in this article, researchers will likely be better able to incorporate strategies to address intervention fidelity, thereby strengthening the validity and generalizability of their results that provide the basis for the development of trustworthy guidelines.

Harmonization guidelines for HLA-peptide multimer assays derived from results of a large scale international proficiency panel of the Cancer Vaccine Consortium.

PURPOSE: The Cancer Vaccine Consortium of the Cancer Research Institute (CVC-CRI) conducted a multicenter HLA-peptide multimer proficiency panel (MPP) with a group of 27 laboratories to assess the performance of the assay. EXPERIMENTAL DESIGN: Participants used commercially available HLA-peptide multimers and a well characterized common source of peripheral blood mononuclear cells (PBMC). The frequency of CD8+ T cells specific for two HLA-A2-restricted model antigens was measured by flow cytometry. The panel design allowed for participants to use their preferred staining reagents and locally established protocols for both cell labeling, data acquisition and analysis. RESULTS: We observed significant differences in both the performance characteristics of the assay and the reported frequencies of specific T cells across laboratories. These results emphasize the need to identify the critical variables important for the observed variability to allow for harmonization of the technique across institutions. CONCLUSIONS: Three key recommendations emerged that would likely reduce assay variability and thus move toward harmonizing of this assay. (1) Use of more than two colors for the staining (2) collect at least 100,000 CD8 T cells, and (3) use of a background control sample to appropriately set the analytical gates. We also provide more insight into the limitations of the assay and identified additional protocol steps that potentially impact the quality of data generated and therefore should serve as primary targets for systematic analysis in future panels. Finally, we propose initial guidelines for harmonizing assay performance which include the introduction of standard operating protocols to allow for adequate training of technical staff and auditing of test analysis procedures.

Development of a Blood Antigen Molecular Profiling Panel using Genotyping Technologies for Patients Requiring Frequent Transfusions

Contexte. Les phénotypes ABO et Rh(D) des donneurs de sang ainsi que des patients transfusés sont analysés de façon routinière pour assurer une complète compatibilité. Ces analyses sont accomplies par agglutination suite à une réaction anticorps-antigènes. Cependant, pour des questions de coûts et de temps d’analyses faramineux, les dons de sang ne sont pas testés sur une base routinière pour les antigènes mineurs du sang. Cette lacune peut résulter à une allo-immunisation des patients receveurs contre un ou plusieurs antigènes mineurs et ainsi amener des sévères complications pour de futures transfusions. Plan d’étude et Méthodes. Pour ainsi aborder le problème, nous avons produit un panel génétique basé sur la technologie « GenomeLab _SNPstream» de Beckman Coulter, dans l’optique d’analyser simultanément 22 antigènes mineurs du sang. La source d’ADN provient des globules blancs des patients préalablement isolés sur papiers FTA. Résultats. Les résultats démontrent que le taux de discordance des génotypes, mesuré par la corrélation des résultats de génotypage venant des deux directions de l’ADN, ainsi que le taux d’échec de génotypage sont très bas (0,1%). Également, la corrélation entre les résultats de phénotypes prédit par génotypage et les phénotypes réels obtenus par sérologie des globules rouges et plaquettes sanguines, varient entre 97% et 100%. Les erreurs expérimentales ou encore de traitement des bases de données ainsi que de rares polymorphismes influençant la conformation des antigènes, pourraient expliquer les différences de résultats. Cependant, compte tenu du fait que les résultats de phénotypages obtenus par génotypes seront toujours co-vérifiés avant toute transfusion sanguine par les technologies standards approuvés par les instances gouvernementales, les taux de corrélation obtenus sont de loin supérieurs aux critères de succès attendus pour le projet. Conclusion. Le profilage génétique des antigènes mineurs du sang permettra de créer une banque informatique centralisée des phénotypes des donneurs, permettant ainsi aux banques de sang de rapidement retrouver les profiles compatibles entre les donneurs et les receveurs.

The effectiveness of scoliosis screening programs: methods for systematic review and expert panel recommendations formulation

Background: Literature on scoliosis screening is vast, however because of the observational nature of available data and methodological flaws, data interpretation is often complex, leading to incomplete and sometimes, somewhat misleading conclusions. The need to propose a set of methods for critical appraisal of the literature about scoliosis screening, a comprehensive summary and rating of the available evidence appeared essential. METHODS: To address these gaps, the study aims were: i) To propose a framework for the assessment of published studies on scoliosis screening effectiveness; ii) To suggest specific questions to be answered on screening effectiveness instead of trying to reach a global position for or against the programs; iii) To contextualize the knowledge through expert panel consultation and meaningful recommendations. The general methodological approach proceeds through the following steps: Elaboration of the conceptual framework; Formulation of the review questions; Identification of the criteria for the review; Selection of the studies; Critical assessment of the studies; Results synthesis; Formulation and grading of recommendations in response to the questions. This plan follows at best GRADE Group (Grades of Recommendation, Assessment, Development and Evaluation) requirements for systematic reviews, assessing quality of evidence and grading the strength of recommendations. CONCLUSIONS: In this article, the methods developed in support of this work are presented since they may be of some interest for similar reviews in scoliosis and orthopaedic fields.

Recognising nominative categorative data

This interactive resource introduces Social Science students to recognition and interpretation of data contained in a table. The RLO uses data based on the causes of death of Rock and R&B musicians. When you view an object note that the panel on the left generated by the repository can be dragged sideways to view the learning object full screen. Item from RLO-CETL.

Institutions & Their Data

A panel presentation at Repository Fringe 2015

Testing the law of one price in food markets: evidence for Colombia using disaggregated data

This paper applies stationarity tests to examine evidence of market integration for a relatively large sample of food products in Colombia. We Önd little support for market integration when using the univariate KPSS tests for stationarity. However, within a panel context and after allowing for cross sectional dependence, the Hadri tests provide much more evidence supporting the view that food markets are integrated or, in other words, that the law of one price holds for most products.

Linking public issues with private troubles: panel studies in developing countries

Accompanying the call for increased evidence-based policy the developed world is implementing more longitudinal panel studies which periodically gather information about the same people over a number of years. Panel studies distinguish between transitory and persistent states (e.g. poverty, unemployment) and facilitate causal explanations of relationships between variables. However, they are complex and costly. A growing number of developing countries are now implementing or considering starting panel studies. The objectives of this paper are to identify challenges that arise in panel studies, and to give examples of how these have been addressed in resource-constrained environments. The main issues considered are: the development of a conceptual framework which links macro and micro contexts; sampling the cohort in a cost-effective way; tracking individuals; ethics and data management and analysis. Panel studies require long term funding, a stable institution and an acceptance that there will be limited value for money in terms of results from early stages, with greater benefits accumulating in the study's mature years. Copyright © 2003 John Wiley & Sons, Ltd.

Occupational choice, socio-economic status and educational attainment: a study of the occupational choices and destinations of young people in the British household panel survey

The article considers young people's occupational choices at the age of 15 in relation to their educational attainment, the occupations of their parents and their actual occupations when they are in their early 20s. It uses data from the British Household Panel Survey over periods of between five and ten years. The young people in the survey are occupationally ambitious: many more aspire to professional, managerial and technical jobs than the likely availability of these occupations. In general ambitions and educational attainment and intentions are well aligned but there are also many instances of misalignment; either people wanting jobs which their educational attainments and intentions will not prepare them for, or people with less ambitious aspirations than their educational performance would justify. Children from more occupationally advantaged families are more ambitious, achieve better educationally and have better occupational outcomes than other children. However, where young people are both ambitious and educationally successful the occupational outcomes are as good for those from disadvantaged as advantaged families. In contrast, where young people are neither ambitious nor educationally successful, the outcomes for those from disadvantaged homes are very much poorer than for other young people. The article suggests that while choice is real it is also heavily constrained for many people. A possible educational implication of the study is that career interventions could be directed at under-ambitious but academically capable young people from disadvantaged backgrounds.

The METAFOR project: preserving data through metadata standards for climate models and simulations

Climate modeling is a complex process, requiring accurate and complete metadata in order to identify, assess and use climate data stored in digital repositories. The preservation of such data is increasingly important given the development of ever-increasingly complex models to predict the effects of global climate change. The EU METAFOR project has developed a Common Information Model (CIM) to describe climate data and the models and modelling environments that produce this data. There is a wide degree of variability between different climate models and modelling groups. To accommodate this, the CIM has been designed to be highly generic and flexible, with extensibility built in. METAFOR describes the climate modelling process simply as "an activity undertaken using software on computers to produce data." This process has been described as separate UML packages (and, ultimately, XML schemas). This fairly generic structure canbe paired with more specific "controlled vocabularies" in order to restrict the range of valid CIM instances. The CIM will aid digital preservation of climate models as it will provide an accepted standard structure for the model metadata. Tools to write and manage CIM instances, and to allow convenient and powerful searches of CIM databases,. Are also under development. Community buy-in of the CIM has been achieved through a continual process of consultation with the climate modelling community, and through the METAFOR team’s development of a questionnaire that will be used to collect the metadata for the Intergovernmental Panel on Climate Change’s (IPCC) Coupled Model Intercomparison Project Phase 5 (CMIP5) model runs.

The lottery-panel task for bi-dimensional parameter-free elicitation of risk attitudes

We propose first, a simple task for the eliciting attitudes toward risky choice, the SGG lottery-panel task, which consists in a series of lotteries constructed to compensate riskier options with higher risk-return trade-offs. Using Principal Component Analysis technique, we show that the SGG lottery-panel task is capable of capturing two dimensions of individual risky decision making i.e. subjects’ average risk taking and their sensitivity towards variations in risk-return. From the results of a large experimental dataset, we confirm that the task systematically captures a number of regularities such as: A tendency to risk averse behavior (only around 10% of choices are compatible with risk neutrality); An attraction to certain payoffs compared to low risk lotteries, compatible with over-(under-) weighting of small (large) probabilities predicted in PT and; Gender differences, i.e. males being consistently less risk averse than females but both genders being similarly responsive to the increases in risk-premium. Another interesting result is that in hypothetical choices most individuals increase their risk taking responding to the increase in return to risk, as predicted by PT, while across panels with real rewards we see even more changes, but opposite to the expected pattern of riskier choices for higher risk-returns. Therefore, we conclude from our data that an “economic anomaly” emerges in the real reward choices opposite to the hypothetical choices. These findings are in line with Camerer's (1995) view that although in many domains, paid subjects probably do exert extra mental effort which improves their performance, choice over money gambles is not likely to be a domain in which effort will improve adherence to rational axioms (p. 635). Finally, we demonstrate that both dimensions of risk attitudes, average risk taking and sensitivity towards variations in the return to risk, are desirable not only to describe behavior under risk but also to explain behavior in other contexts, as illustrated by an example. In the second study, we propose three additional treatments intended to elicit risk attitudes under high stakes and mixed outcome (gains and losses) lotteries. Using a dataset obtained from a hypothetical implementation of the tasks we show that the new treatments are able to capture both dimensions of risk attitudes. This new dataset allows us to describe several regularities, both at the aggregate and within-subjects level. We find that in every treatment over 70% of choices show some degree of risk aversion and only between 0.6% and 15.3% of individuals are consistently risk neutral within the same treatment. We also confirm the existence of gender differences in the degree of risk taking, that is, in all treatments females prefer safer lotteries compared to males. Regarding our second dimension of risk attitudes we observe, in all treatments, an increase in risk taking in response to risk premium increases. Treatment comparisons reveal other regularities, such as a lower degree of risk taking in large stake treatments compared to low stake treatments and a lower degree of risk taking when losses are incorporated into the large stake lotteries. Results that are compatible with previous findings in the literature, for stake size effects (e.g., Binswanger, 1980; Antoni Bosch-Domènech & Silvestre, 1999; Hogarth & Einhorn, 1990; Holt & Laury, 2002; Kachelmeier & Shehata, 1992; Kühberger et al., 1999; B. J. Weber & Chapman, 2005; Wik et al., 2007) and domain effect (e.g., Brooks and Zank, 2005, Schoemaker, 1990, Wik et al., 2007). Whereas for small stake treatments, we find that the effect of incorporating losses into the outcomes is not so clear. At the aggregate level an increase in risk taking is observed, but also more dispersion in the choices, whilst at the within-subjects level the effect weakens. Finally, regarding responses to risk premium, we find that compared to only gains treatments sensitivity is lower in the mixed lotteries treatments (SL and LL). In general sensitivity to risk-return is more affected by the domain than the stake size. After having described the properties of risk attitudes as captured by the SGG risk elicitation task and its three new versions, it is important to recall that the danger of using unidimensional descriptions of risk attitudes goes beyond the incompatibility with modern economic theories like PT, CPT etc., all of which call for tests with multiple degrees of freedom. Being faithful to this recommendation, the contribution of this essay is an empirically and endogenously determined bi-dimensional specification of risk attitudes, useful to describe behavior under uncertainty and to explain behavior in other contexts. Hopefully, this will contribute to create large datasets containing a multidimensional description of individual risk attitudes, while at the same time allowing for a robust context, compatible with present and even future more complex descriptions of human attitudes towards risk.