Outcome measurements in epidermal necrolysis: a systematic review.

Steven Johnson Syndrome (SJS) and Toxic Epidermal Necrolysis (TEN), grouped together under the terminology of epidermal necrolysis (EN), are a spectrum of life-threatening dermatologic conditions. A lack of standardization and validation for existing endpoints has been identified as a key barrier to the comparison of these therapies and development of evidenced-based treatment. Following PRISMA guidelines, we conducted a systematic review of prospective studies involving systemic or topical treatments for EN, including dressing and ocular treatments. Outcomes were separated into mortality assessment, cutaneous outcomes, non-cutaneous clinical outcomes, and mucosal outcomes. The COSMIN Risk of Bias tool was used to assess the quality of studies on reliability and measurement error of outcome measurement instruments. Outcomes across studies assessing treatment in the acute phase of EN were varied. Most data came from prospective case reports and cohort studies representing the lack of available randomized clinical trial data available in EN. Our search did not reveal any EN-specific validated measures or scoring tools used to assess disease progression and outcomes. Less than half of included studies were considered "adequate" for COSMIN risk of bias in reliability and measurement error of outcome measurement instruments. With little consensus about management and treatment of EN, consistency and validation of measured outcomes is of the upmost importance for future studies to compare outcomes across treatments and identify the most effective means of combating the disease with the highest mortality managed by dermatologists.

Patient-centered outcomes and outcome measurements for people aged 65 years and older-a scoping review.

INTRODUCTION: The aging population is a challenge for the healthcare system that must identify strategies that meet their needs. Practicing patient-centered care has been shown beneficial for this patient-group. The effect of patient-centered care is called patient-centered outcomes and can be appraised using outcomes measurements. OBJECTIVES: The main aim was to review and map existing knowledge related to patient-centered outcomes and patient-centered outcomes measurements for older people, as well as identify key-concepts and knowledge-gaps. The research questions were: How can patient-centered outcomes for older people be measured, and which patient-centered outcomes matters the most for the older people? STUDY DESIGN: Scoping review. METHODS: Search for relevant publications in electronical databases, grey literature databases and websites from year 2000 to 2021. Two reviewers independently screened titles and abstracts, followed by full text review and extraction of data using a data extraction framework. RESULTS: Eighteen studies were included, of which six with involvement of patients and/or experts in the process on determine the outcomes. Outcomes that matter the most to older people was interpreted as: access to- and experience of care, autonomy and control, cognition, daily living, emotional health, falls, general health, medications, overall survival, pain, participation in decision making, physical function, physical health, place of death, social role function, symptom burden, and time spent in hospital. The most frequently mentioned/used outcomes measurements tools were the Adult Social Care Outcomes Toolkit (ASCOT), EQ-5D, Gait Speed, Katz- ADL index, Patient Health Questionnaire (PHQ9), SF/RAND-36 and 4-Item Screening Zarit Burden Interview. CONCLUSIONS: Few studies have investigated the older people's opinion of what matters the most to them, which forms a knowledge-gap in the field. Future research should focus on providing older people a stronger voice in what they think matters the most to them.

Study of machine learning techniques for outcome assessment of leptospirosis patients.

Leptospirosis is a global disease that impacts people worldwide, particularly in humid and tropical regions, and is associated with significant socio-economic deficiencies. Its symptoms are often confused with other syndromes, which can compromise clinical diagnosis and the failure to carry out specific laboratory tests. In this respect, this paper presents a study of three algorithms (Decision Tree, Random Forest and Adaboost) for predicting the outcome (cure or death) of individuals with leptospirosis. Using the records contained in the government National System of Aggressions and Notification (SINAN, in portuguese) from 2007 to 2017, for the state of Pará, Brazil, where the temporal attributes of health care, symptoms (headache, vomiting, jaundice, calf pain) and clinical evolution (renal failure and respiratory changes) were used. In the performance evaluation of the selected models, it was observed that the Random Forest exhibited an accuracy of 90.81% for the training dataset, considering the attributes of experiment 8, and the Decision Tree presented an accuracy of 74.29 for the validation database. So, this result considers the best attributes pointed out by experiment 10: time first symptoms medical attention, time first symptoms ELISA sample collection, medical attention hospital admission time, headache, calf pain, vomiting, jaundice, renal insufficiency, and respiratory alterations. The contribution of this article is the confirmation that artificial intelligence, using the Decision Tree model algorithm, depicting the best choice as the final model to be used in future data for the prediction of human leptospirosis cases, helping in the diagnosis and course of the disease, aiming to avoid the evolution to death.

Composite outcome measures in high-impact critical care randomised controlled trials: a systematic review.

BACKGROUND: The use of composite outcome measures (COM) in clinical trials is increasing. Whilst their use is associated with benefits, several limitations have been highlighted and there is limited literature exploring their use within critical care. The primary aim of this study was to evaluate the use of COM in high-impact critical care trials, and compare study parameters (including sample size, statistical significance, and consistency of effect estimates) in trials using composite versus non-composite outcomes. METHODS: A systematic review of 16 high-impact journals was conducted. Randomised controlled trials published between 2012 and 2022 reporting a patient important outcome and involving critical care patients, were included. RESULTS: 8271 trials were screened, and 194 included. 39.1% of all trials used a COM and this increased over time. Of those using a COM, only 52.6% explicitly described the outcome as composite. The median number of components was 2 (IQR 2-3). Trials using a COM recruited fewer participants (409 (198.8-851.5) vs 584 (300-1566, p = 0.004), and their use was not associated with increased rates of statistical significance (19.7% vs 17.8%, p = 0.380). Predicted effect sizes were overestimated in all but 6 trials. For studies using a COM the effect estimates were consistent across all components in 43.4% of trials. 93% of COM included components that were not patient important. CONCLUSIONS: COM are increasingly used in critical care trials; however effect estimates are frequently inconsistent across COM components confounding outcome interpretations. The use of COM was associated with smaller sample sizes, and no increased likelihood of statistically significant results. Many of the limitations inherent to the use of COM are relevant to critical care research.

Machine learning models for abstract screening task - A systematic literature review application for health economics and outcome research.

OBJECTIVE: Systematic literature reviews (SLRs) are critical for life-science research. However, the manual selection and retrieval of relevant publications can be a time-consuming process. This study aims to (1) develop two disease-specific annotated corpora, one for human papillomavirus (HPV) associated diseases and the other for pneumococcal-associated pediatric diseases (PAPD), and (2) optimize machine- and deep-learning models to facilitate automation of the SLR abstract screening. METHODS: This study constructed two disease-specific SLR screening corpora for HPV and PAPD, which contained citation metadata and corresponding abstracts. Performance was evaluated using precision, recall, accuracy, and F1-score of multiple combinations of machine- and deep-learning algorithms and features such as keywords and MeSH terms. RESULTS AND CONCLUSIONS: The HPV corpus contained 1697 entries, with 538 relevant and 1159 irrelevant articles. The PAPD corpus included 2865 entries, with 711 relevant and 2154 irrelevant articles. Adding additional features beyond title and abstract improved the performance (measured in Accuracy) of machine learning models by 3% for HPV corpus and 2% for PAPD corpus. Transformer-based deep learning models that consistently outperformed conventional machine learning algorithms, highlighting the strength of domain-specific pre-trained language models for SLR abstract screening. This study provides a foundation for the development of more intelligent SLR systems.

Multimorbidity prevalence and health outcome prediction: assessing the impact of lookback periods, disease count, and definition criteria in health administrative data at the population-based level.

BACKGROUND: Health administrative databases play a crucial role in population-level multimorbidity surveillance. Determining the appropriate retrospective or lookback period (LP) for observing prevalent and newly diagnosed diseases in administrative data presents challenge in estimating multimorbidity prevalence and predicting health outcome. The aim of this population-based study was to assess the impact of LP on multimorbidity prevalence and health outcomes prediction across three multimorbidity definitions, three lists of diseases used for multimorbidity assessment, and six health outcomes. METHODS: We conducted a population-based study including all individuals ages > 65 years on April 1st, 2019, in Québec, Canada. We considered three lists of diseases labeled according to the number of chronic conditions it considered: (1) L60 included 60 chronic conditions from the International Classification of Diseases (ICD); (2) L20 included a core of 20 chronic conditions; and (3) L31 included 31 chronic conditions from the Charlson and Elixhauser indices. For each list, we: (1) measured multimorbidity prevalence for three multimorbidity definitions (at least two [MM2+], three [MM3+] or four (MM4+) chronic conditions); and (2) evaluated capacity (c-statistic) to predict 1-year outcomes (mortality, hospitalisation, polypharmacy, and general practitioner, specialist, or emergency department visits) using LPs ranging from 1 to 20 years. RESULTS: Increase in multimorbidity prevalence decelerated after 5-10 years (e.g., MM2+, L31: LP = 1y: 14%, LP = 10y: 58%, LP = 20y: 69%). Within the 5-10 years LP range, predictive performance was better for L20 than L60 (e.g., LP = 7y, mortality, MM3+: L20 [0.798;95%CI:0.797-0.800] vs. L60 [0.779; 95%CI:0.777-0.781]) and typically better for MM3 + and MM4 + definitions (e.g., LP = 7y, mortality, L60: MM4+ [0.788;95%CI:0.786-0.790] vs. MM2+ [0.768;95%CI:0.766-0.770]). CONCLUSIONS: In our databases, ten years of data was required for stable estimation of multimorbidity prevalence. Within that range, the L20 and multimorbidity definitions MM3 + or MM4 + reached maximal predictive performance.

Development of a core outcome set for use in research evaluations of interventions for venous leg ulceration: International eDelphi consensus.

INTRODUCTION: Venous leg ulceration (VLU) is a chronic, recurring condition with associated pain, malodour, impaired mobility and susceptibility to infection which in turn significantly impacts an individual's health-related quality of life. Randomised controlled trials (RCTs) aim to determine the efficacy of interventions to improve outcomes. To be useful, these outcomes should be consistently and fully reported across RCTs. A core outcome set (COS) is an agreed-upon standardised set of outcomes which should be, at a minimum, reported in all RCTs for a given indication including that of VLU. AIM: To gain consensus on which outcome domains and outcomes should be considered as core and therefore included in all RCTs of interventions in VLU treatment. METHOD: Two sequential, two round e-Delphi surveys were completed. The first gained consensus on core outcome domains and the second on core outcomes within those domains. Participants included: people with direct experience of having VLUs and their carers, healthcare professionals whose practice included VLU care and researchers within wound care (clinical, academic, industry). RESULTS: Five outcome domains; healing, pain, quality of life, resource use and adverse events, and 11 outcomes were rated as core by participants. The patient and not the limb or ulcer was the preferred unit of analysis for reporting. RECOMMENDATIONS: We recommend investigators report on all five outcome domains, regardless of the type of intervention being evaluated. Future research is needed to identify measurement methods for the 11 identified outcomes. We also recommend investigators follow the CONSORT guidelines (http://www.consort-statement.org/).

Methods for Neuroscience Drug Development: Guidance on Standardization of the Process for Defining Clinical Outcome Strategies in Clinical Trials.

Neurosciences clinical trials continue to have notoriously high failure rates. Appropriate outcomes selection in early clinical trials is key to maximizing the likelihood of identifying new treatments in psychiatry and neurology. The field lacks good standards for designing outcome strategies, therefore The Outcomes Research Group was formed to develop and promote good practices in outcome selection. This article describes the first published guidance on the standardization of the process for clinical outcomes in neuroscience. A minimal step process is defined starting as early as possible, covering key activities for evidence generation in support of content validity, patient-centricity, validity requirements and considerations for regulatory acceptance. Feedback from expert members is provided, regarding the risks of shortening the process and examples supporting the recommended process are summarized. This methodology is now available to researchers in industry, academia or clinics aiming to implement consensus-based standard practices for clinical outcome selection, contributing to maximizing the efficiency of clinical research.

Protocol for the development of a core outcome set and reporting guidelines for locoregional treatment in neoadjuvant systemic breast cancer treatment trials: the PRECEDENT project.

INTRODUCTION: Neoadjuvant systemic anticancer therapy (neoSACT) is increasingly used in the treatment of early breast cancer. Response to therapy is prognostic and allows locoregional and adjuvant systemic treatments to be tailored to minimise morbidity and optimise oncological outcomes and quality of life. Accurate information about locoregional treatments following neoSACT is vital to allow the translation of downstaging benefits into practice and facilitate meaningful interpretation of oncological outcomes, particularly locoregional recurrence. Reporting of locoregional treatments in neoSACT studies, however, is currently poor. The development of a core outcome set (COS) and reporting guidelines is one strategy by which this may be improved. METHODS AND ANALYSIS: A COS for reporting locoregional treatment (surgery and radiotherapy) in neoSACT trials will be developed in accordance with Core Outcome Measures in Effectiveness Trials (COMET) and Core Outcome Set-Standards for Development guidelines. Reporting guidance will be developed concurrently.The project will have three phases: (1) generation of a long list of relevant outcome domains and reporting items from a systematic review of published neoSACT studies and interviews with key stakeholders. Identified items and domains will be categorised and formatted into Delphi consensus questionnaire items. (2) At least two rounds of an international online Delphi survey in which at least 250 key stakeholders (surgeons/oncologists/radiologists/pathologists/trialists/methodologists) will score the importance of reporting each outcome. (3) A consensus meeting with key stakeholders to discuss and agree the final COS and reporting guidance. ETHICS AND DISSEMINATION: Ethical approval for the consensus process will be obtained from the Queen's University Belfast Faculty Ethics Committee. The COS/reporting guidelines will be presented at international meetings and published in peer-reviewed journals. Dissemination materials will be produced in collaboration with our steering group and patient advocates so the results can be shared widely. REGISTRATION: The study has been prospectively registered on the COMET website (https://www.comet-initiative.org/Studies/Details/2854).

Cross-cultural adaptation and psychometric validation of point-of-care outcome assessment tools in Chinese palliative care clinical practice.

BACKGROUND: A standardized national approach to routinely assessing palliative care patients helps improve patient outcomes. However, a quality improvement program-based on person centered outcomes within palliative care is lacking in Mainland China. The well-established Australian Palliative Care Outcome Collaboration (PCOC) national model improves palliative care quality. This study aimed to culturally adapt and validate three measures that form part of the PCOC program for palliative care clinical practice in China: The PCOC Symptom Assessment Scale (PCOC SAS), Palliative Care Problem Severity Scale (PCPSS), Palliative Care Phase. METHODS: A study was conducted on cross-cultural adaptation and validation of PCOC SAS, PCPSS and Palliative Care Phase, involving translation methods, cognitive interviewing, and psychometric testing through paired assessments. RESULTS: Cross-cultural adaptation highlighted the need to strengthen the link between the patient's care plan and the outcome measures to improve outcomes, and the concept of distress in PCOC SAS. Analysis of 368 paired assessments (n = 135 inpatients, 22 clinicians) demonstrated that the PCOC SAS and PCPSS had good and acceptable coherence (Cronbach's a = 0.85, 0.75 respectively). Palliative Care Phase detected patients' urgent needs. PCOC SAS and PCPSS showed fair discriminant and concurrent validity. Inter-rater reliability was fair for Palliative Care Phase (k = 0.31) and PCPSS (k = 0.23-0.30), except for PCPSS-pain, which was moderate (k = 0.53). CONCLUSIONS: The Chinese version of PCOC SAS, PCPSS, and Palliative Care Phase can be used to assess outcomes as part of routine clinical practice in Mainland China. Comprehensive clinical education regarding the assessment tools is necessary to help improve the inter-rater reliability.

Study found increasing use of core outcome sets in Cochrane systematic reviews and identified facilitators and barriers.

OBJECTIVES: In 2019, only 7% of Cochrane systematic reviews (SRs) cited a core outcome set (COS) in relation to choosing outcomes, even though a relevant COS existed but was not mentioned (or cited) for a further 29% of SRs. Our objectives for the current work were to (1) examine the extent to which authors are currently considering COS to inform outcome choice in Cochrane protocols and completed SRs, and (2) understand author facilitators and barriers to using COS. STUDY DESIGN AND SETTING: We examined all completed Cochrane SRs published in the last 3 months of 2022 and all Cochrane protocols published in 2022 for the extent to which they: (a) cited a COS, (b) searched for COS, (c) used outcomes from existing COS, and (d) reported outcome inconsistency among included studies and/or noted the need for COS. One investigator extracted information; a second extractor verified all information, discussing discrepancies to achieve consensus. We then conducted an online survey of authors of the included SRs to assess awareness of COS and identify facilitators and barriers to using COS to inform outcome choice. RESULTS: Objective 1: We included 294 SRs of interventions (84 completed SRs and 210 published SR protocols), of which 13% cited specific COS and 5% did not cite but mentioned searching for COS. A median of 83% of core outcomes from cited COS (interquartile range [IQR] 57%-100%) were included in the corresponding SR. We identified a relevant COS for 39% of SRs that did not cite a COS. A median of 50% of core outcomes from noncited COS (IQR 35%-72%) were included in the corresponding SR. Objective 2: Authors of 236 (80%) of the 294 eligible SRs completed our survey. Seventy-seven percent of authors noted being aware of COS before the survey. Fifty-five percent of authors who did not cite COS but were aware of them reported searching for a COS. The most reported facilitators of using COS were author awareness of the existence of COS (59%), author positive perceptions of COS (52%), and recommendation in the Cochrane Handbook regarding COS use (48%). The most reported barriers related to matching of the scope of the COS and the SR: the COS target population was too narrow/broad relative to the SR population (29%) or the COS target intervention was too narrow/broad relative to the SR intervention (21%). Most authors (87%) mentioned that they would consider incorporating missing core outcomes in the SR/update. CONCLUSION: Since 2019, there is increasing consideration and awareness of COS when choosing outcomes for Cochrane SRs of interventions, but uptake remains low and can be improved further. Use of COS in SRs is important to improve outcome standardization, reduce research waste, and improve evidence syntheses of the relevant effects of interventions across health research.

The impact of blinding on estimated treatment effects in randomized clinical trials on acupuncture: A meta-epidemiological study.

OBJECTIVE: To evaluate the sole impact of blinding patients and outcome assessors in acupuncture randomized controlled trials (RCTs) on treatment effects while considering the type of outcome measures. METHODS: We searched databases for the meta-analyses on acupuncture with both blinded and non-blinded RCTs. Mixed-effects meta-regression models estimated the average ratio of odds ratios (ROR) and differences in standardized mean differences (dSMD) for non-blinded RCTs versus blinded mixed-effects meta-regression model. RESULTS: The study included 96 meta-analyses (1012 trials). The average ROR for lack of patient blinding was 1.08 (95% confidence intervals 0.79-1.49) in 18 meta-analyses with binary patient-reported outcomes. The average ROR for lack of outcome assessor blinding was 0.98 (0.77-1.24) in 43 meta-analyses with binary subjective outcomes. The average dSMD was -0.38 (-0.96 to 0.20) in 10 meta-analyses with continuous patient-reported outcomes. The average dSMD was -0.13 (-0.45 to 0.18) in 25 meta-analyses with continuous subjective outcomes. The results of the subgroup analysis were consistent with the primary analysis findings. CONCLUSIONS: Blinding of participants and outcome assessors does not significantly influence acupuncture treatment efficacy. It underscores the practical difficulties of blinding in acupuncture RCTs and the necessity to distinguish between trials with and without successful blinding to understand treatment expectations' effects. Enhancing blinding procedures' quality and assessment in future research is crucial for improving RCTs' internal validity and reliability.

The use of routinely collected healthcare records for outcome assessment in clinical trials: a UK perspective.

The use of routinely collected electronic healthcare records (EHR) for outcome assessment in clinical trials has been described as a 'disruptive' new technique more than a decade ago. Despite this potential, significant methodological issues and regulatory barriers have hampered the progress in this area. This article discusses the key considerations that trialists should take into account when incorporating EHR into their trials. These include considerations of the clinical relevance of the outcome, data timeliness and quality, ethical and regulatory issues, and some practical considerations for clinical trials units. In addition, this article describes the benefits of using EHR which include cost, reduced trial burden for participants and staff, follow up efficiencies, and improved health economic evaluation procedures. We also describe the major regulatory and start up costs of using EHR in clinical trials. This article focuses on the UK specific EHR landscape in clinical trials and would help researchers and trials units considering the use of this method of outcome data collection in their next trial. If the issues described are mitigated, this method will be a formidable tool for conducting pragmatic clinical trials.

Clinical outcome measures in vision and eye care.

Traditionally, clinical outcome assessments have focused on the patient's perspective through patient-reported outcome assessments; however, given the complexity, integration, and interactions of various participants within the clinical ophthalmology setting, we propose that additional diverse clinical perspectives should be explored in order to appreciate fully the value of care provided to patients. In this review we introduce a framework by which clinical outcome assessments (COAs) can be organized. Our COA framework is composed of five outcome measurements that encompass the perspectives of each player in a patient's care: clinical data-reported outcomes, patient-reported outcomes, clinician-reported outcomes, observer-reported outcomes, and reviewer-reported outcomes. By establishing a standard for evaluating patient care, we hope to address gaps in expectations of patient care and encourage more thoughtful patient-clinician relationships.

Development of a core set of outcome measures to be applied toward breast cancer-related lymphedema core outcome domains.

PURPOSE: For breast cancer survivors (BCS) living with breast cancer-related lymphedema (BCRL), what outcome measures (OMs) are recommended to be used to measure standardized outcome domains to fully assess the burden of the disease and efficacy of interventions? An integral component of a standardized core outcome set (COS) are the OMs used to measure the COS. METHODS: A supplemental online survey was linked to a Delphi study investigating a COS for BCRL. OMs were limited to a maximum of 10 options for each outcome domain (OD). There were 14 ODs corresponding to the International Classification of Functioning, Disability, and Health (ICF) framework and respondents rated the OMs with a Likert level of recommendation. The feasibility of the listed OMs was also investigated for most outpatient, inpatient, and research settings. RESULTS: This study identified 27 standardized OMs with a few ODs having 2-3 highly recommended OMs for proper measurement. A few of the recommended OMs have limitations with reliability due to being semi-quantitative measures requiring the interpretation of the rater. CONCLUSION: Narrowing the choices of OMs to 27 highly recommended by BCRL experts may reduce selective reporting, inconsistency in clinical use, and variability of reporting across interdisciplinary healthcare fields which manage or research BCRL. There is a need for valid, reliable, and feasible OMs that measure tissue consistency. Measures of upper extremity activity and motor control need further research in the BCS with BCRL population.

Study protocol: a core outcome set for perioperative exercise clinical effectiveness trials for lung cancer patients.

BACKGROUND: Outcome assessment in perioperative exercise trials for lung cancer is heterogeneous, often omitting those that are important and patient-relevant. This heterogeneity hinders the synthesis of evidence. To address this issue, a core outcome set, an agreed-upon standardized set of outcomes to be measured and reported, is required to reduce heterogeneity among outcome measurements. This study protocol describes the methodology, aiming to develop a core outcome set for perioperative exercise intervention trials for lung cancer in clinical practice. METHODS: The project will follow the standard methodology recommended by the Core Outcome Measures in Effectiveness Trials (COMET) initiative, which is divided into four steps. Stage I: Conducting a scoping review of outcomes reported in clinical trials and protocols to develop a list of potential outcome domains. Stage II: Conducting semi-structured interviews to obtain important outcomes for patients. Stage III: Choosing the most important outcomes by conducting two rounds of the Delphi exercise. Stage IV: Achieving a consensus in a face-to-face meeting to discuss the final core outcome set. DISCUSSION: This is the first project identified for the core outcome set of perioperative exercise trials in lung cancer, which will enhance the quality, comparability, and usability of future trials and positively impact perioperative exercise and the care of patients with lung cancer. TRIALS REGISTRATION: Core Outcome Measurement in Effectiveness Trials (COMET) Initiative database registration: https://www.comet-initiative.org/Studies/Details/2091.