Clinical research challenges posed by difficult-to-treat depression

Approximately one-third of individuals in a major depressive episode will not achieve sustained remission despite multiple, well-delivered treatments. These patients experience prolonged suffering and disproportionately utilize mental and general health care resources. The recently proposed clinical heuristic of ‘difficult-to-treat depression’ (DTD) aims to broaden our understanding and focus attention on the identification, clinical management, treatment selection, and outcomes of such individuals. Clinical trial methodologies developed to detect short-term therapeutic effects in treatment-responsive populations may not be appropriate in DTD. This report reviews three essential challenges for clinical intervention research in DTD: (1) how to define and subtype this heterogeneous group of patients; (2) how, when, and by what methods to select, acquire, compile, and interpret clinically meaningful outcome metrics; and (3) how to choose among alternative clinical trial design options to promote causal inference and generalizability. The boundaries of DTD are uncertain, and an evidence-based taxonomy and reliable assessment tools are preconditions for clinical research and subtyping. Traditional outcome metrics in treatment-responsive depression may not apply to DTD, as they largely reflect the only short-term symptomatic change and do not incorporate durability of benefit, side effect burden, or sustained impact on quality of life or daily function. The trial methodology will also require modification as trials will likely be of longer duration to examine the sustained impact, raising complex issues regarding control group selection, blinding and its integrity, and concomitant treatments.

Performance evaluation of internal quality control rules, EWMA, CUSUM, and the novel machine learning model

Objectives The present study set out to build a machine learning model to incorporate conventional quality control (QC) rules, exponentially weighted moving average (EWMA), and cumulative sum (CUSUM) with random forest (RF) algorithm to achieve better performance and to evaluate the performances the models using computer simulation to aid laboratory professionals in QC procedure planning. Methods Conventional QC rules, EWMA, CUSUM, and RF models were implemented on the simulation data using an in-house algorithm. The models’ performances were evaluated on 170,000 simulated QC results using outcome metrics, including the probability of error detection (Ped), probability of false rejection (Pfr), average run length (ARL), and power graph. Results The highest Pfr (0.0404) belonged to the 1–2s rule. The 1–3s rule could not detect errors with a 0.9 Ped up to 4 SD of systematic error. The random forest model had the highest Ped for systematic errors lower than 1 SD. However, ARLs of the model require the combined utility of the RF model with conventional QC rules having lower ARLs or more than one QC measurement is required. Conclusions The RF model presented in this study showed acceptable Ped for most degrees of systematic error. The outcome metrics established in this study will help laboratory professionals planning internal QC.

Metrics for quantifying cognitive factors that may underlie individual variation in exoskeleton use

Individual differences in adaptation to exoskeletons have been observed, but are not well understood. Kinematic, kinetic, and physiologic factors are commonly used to assess these systems. Parameters from experimental psychology and gait literature wereadapted to probe the lower extremity perception-cognition-action loop using measures of reaction times, gait task performance, and gait strategy. Parameters were measured in 15 subjects via two tasks: (1) a modified Simon task and (2) a speed-achievement task with secondary go/no-go cues on a self-paced treadmill. Outcome metrics were assessed for significantly different intra- versus inter-subject variability. Reaction time measures from the modified Simon task, as well two speed-achievement metrics and one gait-strategy characteristic we re found to show significant differenc es in intra- versus inter-subject variability. These results suggest that select cognitive factors may differentiate between individuals and be potential predictors for individual variation during exoskeleton system operation.

Testing Social Media Water Conservation Messages that Convey Extension Evaluation Results

In this study, we tested frames Extension professionals could use to promote residential water conservation through social media. We randomly assigned Florida residents to view one of six visual messages with water conservation facts or stories and then measured willingness to engage with education programs and conservation behaviors. There were clear differences in message frame performance, but better performance was highly dependent on outcome metrics used. Therefore, we were unable to identify a preferred frame. These findings need to be further examined in an authentic social media environment to inform best practices in social media message framing for Extension professionals.

Current treatment and outcomes of pediatric gastrointestinal stromal tumors (GIST): a systematic review of published studies

Gastrointestinal stromal tumor (GIST) is a rare cancer of mesenchymal origin mostly seen in adult and elderly populations. Therefore, the prognostic and therapeutic features of pediatric GIST are not clearly defined. Clinical knowledge has been largely extrapolated from case series and adult studies. In this systematic review, we aimed to analyze the health outcome metrics of pediatric GIST. Medline and Embase databases were searched using relevant key terms. The original search retrieved 1,892 titles; 27 studies with 184 patients (68% female) were included for final review. The primary tumors were located in the stomach (165/184, 90%), small bowel (12/184, 7%), and elsewhere (7/184, 4%). Individual patient data were available in 125 cases with a median follow-up of 6.7 years. All patients underwent surgical resection, which varied from wide local excision to total gastrectomy. There were 12 deaths (10%), 65 (52%) patients were alive with no evidence of disease, and 31 cases (25%) were alive with disease. Tumor size > 5 cm, high mitotic index, and spindle morphology were predictive of mortality. Pediatric GIST has a more favorable prognosis and different characteristics versus adult tumors. There is a crucial need for international consensus and specific pediatric guidelines for the treatment of this rare tumor.

Why is Corporate Virtue in the Eye of The Beholder? The Case of ESG Ratings

Despite the rising use of environmental, social, and governance (ESG) ratings, there is substantial disagreement across rating agencies regarding what rating to give to individual firms. As what drives this disagreement is unclear, we examine whether a firm's ESG disclosure helps explain some of this disagreement. We predict and find that greater ESG disclosure actually leads to greater ESG rating disagreement. These findings hold using firm fixed effects, and using a difference-in-differences design with mandatory ESG disclosure shocks. We also find that raters disagree more about ESG outcome metrics than input metrics (policies), and that disclosure appears to amplify disagreement more for outcomes. Lastly, we examine consequences of ESG disagreement and find that greater ESG disagreement is associated with higher return volatility, larger absolute price movements, and a lower likelihood of issuing external financing. Overall, our findings highlight that ESG disclosure generally exacerbates ESG rating disagreement rather than resolving it.

The Scoliosis Research Society adult spinal deformity standard outcome set

Purpose Symptomatic adult spinal deformity (ASD) with an extremely variable presentation with pain, with and without neurogenic leg pain, and/or disturbed sagittal and coronal balance, causes a significant societal burden of disease. It is an important consequence of the aging adult population, generating a plethora of spine-related interventions with variable treatment efficacy and consistently high costs. Recent years have witnessed more than a threefold increase in the prevalence and treatment of ASD, and further increases over the coming decades are expected with the growing elderly population worldwide. The ability to monitor and assess clinical outcomes has not kept pace with these developments. This paper addresses the pressing need to provide a set of common outcome metrics for this growing group of patients with back pain and other disabilities due to an adult spinal deformity. Methods The standard outcome set was created by a panel with global representation, using a thorough modified Delphi procedure. The three-tiered outcome hierarchy (Porter) was used as a framework to capture full cycle of care. The standardized language of the International Classification of Functioning, Disability and Health (WHO-ICF) was used. Results Consensus was reached on a core set of 25 WHO-ICF outcome domains (‘What to measure’); on the accompanying globally available clinician and patient reported measurement instruments and definitions (‘How to measure’), and on the timing of the measurements (‘When to measure’). The current work has brought to light domains not routinely reported in the spinal literature (such as pulmonary function, return to work, social participation), and domains for which no adequate instruments have yet been identified (such as how to clinically quantify in routine practice lumbar spinal stenosis, neurogenic claudication, radicular pain, and loss of lower extremity motor function). Conclusion A standard outcome set was developed for patients undergoing treatment for adult spinal deformity using globally available outcome metrics. The current framework can be considered a reference for further work, and may provide a starting point for routine methodical and systematic monitoring of outcomes. Post-COVID e-health may accelerate the routine capture of these types of data.

Abstract P838: Stroke Center Certification of a Community Hospital Results in Six Fold Increase in Thrombolytic Treatment for Stroke

Introduction: Prior studies that have demonstrated improved quality metrics after stroke certification often have added new neurological services to become certified. We aimed to evaluate the changes in volume of acute stroke/TIA and thrombolytic treatments in a hospital that underwent Primary Stroke Certification after seven years of established inpatient neurology and telestroke support. Methods: A retrospective analysis of prospectively collected data was completed from a community hospital. Data included 20 months prior to stroke certification (including 12 months with a stroke coordinator) and 17 months after certification. Annualized thrombolytic treatment and total stroke/TIA admissions were reviewed. Mann Whitney tests were used to determine if thrombolytic treatment, patients identified for mechanical stroke thrombectomy (MST), or both [total acute ischemic stroke (AIS) treatment] and total stroke/TIA volume per month differed before and after stroke certification. A subgroup analysis used a Mann Whitney to determine if the addition of a stroke coordinator during preparation for certification affected outcome metrics. Results: The hospital admitted 677 stroke/TIA patients during the study period, 230 before (82 without a stroke coordinator, 148 with a stroke coordinator) and 447 after stroke certification. Thrombolytic treatment increased from 2.4 patients per year prior to certification and 14.8 patients per year after stroke certification. The following outcome variables were increased after certification: thrombolytic treatments (1 vs. 0, p<0.001), patients identified for MST (1 vs. 0, p=0.001), total AIS treatments (1 vs. 0, p<0.001) and total stroke/TIA volume (27 vs. 11, p<0.001). Subgroup analysis suggested that preparation with a stroke coordinator was associated with increases in total AIS treatments (p=0.04) and telestroke requests (p=0.04); however, no differences in total stroke/TIA volume (p=0.18), thrombolytic treatments (p=0.08) or MST (p=0.41) were appreciated in absence of stroke coordinator. Conclusions: We found significantly increased rates of thrombolytic treatments, total stroke/TIA volume and patients identified for MST in a community hospital after primary stroke certification.

Benchmarking outcomes on multiple contextual levels in lean healthcare: a systematic review, development of a conceptual framework, and a research agenda

Background Reliable benchmarking in Lean healthcare requires widely relevant and applicable domains for outcome metrics and careful attention to contextual levels. These levels have been poorly defined and no framework to facilitate performance benchmarking exists. Methods We systematically searched the Pubmed, Scopus, and Web of Science databases to identify original articles reporting benchmarking on different contextual levels in Lean healthcare and critically appraised the articles. Scarcity and heterogeneity of articles prevented quantitative meta-analyses. We developed a new, widely applicable conceptual framework for benchmarking drawing on the principles of ten commonly used healthcare quality frameworks and four value statements, and suggest an agenda for future research on benchmarking in Lean healthcare. Results We identified 22 articles on benchmarking in Lean healthcare on 4 contextual levels: intra-organizational (6 articles), regional (4), national (10), and international (2). We further categorized the articles by the domains in the proposed conceptual framework: patients (6), employed and affiliated staff (2), costs (2), and service provision (16). After critical appraisal, only one fifth of the articles were categorized as high quality. Conclusions When making evidence-informed decisions based on current scarce literature on benchmarking in healthcare, leaders and managers should carefully consider the influence of context. The proposed conceptual framework may facilitate performance benchmarking and spreading best practices in Lean healthcare. Future research on benchmarking in Lean healthcare should include international benchmarking, defining essential factors influencing Lean initiatives on different levels of context; patient-centered benchmarking; and system-level benchmarking with a balanced set of outcomes and quality measures.