Health system implementation of the PROMIS Cognitive Function Screener in the Medicare Annual Wellness Visit: framing as abilities versus concerns.

BACKGROUND: Cognitive assessment is a required component of the Medicare Annual Wellness Visit (AWV). In this prospective study, we evaluated acceptability and usefulness of a patient-reported outcome measure (the PROMIS® Cognitive Function Screener, or PRO-CS) to screen for cognitive impairment during the AWV. We compared two versions of the PRO-CS: Abilities and Concerns. METHODS: We developed PRO-CS Abilities and PRO-CS Concerns using items from the PROMIS Cognitive Function item banks. We partnered with a large health system in Pennsylvania to implement an electronic health record (EHR)-integrated version of the 4-item PRO-CS into their AWV workflow. PRO-CS Abilities was implemented in June 2022 and then replaced with PRO-CS Concerns in October 2022. We used EHR data to evaluate scores on Abilities versus Concerns and their association with patient characteristics. We gathered feedback from providers on experiences with the PRO-CS and conducted cognitive interviews with patients to evaluate their preferences for Abilities versus Concerns. RESULTS: Between June 2022 and January 2023, 3,088 patients completed PRO-CS Abilities and 2,614 patients completed PRO-CS Concerns. Mean T-scores for Abilities (54.8) were slightly higher (indicating better cognition) than for Concerns (52.6). 10% of scores on Abilities and 13% of scores on Concerns indicated concern for cognitive impairment (T-score < 45). Both Abilities and Concerns were associated with clinical characteristics as hypothesized, with lower scores for patients with cognitive impairment diagnoses and those requiring assistance with instrumental activities of daily living. Abilities and Concerns had similar negative correlations with depression (r= -0.31 versus r= -0.33) and anxiety (r= -0.28 for both), while Abilities had a slightly stronger positive correlation with self-rated health (r = 0.34 versus r = 0.28). In interviews, providers commented that the PRO-CS could be useful to facilitate conversations about cognition, though several providers noted potential limitations of patient self-report. Feedback from patients indicated a preference for PRO-CS Concerns. CONCLUSIONS: Our findings suggest potential utility of the PRO-CS for cognitive screening in the Medicare AWV. PRO-CS Abilities and Concerns had similar associations with patient clinical characteristics, but the Concerns version was more acceptable to patients.

Variations in surgical practice and short-term outcomes for degenerative lumbar scoliosis and spondylolisthesis: do surgeon training and experience matter?

For diverse procedures, sizable geographic variation exists in rates and outcomes of surgery, including for degenerative lumbar spine conditions. Little is known about how surgeon training and experience are associated with surgeon-level variations in spine surgery practice and short-term outcomes. This retrospective observational analysis characterized variations in surgical operations for degenerative lumbar scoliosis or spondylolisthesis, two common age-related conditions. The study setting was two large spine surgery centers in one region during 2017-19. Using data (International Classification of Diseases-10th edition and current procedural terminology codes) extracted from electronic health record systems, we characterized surgeon-level variations in practice (use of instrumented fusion - a more extensive procedure that involves device-related risks) and short-term postoperative outcomes (major in-hospital complications and readmissions). Next, we tested for associations between surgeon training (specialty and spine fellowship) and experience (career stage and operative volume) and use of instrumented fusion as well as outcomes. Eighty-nine surgeons performed 2481 eligible operations. For the study diagnoses, spine surgeons exhibited substantial variation in operative volume, use of instrumented fusion, and postoperative outcomes. Among surgeons above the median operative volume, use of instrumented fusion ranged from 0% to >90% for scoliosis and 9% to 100% for spondylolisthesis, while rates of major in-hospital complications ranged from 0% to 25% for scoliosis and from 0% to 14% for spondylolisthesis. For scoliosis, orthopedic surgeons were more likely than neurosurgeons to perform instrumented fusion for scoliosis [49% vs. 33%, odds ratio (OR) = 2.3, 95% confidence interval (95% CI) 1.3-4.2, P-value = .006] as were fellowship-trained surgeons (49% vs. 25%, OR = 3.0, 95% CI 1.6-5.8; P = .001). Fellowship-trained surgeons had lower readmission rates. Surgeons with higher operative volumes used instrumented fusion more often (OR = 1.1, 95% CI 1.0-1.2, P < .05 for both diagnoses) and had lower rates of major in-hospital complications (OR = 0.91, 95% CI 0.85-0.97; P = .006). Surgical practice can vary greatly for degenerative spine conditions, even within the same region and among colleagues at the same institution. Surgical specialty and subspecialty, in addition to recent operative volume, can be linked to variations in spine surgeons' practice patterns and outcomes. These findings reinforce the notion that residency and fellowship training may contribute to variation and present important opportunities to optimize surgical practice over the course of surgeons' careers. Future efforts to reduce unexplained variation in surgical practice could test interventions focused on graduate medical education. Graphical Abstract.

Evaluation of Mental Health First Aid in New York City.

More than 155,000 New Yorkers were trained in Mental Health First Aid (MHFA) between 2016 and 2020. Free citywide trainings were made available to all New Yorkers and were disseminated through city agencies and community-based settings. RAND Corporation researchers conducted a mixed-methods study that included a web-based survey of past trainees and a series of focus groups with leaders of community-based organizations and city agency staff to assess the impact of the MHFA trainings and needs for future training. In this article, the authors describe the evaluation activities that took place; the methods behind them; and the results at the individual, agency, and community levels. They also offer recommendations for ways to improve future mental health education efforts. Respondents applied MHFA skills extensively and broadly across their social networks. Nine in ten respondents had contact with an individual with a mental health problem in the past six months. Among those who had contact, 84 percent indicated using their MHFA skills to help a friend or family member, and nearly half reported applying skills with a co-worker, neighbor, or acquaintance. Because MHFA was offered through city agency workplaces and community-based settings, tens of thousands of New Yorkers were given tools to come to the aid of individuals in their personal and professional lives. MHFA may be a promising approach to building supportive social networks, organizations, and communities that are primed to recognize and assist those experiencing mental health challenges.

Electronic health record (EHR)-based PROMIS measures among neurology clinic decedents and survivors: a retrospective cohort analysis.

BACKGROUND: In addition to their standard use to assess real-time symptom burden, patient-reported outcomes (PROs), such as the Patient-Reported Outcomes Measurement Information System (PROMIS), measures offer a potential opportunity to understand when patients are experiencing meaningful clinical decline. If PROs can be used to assess decline, such information can be used for informing medical decision making and determining patient-centered treatment pathways. We sought to use clinically implemented PROMIS measures to retrospectively characterize the final PROMIS report among all patients who completed at least one PROMIS assessment from December 2017-March 2020 in one large health system, stratified by decedents vs. survivors. We conducted a retrospective cohort analysis of decedents (N = 1,499) who received care from outpatient neurology clinical practice within a single, large health system as part of usual care. We also compared decedents to survivors (360 + days before death; N = 49,602) on PROMIS domains and PROMIS-Preference (PROPr) score, along with demographics and clinical characteristics. We used electronic health record (EHR) data with built-in PROMIS measures. Linear regressions assessed differences in PROMIS domains and aggregate PROPr score by days before death of the final PROMIS completion for each patient. RESULTS: Among decedents in our sample, in multivariable regression, only fatigue (range 54.48-59.38, p < 0.0029) and physical function (range 33.22-38.38, p < 0.0001) demonstrated clinically meaningful differences across time before death. The overall PROPr score also demonstrated statistically significant difference comparing survivors (0.19) to PROPr scores obtained 0-29 days before death (0.29, p < 0.0001). CONCLUSIONS: Although clinic completion of PROMIS measures was near universal, very few patients had more than one instance of PROMIS measures reported, limiting longitudinal analyses. Therefore, patient-reported outcomes in clinical practice may not yet be robust enough for incorporation in prediction models and assessment of trajectories of decline, as evidenced in these specialty clinics in one health system. PROMIS measures can be used to effectively identify symptoms and needs in real time, and robust incorporation into EHRs can improve patient-level outcomes, but further work is needed for them to offer meaningful inputs for defining patient trajectories near the end of life. Assessing symptom burden provides an opportunity to understand clinical decline, particularly as people approach the end of life. We sought to understand whether symptoms reported by patients can be used to assess decline in health. Such information can inform decision-making about care and treatments. Of eight symptoms that we assessed, patient reports of fatigue and physical function were associated with clinical decline, as was an overall score of symptom burden. Because few symptoms were associated with decline, patient-reported outcomes in clinical practice may not yet be robust enough for incorporation in prediction models and assessment of trajectories of decline.

Definitions of Chronic Low Back Pain From a Scoping Review, and Analyses of Narratives and Self-Reported Health of Adults With Low Back Pain.

Among those with low back pain (LBP), individuals with chronic LBP (CLBP) face different treatment recommendations and incur the majority of suffering and costs. However, the way CLBP has been defined varies greatly. This study used a scoping review and qualitative and quantitative analyses of data from LBP patients to explore this variation. CLBP in most recent randomized controlled trials (RCTs) was defined by duration of pain, most commonly ≥3 months. However, individuals with LBP most often define CLBP by frequency. CLBP has also been defined using a combination of duration and frequency (16% of RCTs and 20% of individuals), including 6% of recent RCTs that followed the NIH Pain Consortium research task force (RTF) definition. Although not a defining characteristic of CLBP for individuals, almost 15% of recent RCTs required CLBP to have a healthcare provider diagnosis. In our LBP sample moving from ≥3 months to the RTF definition reduced the CLBP group size by 25% and resulted in a group that used more pain management options and reported worse health across all outcome measures. A pain duration definition offers ease of application. However, refinements to this definition (eg, RTF) can identify those who may be better intervention targets. PERSPECTIVE: This article presents the definitions used for CLBP by researchers and individuals, and the impact of these definitions on pain management and health outcomes. This information may help researchers choose better study inclusion criteria and clinicians to better understand their patients' beliefs about CLBP.

Evaluation of PROMIS Cognitive Function Scores and Correlates in a Clinical Sample of Older Adults.

In this study we assessed the utility of self-reported cognitive function using two PROMIS® Cognitive Function (PROMIS-CF) items in an observational clinical sample of patients aged 65 and older (n = 16,249) at a large health system. We evaluated the association of PROMIS-CF scores with clinical characteristics and Montreal Cognitive Assessment (MoCA) scores, and we used logistic regression to examine predictors of 1-year decline in PROMIS-CF scores among patients with available data. PROMIS-CF scores were associated with clinical characteristics as hypothesized, with lower (more impaired) scores for patients with cognitive impairment (CI) diagnoses, multiple comorbidities, and those taking cognitive enhancing or interfering medications. PROMIS-CF scores were also positively associated with MoCA scores. Predictors of 1-year decline in PROMIS-CF scores included CI diagnoses, use of cognitive enhancing medications, higher depression scores, and lower social role function. Our findings suggest potential utility of PROMIS-CF items in a brief patient-administered screening tool for CI.

Sequential Dynamics of Stearoyl-CoA Desaturase-1(SCD1)/Ligand Binding and Unbinding Mechanism: A Computational Study.

Stearoyl-CoA desaturase-1 (SCD1 or delta-9 desaturase, D9D) is a key metabolic protein that modulates cellular inflammation and stress, but overactivity of SCD1 is associated with diseases, including cancer and metabolic syndrome. This transmembrane endoplasmic reticulum protein converts saturated fatty acids into monounsaturated fatty acids, primarily stearoyl-CoA into oleoyl-CoA, which are critical products for energy metabolism and membrane composition. The present computational molecular dynamics study characterizes the molecular dynamics of SCD1 with substrate, product, and as an apoprotein. The modeling of SCD1:fatty acid interactions suggests that: (1) SCD1:CoA moiety interactions open the substrate-binding tunnel, (2) SCD1 stabilizes a substrate conformation favorable for desaturation, and (3) SCD1:product interactions result in an opening of the tunnel, possibly allowing product exit into the surrounding membrane. Together, these results describe a highly dynamic series of SCD1 conformations resulting from the enzyme:cofactor:substrate interplay that inform drug-discovery efforts.

Associations of HCV Knowledge and Medical Mistrust with Being Screened for HCV and Offered HCV Treatment among People with HIV.

An estimated one-fourth of people with HIV in the U.S. are coinfected with hepatitis C virus (HCV). We examined patient-related correlates of HCV screening and treatment in a convenience sample of 1,853 HIV-positive adults in Connecticut, Louisiana, New York, North Carolina, Pennsylvania, and Texas. Overall, 85.1% reported being screened for HCV, and 30.8% reported ever being offered treatment. In multivariate logistic regressions, greater HCV knowledge, lower HCV-related medical mistrust, older age, and prior substance use treatment were associated with higher screening and treatment likelihoods. For screening, Ryan White HIV/AIDS Program eligibility, having a high school education or less, and identifying as "other" race/ethnicity were additionally significant. Mistrust, which has arisen as a response to centuries of systemic racism, mediated the association between combined Black/Latino race/ethnicity and lower screening likelihood. We recommend patient-level (e.g., peer navigation) and provider interventions to integrate HCV screening and treatment into HIV care.

Evaluation of the Connections to Care (C2C) Initiative: Interim Report.

At least one in five adult New Yorkers is likely to meet the criteria for a mental health diagnosis, yet most do not receive mental health services to treat these problems. Mental health problems, such as depression and anxiety, disproportionately affect historically underserved segments of the population, such as racial/ethnic minority and low-income individuals, and these groups are least likely to receive mental health services. The Connections to Care (C2C) Collaborative developed the C2C program, which integrates mental health support into the work of nonclinical community-based organizations (CBOs) through task shifting; task shifting is an approach extending evidence-informed health care skills to community-based partners under the oversight of trained professionals to expand the health care workforce. This study uses data from interviews, surveys, and CBO-provided progress indicators to describe how C2C has been implemented within and across the 15 CBOs. This study also describes study methods and a description of the baseline sample for the impact evaluation at the time of writing.

The quinic acid derivative KZ-41 prevents glucose-induced caspase-3 activation in retinal endothelial cells through an IGF-1 receptor dependent mechanism.

Retinal microaneurysms, an early disease manifestation of diabetic retinopathy, are associated with retinal endothelial cell (REC) death and macular edema. We previously demonstrated that a quinic acid (QA) analog, KZ-41, promoted REC survival by blunting stress-induced p38 MAPK activation. Herein, we sought to expand our understanding of the pro-survival signal transduction pathways actuated by KZ-41. Using human RECs exposed to high glucose (25 mM, 72 hours), we demonstrated that KZ-41 blocks caspase-3 activation by triggering phosphorylation of the PI3K regulatory subunit (p85; Tyr458) and its downstream target Akt (Ser473). Akt signal transduction was accompanied by autophosphorylation of the receptor tyrosine kinase, insulin growth factor-1 receptor (IGF-1R). IGF-1R knockdown using either the tyrosine kinase inhibitor AG1024 or silencing RNA abolished KZ-41's pro-survival effect. Under high glucose stress, caspase-3 activation correlated with elevated ERK1/2 phosphorylation and decreased insulin receptor substrate-1 (IRS-1) levels. KZ-41 decreased ERK1/2 phosphorylation and reversed the glucose-dependent reduction in IRS-1. To gain insight into the mechanistic basis for IGF-1R activation by KZ-41, we used molecular modeling and docking simulations to explore a possible protein:ligand interaction between the IGF-1R kinase domain and KZ-41. Computational investigations suggest two possible KZ-41 binding sites within the kinase domain: a region with high homology to the insulin receptor contains one potential allosteric binding site, and another potential site on the other side of the kinase domain, near the hinge domain. These data, together with previous proof-of-concept efficacy studies demonstrating KZ-41 mitigates pathologic retinal neovascularization in the murine oxygen-induced retinopathy model, suggests that QA derivatives may offer therapeutic benefit in ischemic retinopathies.

Hot water immersion v icepacks for treating the pain of Chironex fleckeri stings: a randomised controlled trial.

OBJECTIVE: To investigate the effectiveness of hot water immersion for relieving the pain of major box jellyfish (Chironex fleckeri) stings.Design, interventions: Open label, randomised controlled trial comparing the effects of hot water immersion (45°C) and icepacks.Setting, participants: 42 patients with suspected C. fleckeri stings treated in the emergency department of the Royal Darwin Hospital during September 2005 - October 2008. MAIN OUTCOME MEASURES: The primary outcome was pain severity, assessed with a visual analogue scale (VAS). Secondary outcomes included crossover to the alternative treatment, use of opioid analgesia, emergency department length of stay (LOS), and delayed urticaria. RESULTS: Of 42 patients (26 males; median age, 19 years; IQR, 13-27 years), 25 were allocated to icepack treatment and 17 to hot water immersion. The demographic and baseline VAS data for the two groups were similar. After 30 minutes of treatment, 11 patients (65%) treated with hot water and 14 (56%) treated with icepacks had clinically improved pain scores (absolute difference, 9%; 95% CI, -22% to 39%; P = 0.75). One patient treated with icepacks crossed over to heat immersion. Two patients in each arm received intravenous opioid analgesia. Median emergency department LOS was 1.6 h (IQR, 1.0-1.8 h) for icepack patients and 2.1 h (IQR, 1.6-2.8 h) for heat immersion patients (P = 0.07). Five of seven patients who were followed up developed delayed urticaria. CONCLUSION: Hot water immersion was no more effective than icepacks for reducing the acute pain of box jellyfish stings, but increased emergency department LOS by about 30 minutes. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry, ACTRN12605000007639.

Ensemble-based docking: From hit discovery to metabolism and toxicity predictions.

This paper describes and illustrates the use of ensemble-based docking, i.e., using a collection of protein structures in docking calculations for hit discovery, the exploration of biochemical pathways and toxicity prediction of drug candidates. We describe the computational engineering work necessary to enable large ensemble docking campaigns on supercomputers. We show examples where ensemble-based docking has significantly increased the number and the diversity of validated drug candidates. Finally, we illustrate how ensemble-based docking can be extended beyond hit discovery and toward providing a structural basis for the prediction of metabolism and off-target binding relevant to pre-clinical and clinical trials.

Assessment of the feasibility of an ultra-low power, wireless digital patch for the continuous ambulatory monitoring of vital signs.

BACKGROUND AND OBJECTIVES: Vital signs are usually recorded at 4-8 h intervals in hospital patients, and deterioration between measurements can have serious consequences. The primary study objective was to assess agreement between a new ultra-low power, wireless and wearable surveillance system for continuous ambulatory monitoring of vital signs and a widely used clinical vital signs monitor. The secondary objective was to examine the system's ability to automatically identify and reject invalid physiological data. SETTING: Single hospital centre. PARTICIPANTS: Heart and respiratory rate were recorded over 2 h in 20 patients undergoing elective surgery and a second group of 41 patients with comorbid conditions, in the general ward. OUTCOME MEASURES: Primary outcome measures were limits of agreement and bias. The secondary outcome measure was proportion of data rejected. RESULTS: The digital patch provided reliable heart rate values in the majority of patients (about 80%) with normal sinus rhythm, and in the presence of abnormal ECG recordings (excluding aperiodic arrhythmias such as atrial fibrillation). The mean difference between systems was less than ±1 bpm in all patient groups studied. Although respiratory data were more frequently rejected as invalid because of the high sensitivity of impedance pneumography to motion artefacts, valid rates were reported for 50% of recordings with a mean difference of less than ±1 brpm compared with the bedside monitor. Correlation between systems was statistically significant (p<0.0001) for heart and respiratory rate, apart from respiratory rate in patients with atrial fibrillation (p=0.02). CONCLUSIONS: Overall agreement between digital patch and clinical monitor was satisfactory, as was the efficacy of the system for automatic rejection of invalid data. Wireless monitoring technologies, such as the one tested, may offer clinical value when implemented as part of wider hospital systems that integrate and support existing clinical protocols and workflows.