Remote-Use Applications of the ALSFRS-R Clinical Outcome Assessment Tool: A Scoping Review.

OBJECTIVES: In 2021, the U.S. Congress passed the ACT for ALS Act. The law encourages development of "tools, methods, and processes" to improve clinical trial efficiency for neurodegenerative diseases. The Amyotrophic Lateral Sclerosis Functional Rating Scale-Revised (ALSFRS-R) is an outcome measure administered during in-person clinic visits and used to support investigational studies for persons living with Amyotrophic Lateral Sclerosis (PALS). Availability of a standardized, remote-use version of the ALSFRS-R may promote more inclusive, decentralized clinical trials. A scoping literature review was conducted to identify existing remote-use ALSFRS-R tools, synthesize feasibility and comparability of administration modes, and summarize barriers and facilitators to inform development of a standardized remote-use ALSFRS-R tool. METHODS: Included studies reported comparisons between remote and in-person, clinician-reported, ALSFRS-R administration and were published in English (2002-2022). References were identified by searching peer-reviewed and gray literature. Twelve studies met inclusion criteria and were analyzed to compare findings within and across modes of administration. RESULTS: Remote modes of ALSFRS-R administration were categorized into four non-mutually exclusive categories: telephone (n = 6), videoconferencing (n = 3), computer or online platforms (n = 3), mobile-apps and wearables (n = 2), and one unspecified telemedicine modality (n = 1). Studies comparing in-person to telephone or videoconferencing administration reported high ALSFRS-R rating correlations and nonsignificant between- mode differences. CONCLUSION: There is insufficient information in the ALSFRS-R literature to support remote clinician administration for collecting high quality data. Future research should engage PALS, care partners and providers to develop a standardized remote-use ALSFRS-R version.

Utility of multimodal sampling and testing during advanced bronchoscopy for diagnosing atypical respiratory infections in a Coccidioides-endemic region.

Background: The role of advanced diagnostic bronchoscopy (ADB) for assessing atypical respiratory infections is unclear. The purpose of this study was to ascertain: (I) the diagnostic utility of ADB-tissue sampling in patients with focal thoracic lesions due to atypical respiratory infections; (II) how multimodal bronchoscopic sampling and testing enhance diagnosis in a Coccidioides-endemic region. Methods: A retrospective observational cohort study analyzing all ADBs performed over a 10-year period in patients with focal thoracic lesions diagnosed with a non-malignant disorder. Only cases which procured lower respiratory tract secretion and tissue samples by ADB, and had both cytohistology and culture results available were included. Results: Among 403 subjects with non-malignant disease, 136 (33.7%) were diagnosed with atypical respiratory infections, with ADB contributing a diagnosis in 119 (87.5%) of these. Coccidioidal disease was independently associated with a cytohistologic diagnosis [odds ratio =7.64, 95% confidence interval (CI): 2.51-23.26; P<0.001]. Mycobacteria were more effectively identified by culture (overall yield of 8.4%, vs. 2.7% by cytohistology; P<0.001). Among subjects for which both respiratory secretion and tissue sampling were dual-tested with culture and cytology/cytohistology, adding ADB-guided transbronchial needle aspiration and/or forceps biopsy (TBNA/TBFB) to bronchoalveolar lavage and/or bronchial washings (BAL/BW) more than doubled the yield for dimorphic fungi, from 7.1% to 15.1% (increase of 8.0%, 95% CI: 5.2-11.9%). For lung lesions, adding tissue culture to dual TBNA/TBFB cytohistology-tested lung samples doubled the proportion diagnosed with atypical infection over using TBNA-cytohistology alone (increase of 15.8%, 95% CI: 10.4-23.1%). Adding lymph node to lung sampling increased the proportion diagnosed with coccidioidomycosis by 8.8% (95% CI: 4.8-15%). Among subjects with atypical respiratory infections, major ADB-related complications occurred in 1.5%. Conclusions: ADB is useful for diagnosing atypical respiratory infections manifesting as focal thoracic lesions. A multimodal approach to both sampling and testing enhances yield, while maintaining a favorable procedure safety profile. Cytohistology testing and nodal sampling are beneficial for pulmonary coccidioidomycosis, and culture for mycobacterial disease. The approach to ADB-sampling should be adjusted according to clinical context and regional infection patterns.

Exploring Bidirectional Relationships: Child Sleep Duration, Child Behavior Problems, and Parenting Stress in Families of Children with Autism Spectrum Disorder.

Background: Youth with Autism Spectrum Disorder (ASD) are at-risk for sleep and behavior problems, and their parents are at-risk for high stress. Child sleep duration, behavior problems, and parenting stress are interrelated; however, directionality of these associations is unclear and research including youth with ASD is lacking. Using a day-to-day, within-person design, this study explores the directionality of these relationships in families of children with ASD. Method: Twenty-six children (ages 3-5, 73.1% male, 65.4% Hispanic/Latino) with ASD and their mothers participated in a 14-day study. Child sleep duration (parent-report and actigraphy), behavior problems, and parenting stress were measured daily. Constructs were decomposed into their within- and between-person components and analyzed with random intercept cross-lagged panel models. Results: While between-person relationships were directionally expected in that shorter sleep, more behavior problems, and greater parenting stress were associated, within-person relationships were complicated. Better-than-average child behavior was associated with less next-day parenting stress, yet more parenting stress than average was associated with better next-day child behavior. As expected, longer-than-average child sleep was associated with less next-day parenting stress, while greater child behavior problems were associated with less sleep that night. Conclusions: Understanding the directionality of associations between child and parent factors allows for the optimization of interventions to improve the quality of life for families of children with ASD. Interventions that target child behavior and/or help parents manage stress while maintaining effective parenting strategies for sleep and behavior may be useful.

Provider Implicit Bias in Prescribing HIV Pre-exposure Prophylaxis (PrEP) to People Who Inject Drugs.

BACKGROUND: Multiple HIV outbreaks among people who inject drugs (PWIDs) have occurred in the USA since 2015, highlighting the need for additional HIV prevention tools. Despite high levels of need, pre-exposure prophylaxis (PrEP) is drastically underutilized among PWIDs. Implicit bias toward PWID held by clinicians may impede PrEP scale-up among these underserved patients. This study examined how primary care providers' (PCPs) clinical decisions related to PrEP can be impacted by biases when the patient has a history of substance use. METHODS: We conducted an online survey of PCPs (n = 208). The survey included the implicit association test (IAT) to assess unconscious attitudes toward PWIDs, direct questions regarding clinicians' explicit PWID attitudes, and an embedded experiment in which we systematically varied the risk behavior of a hypothetical patient and asked PCPs to make clinical judgments. RESULTS: A minority (32%) of PCPs reported explicit PWID bias. The IAT indicated strong implicit PWID bias (meant IAT score = 0.59, p < .0001) among 88% of the sample. Only 9% of PCPs had no implicit or explicit PWID bias. PWID patients were judged as less likely to adhere to a PrEP regimen, less responsible, and less HIV safety conscious than heterosexual or gay male patients. Anticipated lack of adherence mediated PCPs' intent to prescribe PrEP to PWID. CONCLUSIONS: PCPs' bias may contribute to PrEP being under-prescribed to PWID. Implicit and explicit PWID biases were common in our sample. This study illustrates the need to develop and test tailored interventions to decrease biases against PWID in primary care settings.

Racial/Ethnic Variances in COVID-19 Inoculation among Southern California Healthcare Workers.

Healthcare workers (HCWs) from minoritized communities are a critical partner in moving vaccine-hesitant populations toward vaccination, yet a significant number of these HCWs are delaying or deciding against their own COVID-19 vaccinations. Our study aims to provide a more nuanced understanding of vaccine hesitancy among racially and ethnically minoritized HCWs and to describe factors associated with vaccine non-acceptance. Analysis of a sub-sample of racially and ethnically minoritized HCWs (N = 1131), who participated in a cross-sectional study at two large Southern California medical centers, was conducted. Participants completed an online survey consisting of demographics, work setting and clinical role, influenza vaccination history, COVID-19 knowledge, beliefs, personal COVID-19 exposure, diagnosis, and impact on those closest to them. While overall most HCWs were vaccinated (84%), 28% of Black, 19% of Hispanic, and 8% of Asian American HCWs were vaccine-hesitant. Age, education level, occupation, history of COVID-19, and COVID-19 related knowledge were predictive of vaccine hesitancy. We found significant variations in COVID-19 related knowledge and reasons for vaccine hesitancy among Black (governmental mistrust), Hispanic (preference for physiological immunity), and Asian-American HCWs (concern about side effects) who were vaccine-hesitant or not. Our findings highlight racial and ethnic differences in vaccine-hesitancy and barriers to vaccination among HCWs of color. This study indicates the necessity of targeted interventions to reduce vaccine hesitancy that are mindful of the disparities in knowledge and access and differences between and among racial and ethnic groups.

Psychological Pathways to Paranoia and Psychotic-Like Experiences in Daily-Life: The Mediating Role of Distinct Affective Disturbances.

BACKGROUND AND HYPOTHESIS: Influential models of psychosis indicate that the impact of putative causal factors on positive symptoms might be explained partly through affective disturbances. We aimed to investigate whether pathways from stress and self-esteem to positive symptoms, as well as reversal pathways from symptoms to stress and self-esteem, were mediated through specific affective disturbances across the extended psychosis phenotype. STUDY DESIGN: Using experience sampling methodology, 178 participants (65 high-schizotypy, 74 at-risk mental state, and 39 first-episode psychosis) were assessed on levels of momentary stress, self-esteem, anxiety, sadness, psychotic-like experiences (PLE), and paranoia. Multilevel mediation models were fit to examine indirect effects of each of these pathways. Considering evidence of mediation, each indirect pathway will be combined in a single model to explore their relative contributions. STUDY RESULTS: Anxiety, sadness, and self-esteem mediated the pathways from stress to PLE and paranoia in daily-life. In the pathway to paranoia, sadness, and self-esteem showed larger contributions than anxiety. Pathways from self-esteem to PLE and paranoia were mediated by anxiety and sadness, the later showing a larger contribution. Pathways from symptoms to stress, but not from symptoms to self-esteem, were differently explained by emotional states; sadness lost its mediating effect and anxiety was the most important mediator. Few differences across groups were found. CONCLUSIONS: This study lends support to psychological models of psychosis that highlight the relevance of affective disturbances in the risk and expression of psychosis. Furthermore, specific influences of different negative emotional states were identified, which could enhance psychological treatments.

Evaluating the Full Plate Living lifestyle intervention in low-income monolingual Latinas with and without food insecurity.

INTRODUCTION: Food insecurity has long been associated with poor physical and mental health, especially among women from underrepresented minorities. Despite efforts to reduce food insecurity, rates continue to rise and remain disproportionately high among Latinx living in the United States, a group reporting worse mental health symptoms than any other ethnic group during the COVID-19 pandemic. The need to reduce the health burden associated with food insecurity among Latinas is urgent and requires a more targeted and innovative approach. Interventions using a popular education approach have proven effective among underserved populations, especially when these are delivered by community health workers. However, food insecurity status of the participants is often unreported and it is not clear whether or not results vary between those with and without food insecurity. OBJECTIVES: The aim of this quasi-experimental study was to examine physical and mental health changes among Latinas with, and without, food insecurity following a multicomponent health intervention led by community health workers using a popular education approach. METHODS: Enrolled obese Latinas (N = 98) with and without food insecurity responded to demographic, health behaviors and mental health surveys and completed biometric measurements at baseline, immediately following the intervention and at 3 months. RESULTS: At baseline, participants with food insecurity reported more anxiety and depression than those without, but average body mass index was comparable. Depression, anxiety and body mass index were lower at 3 months post and no statistically significant differences were seen between the groups. Participants with food insecurity benefited as much from the intervention as those without.We found that, although community health workers are not licensed healthcare professionals, with proper training and support, they were able to successfully reduce the risk of chronic diseases and improve mental health symptoms among food-insecure Latinas. CONCLUSION: Given the promising results, similar interventions should be implemented on a larger scale in Latino communities among food insecure women. Long-term sustainability should also be explored.

Effectiveness of Angiotensin II for Catecholamine Refractory Septic or Distributive Shock on Mortality: A Propensity Score Weighted Analysis of Real-World Experience in the Medical ICU.

Angiotensin II (ATII) was approved for septic or other distributive shock due to its property of increasing blood pressure within 3 hours. Limited data exist regarding its effectiveness when used in real-world clinical practice. OBJECTIVES: This study examined ATII as a third-line vasopressor based on institutional approval. DESIGN: Retrospective observational cohort study. SETTING AND PARTICIPANTS: Medical ICU at an academic tertiary care medical center. Adult patients requiring 3 or more vasopressor agents for septic shock or other forms of distributed shock from September 1, 2018, to January 31, 2020. MAIN OUTCOMES AND MEASURES: Effect of ATII after norepinephrine and vasopressin on mortality and mean arterial blood pressure response after 3 hours of administration. RESULTS: One-hundred forty-seven patients, 56 receiving ATII and 91 receiving another vasopressor (non-ATII), were enrolled. Patients in the ATII group had higher mortality compared to the non-ATII group, and more required 5 or greater vasopressor agents (p < 0.01). After propensity score weighting, there remains a trend in higher mortality in the ATII compared to non-ATII group, but not statistically significant (86.0% vs 71.0%, p = 0.16). More patients in the ATII group continued to require 5 or greater vasopressor agents compared to the non-ATII group after propensity score weighting (45.9% vs 12.5%, p < 0.01). SOFA score was the only variable associated with mortality (OR = 1.25, 95% CI, 1.05-1.49; p = 0.01). Patients were considered a "responder" if mean arterial pressure greater than 65 mm Hg at 3 hours after the third vasopressor was initiated. Among the ATII group, 37.5% patients were responders compared to 45.1% responders in the non-ATII group (relative risk = 1.07, 95% CI, 0.6-1.93; p = 0.81). CONCLUSIONS AND RELEVANCE: Although previous data support the use of ATII due to its favorable hemodynamic response in patients with distributive shock, there was no observed benefit in mortality or hemodynamic response with ATII as a third-line vasopressor in our study of real-world patients.

A 2-year prospective analysis of insomnia as a mediator of the relationship between androgen deprivation therapy and perceived cognitive function in men with prostate cancer.

BACKGROUND: Androgen deprivation therapy (ADT) may affect cognitive function in men with prostate cancer (PCa). This study examined whether insomnia symptoms mediate the relationship between ADT and perceived cognitive function and whether depressive symptoms, fatigue severity, and physical activity moderate the strength of this relationship. METHODS: This was a prospective study of ADT recipients (n = 83) who were matched with control patients with PCa who were not on ADT (n = 92) and with controls with no history of cancer (n = 112) over a 2-year follow-up period. Perceived cognitive function and satisfaction were assessed with the Everyday Cognition Scale. Insomnia was assessed with the Insomnia Severity Index. Multilevel mediation analyses were conducted to estimate the indirect effect of ADT on perceived cognitive function through insomnia symptoms. Exploratory moderated mediation analyses assessed whether the indirect effect of ADT on perceived cognitive function through insomnia symptoms was dependent on levels of fatigue, depression, or physical activity. RESULTS: Insomnia symptoms significantly mediated the relationship between receipt of ADT and perceived cognitive function (P < .001) and satisfaction with cognition (P < .001) after controlling for comorbidities. Men with greater fatigue had a more pronounced association of ADT with insomnia severity. Men with greater depressive symptoms had a stronger association between insomnia severity and worse perceived cognitive function. Physical activity was not a significant moderator of the relationship between ADT and perceived cognitive function. CONCLUSIONS: Insomnia influenced the relationship between ADT and perceived cognitive abilities. Interventions to address insomnia, fatigue, and depression may improve perceived cognitive function.

Efficient Likelihood Estimation of Generalized Structural Equation Models with a Mix of Normal and Nonnormal Responses.

A maximum likelihood estimation routine is presented for a generalized structural equation model that permits a combination of response variables from various distributions (e.g., normal, Poisson, binomial, etc.). The likelihood function does not have a closed-form solution and so must be numerically approximated, which can be computationally demanding for models with several latent variables. However, the dimension of numerical integration can be reduced if one or more of the latent variables do not directly affect any nonnormal endogenous variables. The method is demonstrated using an empirical example, and the full estimation details, including first-order derivatives of the likelihood function, are provided.

Maximum Likelihood Estimation of Multilevel Structural Equation Models with Random Slopes for Latent Covariates.

A maximum likelihood estimation routine for two-level structural equation models with random slopes for latent covariates is presented. Because the likelihood function does not typically have a closed-form solution, numerical integration over the random effects is required. The routine relies upon a method proposed by du Toit and Cudeck (Psychometrika 74(1):65-82, 2009) for reformulating the likelihood function so that an often large subset of the random effects can be integrated analytically, reducing the computational burden of high-dimensional numerical integration. The method is demonstrated and assessed using a small-scale simulation study and an empirical example.

Estimating Complex Measurement and Growth Models Using the R Package PLmixed.

Measurement models, such as factor analysis and item response theory models, are commonly implemented within educational, psychological, and behavioral science research to mitigate the negative effects of measurement error. These models can be formulated as an extension of generalized linear mixed models within a unifying framework that encompasses various kinds of multilevel models and longitudinal models, such as partially nonlinear latent growth models. We introduce the R package PLmixed, which implements profile maximum likelihood estimation to estimate complex measurement and growth models that can be formulated within the general modeling framework using the existing R package lme4 and function optim. We demonstrate the use of PLmixed through two examples before concluding with a brief overview of other possible models.

Etiological Distinction Across Dimensions of Math Anxiety.

Analyses have suggested math anxiety is a multidimensional construct. However, previous behavioral genetic work examining math anxiety was unidimensional. Thus, the purpose of the present study was to examine different approaches for specifying behavioral genetic models of math anxiety as a multidimensional construct. Three models were compared: a unidimensional model, a three dimension multidimensional model, and a bi-factor model, which partitioned variance into one common factor shared across three dimensions of math anxiety and examined residual variance in each dimension. The best fitting model was a bi-factor AE model, which suggested moderate heritability of general math anxiety and that each dimension of math anxiety had unique etiological influences not accounted for by shared variance with the general math anxiety factor. Thus, while there was evidence of shared etiology, there was also evidence of some etiological distinction across dimensions of math anxiety. The results demonstrate the importance of taking into account the dimensionality of the scale when interpreting similarity across twins.

Regression-based statistical mediation and moderation analysis in clinical research: Observations, recommendations, and implementation.

There have been numerous treatments in the clinical research literature about various design, analysis, and interpretation considerations when testing hypotheses about mechanisms and contingencies of effects, popularly known as mediation and moderation analysis. In this paper we address the practice of mediation and moderation analysis using linear regression in the pages of Behaviour Research and Therapy and offer some observations and recommendations, debunk some popular myths, describe some new advances, and provide an example of mediation, moderation, and their integration as conditional process analysis using the PROCESS macro for SPSS and SAS. Our goal is to nudge clinical researchers away from historically significant but increasingly old school approaches toward modifications, revisions, and extensions that characterize more modern thinking about the analysis of the mechanisms and contingencies of effects.