ObjectivesIn 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.MethodsIncluded 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.ResultsRemote 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.ConclusionThere 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.

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.

ISPOR has recently updated its recommendations on the evidence needed to support measurement comparability among modes of data collection for patient-reported outcome measures (PROMs).1O'Donohoe P, Reasner DS, Kovacs SM, et al. Updated recommendations on evidence needed to support measurement comparability among modes of data collection for patient-reported outcome measures: a Good Practices Report of an ISPOR Task Force. Value Health. In pressGoogle Scholar This new ISPOR Good Practices report is an update to the recommendations from the ISPOR 2009 Electronic Patient-Reported Outcomes (ePROs)2Coons S.J. Gwaltney C.J. Hays R.D. et al.Recommendations on evidence needed to support measurement equivalence between electronic and paper-based patient-reported outcome (PRO) measures: ISPOR ePRO Good Research Practices Task Force report.Value Health. 2009; 12: 419-429Abstract Full Text PDF PubMed Scopus (360) Google Scholar and 2014 PRO Mixed Modes Good Research Practices Task Force3Eremenco S. Coons S.J. Paty J. et al.PRO data collection in clinical trials using mixed modes: report of the ISPOR PRO mixed modes good research practices task force.Value Health. 2014; 17: 501-516Abstract Full Text Full Text PDF PubMed Scopus (45) Google Scholar reports. The final report, which was the product of substantial effort by task force members, incorporates feedback from 2 rounds of written review by ISPOR's Clinical Outcomes Assessment (COA) Special Interest Group. Finalization of these recommendations is an important accomplishment given the enormous amount of new research in this field, the challenges of collaborating across 2 separate task forces, and the coordination needed to achieve consensus among the diverse stakeholders represented, including the US Food and Drug Administration, academia, research organizations, electronic COA service providers, and the pharmaceutical industry. The COA field has evolved since the 2009 and 2014 reports were published, especially as researchers navigate collecting COA data during a pandemic. Those earlier reports created the foundation of a "faithful migration" of instruments from 1 mode to another, typically from paper-based administration to electronic data collection. The stated goal of a faithful migration was ensuring that subjects interpret and respond to the questions/items on the PRO instrument the same way, regardless of the mode of data collection. Furthermore, earlier reports' recommendations discouraged mixing modes within a single study, if possible, especially if there was not documented and sufficient evidence to support pooling scores from the different modes. Multiple research designs for gathering necessary evidence were described for both qualitative and quantitative studies. Finally, readers were warned of the risk of increased measurement error caused by the pooled scores, which may lead to a loss of power to detect treatment benefit, and they were cautioned against ignoring their recommendations that discouraged mixing modes. Between the 2014 and 2023 reports, the COA field experienced many changes. The 2023 report provides an excellent summary of the immense quantity of published research in this area, with detailed references that can facilitate deeper investigation. Building upon these resources and the insights from the task force members, the 2023 report authors describe 2 important goals for the update:1.To empower readers to make a meaningful assessment of their specific situation, which will vary by PROM, technology, and patient population; and2.To make the good practices generalizable enough to apply to future scenarios and technologies. The report goes a long way toward meeting these goals, but ISPOR could produce a valuable and practical companion to the report, by providing case studies of the complete process. These case studies could serve as a detailed roadmap for considering measurement comparability and evaluating supportive evidence. The report states that additional testing is unnecessary if, (1) a faithful migration has been completed following ePRO design best practices and (2) sufficient evidence exists to support the changes implemented. In these cases, providing evidence of best practices being followed and a summary of the existing literature should be adequate. One way to demonstrate that best practices have been followed, as recommended in the report, is to document an expert screen review from a qualified individual. It seems plausible that the expert screen reviewer would be conducting an informal forward and backward migration assessment, similar to the evaluation process conducted to support language/cultural translations. The documentation of the expert screen review may take a similar form to the translation certificates typically provided in support of a PRO with multiple translations included in a specific study. Although this report provides a consolidation of the research at this point and outlines good practice, there will be further debate on a number of issues. One debate is the remaining use of the term equivalence: "Over the last decade, a substantial amount of evidence emerged that repeatedly demonstrated measurement comparability (also referred to as 'equivalence') between paper and electronic modes, and among different electronic modes for a multitude of PROMs, meaning that scores recorded for the same item using different modes of data collection fall within an accepted range of each other."1O'Donohoe P, Reasner DS, Kovacs SM, et al. Updated recommendations on evidence needed to support measurement comparability among modes of data collection for patient-reported outcome measures: a Good Practices Report of an ISPOR Task Force. Value Health. In pressGoogle Scholar However, comparability is not equivalence. As mentioned later in this report, multiple studies have demonstrated that capturing PROM data electronically can result in more complete data, improved compliance related to the timing of completion, and avoidance of data entry errors and skip pattern problems. With these advantages, electronic data capture is likely to result in less measurement error and "better" measurement rather than "equivalent" measurement. Given the conventional use of ePRO instruments, the evidence cited in the new report is adequate for comparability purposes, but we suggest that the quantitative evidence proposed does not support the strict definition of equivalence. The report also suggests that "for evidence to be considered sufficient, it should be relevant to the question (ie, involve the measure of interest or a similar measure), be unbiased and reflect balanced research, and support the assumption of measurement comparability and, furthermore, the preponderance of available evidence should point to the same conclusion." We agree with this, but we recommend that greater emphasis is placed on the "use" of the measure's scores when considering comparability. Measures are neither valid nor invalid; validity concerns the use of the measure, and so it is important for researchers to carefully consider whether the evidence is sufficient to support the proposed use of the measure. The relevance of the supporting evidence may be judged as inadequate based on details of the intended study design and the construction of the study endpoints using the PRO scores. For example, typical comparability studies are conducted over a relatively short timeframe and, by necessity, focus on patients who are stable in their disease state. Clinical trials often span several years and patients may experience significant progression or deterioration in disease severity. In such circumstances, evidence suggesting that these long-term changes in the patients' status do not affect the comparability of scores across time (ie, severity) would be needed. Another topic to consider, which is specifically related to the transition to ePRO and "bring your own device," is security and privacy. For example, in an environment with an increased use of bots, administrations that are not secure risk data integrity and, therefore, the scores based on ePRO could include greater measurement error rather than less. Discussions of these topics are beyond the remit of the report, but they are still important to the process of faithful migration and achieving the advantages of electronic administration. Coons et al4Coons S.J. Eremenco S. Lundy J.J. O'Donohoe P. O'Gorman H. Malizia W. Capturing patient-reported outcome (PRO) data electronically: the past, present, and promise of EPRO measurement in clinical trials.Patient. 2015; 8: 301-309Crossref PubMed Scopus (126) Google Scholar provide the key points to consider. The critical question is the use of scores. In most clinical trial programs, the focus is on group-level decisions, rather than on individual decisions (in which score equivalence would be the hurdle rather than comparability). We agree that it is not often necessary to do a full comparability study, but we think that it is still useful to at least collect relevant data within the clinical trial of interest that can be useful for assessing the mode effect. Such practices are similar to the inclusion of other aspects of the study design (eg, site, baseline value) within the core efficacy evaluations to assess the robustness of conclusions. If there is concern about modes not being adequately mixed across treatment groups, and if the sample size allows, post hoc evaluations - such as a review of the empirical cumulative distribution functions by treatment and mode may be considered. The typical quantitative evaluation described in the report (and adequate for the typical faithful migration) is based on smaller sample sizes and methods such as intraclass correlation coefficients, Bland-Altman plots, and comparison of psychometric properties (eg, construct validity correlations, internal consistency reliability) to assess the similarities in the patterns of results. These studies are likely powered to detect only large-score differences. If the evaluation is intended for individual decisions, Lee et al5Lee M.K. Beebe T.J. Yost K.J. et al.Score equivalence of paper-, tablet-, and interactive voice response system-based versions of PROMIS, PRO-CTCAE, and numerical rating scales among cancer patients.J Patient Rep Outcomes. 2021; 5: 95Crossref PubMed Scopus (2) Google Scholar and Terluin et al6Terluin B. Brouwers E.P.M. Marchand M.A.G. de Vet H.C.W. Assessing the equivalence of web-based and paper-and-pencil questionnaires using differential item and test functioning (DIF and DTF) analysis: a case of the Four-Dimensional Symptom Questionnaire (4DSQ).Qual Life Res. 2018; 27: 1191-1200Crossref PubMed Scopus (8) Google Scholar describe methods aimed at assessing score equivalence that incorporate comparisons using differential item functioning, differential test functioning, and a priori equivalence margins. The sample sizes for these studies were quite large and supported these more sophisticated quantitative analyses. For designs that may result in a large proportion of participants changing modes throughout the study, we agree with the report that researchers should consider stricter assumptions regarding device selection. For example, suppose the device chosen at a specific time point depends, to some degree on the disease severity level of the patient. Including the mode of data collection as a covariate within the efficacy analysis would mask the estimated (adjusted) differences on the PRO. If the scores from different modes are not comparable, they would have to be adjusted before the analysis using, for example, item-response-theory-based estimates that account for different mode effects or scores equated across modes. When the impact of mode switching is a concern, it may be worthwhile to additionally collect data on why a particular device was chosen. These data could be used to develop an argument for why the device changing was not problematic. The task force closed its report with a statement of hope that researchers can now focus on the power of technology to provide patient experience insights, given that the comparability question has been "answered." As a next step, we look forward to future reports in which the comparability or equivalence of scores are no longer the goals, because the technologies themselves have enabled us to capture what matters most to patients about their experiences. We may be able to go beyond our present-day assessments, by using tailored measures based on what matters most to each individual participant, and through the increased use of computerized adaptive measures.

Objective:Individuals with Autism Spectrum Disorder (ASD) or Early-Onset Psychosis (EOP) both experience substantial difficulties with social cognition (Spek et al. 2012; Lanillos et al. 2020); however, the impact of therapy and medication use on their social cognition has not yet been examined (Lai et al. 2014; Schiffman et al. 2018). This project will explore the effects of the history of therapy and medication use as moderating variables between neural architecture and social cognition performance.Participants and Methods:T1-weighted imaging data were acquired on a 3T Siemens scanner for 51 ASD and EOP participants (Mean Age = 16.33), with 41 individuals endorsing history of therapy and 23 endorsing history of medication use across groups. Cortical thickness was calculated using FreeSurfer imaging analysis software (v5.3; Fischel et al., 2002) for social brain regions including inferior parietal lobe (IPL), middle temporal lobe (MPL), caudal anterior cingulate cortex (cACC), rostral anterior cingulate cortex (rACC), fusiform gyrus, precuneus cortex, and insular cortex. The Awareness of Social Inference Test (TASIT; McDonald et al., 2006) was administered to assess social cognition performance. After controlling for individuals that had a history of both therapy and medication use, Pearson's correlations were utilized to examine the relationship between cortical thickness and social cognition performance in ASD and EOP patients. The PROCESS Procedure moderation analysis in SPSS was utilized to determine if history of therapy or medication use moderated the relationship between cortical thickness and social cognition performance (Hayes, 2018).Results:Across groups, there was a negative association between an individual's cACC thickness and TASIT Do score (r = -.415, p = .005) as well as the total TASIT score (r = -.325, p = .031). Additionally, there was a positive association between an individual's precuneus cortical thickness and their TASIT Say score (r = .440, p = .003). Results of the moderation analyses revealed that lack of medication use was associated with greater rACC thickness and higher TASIT Say score (R2 Change = .1281 mm, p = .0191). Additionally, lack of past therapy experience was associated with greater insular thickness and higher TASIT Think scores (R2 Change = .1957 mm, p = .0033). Conversely, past therapy history was associated with greater fusiform gyrus thickness and higher TASIT Say score (R2 Change = .1115 mm, p =.0262).Conclusions:Our results suggest that for individuals without a history of therapy or medication use, higher cortical thickness of the rACC and insula support better social cognition performance; whereas for individuals with past therapy experience, higher cortical thickness of the fusiform cortex underlies better social cognition performance. Collectively, these findings suggest that an individual's history of therapy or medication use may be relevant variables to consider when examining the relationship between neural cortical thickness and social cognition performance in these neuropsychiatric conditions.

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.

Objective Youth who experience behavioral and emotional problems are at risk for sleep disturbance, while sleep disturbance also perpetuates behavioral and emotional problems. While the relationship between sleep and psychopathology in clinical mental health samples is well-established, exploration of the underlying mechanisms maintaining this relationship is limited. The purpose of this study is to explore within-person variability in emotion regulation as a mechanism of the relationship between sleep and psychopathology in a clinical youth sample. Methods Using a within-person design, 25 children (ages 6–11; 64% male; 44% non-Hispanic White) presenting to outpatient behavioral health treatment with mental health concerns were recruited to participate in a 14-day study. Daily reports of objective sleep duration via actigraphy, self-reported subjective sleepiness, and parent-reported internalizing and externalizing problems and emotion regulation were collected. Multilevel mediation analyses were used to examine the mediating effect of emotion regulation on the daily-level relationship between sleep and behavior problems. Results At the within-person level, emotion dysregulation was a significant mediator of the relationships between objective sleep duration and both externalizing [MCCI (0.0005–0.0063)] and internalizing problems [MCCI (0.0001–0.0025)]. Contrary to hypotheses, when youth slept more than usual, internalizing and externalizing problems were worse through the indirect effect of increased emotion dysregulation. Conclusions Inconsistencies in schedules and routines, even if in a positive direction, may have short-term negative consequences for youth with emotional and behavioral concerns. Future research should look to address sleep variability and how deviations in routine may impact behavior more broadly, through the indirect effects of emotion regulation.

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.

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.

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.

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.

IMPORTANCE:. 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 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.

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.

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.

Clinical psychological science is improved when it seeks to understand not only whether an effect exists but also how that effect operates and its boundary conditions. Mediation and moderation analysis are widely used in clinical psychological research to explore and test hypotheses about the mechanisms by which causal effects operate and the contingencies of those effects. Their integration as conditional process analysis allows for the examination of the contingencies of those mechanisms – for whom or in what circumstances a particular mechanism is in operation or whether it is strong as opposed to weak. This chapter reviews the fundamentals of mediation, moderation, and conditional process analysis using ordinary least squares regression, commenting along the way on good practice as well as various misunderstandings in circulation. It illustrates the application of these fundamentals and their implementation using the PROCESS macro for SPSS and SAS.