A real-world data analysis of predictors of early mortality after a diagnosis of multiple myeloma.

BACKGROUND: Despite the increased availability and use of novel therapies for multiple myeloma, early mortality is a pervasive challenge with a significant impact on older adults. Reported rates and predictors of early mortality have varied in the literature, with most studies seldom focusing on community-treated patients. METHODS: In this retrospective cohort analysis of a real-world electronic health record-derived deidentified database of 7512 patients newly diagnosed with multiple myeloma between January 1, 2011, and February 2, 2021, and treated primarily in US-based community oncology practices, factors associated with early mortality (defined as death within 6 months after the multiple myeloma diagnosis) were examined with the use of binary logistic regression. RESULTS: The median age was 70 years overall. We found an overall early mortality rate of 8.3%, with 73% of early deaths occurring in those aged ≥70 years. Among the early deaths, only 49 patients (8.7%) had documented disease progression before death (median time to progression, 30 days [interquartile range, 7-53 days]). Baseline factors associated with higher odds of early mortality included an Eastern Cooperative Oncology Group performance status (ECOG PS) ≥ 2, Revised International Staging System (R-ISS) stage III, an age ≥ 70 years, receipt of proteasome inhibitor-doublet therapy, a light-chain isotype, and the presence of renal dysfunction (estimated glomerular filtration rate < 30 mL/min). Among those aged ≥70 years, ECOG PS ≥ 2 and R-ISS stage III remained the strongest predictors of early mortality. CONCLUSIONS: Early mortality disproportionately affects older adults (aged ≥70 years) with multiple myeloma. Interventions to support this population are needed to reduce disparate survival outcomes. PLAIN LANGUAGE SUMMARY: Factors associated with an increased risk of dying within 6 months (early mortality) of a new diagnosis of multiple myeloma (MM) among 7512 mostly community-treated patients with MM were evaluated. The early mortality rate was 8.3%; among those deaths, 49 patients (8.7%) had documented evidence of MM progression before death. The risk of early mortality was greatest for older patients (aged ≥70 years) and those with a poor performance status, poor kidney function, a higher disease stage, and light-chain MM and those receiving two-drug MM therapies. These findings highlight the need for supportive interventions geared toward older adults with MM.

Clinical Presentation, Risk Factors, and Outcomes of Immune Effector Cell-Associated Neurotoxicity Syndrome Following Chimeric Antigen Receptor T Cell Therapy: A Systematic Review.

Chimeric antigen receptor (CAR) T cell therapy is a novel therapy for patients with relapsed or refractory hematologic malignancies. Most CAR T cell therapy recipients will experience clinical features of the immune effector cell-associated neurotoxicity syndrome (ICANS), a potentially life-threatening condition. Here we describe the clinical, biological, and radiological findings associated with ICANS in adults with hematologic malignancies treated with CAR T cell therapy, as well as the acute and long-term outcomes of ICANS. A literature search of Ovid Medline, Embase, PubMed, Scopus, Web of Science Core Collection, Cochrane Library, and Google Scholar was conducted from each database's inception through February 1, 2022, using search terms reflecting CAR T cell therapy and ICANS. We included studies that enrolled adults (age ≥18 years) who received CAR T cell therapy as management for hematologic malignancies and reported the clinical presentation, predictors, and/or acute or long-term outcomes of ICANS. Two reviewers independently extracted data following the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analysis) reporting guidelines. Quality was assessed using the Joanna Briggs Institute critical appraisal tool for cohort studies. Of the 2928 studies screened, 23 observational studies (10 prospective, 11 retrospective, 1 mixed design, and 1 cross-sectional) with a total of 1666 participants met our eligibility criteria and were included in our review. The most common hematologic malignancies were diffuse large B cell lymphoma, acute lymphocytic leukemia, non-Hodgkin lymphoma, and chronic lymphocytic leukemia. ICANS onset was most often associated with the presence and severity of cytokine release syndrome, as well as with C-reactive protein and ferritin levels. Aphasia was the most common ICANS-related symptom reported, although the neurologic manifestations of ICANS were highly variable. Neuroimaging studies (magnetic resonance imaging or computed tomography) were often normal in cases of ICANS; however, electroencephalography often showed generalized background slowing, abnormal rhythmic, and periodic discharge patterns. The pooled mean (± SD) onset of ICANS was 6.4 ± 3.2 days, with a pooled mean duration of 8.3 ± 10.5 days. Two of the 23 studies (9%) reported 5 ICANS-related deaths among 233 participants. A subset of patients experienced persistent neurocognitive complaints at ≥1-year after CAR T cell therapy. The clinical presentation, onset, severity, long-term sequelae, and grading system of ICANS are variable. Future studies should consider using a consensus grading/reporting scale that would permit cross-trial comparisons of the safety profile of various CAR T cell products and enable the development of interventions to mitigate or manage these neurotoxicities. © 2022 American Society for Transplantation and Cellular Therapy. Published by Elsevier Inc. This systematic review was conducted according to a published protocol (PROSPERO CRD42020207864) and followed the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) and Synthesis without Meta-Analysis (SWiM) in systematic review reporting guidelines (Supplementary Table S1) [15,16].

Evidence to Support Universal Blood Pressure Screening in School-Based Clinical Settings.

BACKGROUND: Most pediatric elevated blood pressure (BP) remains undiagnosed. The American Academy of Pediatrics states "there is limited evidence to support school-based measurement of children's BP." We explored the utility school-based BP screening. METHODS: A cross-sectional sample of 4096 students ages 6 to 17 from Title 1 Miami-Dade Public Schools (50% female, 71% non-Hispanic black, 26% Hispanic) had their systolic/diastolic BP (SBP/DBP) and body mass index (BMI) collected over the 2016 to 2017 or 2017 to 2018 school years. Relative risks (RRs) ratios were calculated to estimate normal/elevated SBP/DBP by BMI percentile, ethnicity, and sex. RESULTS: Overall, 26.4% had at least one elevated BP measurement, of which 59% were not obese. RR for obese status was significant for all categories of elevated BP (RRs > 1.88, p < .0001). Being either female (RR = 1.34, p = .009) or Hispanic (RR = 1.31, p = .014) was significantly associated with elevated DBP. BMI accounted for <10% of the variation in BP (SBP: F(1, 4095) = 367.6, adjusted R2  = .08, p < .0001; DBP: F(1, 4095) = 93.3, adjusted R2  = .02, p < .0001). CONCLUSION: These findings support providing BP screenings in school settings. Low-income and minority students often have limited access to health care, higher obesity rates, and unhealthy behaviors. Our findings support universal school-based BP screening regardless of weight status, particularly among ethnically diverse populations.

Cognition, social cognition, and Self-assessment in schizophrenia: prediction of different elements of everyday functional outcomes.

A growing body of research has shown that two domains of cognition, neurocognition and social cognition, predict different domains of real-world outcomes in people with schizophrenia. Social cognition has been shown to predict social outcomes but not non-social outcomes (e.g. living independently), and neurocognition provides minimal prediction of social outcomes (e.g. interpersonal relationships). The differing predictive value of neurocognition and social cognition has led to an exploration of potential factors that interact with cognition to influence everyday outcomes. Functional skills, negative symptoms, and self-assessment have shown particularly promising relationships with cognitive ability. Several consensus studies have pinpointed valid performance-based assessments. High-contact informant ratings have additionally been shown to be highly accurate. The emerging understanding of divergent patterns of predicting outcomes and reliable assessments present an opportunity to improve treatment targets and real-world outcomes for individuals with schizophrenia. In particular, a recently defined component of metacognition has shown particular promise. Introspective accuracy (IA) addresses how well individuals evaluate their own abilities. Emerging research has found that IA of neurocognitive ability better predicts everyday functional deficits than scores on performance-based measures of neurocognitive skills and has found that IA of social cognition accounts unique variance in real world disability above social cognitive abilities. Intriguingly, IA of neurocognition appears to preferentially predict non-social outcomes while IA of social cognition predicts social outcomes.

Impaired introspective accuracy in schizophrenia: an independent predictor of functional outcomes.

INTRODUCTION: Individuals with schizophrenia present across a spectrum of symptomatology. Disability remains a debilitating reality across varying disease presentations and remains pervasive despite psychiatric medications. Cognition (neuro/social cognition) and negative symptoms have emerged as the strongest predictors of real-world disability, but account for <50% of the variance in outcomes. METHODS: Our attempts to determine what accounts for the remaining 50% of variance has shown that poor introspective accuracy (IA) may be the most potent predictor of functional outcomes 25% of individuals with schizophrenia. We define IA as the adequacy of self-assessments of ability, skills, performance, or decisions. We suggest that IA is a progression of metacognition and can extend beyond cognition to include misestimation of prior and likely future performance in social or other adaptively relevant situations. RESULTS: Additionally, IA is bidirectional and self-orientated. Emerging research has found that IA of neurocognitive ability better predicts everyday functional deficits than scores on performance-based measures or neurocognitive skills and has found that IA of social cognition accounts unique variance in real-world disability above social cognitive performance. DISCUSSION: We argue that impaired IA, affecting 25-50% of patients with schizophrenia, in the absence or minimal presence of other impairments might be the most powerful predictor of functional outcomes.

Self-assessment of social cognitive ability in schizophrenia: Association with social cognitive test performance, informant assessments of social cognitive ability, and everyday outcomes.

BACKGROUND: Impairments in self-assessment are common in people with schizophrenia and impairments in self-assessment of cognitive ability have been found to predict impaired functional outcome. In this study, we examined self-assessment of social cognitive ability and related them to assessments of social cognition provided by informants, to performance on tests of social cognition, and to everyday outcomes. The difference between self-reported social cognition and informant ratings was used to predict everyday functioning. METHODS: People with schizophrenia (n=135) performed 8 different tests of social cognition. They were asked to rate their social cognitive abilities on the Observable Social Cognition Rating Scale (OSCARs). High contact informants also rated social cognitive ability and everyday outcomes, while unaware of the patients' social cognitive performance and self-assessments. Social competence was measured with a performance-based assessment and clinical ratings of negative symptoms were also performed. RESULTS: Patient reports of their social cognitive abilities were uncorrelated with performance on social cognitive tests and with three of the four domains of functional outcomes. Differences between self-reported and informant rated social cognitive ability predicted impaired everyday functioning across all four functional domains. This difference score predicted disability even when the influences of social cognitive performance, social competence, and negative symptoms were considered. IMPLICATIONS: Mis-estimation of social cognitive ability was an important predictor of social and nonsocial outcomes in schizophrenia compared to performance on social cognitive tests. These results suggest that consideration of self-assessment is critical when attempting to evaluate the causes of disability and when trying to implement interventions targeting disability reduction.