Psychometric reliability, validity, and generalizability of 3MSE scores among American Indian adults: the Strong Heart Study.

OBJECTIVE: Modified Mini-Mental State Examination (3MSE) is often used to screen for dementia, but little is known about psychometric validity in American Indians. METHODS: We recruited 818 American Indians aged 65-95 for 3MSE examinations in 2010-2013; 403 returned for a repeat examination in 2017-2019. Analyses included standard psychometrics inferences for interpretation, generalizability, and extrapolation: factor analysis; internal consistency-reliability; test-retest score stability; multiple indicator multiple cause structural equation models. RESULTS: This cohort was mean age 73, majority female, mean 12 years education, and majority bilingual. The 4-factor and 2nd-order models fit best, with subfactors for orientation and visuo-construction (OVC), language and executive functioning (LEF), psychomotor and working memory (PMWM), verbal and episodic memory (VEM). Factor structure was supported for both research and clinical interpretation, and factor loadings were moderate to high. Scores were generally consistent over mean 7 years. Younger participants performed better in overall scores, but not in individual factors. Males performed better on OVC and LEF, females better on PMWM. Those with more education performed better on LEF and worse on OVC; the converse was true for bilinguals. All differences were significant, but small. CONCLUSION: These findings support use of 3MSE for individual interpretation in clinic and research among American Indians, with moderate consistency, stability, reliability over time. Observed extrapolations across age, sex, education, and bilingual groups suggest some important contextual differences may exist.

Psychometric Properties of Controlled Oral Word Association (COWA) Test and Associations With Education and Bilingualism in American Indian Adults: The Strong Heart Study.

The Controlled Oral Word Association (COWA) test is used to assess phonemic fluency and executive function. Formal validation of test scores is important for accurate cognitive evaluation. However, there is a dearth of psychometric validation among American Indian adults. Given high burden of dementia risk and key contextual factors associated with cognitive assessments, this represents a critical oversight. In a large, longitudinal population-based cohort study of adult American Indians, we examined several validity inferences for COWA, including scoring, generalization, and extrapolation inferences, by investigation of factor structure, internal consistency, test-retest reliability, and differential test functioning. We found adequate unidimensional model fit, with high factor loadings. Internal consistency reliability and test-retest reliability were 0.88 and 0.77, respectively, for the full group. COWA scores were lowest among the oldest, lowest education, bilingual speakers; group effects for sex and bilingual status were small; age effect was medium; and education effect was largest. However, Wide Range Achievement Test (WRAT) score effect was stronger than education effect, suggesting better contextualization may be needed. These results support interpretation of total COWA score, including across sex, age, or language use strata.

Latent profile similarity of middle and high school youth risk and needs.

Research concerning school success and completion has grown increasingly complex with the number of proposed associated risk and needs domains. As the number of domains expands, various data analytical techniques have been employed to understand them, including the modeling of latent profiles, to better understand how risks and needs aggregate at the level of individual persons. Latent profile analysis helps identify individuals' subgroups based on salient combinations of characteristics. The present study used latent profile analysis and a systematic profile similarity approach to examine the profiles across middle and high school student cohorts. The study replicates the profiles of previous work with high school students and extends this to middle school students. We used two independent cohorts to replicate a 3-profile solution for middle and high school samples. Results supported a similar 3-profile solution for both samples, with minor discrepancies. Results are discussed with respect to the replication and extension of the 3-profile model and its application to efforts to improve outcomes for youth in both grade level cohorts.

Real-world outcomes of systemic therapy in locally advanced, recurrent or metastatic cutaneous squamous cell carcinoma.

Aim: Real-world treatment patterns and clinical outcomes in advanced cutaneous squamous cell carcinoma were evaluated. Methods: Adults receiving their first systemic therapy for unresectable, locally advanced or recurrent/metastatic cutaneous squamous cell carcinoma from 4 September 2014 to 30 June 2017, were evaluated. The primary end point was real-world overall response rate per Response Evaluation Criteria in Solid Tumors or physician assessment. Time-to-event outcomes were assessed using the Kaplan-Meier method. Results: Of 51 eligible patients, the median age was 76 years, 80% were male and 65% had an Eastern Cooperative Oncology Group score of 0-1. The most common regimens were cetuximab (51%) and carboplatin + paclitaxel (22%). Median real-world overall response rate ranged from 9.8% per Response Evaluation Criteria in Solid Tumors to 43.1% when supplemented by physician assessment. Median overall survival was 10.7 months, and median time to next treatment was 7.5 months. Conclusion: Survival in advanced cutaneous squamous cell carcinoma was short. Real-world overall response rate was lower with Response Evaluation Criteria in Solid Tumors than physician assessment.

This study looked at chemotherapy treatments and responses in patients receiving treatment for advanced cutaneous squamous cell carcinoma, a type of skin cancer. Patients had advanced and metastatic cancer that could not be cured by radiation or surgery. Most of the patients were white males, and their median age was 76 years. About two-thirds of the patients in the study had their original cancer in the head and neck, and in most patients (approximately 80%), the cancer had spread, mostly to the lungs or lymph nodes. Half of the patients in the study were treated with cetuximab, and about a quarter received platinum chemotherapy or other cetuximab-based treatment. The study examined how response to treatment may be measured in clinical care and clinical trials. Response to treatment and length of survival were short: patients responded to treatment for a median of 9 months and survived for a median of 10.7 months.

Prognostic impact of PD-L1 in oropharyngeal cancer after primary curative radiotherapy and relation to HPV and tobacco smoking.

Background: Incidence of oropharyngeal squamous cell carcinoma (OPSCC) is rising rapidly in many western countries due to Human papillomavirus (HPV) and tobacco smoking, with a considerable overlap. Immunotherapy directed at the PD1/PD-L1 axis have shown promise in head and neck cancer and other cancer types. PD-L1 expression may indicate a poorer prognosis, and at the same time indicate a possible benefit of anti-PD-L1 immunotherapeutic agents. The primary aim of this study was to establish the prognostic effect of PD-L1 expression after primary curative radiotherapy alone.Material and methods: A cohort of 303 OPSCC patients treated with primary, curative intended radiotherapy was established. PD-L1 expression was evaluated by immunohistochemistry on formalin fixed, paraffin embedded tissue sections. PD-L1 positivity was defined as a Combined Positive Score (CPS) ≥1, indicating staining of either tumor cells, lymphocytes or macrophages.Results: Median follow-up was 5.3 years. With 199 deaths, there was no difference in overall survival between patients with PD-L1+ and PD-L1- tumors (adjusted hazard ratio [aHR] and 95% confidence interval [CI]: 1.0 [0.71-1.4]). Also, locoregional failure was similar between the two groups (aHR 1.1 [CI: 0.68 - 1.7]). Tumors were PD-L1+ in 76% of cases, significantly more among HPV p16+ tumors (82% vs. 70%, p = .01). Interestingly, higher prevalence of PD-L1+ expression was seen in HPV p16+ patients with <10 pack-years of tobacco-smoking (93%) compared to HPV p16+ smokers (76%) or HPV p16-negative patients (70%) (p = .003).Conclusion: PD-L1 expression had no prognostic significance in OPSCC patients treated with primary radiotherapy alone. A substantial proportion of OPSCC tumors show PD-L1 overexpression, especially in HPV p16+ tumors in patients with little or no smoking history.

Patient-reported outcomes in KEYNOTE-087, a phase 2 study of pembrolizumab in patients with classical Hodgkin lymphoma.

In KEYNOTE-087, pembrolizumab had a 69% overall response rate and acceptable safety in patients with relapsed/refractory classical Hodgkin lymphoma (rrHL). We assessed health-related quality of life (HRQoL) in KEYNOTE-087. The European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (QLQ-C30) and the EuroQoL Five Dimensions Questionnaire 3-level version (EQ-5D) were administered to 206 patients across three cohorts defined by lymphoma progression after: (1) autologous stem cell transplantation (ASCT) and subsequent brentuximab vedotin (BV) (n = 69); (2) salvage chemotherapy and BV (n = 79); and (3) ASCT without post-transplantation BV (n = 58). Compliance/completion rates were ≥90% at week 12 and ≥70% at week 24. QLQ-C30 global health status/QoL and EQ-5D visual analog scale scores showed mean increases from baseline in overall health at all assessed timepoints. With few exceptions, mean improvements from baseline to weeks 12 and 24 in QLQ-C30 functional and symptom scores occurred in all cohorts.Clinicaltrials.gov identifier: NCT02453594.

Medication Management Performance and Associated Cognitive Correlates in Healthy Older Adults and Older Adults with aMCI.

OBJECTIVE: Difficulties managing medications, particularly among older adults experiencing cognitive deficits, is an important contributing factor to medication nonadherence that may have significant negative financial and health outcomes. The current study examined the performance of healthy older adults' (HOA) and individuals with amnestic mild cognitive impairment (aMCI) on the medication management abilities assessment's (MMAA, a performance-based measure of medication management) original scoring criteria and derived error process measures, assessing medication overtaking and undertaking magnitude. Exploratory correlations between performances on the MMAA and self-reported confidence in medication management skills and cognitive abilities were also examined. METHOD: A sample of 25 HOAs with aMCI and 25 age- and education-matched HOAs completed the MMAA, a self-reported medication management confidence rating and a battery of neuropsychological tests. RESULTS: HOAs performed significantly better on the MMAA score and committed significantly less process errors than individuals with aMCI. Despite these differences in MMAA performance, the HOA and aMCI groups rated similar high levels of confidence in their ability to manage a new medication routine. Notably, while the HOA group's performance on all of the MMAA measures did not relate to cognitive measures, the aMCI group's performance on the MMAA score was significantly related to memory and executive functioning and a new process error score for overtaking was related to processing speed. CONCLUSIONS: Although these results present promising potential for the MMAA as a measure of medication management in a clinical setting, further studies need to examine the validity of the MMAA against real-world adherence measures.

Cardiac dysfunction among soft tissue sarcoma patients in Denmark.

PURPOSE: Soft tissue sarcoma (STS) patients may experience post-treatment cardiotoxicity, yet no population-based data exist. We examined the incidence of left ventricular ejection fraction (LVEF) decline, heart failure, and cardiac death following STS diagnosis among adults, using Danish patient registries and medical record review. PATIENTS AND METHODS: LVEF decline was examined in a regional cohort of STS patients diagnosed during 1997-2011 in Western Denmark for whom cardiac imaging data were available. LVEF decline was defined as an absolute decline from baseline to follow-up of 10% or more, or, where baseline imaging was not available, a decline below the lower limit of normal (or 40%) for a follow-up LVEF. Heart failure and cardiac death were investigated in a national Danish cohort of all STS patients diagnosed from 2000 to 2009. We followed patients from STS diagnosis until heart failure, cardiac death, emigration or December 31, 2012 (whichever occurred first). RESULTS: The incidence rate of LVEF decline for the regional cohort with follow-up data (N=100, five events) or baseline and follow-up measurements (N=75, 19 events) was 16.8 (95% confidence interval [CI]: 7.0-40.3) and 108 (95% CI: 69-170), respectively, per 1,000 person-years. In the national cohort (N=1,187), the incidence of heart failure (40 events) and cardiac death (15 events) was 7.3 (95% CI: 5.4-10.0) and 2.7 (95% CI: 1.6-4.5), respectively, per 1,000 person-years. The strongest predictors of heart failure were doxorubicin treatment (hazard ratio [HR] =2.2, 95% CI: 0.5-10.2) and pre-existing cardiovascular disease (HR=6.3, 95% CI: 0.98-40.6). CONCLUSION: LVEF decline occurred more frequently compared to heart failure or cardiac death in a nationally representative cohort of Danish STS patients.

Energetic salts with π-stacking and hydrogen-bonding interactions lead the way to future energetic materials.

Among energetic materials, there are two significant challenges facing researchers: 1) to develop ionic CHNO explosives with higher densities than their parent nonionic molecules and (2) to achieve a fine balance between high detonation performance and low sensitivity. We report a surprising energetic salt, hydroxylammonium 3-dinitromethanide-1,2,4-triazolone, that exhibits exceptional properties, viz., higher density, superior detonation performance, and improved thermal, impact, and friction stabilities, then those of its precursor, 3-dinitromethyl-1,2,4-triazolone. The solid-state structure features of the new energetic salt were investigated with X-ray diffraction which showed π-stacking and hydrogen-bonding interactions that contribute to closer packing and higher density. According to the experimental results and theoretical analysis, the newly designed energetic salt also gives rise to a workable compromise in high detonation properties and desirable stabilities. These findings will enhance the future prospects for rational energetic materials design and commence a new chapter in this field.

Tetranitroacetimidic acid: a high oxygen oxidizer and potential replacement for ammonium perchlorate.

Considerable work has been focused on developing replacements for ammonium perchlorate (AP), a primary choice for solid rocket and missile propellants, due to environmental concerns resulting from the release of perchlorate into groundwater systems [corrected]. Additionally, the generation of hydrochloric acid contributes to high concentrations of acid rain and to ozone layer depletion. En route to synthesizing salts that contain cationic FOX-7, a novel, high oxygen-containing oxidizer, tetranitroacetimidic acid (TNAA), has been synthesized and fully characterized. The properties of TNAA were found to be exceptional, with a calculated specific impulse exceeding that of AP, leading to its high potential as a replacement for AP. TNAA can be synthesized easily in a one-step process by the nitration of FOX-7 in high yield (>93%). The synthesis, properties, and chemical reactivity of TNAA have been examined.

New roles for 1,1-diamino-2,2-dinitroethene (FOX-7): halogenated FOX-7 and azo-bis(diahaloFOX) as energetic materials and oxidizers.

The syntheses and full characterization of two new halogenated 1,1-diamino-2,2-dinitroethene (FOX-7) compounds and three halogenated azo-bridged FOX-7 derivatives are described. Some of these new structures demonstrate properties that approach those of the commonly used secondary explosive RDX (cyclo-1,3,5-trimethylene-2,4,6-trinitramine). All the compounds display hypergolic properties with common hydrazine-based fuels and primary aliphatic amines (ignition delay times of 2-53 ms). This is a new role that has yet to be reported for FOX-7 and its derivatives. Their physical and energetic properties have been investigated. All compounds were characterized by single-crystal X-ray crystallography, elemental analysis, infrared spectra, and differential scanning calorimetry. These new molecules as energetic materials and hypergolic oxidizers contribute to the expansion of the chemistry of FOX-7.

Cardiovascular events in cancer patients treated with highly or moderately emetogenic chemotherapy: results from a population-based study.

Studies on cardiovascular safety in cancer patients treated with highly or moderately emetogenic chemotherapy (HEC or MEC), who may have taken the antiemetic, aprepitant, have been limited to clinical trials and postmarketing spontaneous reports. Our study explored background rates of cardiovascular disease (CVD) events among HEC- or MEC-treated cancer patients in a population-based setting to contextualize events seen in a new drug development program and to determine at a high level whether rates differed by aprepitant usage. Medical and pharmacy claims data from the 2005-2007 IMPACT National Benchmark Database were classified into emetogenic chemotherapy categories and CVD outcomes. Among 5827 HEC/MEC-treated patients, frequencies were highest for hypertension (16-21%) and composites of venous (7-12%) and arterial thromboembolic events (4-7%). Aprepitant users generally did not experience higher frequencies of events compared to nonusers. Our study serves as a useful benchmark of background CVD event rates in a population-based setting of cancer patients.

1,1-Diamino-2,2-dintroethene (FOX-7) in copper and nickel diamine complexes and copper FOX-7.

1,1-Diamino-2,2-dinitroethene (FOX-7) reacts readily with copper nitrate in an aqueous solution of potassium hydroxide to form pea green Cu(FOX)(2)(H(2)O)(2) (5). FOX-7 complexes of copper and nickel supported by a variety of diamines including Cu(en)(2)(FOX)(2)(H(2)O) (1), Cu(pn)(2)(FOX)(2) (2), Cu(bipy)(FOX)(2)(H(2)O)(4) (3a), Cu(bipy)(2)(FOX)(2)(H(2)O)(2.5) (3b), Cu(bipy)(FOX)(2)(DMSO)(2)·2DMSO (3c), Cu(phen)(3)(FOX)(2)(H(2)O)(3) (4), (Ni)(2)(phen)(6)(FOX)(4)(NO(3))(3)(H(2)O)(2) (6), and Ni(bipy)(3)(FOX)(2)(H(2)O)(4) (7a) were obtained via metathesis reactions with potassium-FOX (K-FOX). Surprisingly FOX-7, in the presence of Ni(II) and bipyridyl in a mixed solvent of methanol and dimethyl sulfoxide, gave a chelated FOX carbamate anion resulting in the compound Ni(bipy)(2)(FOX-CO(2))·(DMSO) (7b). All metal salts were characterized by infrared, elemental analysis, and differential scanning calorimetry (DSC). Single-crystal X-ray diffraction structures were obtained for compounds 1, 2, 3c, 6, and 7b.

Dichlorodiphenyldichloroethane and polychlorinated biphenyls: intraindividual changes, correlations, and predictors in healthy women from the southeastern United States.

Dichlorodiphenyldichloroethane (DDE) and polychlorinated biphenyls (PCB) are widespread environmental contaminants that have been postulated to increase the risk of diseases such as non-Hodgkin's lymphoma, breast cancer, as well as lead to early menopause. Studies assessing the effect of organochlorine exposure often can only measure organochlorine levels once, such as at study enrollment, which may not be an etiologically relevant time period. We assessed the temporal changes in DDE and PCBs and the predictors of those changes using interview data and DDE and PCB measures collected from 123 women who were enrolled in a baseline study from 1978 to 1982 and followed up in 2003 to 2004. Baseline and follow-up organochlorine levels were compared using Spearman correlations (r(s)), and predictors of the rate of change in log concentration were evaluated using linear regression models. Although serum concentrations dramatically declined (median follow-up to baseline concentration ratio was 16% for DDE and 45% for PCB), baseline and follow-up measures were strongly correlated for DDE (r(s)=0.72) and moderately correlated for PCBs (r(s)=0.43). Prediction of follow-up PCB levels was substantially improved (r(s)=0.75) with data on initial concentration, length of lactation, baseline body mass index, and percent change in body fat, whereas DDE prediction improved slightly (r(s)=0.83) with data on lactation and baseline body mass index. These findings suggest that a single organochlorine measure provides considerable information on relative ranking at distant times and that the predictive power can be improved, particularly for PCBs, with information on a few predictors.