Post hospital admission blood lactate measurements are associated with mortality but not neurologic morbidity in children with cerebral malaria.

BACKGROUND: In children with cerebral malaria (CM) admission blood lactate has previously guided intravenous fluid therapy and been validated as a prognostic biomarker associated with death. The usefulness of post-admission measurements of blood lactate in children with CM is less clear. The strength of association between blood lactate and neurological sequelae in CM survivors, as well as the optimal duration of post-admission measurements of blood lactate to identify children at higher risk of adverse outcomes is unknown. METHODS: A retrospective cohort study of 1674 Malawian children with CM hospitalized from 2000 to 2018 who had blood lactate measurements every 6 h for the first 24 h after admission was performed. The strength of association between admission lactate or values measured at any time point in the first 24 h post-admission and outcomes (mortality and neurological morbidity in survivors) was estimated. The duration of time after admission that lactate remained a valid prognostic biomarker was assessed. RESULTS: When lactate is analysed as a continuous variable, children with CM who have higher values at admission have a 1.05-fold higher odds (95% CI 0.99-1.11) of death compared to those with lower lactate values. Children with higher blood lactate at 6 h have 1.16-fold higher odds (95% CI 1.09-1.23) of death, compared to those with lower values. If lactate levels are dichotomized into hyperlactataemic (lactate > 5.0 mmol/L) or not, the strength of association between admission lactate and mortality increases (OR = 2.49, 95% CI 1.47-4.22). Blood lactate levels obtained after 18 h post-admission are not associated with outcomes. Similarly, the change in lactate concentrations through time during the first 24 h of hospital admission is not associated with outcomes. Blood lactate during hospitalization is not associated with adverse neurologic outcomes in CM survivors. CONCLUSIONS: In children with CM, blood lactate is associated with death but not neurologic morbidity in survivors. To comprehensively estimate prognosis, blood lactate in children with CM should be assessed at admission and for 18 h afterwards.

Prescribing patterns in patients with obsessive-compulsive disorder: Retrospective, single-center study.

INTRODUCTION: Obsessive-compulsive disorder (OCD) is marked by a high rate of treatment resistance. Patients are often left trialing medications within multiple drug classes with little response, causing heterogeneity to emerge in prescribing patterns. This analysis seeks to investigate the selection and dosing of the pharmacotherapy utilized, to portray an overview of prescribing trends in the United States. METHODS: This retrospective, single center, review of electronic medical records investigated the pharmacotherapy utilization of patients with a primary diagnosis of OCD. Two hundred and ninety-five patients who received OCD treatment at an urban, academic medical center were included in the study. Patients were included in the review if they were at least eighteen years of age and were assigned a diagnosis of OCD according to DSM-5 criteria. RESULTS: Psychotropic pharmacotherapy was integrated into the care of 93% of patients. Selective serotonin reuptake inhibitors were the most utilized medication class at 85% followed by benzodiazepines (47%) and second-generation antipsychotics (37%). Tricyclic antidepressants and first-generation antipsychotics were the two medication classes utilized the least at 13% and 2% respectively. Additionally, mood stabilizers and serotonin-norepinephrine reuptake inhibitors were utilized at rates of 8% and 16%, respectively. CONCLUSIONS: Evidence-based treatment guidelines are being followed with varying augmentation strategies widely prevalent, thus displaying the heterogeneity in treating OCD. A high rate of benzodiazepine utilization highlights a practice trend with potential ties to clinical factors, such as the latency to treatment effect of other first-line pharmacotherapies. Future prospective studies are required to determine the cultural, pharmacoeconomic and pharmacogenomic factors that contribute to the variation in prescribing practices and whether these variations influence treatment outcomes.

Intake profile, milk production and energy balance of early lactation spring calving Holstein Friesian and Jersey x Holstein Friesian dairy cows in high utilisation pasture-based systems.

Early lactation is a critical period for dairy cows as energy requirements rapidly increase with the onset of lactation, however, early lactation dry matter intakes (DMI) in pasture-based systems are under-measured. The objectives of this study were 1) to measure and profile total DMI (TDMI) and animal performance of dairy cows during early lactation in a pasture-based system 2) to investigate early lactation energy balance in pasture-based systems and 3) to examine production efficiencies including TDMI and milk solids production per 100 kg bodyweight. Eighty spring-calving dairy cows were allocated to a grazing group as they calved over a 2 year period (2021 and 2022). Cows were offered a daily herbage allowance to achieve a post-grazing sward height of 4 cm with silage supplementation when necessary due to inclement weather. Total DMI was measured using the n-alkane technique over a 12 week period from 1st of February to the 23rd of April. Total DMI and daily milk yield were significantly affected by parity with both variables being greatest for third parity animals (17.7 kg DM and 26.3 kg/cow/day, respectively), lowest for first parity (13.2 kg DM and 19.6 kg/cow/day, respectively) and intermediate for second parity animals (16.8 kg DM and 24.1 kg/cow/day, respectively). Peak TDMI was reached on wk 10 for first parity animals (14.6 kg DM), wk 11 for second parity animals (19.3 kg DM) and wk 12 for third parity animals (19.9 kg DM). Parity also had a significant effect on UFL (feed units for milk) feed balance as first parity animals experienced a greater degree of negative energy balance (-3.2 UFL) compared with second and third parity animals (-2.3 UFL). Breed and parity had an effect on production efficiencies during the first 12 weeks of lactation as Jersey x Holstein Friesian cows had greater TDMI/100 kg bodyweight and milk solids/100 kg bodyweight compared with Holstein Friesian cows.

Predicting methane emissions of individual grazing dairy cows from spectral analyses of their milk samples.

Data on the enteric methane emissions of individual cows are useful not just in assisting management decisions and calculating herd inventories but also as inputs for animal genetic evaluations. Data generation for many animal characteristics, including enteric methane emissions, can be expensive and time consuming, so being able to extract as much information as possible from available samples or data sources is worthy of investigation. The objective of the present study was to attempt to predict individual cow methane emissions from the information contained within milk samples, specifically the spectrum of light transmittance across different wavelengths of the mid-infrared (MIR) region of the electromagnetic spectrum. A total of 93,888 individual spot measures of methane (i.e., individual samples of an animal's breath when using the GreenFeed technology) from 384 lactations on 277 grazing dairy cows were collapsed into weekly averages expressed as grams per day; each weekly average coincided with a MIR spectral analysis of a morning or evening individual cow milk sample. Associations between the spectra and enteric methane measures were performed separately using partial least squares regression or neural networks with different tuning parameters evaluated. Several alternative definitions of the enteric methane phenotype (i.e., average enteric methane in the 6 d preceding or 6 d following taking the milk sample or the average of the 6 d before and after the milk sample, all of which also included the enteric methane emitted on the day of milk sampling), the candidate model features (e.g., milk yield, milk composition, and milk MIR) as well as validation strategy (i.e., cross-validation or leave-one-experimental treatment-out) were evaluated. Irrespective of the validation method, the prediction accuracy was best when the average of the milk MIR from the morning and evening milk sample was used and the prediction model was developed using neural networks; concurrently including milk yield and days in milk in the prediction model generated superior predictions relative to just the spectral information alone. Furthermore, prediction accuracy was best when the enteric methane phenotype was the average of at least 20 methane spot measures across a 6-d period flanking each side of the milk sample with associated spectral data. Based on the strategy that achieved the best accuracy of prediction, the correlation between the actual and predicted daily methane emissions when based on 4-fold cross-validation varied per validation stratum from 0.68 to 0.75; the corresponding range when validated on each of the 8 different experimental treatments focusing on alternative pasture grazing systems represented in the dataset varied from 0.55 to 0.71. The root mean square error of prediction across the 4-folds of cross-validation was 37.46 g/d, whereas the root mean square error averaged across all folds of leave-one-treatment-out was 37.50 g/d. Results suggest that even with the likely measurement errors contained within the MIR spectrum and gold standard enteric methane phenotype, enteric methane can be reasonably well predicted from the infrared spectrum of milk samples. What is yet to be established, however, is whether (a) genetic variation exists in this predicted enteric methane phenotype and (b) selection on estimates of genetic merit for this phenotype translate to actual phenotypic differences in enteric methane emissions.

The impact of twice daily 3-nitroxypropanol supplementation on enteric methane emissions in grazing dairy cows.

Although 3-NOP has been proven to reduce enteric methane (CH4) by ∼30% in indoor systems of dairying when the additive is mixed throughout a total mixed ration (TMR), there has been very limited research to date in grazing systems in which the most convenient method of additive supplementation is at milking twice daily. To investigate the effect of twice daily 3-NOP supplementation on enteric CH4 emissions, a 12-week study was undertaken in which treatment cows (n = 26) were supplemented with 3-NOP (80 mg per kg dry matter intake; DMI) twice daily at morning and evening milking, while control cows (n = 26) received no additive supplementation. Enteric CH4, hydrogen (H2) and carbon dioxide (CO2) were measured using GreenFeed units, while milk production, body weight (BW), body condition score (BCS) and DMI were monitored to determine the effect of 3-NOP supplementation on productivity. There was no significant effect of 3-NOP supplementation on any of the aforementioned parameters with the exception of CH4 and H2 production, respectively. Cows supplemented with 3-NOP produced ∼36% more H2 (P < 0.001) across a 24-h period, with reductions in CH4 production of 28.5% recorded in the 3 h after additive consumption (P < 0.001), however, levels of CH4 production returned to that of the control group thereafter. When CH4 production was considered across the entire 24-h period, the cows offered 3-NOP produced ∼5% less CH4 than the control (P < 0.050). Future research should focus on methods to increase the efficacy of the additive throughout the day which would include the deployment of a slow-release form or an out of parlor feeding system that allows animals consume the product at additional time points.

Awareness of Narrative Identity Questionnaire (ANIQ) in Early Adolescents: Psychometric Evaluation and Association with Features of Personality Disorder.

Identity formation is central to adolescent development. Challenges in establishing a stable sense of self is associated with maladaptive identity function, which has been recognized as a core feature of personality pathology. The narrative identity framework offers a unique lens to garner salient information about one's sense of self. The Awareness of Narrative Identity Questionnaire (ANIQ) is a self-report measure of narrative identity validated in adults but is yet to be validated in adolescents. The current study aimed to conduct the first psychometric evaluation of the ANIQ in a sample of 205 youth aged 10-14 years (M = 12.1 ± 1.06 years; 50.7% female; 73.7% Hispanic) recruited from a public charter school. Results confirmed the four-factor structure of the ANIQ and showed high internal consistency. Convergent validity was supported through negative associations between the ANIQ and borderline personality features and identity diffusion. Incremental validity of the ANIQ over identity diffusion in predicting borderline personality features was also examined, but not supported. Overall, results support the ANIQ as a promising instrument for the assessment of narrative identity in youth. However, some improvements to the ANIQ might be necessary in order to use it as a clinical tool in identifying youth with personality pathology.

First Psychometric Evaluation of the English Version of the Semi-Structured Interview for Personality Functioning (STiP-5.1).

The Alternative Model for Personality Disorders provides a dimensional framework for the conceptualization of personality disorders where Criterion A concerns the assessment of one's level of personality functioning (LPF). This study examines the psychometric properties of the English translation of the Semi-Structured Interview for Personality Functioning (STiP-5.1) to validate this translation for the assessment of LPF in English-speaking populations; and examine whether this measure increments self-report measures of LPF and personality pathology in predicting general functioning. The sample consisted of 129 emerging adults between 18 and 25 years of age (M = 20.54, SD = 2.08) from a mixed college and clinical sample. Results support a unidimensional factor structure of the STiP-5.1, good internal consistency, and high inter-rater reliability. Construct validity was supported through associations of the STiP-5.1 with self-report measures of LPF and personality pathology. The STiP-5.1 incremented self-report measures of personality pathology in predicting functional impairment, though additional variance explained was modest. Finally, STiP-5.1 scores differentiated individuals who obtained a score at or above the clinical cutoff from those below on self-report measures of personality pathology and LPF with large effect sizes. Findings support the validity of the English translation of the STiP-5.1 for the assessment of LPF.

Central arterial stiffening and intracranial atherosclerosis: the atherosclerosis risk in communities neurocognitive study (ARIC-NCS): Aortic stiffness & intracranial atherosclerosis.

OBJECTIVES: Previous studies suggest an association between central arterial stiffness (CAS) and intracranial atherosclerotic disease (ICAD) among Asian participants with stroke or hypertension; this association has not been evaluated in United States populations. We assessed the cross-sectional association of CAS with ICAD presence and burden in late-life, and differences in association by age, sex, and race. MATERIALS AND METHODS: We conducted a cross-sectional analysis of 1,285 Atherosclerosis Risk in Communities Study participants [mean age 75 (standard deviation: 5) years, 38 % male, 20  % Black] at Visit 5 (2011-2013). CAS was measured as carotid-femoral pulse wave velocity (cfPWV) using the Omron VP-1000 Plus. ICAD was assessed using high-resolution vessel wall MRI and MR angiography. We evaluated associations of a 1 standard deviation (SD) cfPWV (3.02 m/s) and high vs. non-high cfPWV (≥ 13.57 m/s vs. < 13.57 m/s) with presence of plaques (yes/no) and plaque number (0, 1-2, and >2) using multivariable logistic and ordinal logistic regression models adjusted for covariates. RESULTS: Each one SD greater cfPWV was associated with higher odds of plaque presence (odds ratio (OR)=1.32, 95 % confidence interval (CI): 1.22, 1.43), and an incrementally higher odds of number of plaques (OR 1-2 vs. 0 plaques = 1.21, 95 % CI: 1.10, 1.33; OR >2 vs. 0 plaques = 1.51, 95 % CI: 1.33,1.71). Results suggested differences by race, with greater magnitude associations among Black participants. CONCLUSIONS: CAS was positively associated with ICAD presence and burden; cfPWV may be a useful subclinical vascular measure for identification of individuals who are at high risk for cerebrovascular disease.

The Effect of Diesel Exhaust Particles on Adipose Tissue Mitochondrial Function and Inflammatory Status.

Air pollution poses a significant global health risk, with fine particulate matter (PM2.5) such as diesel exhaust particles (DEPs) being of particular concern due to their potential to drive systemic toxicities through bloodstream infiltration. The association between PM2.5 exposure and an increased prevalence of metabolic disorders, including obesity, metabolic syndrome, and type 2 diabetes mellitus (T2DM), is evident against a backdrop of rising global obesity and poor metabolic health. This paper examines the role of adipose tissue in mediating the effects of PM2.5 on metabolic health. Adipose tissue, beyond its energy storage function, is responsive to inhaled noxious stimuli, thus disrupting metabolic homeostasis and responding to particulate exposure with pro-inflammatory cytokine release, contributing to systemic inflammation. The purpose of this study was to characterize the metabolic response of adipose tissue in mice exposed to either DEPs or room air (RA), exploring both the adipokine profile and mitochondrial bioenergetics. In addition to a slight change in fat mass and a robust shift in adipocyte hypertrophy in the DEP-exposed animals, we found significant changes in adipose mitochondrial bioenergetics. Furthermore, the DEP-exposed animals had a significantly higher expression of adipose inflammatory markers compared with the adipose from RA-exposed mice. Despite the nearly exclusive focus on dietary factors in an effort to better understand metabolic health, these results highlight the novel role of environmental factors that may contribute to the growing global burden of poor metabolic health.

Heterogeneous integration of a III-V quantum dot laser on high thermal conductivity silicon carbide.

Heat accumulation prevents semiconductor lasers from operating at their full potential. This can be addressed through heterogeneous integration of a III-V laser stack onto non-native substrate materials with high thermal conductivity. Here, we demonstrate III-V quantum dot lasers heterogeneously integrated on silicon carbide (SiC) substrates with high temperature stability. A large T0 of 221 K with a relatively temperature-insensitive operation occurs near room temperature, while lasing is sustained up to 105°C. The SiC platform presents a unique and ideal candidate for realizing monolithic integration of optoelectronics, quantum, and nonlinear photonics.

An ecological and epidemiological single-season survey of Anaplasma and Ehrlichia positive ticks in Victoria Falls National Park, Zimbabwe.

There is an urgent need for continued research on the ecology of tick-borne diseases in Africa. Our objective was to provide a preliminary description of the ecology and epidemiology of tick species, tick-borne pathogens, and animal hosts in Zimbabwe, focusing efforts at Victoria Falls National Park, for a single season. We tested the hypothesis that tick surveillance and pathogen screening data can be used to model associations among ticks, hosts, and pathogens. We collected ticks from domesticated animals and wildlife in Zimbabwe and screened the ticks for the presence of Anaplasma and Ehrlichia bacteria. Nearly 30% of the screened ticks were PCR-positive; 89% of tick species were PCR-positive, and 88% of animal species carried at least one PCR-positive tick. We sequenced a subset of amplicons that were similar to three Anaplasma species and three Ehrlichia species. The odds of a tick being PCR-positive increased when many ticks were collected from the host or the tick was collected from a cow (domesticated animal). Tick species shared host species more often than expected. We demonstrate that ticks in northwestern Zimbabwe present a One Health problem for nearby wildlife and humans.

Heterocyclic amines reduce insulin-induced AKT phosphorylation and induce gluconeogenic gene expression in human hepatocytes.

Heterocyclic amines (HCAs) are well-known for their mutagenic properties. One of the major routes of human exposure is through consumption of cooked meat, as certain cooking methods favor formation of HCAs. Recent epidemiological studies reported significant associations between dietary HCA exposure and insulin resistance and type II diabetes. However, no previous studies have examined if HCAs, independent of meat consumption, contributes to pathogenesis of insulin resistance or metabolic disease. In the present study, we have assessed the effect of three HCAs commonly found in cooked meat (2-amino-3,4,8-trimethylimidazo[4,5-f]quinoxaline [MeIQ], 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline [MeIQx], and 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine [PhIP]) on insulin signaling and glucose production. HepG2 or cryopreserved human hepatocytes were treated with 0-50 µM of MeIQ, MeIQx, or PhIP for 3 days. Treatment of HepG2 cells and hepatocytes with MeIQ and MeIQx resulted in a significant reduction in insulin-induced AKT phosphorylation, suggesting that HCA exposure decreases hepatic insulin signaling. HCA treatment also led to significant increases in expression of gluconeogenic genes, G6PC and PCK1, in both HepG2 and cryopreserved human hepatocytes. Additionally, the level of phosphorylated FOXO1, a transcriptional regulator of gluconeogenesis, was significantly reduced by HCA treatment in hepatocytes. Importantly, HCA treatment of human hepatocytes led to increases in extracellular glucose level in the presence of gluconeogenic substrates, suggesting that HCAs induce hepatic glucose production. The current findings suggest that HCAs induce insulin resistance and promote hepatic glucose production in human hepatocytes. This implicates that exposure to HCAs may lead to the development of type II diabetes or metabolic syndrome.

Association Between Change in Physical Activity During Pregnancy and Infant Birth Weight.

OBJECTIVE: We assessed whether total, recreational, and non-recreational physical activity (PA) assessed twice during pregnancy, and its change, were associated with infant birth weight and small for gestational age (SGA). METHODS: We included 1467 Pregnancy, Infection, and Nutrition 3 Study participants who self-reported PA at time 1 (T1: 17-22 weeks' gestation) and time 2 (T2: 27-30 weeks' gestation). We assessed last week absolute intensities of PA (moderate: 4.7-7.1 METs; and vigorous: > 7.1 METs) and perceived intensities. Change in hours/week of PA was assessed continuously or categorically (increase or decrease ≥ 1 hour, and no change). Associations of continuous PA hours/week at T1, T2, and its change, with sex-specific z-scores of birth weight, were assessed using multivariable linear robust regressions. We used logistic regressions to assess categorical PA measures with SGA. Models were adjusted for adequacy of maternal weight gain, general health, maternal age, parity, race/ethnicity, and smoking. RESULTS: Hours/week of total and recreational absolute intensities of PA at T1, T2, and its change were generally not associated with birth weight, although two measures of non-recreational PA at T2 and its change were associated with increased birth weight. Perceived intensities of PA (at T1, T2, and its change) were largely not associated with sex-specific z-scores of infant birth weight. Absolute and perceived intensity PA were not associated with SGA. CONCLUSIONS FOR PRACTICE: In this observational cohort, increases and decreases in PA during pregnancy were not associated with differential changes in birthweight or SGA.

Hexavalent chromium increases the metabolism and genotoxicity of aromatic amine carcinogens 4-aminobiphenyl and ß-naphthylamine in immortalized human lung epithelial cells.

Humans are exposed to carcinogenic chemicals via occupational and environmental exposures. Common chemicals of concern that can occur in exposures together are aromatic amines (e.g., 4-aminobiphenyl [4-ABP] and ß-naphthylamine [BNA]) and hexavalent chromium (Cr[VI]). Arylamine N-acetyltransferases 1 and 2 (NAT1 and NAT2) are key to the metabolism of aromatic amines and their genotoxicity. The effects of Cr(VI) on the metabolism of aromatic amines remains unknown as well as how it may affect their ensuing toxicity. The objective of the research presented here is to investigate the effects of Cr(VI) on the metabolism and genotoxicity of 4-ABP and BNA in immortalized human lung epithelial cells (BEP2D) expressing NAT1 and NAT2. Exposure to Cr(VI) for 48 h increased NAT1 activity (linear regression analysis: P < 0.0001) as measured by N-acetylation of para-aminobenzoic acid (PABA) in BEP2D cells but not NAT2 N-acetylation of sulfamethazine, which are prototypic NAT1 and NAT2 substrates respectively. Cr(VI) also increased the N-acetylation of 4-ABP and BNA. In BEP2D cells the N-acetylation of 4-ABP (1-3 µM) exhibited a dose-dependent increase (linear regression analysis: P < 0.05) following co-incubation with 0-3 µM Cr(VI). In BEP2D cells, incubation with Cr(VI) caused dose-dependent increases (linear regression analysis: P < 0.01) in expression of CYP1A1 protein and catalytic activity. For genotoxicity, BEP2D cells were exposed to 4-ABP or BNA with/without Cr(VI) for 48 h. We observed dose-dependent increases (linear regression analysis: P < 0.01) in phospho-γH2AX protein expression for combined treatment of 4-ABP or BNA with Cr(VI). Further using a CYP1A1 inhibitor (α-naphthoflavone) and NAT1 siRNA, we found that CYP1A1 inhibition did not reduce the increased N-acetylation or genotoxicity of BNA by Cr(VI), while NAT1 inhibition did reduce increases in BNA N-acetylation and genotoxicity by Cr(VI). We conclude that during co-exposure of aromatic amines and Cr(VI) in human lung cells, Cr(VI) increased NAT1 activity contributing to increased 4-ABP and BNA genotoxicity.

Do Positive Psychological Factors Equally Predict Resistance to Upper Respiratory Infections in African and European Americans?

Research has consistently shown that positive psychological constructs are linked to better physical health, but few studies have examined the role that race plays in this connection. We explored whether positive self-evaluations were equally protective against upper respiratory infection for 271 African American adults and 700 European American adults in a series of virus-exposure studies. Participants were assessed at baseline for psychological functioning and physical health, quarantined and exposed experimentally to a respiratory virus, and then monitored for infection and symptoms. Regression analyses revealed significant interactions between race and multiple positive psychological factors; several factors that were helpful to European Americans were unhelpful or even harmful to African Americans. Building on past work showing cross-cultural variation in the health correlates of affect, this study provides evidence that the health benefits of positive psychological constructs may not be universal and points to the need to explore factors that underpin these observed differential patterns.

Skilled Nursing and Inpatient Rehabilitation Facility Use by Medicare Fee-for-Service Beneficiaries Discharged Home After a Stroke: Findings From the COMPASS Trial.

OBJECTIVES: To examine the effect of a comprehensive transitional care model on the use of skilled nursing facility (SNF) and inpatient rehabilitation facility (IRF) care in the 12 months after acute care discharge home following stroke; and to identify predictors of experiencing a SNF or IRF admission following discharge home after stroke. DESIGN: Cluster randomized pragmatic trial SETTING: Forty-one acute care hospitals in North Carolina. PARTICIPANTS: 2262 Medicare fee-for-service beneficiaries with transient ischemic attack or stroke discharged home. The sample was 80.3% White and 52.1% female, with a mean (SD) age of 74.9 (10.2) years and a mean ± SD National Institutes of Health stroke scale score of 2.3 (3.7). INTERVENTION: Comprehensive transitional care model (COMPASS-TC), which consisted of a 2-day follow-up phone call from the postacute care coordinator and 14-day in-person visit with the postacute care coordinator and advanced practice provider. MAIN OUTCOME MEASURES: Time to first SNF or IRF and SNF or IRF admission (yes/no) in the 12 months following discharge home. All analyses utilized multivariable mixed models including a hospital-specific random effect to account for the non-independence of measures within hospital. Intent to treat analyses using Cox proportional hazards regression assessed the effect of COMPASS-TC on time to SNF/IRF admission. Logistic regression was used to identify clinical and non-clinical predictors of SNF/IRF admission. RESULTS: Only 34% of patients in the intervention arm received COMPASS-TC per protocol. COMPASS-TC was not associated with a reduced hazard of a SNF/ IRF admission in the 12 months post-discharge (hazard ratio, 1.20, with a range of 0.95-1.52) compared to usual care. This estimate was robust to additional covariate adjustment (hazard ratio, 1.23) (0.93-1.64). Both clinical and non-clinical factors (ie, insurance, geography) were predictors of SNF/IRF use. CONCLUSIONS: COMPASS-TC was not consistently incorporated into real-world clinical practice. The use of a comprehensive transitional care model for patients discharged home after stroke was not associated with SNF or IRF admissions in a 12-month follow-up period. Non-clinical factors predictive of SNF/IRF use suggest potential issues with access to this type of care.

Predicting viral load suppression by self-reported adherence, pharmacy refill counts and real time medication monitoring among people living with HIV in Tanzania.

INTRODUCTION: Monitoring of adherence to antiretroviral treatment (ART) is of utmost importance to prevent treatment failure. Several measures to monitor adherence have been applied in low-resource settings and they all have pros and cons. Our objective was to examine whether any of the following adherence measures is a better predictor of participants' viral load suppression: (1) self-report, (2) pharmacy refill count, (3) Real Time Medication Monitoring (RTMM), (4) a combination of self-report and pharmacy refill count or (5) all three adherence assessment methods combined. METHODOLOGY: This was a post-hoc analysis of data from our 48-week REMIND-HIV randomized controlled trial in which adherence to ART was measured using self-report, pharmacy refill counts and RTMM among ART-experienced adults living with HIV subjectively judged to be nonadherent to ART. For each adherence measure, we calculated sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) for predicting virological failure defined as a viral load (VL) of > 20 copies/mL. To determine at which percentage of adherence the prediction was strongest, we evaluated adherence cut-offs of 80%, 85%, 90%, 95% and 100% using receiver operating characteristic (ROC) curves. VL data were obtained after 48 weeks of follow-up in the trial. RESULTS: A total of 233 people living with HIV (PLHIV) were included in this analysis. When comparing the ability of self-reported adherence with pharmacy refill count and RTMM adherence to predict viral load > 20 copies/ml, self-reported adherence had the lowest sensitivity, ranging from 6 to 17%, but the highest specificity, ranging from 100 to 86%, depending on cut-off values from 80 to 100%. Area under the ROC curves (AUC) were 0.54 for RTMM, 0.56 for pharmacy refill count and 0.52 for self-report, indicating low discriminatory capacity for each of the adherence measures. When we combined the self-report and pharmacy refill count measures, sensitivity increased, ranging from 28 to 57% but specificity decreased, ranging from 83 to 53%. When all three measures were combined, we observed the highest value of sensitivity, ranging from 46 to 92%, and PPV, ranging from 32 to 36%, at high cut-offs ranging from 80 to 100%. Upon combination of three adherence measures, the AUC increased to 0.59. CONCLUSION: Our results show that adherence assessed exclusively by self-report, pharmacy refill count or RTMM were insufficiently sensitive to predict virologic failure. Sensitivity markedly improved by combining all three measures, but the practical feasibility of such an approach would need to be studied.

Fearlessness about death and suicide planning predict lethality of adolescent suicide attempts during and following treatment.

INTRODUCTION: The rate of adolescent suicide attempt has increased drastically over the past 10 years. However, little is known regarding what predicts a more versus less lethal attempt, which is of critical interest to clinicians managing this at-risk population. We sought to extend the study of lethality in adolescents by exploring its relationship with two recognized risk-factors for suicide attempt: fearlessness about death (FAD) and suicide planning. METHODS: Participants (N = 254) were administered measures of FAD and depressive symptoms upon entering intensive outpatient treatment for adolescents exhibiting suicidal thoughts and behaviors. Attempts made between treatment entry and 6 months following discharge (n = 47) were scored on a 4-point ordinal scale of lethality. The resulting continuum ranged from no attempt to attempts of low to moderate levels of lethality. RESULTS: FAD and suicide planning distinguished between levels of lethality of future attempt at the bivariate and multivariate level. FAD's predictive relationship with lethality while controlling for age, sex, depression, and prior attempt diminished when suicide planning was covaried. CONCLUSION: FAD and suicide planning significantly predicted more versus less lethal future attempts in our sample of adolescents in a clinical setting. Our findings suggest that FAD influences the lethality of a future attempt by promoting planning for suicide. More studies are needed to assess whether the brief FAD scale might be a valuable adjunct in the clinical management of youth with suicidal thoughts and behaviors.

Real-world analysis of clinical and economic impact of 21-gene recurrence score (RS) testing in early-stage breast cancer (ESBC) in Ireland.

PURPOSE: Results from TAILOR-X suggest that up to 70% of hormone receptor-positive (HR+) node-negative (N0) ESBC patients (pts) may avoid chemotherapy (CT) with RS ≤ 25. We assess clinical and economic impacts of RS testing on treatment using real-world data. METHODS: From October 2011 to February 2019, a retrospective, cross-sectional observational study was conducted of HR+ N0 ESBC pts who had RS testing in Ireland. Pts were classified low risk (RS ≤ 25) and high risk (RS > 25). Clinical risk was calculated. Data were collected via electronic patient records. Cost data were supplied by the National Healthcare Pricing Regulatory Authority. RESULTS: 963 pts. Mean age is 56 years. Mean tumour size is 1.7 cm. 114 (11.8%), 635 (66%), 211 (22%), 3 (0.2%) pts had G1, G2, G3 and unknown G, respectively. 796 pts (82.8%) low RS, 159 (16.5%) high RS and 8 pts (0.7%) unknown RS. 263 pts (26%) were aged ≤ 50 at diagnosis; 117 (45%) had RS 0-15, 63 (24.5%) 16-20, 39 (15.3%) 21-25 and 40 (15.2%) RS 26-100. 4 pts (1.5%) had unknown RS. Post-RS testing, 602 pts (62.5%) had a change in CT decision; 593 changed to hormone therapy (HT) alone. In total, 262 pts received CT. Of pts receiving CT; 138 (53%) had RS > 25, 124 (47%) had RS ≤ 25. Of pts aged ≤ 50, 153 (58%) had high clinical risk, of whom 28 had RS 16-20. Assay use achieved a 62.5% change in treatment with 73% of pts avoiding CT. This resulted in savings of €4 million in treatment costs. Deducting assay costs, savings of €1.9 million were achieved. CONCLUSION: Over the 8 years of the study, a 62.5% reduction in CT use was achieved with savings of over €1,900,000.

Pregnancy-associated breast cancer: evaluating maternal and foetal outcomes. A national study.

PURPOSE: Pregnancy-associated breast cancer (PABC) is defined as breast cancer diagnosed during the gestational period (gp-PABC) or in the first postpartum year (pp-PABC). Despite its infrequent occurrence, the incidence of PABC appears to be rising due to the increasing propensity for women to delay childbirth. We have established the first retrospective registry study of PABC in Ireland to examine specific clinicopathological characteristics, treatments, and maternal and foetal outcomes. METHODS: This was a national, multi-site, retrospective observational study, including PABC patients treated in 12 oncology institutions from August 2001 to January 2020. Data extracted included information on patient demographics, tumour biology, staging, treatments, and maternal/foetal outcomes. Survival data for an age-matched breast cancer population over a similar time period was obtained from the National Cancer Registry of Ireland (NCRI). Standard biostatistical methods were used for analyses. RESULTS: We identified 155 patients-71 (46%) were gp-PABC and 84 (54%) were pp-PABC. The median age was 36 years. Forty-four patients (28%) presented with Stage III disease and 25 (16%) had metastatic disease at diagnosis. High rates of triple-negative (25%) and HER2+ (30%) breast cancer were observed. We observed an inferior 5-year overall survival (OS) rate in our PABC cohort compared to an age-matched breast cancer population in both Stage I-III (77.6% vs 90.9%) and Stage IV disease (18% vs 38.3%). There was a low rate (3%) of foetal complications. CONCLUSION: PABC patients may have poorer survival outcomes. Further prospective data are needed to optimise management of these patients.