Treating relapsed/refractory mature T- and NK-cell neoplasms with tislelizumab: a multicenter open-label phase 2 study.

Patients with relapsed/refractory (R/R) mature T- and natural killer (NK)-cell neoplasms lack effective treatments after failure of standard therapies. This phase 2 study evaluated the efficacy and safety of the programmed cell death protein 1 inhibitor tislelizumab in these patients. Seventy-seven patients were treated with 200 mg tislelizumab every 3 weeks. Twenty-two patients with extranodal NK-/T-cell lymphomas were enrolled in cohort 1; 44 patients with peripheral T-cell lymphoma (PTCL) were enrolled in cohort 2 (21 patients had PTCL not otherwise specified, 11 patients had angioimmunoblastic T-cell lymphoma, and 12 patients had anaplastic large-cell lymphoma). Cohort 3 comprised 11 patients with cutaneous T-cell lymphoma, of which 8 patients had mycosis fungoides (MF) and 3 had Sézary syndrome. Of the 77 patients, 76.6% had advanced-stage disease, 51.9% had refractory disease, and 49.4% received ≥3 prior systemic regimens. Promising efficacy was observed in cohort 3 (median follow-up [FU], 16.6 months; overall response rate [ORR], 45.5%; complete response [CR], 9.1%; median duration of response [DOR], 11.3 months; median progression-free survival, 16.8 months; median overall survival, not reached). Modest efficacy was observed in cohort 1 (median FU, 8.4 months; ORR, 31.8%; CR, 18.2%; median DOR, not reached) and cohort 2 (median FU, 9.3 months; ORR, 20.5%; CR, 9.1%; median DOR, 8.2 months). Most treatment-related adverse events were grade 1 or 2, and the safety profile was consistent with the known safety profile of tislelizumab. In conclusion, tislelizumab was well tolerated, achieving modest efficacy in R/R mature T- and NK-cell neoplasms, with some long-lasting remissions. This trial was registered at www.clinicaltrials.gov as #NCT03493451.

2-D path following for fixed wing UAV using global fast terminal sliding mode control.

This paper considers the finite time convergence problem of 2-D path following for fixed wing unmanned air vehicle. Firstly, the UAV path following model is divided into an outer guidance loop and an inner control loop. Then, the guidance loop and control loop controllers of the UAV are derived by global fast terminal sliding mode control technique, which is able to guarantee the system state variables converge to expected values in finite time and eliminate the chattering phenomenon caused by the switching control action. Furthermore, the stability of the two-loops system is proven by Lyapunov stability theory. Finally, the simulation results are shown to verify the performance of the proposed method.

Deiters Cells Act as Mechanical Equalizers for Outer Hair Cells.

The outer hair cells in the mammalian cochlea are cellular actuators essential for sensitive hearing. The geometry and stiffness of the structural scaffold surrounding the outer hair cells will determine how the active cells shape mammalian hearing by modulating the organ of Corti (OoC) vibrations. Specifically, the tectorial membrane and the Deiters cell are mechanically in series with the hair bundle and soma, respectively, of the outer hair cell. Their mechanical properties and anatomic arrangement must determine the relative motion among different OoC structures. We measured the OoC mechanics in the cochleas acutely excised from young gerbils of both sexes at a resolution fine enough to distinguish the displacement of individual cells. A three-dimensional finite element model of fully deformable OoC was exploited to analyze the measured data in detail. As a means to verify the computer model, the basilar membrane deformations because of static and dynamic stimulations were measured and simulated. Two stiffness ratios have been identified that are critical to understand cochlear physics, which are the stiffness of the tectorial membrane with respect to the hair bundle and the stiffness of the Deiters cell with respect to the outer hair cell body. Our measurements suggest that the Deiters cells act like a mechanical equalizer so that the outer hair cells are constrained neither too rigidly nor too weakly.SIGNIFICANCE STATEMENT Mammals can detect faint sounds thanks to the action of mammalian-specific receptor cells called the outer hair cells. It is getting clearer that understanding the interactions between the outer hair cells and their surrounding structures such as the tectorial membrane and the Deiters cell is critical to resolve standing debates. Depending on theories, the stiffness of those two structures ranges from negligible to rigid. Because of their perceived importance, their properties have been measured in previous studies. However, nearly all existing data were obtained ex situ (after they were detached from the outer hair cells), which obscures their interaction with the outer hair cells. We quantified the mechanical properties of the tectorial membrane and the Deiters cell in situ.

The MAGNOLIA Trial: Zanubrutinib, a Next-Generation Bruton Tyrosine Kinase Inhibitor, Demonstrates Safety and Efficacy in Relapsed/Refractory Marginal Zone Lymphoma.

PURPOSE: Marginal zone lymphoma (MZL) is an uncommon non-Hodgkin lymphoma with malignant cells that exhibit a consistent dependency on B-cell receptor signaling. We evaluated the efficacy and safety of zanubrutinib, a next-generation selective Bruton tyrosine kinase inhibitor, in patients with relapsed/refractory (R/R) MZL. PATIENTS AND METHODS: Patients with R/R MZL were enrolled in the phase II MAGNOLIA (BGB-3111-214) study. The primary endpoint was overall response rate (ORR) as determined by an independent review committee (IRC) based on the Lugano 2014 classification. RESULTS: Sixty-eight patients were enrolled. After a median follow-up of 15.7 months (range, 1.6 to 21.9 months), the IRC-assessed ORR was 68.2% and complete response (CR) was 25.8%. The ORR by investigator assessment was 74.2%, and the CR rate was 25.8%. The median duration of response (DOR) and median progression-free survival (PFS) by independent review was not reached. The IRC-assessed DOR rate at 12 months was 93.0%, and IRC-assessed PFS rate was 82.5% at both 12 and 15 months. Treatment was well tolerated with the majority of adverse events (AE) being grade 1 or 2. The most common AEs were diarrhea (22.1%), contusion (20.6%), and constipation (14.7%). Atrial fibrillation/flutter was reported in 2 patients; 1 patient had grade 3 hypertension. No patient experienced major hemorrhage. In total, 4 patients discontinued treatment due to AEs, none of which were considered treatment-related by the investigators. CONCLUSIONS: Zanubrutinib demonstrated high ORR and CR rate with durable disease control and a favorable safety profile in patients with R/R MZL.

Risk of in-hospital falls among medications commonly used for insomnia in hospitalized patients.

STUDY OBJECTIVES: To investigate the risk of in-hospital falls among patients receiving medications commonly used for insomnia in the hospital setting. METHODS: Retrospective cohort study of all adult hospitalizations to a large academic medical center from January, 2007 to July, 2013. We excluded patients admitted for a primary psychiatric disorder. Medication exposures of interest, defined by pharmacy charges, included benzodiazepines, non-benzodiazepine benzodiazepine receptor agonists, trazodone, atypical antipsychotics, and diphenhydramine. In-hospital falls were ascertained from an online patient safety reporting system. RESULTS: Among the 225,498 hospitalizations (median age = 57 years; 57.9% female) in our cohort, 84,911 (37.7%) had exposure to at least one of the five medication classes of interest; benzodiazepines were the most commonly used (23.5%), followed by diphenhydramine (8.3%), trazodone (6.6%), benzodiazepine receptor agonists (6.4%), and atypical antipsychotics (6.3%). A fall occurred in 2,427 hospitalizations (1.1%). The rate of falls per 1,000 hospital days was greater among hospitalizations with exposure to each of the medications of interest, compared to unexposed: 3.6 versus 1.7 for benzodiazepines (adjusted hazard ratio [aHR] 1.8, 95%CI 1.6-1.9); 5.4 versus 1.8 for atypical antipsychotics (aHR 1.6, 95%CI 1.4-1.8); 3.0 versus 2.0 for benzodiazepine receptor agonists (aHR 1.5, 95%CI 1.3-1.8); 3.3 versus 2.0 for trazodone (aHR 1.2, 95%CI 1.1-1.5); and 2.5 versus 2.0 for diphenhydramine (aHR 1.2, 95%CI 1.03-1.5). CONCLUSIONS: In this large cohort of hospitalizations at an academic medical center, we found an association between each of the sedating medications examined and in-hospital falls. Benzodiazepines, benzodiazepine receptor agonists, and atypical antipsychotics had the strongest associations.

Identification of Plasma Proteome Signatures Associated With Surgery Using SOMAscan.

OBJECTIVES: To characterize the proteomic signature of surgery in older adults and association with postoperative outcomes. SUMMARY OF BACKGROUND DATA: Circulating plasma proteins can reflect the physiological response to and clinical outcomes after surgery. METHODS: Blood plasma from older adults undergoing elective surgery was analyzed for 1305 proteins using SOMAscan. Surgery-associated proteins underwent Ingenuity Pathways Analysis. Selected surgery-associated proteins were independently validated using Luminex or enzyme-linked immunosorbent assay methods. Generalized linear models estimated correlations with postoperative outcomes. RESULTS: Plasma from a subcohort (n = 36) of the Successful Aging after Elective Surgery (SAGES) study was used for SOMAscan. Systems biology analysis of 110 proteins with Benjamini-Hochberg (BH) corrected P value ≤0.01 and an absolute foldchange (|FC|) ≥1.5 between postoperative day 2 (POD2) and preoperative (PREOP) identified functional pathways with major effects on pro-inflammatory proteins. Chitinase-3-like protein 1 (CHI3L1), C-reactive protein (CRP), and interleukin-6 (IL-6) were independently validated in separate validation cohorts from SAGES (n = 150 for CRP, IL-6; n = 126 for CHI3L1). Foldchange CHI3L1 and IL-6 were associated with increased postoperative complications [relative risk (RR) 1.50, 95% confidence interval (95% CI) 1.21-1.85 and RR 1.63, 95% CI 1.18-2.26, respectively], length of stay (RR 1.35, 95% CI 0.77-1.92 and RR 0.98, 95% CI 0.52-1.45), and risk of discharge to postacute facility (RR 1.15, 95% CI 1.04-1.26 and RR 1.11, 95% CI 1.04-1.18); POD2 and PREOP CRP difference was associated with discharge to postacute facility (RR 1.14, 95% CI 1.04-1.25). CONCLUSION: SOMAscan can identify novel and clinically relevant surgery-induced protein changes. Ultimately, proteomics may provide insights about pathways by which surgical stress contributes to postoperative outcomes.

Comparative Accuracy and Efficiency of Four Delirium Screening Protocols.

BACKGROUND/OBJECTIVES: Systematic screening can improve detection of delirium, but lack of time is often cited as why such screening is not performed. We investigated the time required to implement four screening protocols that use the Ultra-Brief two-item screener for delirium (UB-2) and the 3-Minute Diagnostic Interview for Confusion Assessment Method (CAM)-defined Delirium (3D-CAM), with and without a skip pattern that can further shorten the assessment. Our objective was to compare the sensitivity, specificity, and time required to complete four protocols: (1) full 3D-CAM on all patients, (2) 3D-CAM with skip on all patients, (3) UB-2, followed by the full 3D-CAM in "positives," and (4) UB-2, followed by the 3D-CAM with skip in "positives." DESIGN: Comparative efficiency simulation study using secondary data. SETTING: Two studies (3D-CAM and Researching Efficient Approaches to Delirium Identification (READI)) conducted at a large academic medical center (3D-CAM and READI) and a small community hospital (READI only). PARTICIPANTS: General medicine inpatients, aged 70 years and older (3D-CAM, n = 201; READI, n = 330). MEASUREMENTS: We used 3D-CAM data to simulate the items administered under each protocol and READI data to calculate median administration time per item. We calculated sensitivity, specificity, and total administration time for each of the four protocols. RESULTS: The 3D-CAM and READI samples had similar characteristics, and all four protocols had similar simulated sensitivity and specificity. Mean administration times were 3 minutes 13 seconds for 3D-CAM, 2 minutes 19 seconds for 3D-CAM with skip, 1 minute 52 seconds for UB-2 + 3D-CAM in positives, and 1 minute 14 seconds for UB-2 + 3D-CAM with skip in positives, which was 1 minute 59 seconds faster than the 3D-CAM (P < .001). CONCLUSION: The UB-CAM, consisting of the UB-2, followed in positives by the 3D-CAM with skip pattern, is a time-efficient delirium screening protocol that holds promise for increasing systematic screening for delirium in hospitalized older adults.

Antipsychotics and the Risk of Mortality or Cardiopulmonary Arrest in Hospitalized Adults.

OBJECTIVES: Prior studies in outpatient and long-term care settings demonstrated increased risk for sudden death with typical and atypical antipsychotics. To date, no studies have investigated this association in a general hospitalized population. We sought to evaluate the risk of death or nonfatal cardiopulmonary arrest in hospitalized adults exposed to antipsychotics. DESIGN: Retrospective cohort study. SETTING: Large academic medical center in Boston, Massachusetts. PARTICIPANTS: All hospitalizations between 2010 and 2016 were eligible for inclusion. We excluded those admitted directly to the intensive care unit (ICU), obstetric and gynecologic or psychiatric services, or with a diagnosis of a psychotic disorder. INTERVENTION: Typical and atypical antipsychotic administration, defined by pharmacy charges. MEASUREMENTS: The primary outcome was death or nonfatal cardiopulmonary arrest during hospitalization (composite). RESULTS: Of 150 948 hospitalizations in our cohort, there were 691 total events (515 deaths, 176 cardiopulmonary arrests). After controlling for comorbidities, ICU time, demographics, admission type, and other medication exposures, typical antipsychotics were associated with the primary outcome (hazard ratio [HR] = 1.6; 95% confidence interval [CI] = 1.1-2.4; P = .02), whereas atypical antipsychotics were not (HR = 1.1; 95% CI = .8-1.4; P = .5). When focusing on adults age 65 years and older, however, both typical and atypical antipsychotics were associated with increased risk of death or cardiopulmonary arrest (HR = 1.8; 95% CI = 1.1-2.9; and HR = 1.4; 95% CI = 1.1-2.0, respectively). Sensitivity analyses using a propensity score approach and a cohort of only patients with delirium both yielded similar results. CONCLUSION: In hospitalized adults, typical antipsychotics were associated with increased mortality or cardiopulmonary arrest, whereas atypical antipsychotics were only associated with increased risk among adults age 65 years and older. Providers should be thoughtful when prescribing antipsychotic medications, especially to older adults in settings where data regarding benefit are lacking. J Am Geriatr Soc 68:544-550, 2020.

Ultra-brief Screeners for Detecting Delirium Superimposed on Dementia.

OBJECTIVE: Delirium superimposed on dementia (DSD) is common, morbid, and costly, yet frequently undiagnosed. Our study aimed to develop a brief screening test to improve health care worker recognition of DSD. DESIGN/SETTING/PARTICIPANTS: Older hospitalized adults with dementia were prospectively enrolled from medical and surgical inpatient units of 3 hospitals (2 in Pennsylvania, 1 in Tennessee). MEASURES: The reference standard delirium assessment used Confusion Assessment Method (CAM) criteria and was based on a structured interview including the Mini-Mental State Examination, interviewer observations, and medical record review. To develop the screening test, 1-, 2-, and 3-item combinations from the reference standard assessment were analyzed to determine their sensitivity and specificity in diagnosing delirium presence in a dementia population compared to the reference standard. For multiple-item screeners, error on 1 or more items was considered a positive screen. RESULTS: Overall, 391 older adults with dementia were enrolled (mean age: 83.9 years, 71.1% female), and 95 (24.4%) developed DSD during their hospitalization, based on the reference standard. The best single-item screen for DSD was "What day of the week is it?" with 84% sensitivity [95% confidence interval (CI): 0.75, 0.91] and 41% specificity (CI: 0.35, 0.47). The best 2-item screen was "list the days of the week backwards" and "What day of the week is it?" with 93% sensitivity (CI: 0.85, 0.97) and 30% specificity (CI: 0.25, 0.36). The best 3-item screen was "list the days of the week backwards," "What type of place is this? [hospital]" and "Does the patient appear sleepy?" with 94% sensitivity (CI: 0.87, 0.98) and 42% specificity (CI: 0.36, 0.48). CONCLUSIONS/IMPLICATIONS: We identified a 3-item DSD screener with excellent sensitivity but limited specificity. This screener can be used to quickly rule out DSD in populations with a high prevalence of dementia and is a promising step toward developing efficient tools for DSD recognition among care providers.

Growth of Polystyrene Pillars in Electric Field.

Surface patterning on polymer films, which is a self-assembly process under the action of external and/or internal impetus, has a variety of applications, including drug delivery and flexible electronics. In this work, we study the growth of polystyrene pillars in the electric field for different combinations of annealing temperature, film thickness, and electrode separation (electric field intensity). There are five stages for the growth of the polystyrene pillars for all the configurations used in this work, including a nucleation stage, a linear growth stage, an acceleration stage in the pillar length prior to the contact between the top surface of a pillar and the upper electrode, a radial growth stage after the contact, and a stationary stage without further growth of the pillar. In the linear growth stage, there exist linear relationships between the pillar length and the annealing time and between the square of the pillar diameter and the annealing time. The activation energies for the rate processes controlling the radial growth and the length growth in the linear growth stage are 30.2 and 25.3 kJ/mol, respectively. There are two rate processes controlling the radial growth of the pillars: one is the field-induced flow of polymer through the polymer film to the roots of pillars and the other is the coalescence of pillars. The activation energy for the coalescence is 16.5 kJ/mol. The results obtained in this work offer a practical route to control the geometrical dimensions of polymer pillars through the processing parameters.

Probing hair cell's mechano-transduction using two-tone suppression measurements.

When two sound tones are delivered to the cochlea simultaneously, they interact with each other in a suppressive way, a phenomenon referred to as two-tone suppression (2TS). This nonlinear response is ascribed to the saturation of the outer hair cell's mechano-transduction. Thus, 2TS can be used as a non-invasive probe to investigate the fundamental properties of cochlear mechano-transduction. We developed a nonlinear cochlear model in the time domain to interpret 2TS data. The multi-scale model incorporates cochlear fluid dynamics, organ of Corti (OoC) mechanics and outer hair cell electrophysiology. The model simulations of 2TS show that the threshold amplitudes and rates of low-side suppression are dependent on mechano-transduction properties. By comparing model responses to existing 2TS measurement data, we estimate intrinsic characteristics of mechano-transduction such as sensitivity and adaptation. For mechano-transduction sensitivity at the basal location (characteristic frequency of 17 kHz) at 0.06 nm-1, the simulation results agree with 2TS measurements of basilar membrane responses. This estimate is an order of magnitude higher than the values observed in experiments on isolated outer hair cells. The model also demonstrates how the outer hair cell's adaptation alters the temporal pattern of 2TS by modulating mechano-electrical gain and phase.

Brownian motion and Einstein relation for migration of coffee particles in coffee suspensions.

BACKGROUND: The migration of particles in a liquid plays an important role in determining the stability of the corresponding suspension. The preparation of a cup of coffee involves the migration/dispersion of coffee particles in aqueous solutions. We investigate the Brownian motion of coffee particles in coffee suspensions at different temperatures for three different coffee beans via the migration of the coffee particles of the coffee suspensions in water. RESULTS: The activation energies for the Brownian motion of the coffee particles are in the range 23.5-32.0 kJ mol-1 , relatively independent of the size of the coffee particles used in the present study. The viscosities of the coffee suspensions are measured as a function of temperature and then used to correlate with the gradient-diffusion coefficient for the Brownian motion of the coffee particles. The activation energies of the rate process controlling the viscous flow of the coffee suspensions are in the range 12.7-14.1 kJ mol-1 . CONCLUSION: The correlation between the viscosity and gradient-diffusion coefficient of the coffee suspensions generally follows the Einstein relation. A temperature dependence exists for the viscosity and gradient-diffusion coefficient of the coffee suspensions, which can be used to understand the brewing of coffee at high temperatures with respect to product refinement. © 2019 Society of Chemical Industry.

Development of a Dynamic Multi-Protein Signature of Postoperative Delirium.

Background: Delirium is common, morbid, and costly, yet its biology is poorly understood. We aimed to develop a multi-protein signature of delirium by identifying proteins associated with delirium from unbiased proteomics and combining them with delirium biomarkers identified in our prior work (interleukin [IL]-6 and IL-2). Methods: We used the Successful Aging after Elective Surgery (SAGES) Study of adults age ≥70 undergoing major noncardiac surgery (N = 560; 24% delirium). Plasma was collected preoperatively (PREOP) and on postoperative day 2 (POD2). In a nested matched case-control study involving 12 pairs of delirium cases and no-delirium controls, isobaric tags for relative and absolute quantitation-based (iTRAQ) mass spectrometry proteomics was applied to identify the top set of delirium-related proteins. With these proteins, we then conducted enzyme-linked immunosorbent assay (ELISA) confirmation, and if confirmed, ELISA validation in 75 matched pairs. Multi-marker conditional logistic regression was used to select the "best" PREOP and POD2 models for delirium. Results: We identified three proteins from iTRAQ: C-reactive protein (CRP), zinc alpha-2 glycoprotein (AZGP1), and alpha-1 antichymotrypsin (SERPINA3). The "best" multi-protein models of delirium included: PREOP: CRP and AZGP1 (Bayesian information criteria [BIC]: 93.82, c-statistic: 0.77); and POD2: IL-6, IL-2, and CRP (BIC: 87.11, c-statistic: 0.84). Conclusion: The signature of postoperative delirium is dynamic, with some proteins important before surgery (risk markers) and others at the time of delirium (disease markers). Our dynamic, multi-protein signature for delirium improves our understanding of delirium pathophysiology and may identify patients at-risk of this devastating disorder that threatens independence of older adults.

Relationship of the Duke jeopardy score combined with minimal lumen diameter as assessed by computed tomography angiography to the hemodynamic relevance of coronary artery stenosis.

OBJECTIVES: To study the diagnostic performance of the ratio between the Duke jeopardy score (DJS) and the minimal lumen diameter (MLD) (DJS/MLDCT ratio) as assessed by coronary computed tomographic angiography (CTA) for differentiating functionally significant from non-significant coronary artery stenoses, with reference to invasive fractional flow reserve (FFR). METHODS: Patients who underwent both coronary CTA and FFR measurement during invasive coronary angiography (ICA) within 2 weeks were retrospectively included in the study. Invasive FFR measurement was performed in patients with intermediate to severe coronary stenoseis. DJS/MLDCT ratio and anatomical parameters were recorded. Lesions with FFR ≤0.80 were considered to be functionally significant. RESULTS: One hundred and sixty-one patients with 175 lesions were included into the analysis. Diameter stenosis in CT, area stenosis, plaque burden, lesion length (LL), ICA-based stenosis degree, DJS, LL/MLD4 ratio, DJS/MLA ratio as well as DJS/MLD ratio were all significantly different between hemodynamically significant and non-significant lesions (p<0.05 for all). ROC curve analysis determined the optimal cut-off value for DJS/MLDCT ratio to be 1.96 (area under curve = 0.863, 95 % confidence interval = 0.803-0.910), yielding a high diagnostic accuracy (86.9%, 152/175). CONCLUSIONS: In coronary artery stenoses detected by coronary CTA, the DJS/MLD ratio is able to predict hemodynamic relevance.

Pilot Study of a Two-Step Delirium Detection Protocol Administered By Certified Nursing Assistants, Physicians, and Registered Nurses.

The feasibility and acceptability of a two-step screening protocol for delirium identification was pilot tested. Step 1, a screening tool, comprises two items: "Please tell me the day of the week," and "Please tell me the months of the year backwards starting with December." If either/both items are incorrect, Step 2, a 3-minute diagnostic assessment, follows. Trained researchers enrolled 24 hospitalized older adults and identified 22% to be delirious after a reference standard assessment. Thereafter, physicians and RNs completed the two-step protocol, whereas certified nursing assistants (CNAs) completed the screener only, on the same patients. All three clinical assessments were successfully completed in 100% of enrolled participants and within the target 2-hour time window in 91%. The screener and two-step protocol achieved high sensitivities and specificities in RNs, CNAs, and physicians. Qualitative information on barriers to and facilitators of implementation was also collected. Nurses and other clinicians can feasibly implement this ultra-brief screener and two-step protocol, which holds promise to improve delirium identification. [Journal of Gerontological Nursing, 44(5), 18-24.].

The quantitative link of lung clearance index to bronchial segments affected by bronchiectasis.

In adult patients with cystic fibrosis (CF), the lung clearance index (LCI) derived from the multiple breath washout relates to both acinar and conductive ventilation heterogeneity. The latter component predicts an association between LCI and the number of bronchial segments affected by bronchiectasis. Here, we experimentally demonstrated this association in patients with CF, and also examined an ancillary group of patients with non-CF bronchiectasis. We conclude that lung disease severity in terms of number of bronchial segments results in an associated LCI increase, likely constituting a portion of LCI that cannot be reversed by treatment in patients with CF lung disease.

Antipsychotics and the Risk of Aspiration Pneumonia in Individuals Hospitalized for Nonpsychiatric Conditions: A Cohort Study.

BACKGROUND/OBJECTIVES: Off-label use of antipsychotics is common in hospitals, most often for delirium management. Antipsychotics have been associated with aspiration pneumonia in community and nursing home settings, but the association in hospitalized individuals is unexplored. We aimed to investigate the association between antipsychotic exposure and aspiration pneumonia during hospitalization. DESIGN: Retrospective cohort study. SETTING: Large academic medical center. PARTICIPANTS: All adult hospitalizations between January 2007 and July 2013. We excluded outside hospital transfers, hospitalizations shorter than 48 hours, and psychiatric hospitalizations. MEASUREMENTS: Antipsychotic use defined as any pharmacy charge for an antipsychotic medication. Aspiration pneumonia was defined according to a discharge diagnosis code for aspiration pneumonia not present on admission and validated using chart review. A generalized estimating equation was used to control for 43 potential confounders. RESULTS: Our cohort included 146,552 hospitalizations (median age 56; 39% male). Antipsychotics were used in 10,377 (7.1%) hospitalizations (80% atypical, 35% typical, 15% both). Aspiration pneumonia occurred in 557 (0.4%) hospitalizations. The incidence of aspiration pneumonia was 0.3% in unexposed individuals and 1.2% in those with antipsychotic exposure (odds ratio (OR) = 3.9, 95% confidence interval (CI) = 3.2-4.8). After adjustment, antipsychotic exposure was significantly associated with aspiration pneumonia (adjusted OR = (aOR) = 1.5, 95% CI = 1.2-1.9). Similar results were demonstrated in a propensity-matched analysis and in an analysis restricted to those with delirium or dementia. The magnitude of the association was similar for typical (aOR = 1.4, 95% CI = 0.94-2.2) and atypical (aOR = 1.5, 95% CI = 1.1-2.0) antipsychotics. CONCLUSION: Antipsychotics were associated with greater odds of aspiration pneumonia after extensive adjustment for participant characteristics. This risk should be considered when prescribing antipsychotics in the hospital.

Understanding the relationship between religiosity and caregiver-adolescent communication about sex within African-American families.

Caregiver-adolescent communication about sex plays a critical role in the sexual socialization of youth. Many caregivers, however, do not engage their youth in such conversations, potentially placing them at risk for negative sexual health outcomes. Lack of caregiver-adolescent communication about sex may be particularly harmful for rural African American youth, as they often report early sex initiation and are disproportionately impacted by STIs. Moreover, sexual communication may be particularly challenging for families with strong religious backgrounds, potentially affecting the occurrence and breadth of topics covered during communication. Study aims were to: determine whether there was a relationship between caregiver religiosity and type of topics covered during communication about sex (e.g., general sexual health vs. positive aspects of sexuality) among 435 caregivers of early adolescent, African American youth; and if so, identify factors that might explain how religiosity affects communication about sex. Results indicated that caregiver religiosity was positively associated with communication about general, but not positive aspects of sexuality for caregivers of males. Attitudes towards communication about sex and open communication style mediated the relationship. There was no association between religiosity and communication about sex for caregivers of females. The findings from this study could provide a base to better understand and support the sexual socialization process within religious, African American families.