Pathways explaining racial/ethnic and socio-economic disparities in brain white matter integrity outcomes in the UK Biobank study.

Pathways explaining racial/ethnic and socio-economic status (SES) disparities in white matter integrity (WMI) reflecting brain health, remain underexplored, particularly in the UK population. We examined racial/ethnic and SES disparities in diffusion tensor brain magnetic resonance imaging (dMRI) markers, namely global and tract-specific mean fractional anisotropy (FA), and tested total, direct and indirect effects through lifestyle, health-related and cognition factors using a structural equations modeling approach among 36,184 UK Biobank participants aged 40-70 y at baseline assessment (47% men). Multiple linear regression models were conducted, testing independent associations of race/ethnicity, socio-economic and other downstream factors in relation to global mean FA, while stratifying by Alzheimer's Disease polygenic Risk Score (AD PRS) tertiles. Race (Non-White vs. White) and lower SES predicted poorer WMI (i.e. lower global mean FA) at follow-up, with racial/ethnic disparities in FAmean involving multiple pathways and SES playing a central role in those pathways. Mediational patterns differed across tract-specific FA outcomes, with SES-FAmean total effect being partially mediated (41% of total effect = indirect effect). Furthermore, the association of poor cognition with FAmean was markedly stronger in the two uppermost AD PRS tertiles compared to the lower tertile (T2 and T3: ß±SE: -0.0009 ± 0.0001 vs. T1: ß±SE: -0.0005 ± 0.0001, P < 0.001), independently of potentially confounding factors. Race and lower SES were generally important determinants of adverse WMI outcomes, with partial mediation of socio-economic disparities in global mean FA through lifestyle, health-related and cognition factors. The association of poor cognition with lower global mean FA was stronger at higher AD polygenic risk.

Growth Differentiation Factor 15 and Diet Quality Trajectory Interact to Determine Frailty Incidence among Middle-Aged Urban Adults.

BACKGROUND: Elevated plasma growth differentiation factor 15 (GDF15) and poor diet quality may be associated with increased frailty incidence, although their interactive associations have not been assessed in urban middle-aged adults. OBJECTIVES: We aimed to examine GDF15 and its interactive association with diet quality in relation to frailty incidence among a sample of middle-aged urban adults. METHODS: The relationship between GDF15 and diet quality trajectories in relation to incident frailty was examined in a longitudinal study of participants in the Healthy Aging in Neighborhoods of Diversity across the Life Span (2004-2017). Serum GDF15 concentration and frailty incidence were primary exposure and outcome, respectively. Group-based trajectory models were used to assess diet quality trajectories (≤3 visits/participant, N = 945, N' = 2247 observations) using the Healthy Eating Index 2010 version (HEI-2010), Dietary Inflammatory Index, and mean adequacy ratio (MAR). Cox proportional hazards models were used, testing interactive associations of GDF15 and diet quality trajectories with frail/prefrail incidence (N = 400 frailty-free at first visit, N' = 604 observations, n = 168 incident frail/prefrail). RESULTS: Both elevated GDF15 and lower diet quality trajectories were associated with a lower probability of remaining nonfrail (≤13 y follow-up). Among females, the "high diet quality" HEI-2010 trajectory had a hazard ratio (HR) of 0.15 [95% confidence interval (CI): 0.04, 0.54; P = 0.004; fully adjusted model] when compared with the "low diet quality" trajectory group. Among males only, there was an antagonistic interaction between lower HEI-2010 trajectory and elevated GDF15. Specifically, the HR for GDF15-frailty in the higher diet quality trajectory group (high/medium combined), and among males, was 2.69 (95% CI: 1.06, 6.62; P = 0.032), whereas among the lower diet quality trajectory group, the HR was 0.94 (95% CI: 0.49, 1.80; P = 0.86). Elevated GDF15 was independently associated with frailty among African American adults. CONCLUSIONS: Pending replication, we found an antagonistic interaction between GDF15 and HEI-2010 trajectory in relation to frailty incidence among males.

Pathways explaining racial/ethnic and socio-economic disparities in dementia incidence: the UK Biobank study.

BACKGROUND: Pathways explaining racial/ethnic disparities in dementia risk are under-evaluated. METHODS: We examine those disparities and their related pathways among UK Biobank study respondents (50-74 y, N = 323,483; 3.6% non-White minorities) using a series of Cox proportional hazards and generalized structural equations models (GSEM). RESULTS: After ≤15 years, 5,491 all-cause dementia cases were diagnosed. Racial minority status (RACE_ETHN, Non-White vs. White) increased dementia risk by 24% (HR = 1.24, 95% CI: 1.07-1.45, P = 0.005), an association attenuated by socio-economic status (SES), (HR = 1.12, 95% CI: 0.96-1.31). Total race-dementia effect was mediated through both SES and Life's Essential 8 lifestyle sub-score (LE8LIFESTYLE), combining diet, smoking, physical activity, and sleep factors. SES was inversely related to dementia risk (HR = 0.69, 95% CI: 0.67, 0.72, P < 0.001). Pathways explaining excess dementia risk among racial minorities included 'RACE_ETHN(-) → SES(-) → DEMENTIA', 'RACE_ETHN(-) → SES(-) → Poor cognitive performance, COGN(+) → DEMENTIA' and 'RACE_ETHN(-) → SES(+) → LE8LIFESTYLE(-) → DEMENTIA'. CONCLUSIONS: Pending future interventions, lifestyle factors including diet, smoking, physical activity, and sleep are crucial for reducing racial and socio-economic disparities in dementia.

Tenofovir vaginal film as a potential MPT product against HIV-1 and HSV-2 acquisition: formulation development and preclinical assessment in non-human primates.

Tenofovir (TFV) is an adenosine nucleotide analog with activity against HIV and HSV-2. Secondary analyses of clinical trials evaluating TFV gel as pre-exposure prophylaxis (PrEP) for HIV have shown that gel formulations of TFV provide significant protection against both HIV and HSV-2 acquisition in women who had evidence of use. An alternate quick-dissolving polymeric thin film, to deliver TFV (20 and 40 mg) has been developed as a potential multipurpose technology (MPT) platform. Film formulation was developed based on excipient compatibility, stability, and ability to incorporate TFV doses. Placebo, low dose (20 mg), and high dose (40 mg) films were utilized in these studies. The developed film platform efficiently incorporated the high dose of TFV (40 mg/film), released more than 50% of drug in 15 min with no in vitro toxicity. Pharmacological activity was confirmed in an ex vivo HIV-1 challenge study, which showed a reduction in HIV-1 infection with TFV films. Films were stable at both doses for at least 2 years. These films were found to be safe in macaques with repeated exposure for 2 weeks as evidenced by minimal perturbation to tissues, microbiome, neutrophil influx, and pH. Macaque sized TFV film (11.2 mg) evaluated in a pigtail macaque model showed higher vaginal tissue concentrations of TFV and active TFV diphosphate compared to a 15 mg TFV loaded gel. These studies confirm that TFV films are stable, safe and efficiently deliver the drug in cervicovaginal compartments supporting their further clinical development.

Allostatic Load and Cognitive Function Among Urban Adults in the Healthy Aging in Neighborhoods of Diversity across the Life Span Study.

BACKGROUND: Cross-sectional studies have linked cognition to allostatic load (AL) which reflects multisystem dysregulation from life course exposure to stressors. OBJECTIVE: To examine baseline and changes in AL and their relationships with 11 cognitive function test scores, while exploring health disparities according to sex and race. METHODS: Longitudinal [Visit 1 (2004-2009) and Visit 2 (2009-2013)] data were analyzed from 2,223 Healthy Aging in Neighborhoods of Diversity across the Life Span participants. We calculated AL total score using cardiovascular, metabolic, and inflammatory risk indicators, and applied group-based trajectory modeling to define AL change. RESULTS: Overall and stratum-specific relationships were evaluated using mixed-effects linear regression models that controlled for socio-demographic, lifestyle, and health characteristics. Baseline AL was significantly associated with higher log-transformed Part A Trail Making Test score [Loge (TRAILS A)] (ß= 0.020, p = 0.004) and increasing AL was associated with higher Benton Visual Retention Test score [BVRT] (ß= 0.35, p = 0.002) at baseline, in models that controlled for age, sex, race, poverty status, education, literacy, smoking, drug use, the 2010 healthy eating index and body mass index. Baseline AL and AL change were not related to change in cognitive function between visits. There were no statistically significant interaction effects by sex or race in fully-adjusted models. CONCLUSION: At baseline, AL was associated with worse attention or executive functioning. Increasing AL was associated with worse non-verbal memory or visuo-constructional abilities at baseline. AL was not related to change in cognitive function over time, and relationships did not vary by sex or race.

Longitudinal association of allostatic load with depressive symptoms among urban adults: Healthy Aging in Neighborhoods of Diversity across the Life Span study.

BACKGROUND: Evidence suggests that lifetime exposure to stressful life events and chronic stressors may be linked to geriatric depression. Allostatic load (AL) is considered a mediator of the stress-health relationship and has been linked to psychosocial factors reflecting health disparities. The purpose of this study was to examine the longitudinal associations of AL with depressive symptoms scores among urban adults, before and after stratifying by sex and race. METHODS: Secondary analyses were performed using Visit 1 (2004-2009), Visit 2 (2009-2013) and Visit 3 (2013-2017) data collected on 2298 Healthy Aging in Neighborhoods of Diversity across the Life Span study participants (baseline age: 30-64 y). AL at Visit 1 (ALv1) and z-transformed probability of higher AL trajectory (ALtraj) between Visits 1 and 3 were calculated using cardiovascular, metabolic and inflammatory risk indicators. The 20-item Center for Epidemiologic Studies Depression (CES-D) scale was used to calculate total and domain-specific depressive symptoms scores. Mixed-effects linear models controlled for socio-demographic, lifestyle and health characteristics. RESULTS: In fully adjusted models, a positive cross-sectional relationship was observed between ALv1 and "somatic complaints" depressive symptoms (ß = 0.21, P = 0.006) score at Visit 1, whereas ALtraj was associated with increasing depressive symptoms score (ß = 0.086, P = 0.003) between Visits 1 and 3. An inverse relationship was observed between ALtraj and "positive affect" depressive symptoms score at Visit 1 among women (ß = -0.31, P < 0.0001) and White adults (ß = -0.32, P = 0.004). Among women, ALtraj was also positively related to change in "somatic complaints" depressive symptoms score between Visits 1 and 3 (ß = 0.043, P = 0.020). CONCLUSIONS: Among urban adults, AL may be associated with "somatic complaints" depressive symptoms at baseline. Higher AL trajectories may predict increasing depressive symptoms (overall) and increasing "somatic complaints" depressive symptoms (among women). A higher AL trajectory may be associated with lower "positive affect" depressive symptoms at baseline among women and White adults only.

Pathways explaining racial/ethnic and socio-economic disparities in incident all-cause dementia among older US adults across income groups.

Differential racial and socioeconomic disparities in dementia incidence across income groups and their underlying mechanisms remain largely unknown. A retrospective cohort study examining all-cause dementia incidence across income groups was conducted linking third National Health and Nutrition Examination Surveys (NHANES III) to Centers for Medicare and Medicaid Services-Medicare data over ≤26 y of follow-up (1988-2014). Cox regression and generalized structural equations models (GSEM) were constructed among adults aged≥60 y at baseline (N = 4,592). Non-Hispanic Black versus White (NHW) adults had higher risk of dementia in age and sex-adjusted Cox regression models (HR = 1.34, 95%CI: 1.15-1.55, P < 0.001), an association that was attenuated in the SES-adjusted model (HR = 1.15, 95%CI: 1.01-1.34, P = 0.092). SES was inversely related to dementia risk overall (per Standard Deviation, HR = 0.80, 95% CI:0.69-0.92, P = 0.002, Model 2), mainly within the middle-income group. Within the lowest and middle-income groups and in socio-economic status (SES)-adjusted models, Mexican American participants were at lower all-cause dementia risk compared with their NHW counterparts. GSEM models further detected 3 pathways explaining >55% of the total effect of SES on dementia risk (Total effect = -0.160 ± 0.067, p = 0.022), namely SES→LIFESTYLE→DEMENTIA (Indirect effect (IE) = -0.041 ± 0.014, p = 0.004), SES→LIFESTYLE→COGN→DEMENTIA (IE = -0.006 ± 0.001, p < 0.001), SES→COGN→DEMENTIA(IE = -0.040 ± 0.008, p < 0.001), with the last two remaining significant or marginally significant in the uppermost income groups. Diet and social support were among key lifestyle factors involved in socio-economic disparities in dementia incidence. We provide evidence for modifiable risk factors that may delay dementia onset differentially across poverty-income ratio groups, underscoring their importance for future observational and intervention studies.

Psychotropic medication use and Parkinson's disease risk amongst older women.

OBJECTIVE: To examine associations of antidepressant, anxiolytic and hypnotic use amongst older women (≥65 years) with incident Parkinson's Disease (PD), using data from Women's Health Initiative linked to Medicare claims. METHODS: PD was defined using self-report, first diagnosis, medications and/or death certificates and psychotropic medications were ascertained at baseline and 3-year follow-up. Cox regression models were constructed to calculate adjusted hazard ratios (aHR) with 95% confidence intervals (CI), controlling for socio-demographic, lifestyle and health characteristics, overall and amongst women diagnosed with depression, anxiety and/or sleep disorders (DASD). RESULTS: A total of 53,996 WHI participants (1,756 PD cases)-including 27,631 women diagnosed with DASD (1,137 PD cases)-were followed up for ~14 years. Use of hypnotics was not significantly associated with PD risk (aHR = 0.98, 95% CI: 0.82, 1.16), whereas PD risk was increased amongst users of antidepressants (aHR = 1.75, 95% CI: 1.56, 1.96) and anxiolytics (aHR = 1.48, 95% CI: 1.25, 1.73). Compared to non-users of psychotropic medications, those who used 1 type had ~50% higher PD risk, whereas those who used ≥2 types had ~150% higher PD risk. Women who experienced transitions in psychotropic medication use ('use to non-use' or 'non-use to use') between baseline and 3-year follow-up had higher PD risk than those who did not. We obtained similar results with propensity scoring and amongst DASD-diagnosed women. INTERPRETATION: The use of antidepressants, anxiolytics or multiple psychotropic medication types and transitions in psychotropic medication use was associated with increased PD risk, whereas the use of hypnotics was not associated with PD risk amongst older women.

Sleep and affective disorders in relation to Parkinson's disease risk among older women from the Women's Health Initiative.

OBJECTIVES: To evaluate sleep and affective (mood/anxiety) disorders as clinical predictors of incident Parkinson's disease (PD) among women ≥65 years of age. METHODS: We performed secondary analyses with available data from the Women's Health Initiative Clinical Trials and Observational Study linked to Medicare claims. Sleep, mood and anxiety disorders at baseline were defined using diagnostic codes. Incident PD was defined using self-reported PD, first PD diagnosis, use of PD medications, and/or deaths attributed to PD. Cox regression was applied to estimate hazard ratios (HR) with 95 % confidence intervals (CI), controlling for socio-demographic/lifestyle/health characteristics. Time-to-event was calculated from baseline (1993-1998) to year of PD event, loss to follow-up, death, or December 31, 2018, whichever came first. RESULTS: A total of 53,996 study-eligible WHI participants yielded 1756 (3.25 %) PD cases over ~14.39 (±6.18) years of follow-up. The relative risk for PD doubled among women with affective disorders (HR = 2.05, 95 % CI: 1.84, 2.27), mood disorders (HR = 2.18, 95 % CI: 1.97, 2.42) and anxiety disorders (HR = 1.97, 95 % CI: 1.75, 2.22). Sleep disorders alone (without affective) were not significantly associated with PD risk (HR = 0.85, 95 % CI: 0.69, 1.04), whereas affective disorders alone (without sleep) (HR = 1.93, 95 % CI: 1.72, 2.17) or in combination with sleep disorders (HR = 2.18, 95 % CI: 1.85, 2.56) were associated with twice the PD risk relative to no sleep/affective disorders. LIMITATIONS: Observational design; Selection bias; Information bias; Generalizability. CONCLUSIONS: Among older women, joint sleep/affective disorders and affective disorders alone are strong clinical predictors of incident PD over 14 years.

Association of Serum Antioxidant Vitamins and Carotenoids With Incident Alzheimer Disease and All-Cause Dementia Among US Adults.

BACKGROUND AND OBJECTIVES: Serum antioxidant vitamins and carotenoids may protect against neurodegeneration with age. We examined associations of these nutritional biomarkers with incident all-cause and Alzheimer disease (AD) dementia among US middle-aged and older adults. METHODS: Using data from the third National Health and Nutrition Examination Surveys (1988-1994), linked with Centers for Medicare & Medicaid follow-up data, we tested associations and interactions of serum vitamins A, C, and E and total and individual serum carotenoids and interactions with incident AD and all-cause dementia. Cox proportional hazards regression models were conducted. RESULTS: After ≤26 years follow-up (mean 16-17 years, 7,283 participants aged 45-90 years at baseline), serum lutein+zeaxanthin was associated with reduced risk of all-cause dementia (65+ age group), even in the lifestyle-adjusted model (per SD: hazard ratio [HR] 0.93, 95% CI 0.87-0.99; p = 0.037), but attenuated in comparison with a socioeconomic status (SES)-adjusted model (HR 0.92, 95% CI 0.86-0.93; p = 0.013). An inverse relationship was detected between serum ß-cryptoxanthin (per SD increase) and all-cause dementia (45+ and 65+) for age- and sex-adjusted models (HR 0.86, 95% CI 0.80-0.93; p < 0.001 for 45+; HR 0.86, 95% CI 0.80-0.93; p = 0.001 for 65+), a relationship remaining strong in SES-adjusted models (HR 0.89, 95% CI 0.82-0.96; p = 0.006 for 45+; HR 0.88, 95% CI 0.81-0.96; p = 0.007 for 65+), but attenuated in subsequent models. Antagonistic interactions indicate putative protective effects of 1 carotenoid may be observed at lower levels other carotenoids or antioxidant vitamin. DISCUSSION: Incident all-cause dementia was inversely associated with serum lutein+zeaxanthin and ß-cryptoxanthin levels. Further studies with time-dependent exposures and randomized trials are needed to test neuroprotective effects of supplementing the diet with select carotenoids. CLASSIFICATION OF EVIDENCE: This study provides Class II evidence that incident all-cause dementia was inversely associated with serum lutein+zeaxanthin and ß-cryptoxanthin levels.

Admission glycemic gap in the assessment of patients with intracerebral hemorrhage.

BACKGROUND: Intracerebral hemorrhage (ICH) is the most common type of hemorrhagic stroke. Glycemic gap, determined by the difference between glucose and the HbA1c-derived average glucose, predicts poor outcomes in various clinical settings. Our main objective was to evaluate association of some admission factors and outcomes in relation to admission glycemic gap (AGG) in patients with ICH. METHODS: We retrospectively analyzed 506 adult patients with ICH between 2014 and 2019. AGG was defined as A1c-derived average glucose (28.7×HbA1c-46.7) subtracted from admission glucose. Admission factors and hospital outcomes indicative of poor outcome (i.e. death, gastrostomy tube, tracheostomy, and discharge status) were compared between patients with elevated (greater than 80 mg/dL) vs. non-elevated (less than or equal-to 80 mg/dL) AGG. Pearson chi-square test was used for independence, and multivariate analysis was used for association. SPSS and excel were used for all data analysis. RESULTS: We found that 67 of 506 (13%) ICH patients had elevated AGG with a mean of 137.3 mg/dL compared to 439 (87%) non-elevated AGG with a mean of 12.6 mg/dL. While mean and standard deviation values for age, weight,and body mass index were comparable between groups, the elevated AGG group had significantly higher admission glucose (286.1 ± 84.3 vs. 140.1 ± 42.5, p < 0.001), higher lactic acid (3.26 ± 2.04 mmol/L vs. 1.99 ± 1.33 mmol/L, p < 0.001), lower Glasgow Coma Scale (GCS) scores (7.70 ± 4.28 vs. 11.24 ± 4.14, p < 0.001), and higher ICH score (median 3, IQR 2-4 vs. median 1, IQR 0-3, p < 0.001). Higher AGG was associated with an increased likelihood of mechanical ventilation, and in-hospital mortality (74.6% vs. 38.3% and 47.8% vs. 15.0% respectively, p < 0.001). Placements of tracheostomy and gastrostomy were similar between the two groups (13.4% vs. 11.8%, p = 0.69% and 1.5% and 4.6%, p = 0.34 respectively). The higher AGG group had a more common poor discharge outcome to either long-term acute care, skilled nursing facility, and/or hospice (65.7% vs. 42.6%, p < 0.001). Hospital cost and length of hospitalization did not differ significantly. Although AGG was not an independent predictor of poor outcome, multivariate analysis showed it was significantly associated with poor outcome while admission glucose was not (p < 0.001 vs. p = 0.167). CONCLUSION: Elevated AGG was associated with worse GCS and ICH scores on admission, as well as need for mechanical ventilation, in hospital mortality and poor discharge status. Elevated AGG has value in prediction of outcome, but existing understanding is limited.

Caregiver Status and Diet Quality in Community-Dwelling Adults.

OBJECTIVE: We investigated cross-sectional and longitudinal associations of diet quality with middle-aged caregiver status. METHODS: Caregiving in the Healthy Aging in Neighborhoods of Diversity across the Life Span (HANDLS) study (57.7% women, 62% African American (AA)) was measured at waves 3 (2009-2013) and 4 (2013-2017) (mean follow-up time 4.1 years). Diet quality was assessed by the Healthy Eating Index 2010 (HEI-2010) derived from two separate 24 h diet recalls. Multivariable ordinary least square regression was performed for cross-sectional analyses of the association of wave 4 caregiving with wave 4 HEI-2010. Wave 3 caregiving was examined both cross-sectionally and with annual rate of change in HEI using mixed-effects linear regression Models. Multivariable models were adjusted for age, sex, and poverty status. RESULTS: Cross-sectional analyses at wave 4 demonstrate an inverse association of frequent caregiving ("Daily or Weekly" vs. "Never") for grandchildren with HEI-2010 total score (i.e., lower diet quality) among Whites (ß = -2.83 ± 1.19, p = 0.03, Model 2) and AAs (ß = -1.84 ± 0.79, p = 0.02,). The "cross-sectional" analysis pertaining to grandchildren caregiving frequency suggested that frequent caregiving (i.e., "Daily or Weekly" vs. "Never" (ß = -2.90 ± 1.17, p = 0.04)) only among Whites was inversely related to HEI-2010 total score. Total HEI-2010 score was also related to caring (Model 1), for the elderly over "5 years vs. Never" among Whites (-7.31 ± 3.54, p = 0.04, Model 2). Longitudinally, we found slight potential improvement in diet quality over time ("Daily or Weekly" vs. Never by TIME interaction: +0.88 ± 0.38, p = 0.02) with frequent caregiving among Whites, but not so among AAs. CONCLUSIONS: Frequent caring for grandchildren had an inverse relationship with the diet quality of White and AA urban middle-aged caregivers, while caring for elderly was inversely linked to diet quality among Whites only. Longitudinal studies should address the paucity of research on caregivers' nutritional quality.

Corrigendum: Vitamin D, Folate, and Cobalamin Serum Concentrations Are Related to Brain Volume and White Matter Integrity in Urban Adults.

[This corrects the article DOI: 10.3389/fnagi.2020.00140.].

Antimicrobial stewardship solutions with a smart innovative tool.

BACKGROUND: Antimicrobial consumption has been increasing lately. Hence, effective strategies are required to control antimicrobial use and decrease the development of antimicrobial resistance. OBJECTIVE: To evaluate the impact of the use of a mobile app on the implementation of antimicrobial stewardship program (ASP) interventions. METHODS: This was a longitudinal study conducted at El-Nile Badrawi Hospital in Cairo, Egypt, on inpatients receiving antimicrobials from January 2018 to December 2019. The study included 2 phases: the preimplementation phase, which included a paper-based ASP developed according to the Centers for Disease Control and Prevention Core Elements of Hospital Antibiotic Stewardship Programs 2014, and the mobile app phase where the MEDIcare Pro mobile app was developed and used in ASP intervention implementation. The study outcomes were antimicrobial consumption and cost, length of hospital and intensive care unit (ICU) stay, 30-day mortality rate and readmission rate, and detection of drug-related problems (DRPs). RESULTS: The mobile app statistically significantly decreased antimicrobial consumption from 75.1 defined daily dose (DDD)/100 bed-days in the preimplementation phase to 64.65 DDD/100 bed-days in the mobile app phase, with a total cost savings of E£1,237,476. There was a significant reduction in the length of ICU stay, with a mean difference of 1.63 days between the 2 phases, but no significance was detected regarding length of hospital stay or readmission rate. There was a statistically significant decrease in mortality rate from 1.17% in the preimplementation phase to 0.83% in the mobile app phase (P = 0.02). The frequency of DRPs detected by pharmacists statistically significantly increased from 0.54/100 bed-days in the preimplementation phase to 3.23/100 bed-days in the mobile app phase. CONCLUSION: The use of a mobile app was found to be effective, applicable, and usable in guiding health professionals on rational antimicrobial use.

Preparation and characterization of 96-well microplates coated with molecularly imprinted polymer for determination and biosimilarity assessment of recombinant human erythropoietin.

Synthesis and applications of molecularly imprinted polymers (MIP) are rapidly growing. In this study, a biomimetic MIP was prepared through silanes polymerization on the surface of 96-well microplates using recombinant human erythropoietin-alfa (rhEPO) as a template molecule. The rhEPO was immobilized onto the plate surface using bi-functional cross-linker and a thin imprinted layer following sol-gel procedure was constructed. After template extraction, uniform three-dimensional cavities compatible with the configuration of rhEPO were obtained. The rhEPO-MIP preparation was optimized using 2-level factorial design and response surface design where polymerization time and interactions between the different variable were found to be the most significant factors. Size-exclusion chromatography (SEC) was used to monitor the stability of the rhEPO under the investigated polymerization conditions. Determination of rhEPO using the MIP microplate showed good dynamic response fitting to the 4 PL regression model (0.9962) over a concentration range of 10.00 - 100.00 ng mL-1. Adsorption of rhEPO onto MIP followed the Langmuir isotherm model (r = 0.9957, χ2 =0.02786) with pseudo-second-order kinetics (r = 0.9984). The surface of the rhEPO-MIP was characterized using scanning electron microscopy (SEM) while step-by-step surface modification was tracked using Fourier transform infrared (FTIR) spectroscopy. The rhEPO-MIP was able to distinguish between the rhEPO-alfa template and modified rhEPO molecules; rhEPO-beta, hyperglycosylated and pegylated forms (imprinting factors < 2) and in the commonly used formulation additive human serum albumin (HSA) (R% = 113.96 -95.22%). The rhEPO-MIP was applied to compare the receptor-binding pattern to rhEPO and its biosimilars / structural analogues. The results were cross-validated using the conventional assay protocol (RP-HPLC and ELISA) and an acceptable correlation was observed with RP-HPLC (maximum deviation is 7.78%). This work confirmed the applicability of rhEPO-MIP with its unique binding features for batch release, stability and biosimilarity assessment as well as subsequent evaluation of batch-to-batch consistency during bioproduction of target analytes.

Regional variation in outcomes and healthcare resources utilization in, emergency department visits for syncope.

BACKGROUND: Management of patients with syncope lacks standardization. We sought to assess regional variation in hospitalization rates and resource utilization of patients with syncope. METHODS: We identified adults with syncope using the Nationwide Emergency Department Sample from years 2006 to 2014. Demographics and comorbidity characteristics were compared across geographic regions in the US. Multiple regression was conducted to compare outcomes. RESULTS: 9,132,176 adults presented with syncope. Syncope in the Northeast (n = 1,831,889) accounted for 20.1% of visits; 22.6% in the Midwest (n = 2,060,940), 38.5% in the South (n = 3,527,814) and 18.7% in the West (n = 1,711,533). Mean age was 56 years with 57.7% being female. The Northeast had the highest risk-adjusted hospitalization rate (24.5%) followed by the South (18.6%, ORadj 0.58; 95% CI 0.52-0.65, p < 0.001), the Midwest (17.2%, ORadj 0.51; 95% CI 0.46-0.58, p < 0.001) and West (15.8%, ORadj 0.45; 95% CI 0.39-0.51, p < 0.001). Risk-adjusted rates of syncope hospitalizations significantly declined from 25.8% (95% CI 24.8%-26.7%) in 2006 to 11.7% (95% CI 11.0%-12.5%) in 2014 (Ptrend < 0.001). The Northeast had the lowest risk-adjusted ED (Emergency Department) service charges per visit ($3320) followed by the Midwest ($4675, IRRadj 1.41; 95% CI 1.30-1.52, p < 0.001), the West ($4814, IRRadj 1.45; 95% CI 1.31-1.60, p < 0.001) and South ($4969, IRRadj 1.50; 95% CI 1.38-1.62, p < 0.001). Service charges increased from $3047/visit (95% CI $2912-$3182) in 2006 to $6267/visit (95% CI $5947-$6586) in 2014 (Ptrend < 0.001). CONCLUSIONS: Significant regional variability in hospitalization rates and ED service charges exist among patients with syncope. Standardizing practices may be needed to reduce variability.

5-Axis CNC Micromilling for Rapid, Cheap, and Background-Free NMR Microcoils.

The superior mass sensitivity of microcoil technology in nuclear magnetic resonance (NMR) spectroscopy provides potential for the analysis of extremely small-mass-limited samples such as eggs, cells, and tiny organisms. For optimal performance and efficiency, the size of the microcoil should be tailored to the size of the mass-limited sample of interest, which can be costly as mass-limited samples come in many shapes and sizes. Therefore, rapid and economic microcoil production methods are needed. One method with great potential is 5-axis computer numerical control (CNC) micromilling, commonly used in the jewelry industry. Most CNC milling machines are designed to process larger objects and commonly have a precision of >25 µm (making the machining of common spiral microcoils, for example, impossible). Here, a 5-axis MiRA6 CNC milling machine, specifically designed for the jewelry industry, with a 0.3 µm precision was used to produce working planar microcoils, microstrips, and novel microsensor designs, with some tested on the NMR in less than 24 h after the start of the design process. Sample wells could be built into the microsensor and could be machined at the same time as the sensors themselves, in some cases leaving a sheet of Teflon as thin as 10 µm between the sample and the sensor. This provides the freedom to produce a wide array of designs and demonstrates 5-axis CNC micromilling as a versatile tool for the rapid prototyping of NMR microsensors. This approach allowed the experimental optimization of a prototype microstrip for the analysis of two intact adult Daphnia magna organisms. In addition, a 3D volume slotted-tube resonator was produced that allowed for 2D 1H-13C NMR of D. magna neonates and exhibited 1H sensitivity (nLODω600 = 1.49 nmol s1/2) close to that of double strip lines, which themselves offer the best compromise between concentration and mass sensitivity published to date.

The Relationship of Diet Quality with Proportion of Daily Energy Contributed by Sandwiches Varies by Age over Adulthood in Racially and Socioeconomically Diverse Adults.

Sandwiches are considered a staple in diets of United States adults. Previous research with Healthy Aging in Neighborhoods of Diversity across the Life Span study participants revealed that 16% consume a sandwich dietary pattern providing with 44% of their daily energy. Yet, little is known about the effect of sandwiches on diet quality over time. The study objectives were to determine the relationship of energy contributed by sandwiches to diet quality in this socioeconomically and racially diverse sample categorized by age (<50 years and ≥50 years at baseline) and to describe patterns of sandwich consumption over ~12 years. The analyses included a series of linear mixed-effects regression models, with age as the time variable centered at 50 years. In each model, the main outcome was Healthy Eating Index-2010 score with up to three scores, while the main predictor was % total energy from sandwiches (0, >0-20%, >20%) measured concurrently at each visit. Diet quality of older men with income <125% poverty improved over time for those consuming >0-20% and >20% energy from sandwiches compared to young women with incomes >125% poverty who were non-reporters of sandwiches (ß ± SE: 10.93 ± 5.27, p = 0.01; 13.11 ± 4.96, p = 0.01, respectively). The three most common sandwich types reported, in descending order, were cold cuts, beef, and poultry.

Aspects of Dietary Diversity Changes across Adulthood in Racially Diverse Adults.

Knowledge of various aspects of dietary diversity (DD)-an essential healthful dietary component-across adulthood is limited. This study examined three DD aspects over time in racially diverse adults. Participants were from the National Institute on Aging, Healthy Aging in Neighborhoods of Diversity across the Life Span study. DD measures were calculated at baseline (N = 2177), and first and second examination follow-ups (N = 2140 and N = 2066, respectively) using two 24-h recalls. The count was based on the consumption of ≥50% of an equivalent from 21 food groups. Evenness was derived using the Berry-Index adjusted by the food's health value; dissimilarity, by Mahalanobis Distance. Mixed-effects linear regression models were conducted to test changes in DD across adulthood, adjusting for sex, race, poverty status and education as fixed effects, and adjusting for smoking, age and energy as time-dependent variables. Only dissimilarity showed significant interactions of time × race (p = 0.0005), and time × poverty status (p = 0.0325), indicating a slower rate of increase over time in dissimilarity scores among Whites compared with African-Americans and those with income >125% poverty versus <125% poverty. A significant interaction between time×energy (p < 0.0001) was noted for both evenness and dissimilarity scores. To our knowledge, this is the first study to document the differential change in dissimilarity scores by race and income over time.

Vitamin D, Folate, and Cobalamin Serum Concentrations Are Related to Brain Volume and White Matter Integrity in Urban Adults.

Background and objectives: Lower vitamin status has been linked to cognitive deficits, pending mechanistic elucidation. Serum 25-hydroxyvitamin D [25(OH)D], folate and cobalamin were explored against brain volumes and white matter integrity (WMI). Methods: Three prospective waves from Healthy Aging in Neighborhoods of Diversity Across the Life Span (HANDLS) study were used [Baltimore, City, MD, 2004-2015, N = 183-240 urban adults (Agev1: 30-64 years)]. Serum vitamin 25-hydroxyvitamin D [25(OH)D], folate and cobalamin concentrations were measured at visits 1 (v1: 2004-2009) and 2 (v2: 2009-2013), while structural and diffusion Magnetic Resonance Imaging (sMRI/dMRI) outcomes were measured at vscan: 2011-2015. Top 10 ranked adjusted associations were corrected for multiple testing using familywise Bonferroni (FWER <0.05) and false discovery rates (FDR, q-value < 0.10). Results: We found statistically significant (FWER < 0.05; ß±SE) direct associations of 25(OH)D(v1) with WM volumes [overall: +910 ± 336/males: +2,054 ± 599], occipital WM; [overall: +140 ± 40, males: +261 ± 67 and Agev1 > 50 years: +205 ± 54]; parietal WM; [overall: +251 ± 77, males: +486 ± 129 and Agev1 > 50 years: +393 ± 108] and left occipital pole volume [overall: +15.70 ± 3.83 and above poverty: 19.0 ± 4.3], findings replicated for 25(OH)D (v2-v1) annualized exposure, which was also linked with greater WMI (fractional anisotropy, FA) in the anterior limb of the internal capsule (ALIC); FWER < 0.05 [Overall: +0.0020 ± 0.0004; Whites: +0.0024 ± 0.0004] and in the cingulum (hippocampus) [Overall: +0.0016 ± 0.0004]. Only trends were detected for cobalamin exposures (q < 0.10), while serum folate (v1) was associated with lower mean diffusivity (MD) in ALIC, reflecting greater WMI, overall. Conclusions: Among urban adults, serum 25(OH)D status and increase were consistently linked to larger occipital and parietal WM volumes and greater region-specific WMI. Pending longitudinal replication of our findings, randomized controlled trials of vitamin D supplementation should be conducted against brain marker outcomes.