Evaluation of an outreach programme for patients with COVID-19 in an integrated healthcare delivery system: a retrospective cohort study.

OBJECTIVES: In the first year of the COVID-19 pandemic, health systems implemented programmes to manage outpatients with COVID-19. The goal was to expedite patients' referral to acute care and prevent overcrowding of medical centres. We sought to evaluate the impact of such a programme, the COVID-19 Home Care Team (CHCT) programme. DESIGN: Retrospective cohort. SETTING: Kaiser Permanente Northern California. PARTICIPANTS: Adult members before COVID-19 vaccine availability (1 February 2020-31 January 2021) with positive SARS-CoV-2 tests. INTERVENTION: Virtual programme to track and treat patients with 'CHCT programme'. OUTCOMES: The outcomes were (1) COVID-19-related emergency department visit, (2) COVID-19-related hospitalisation and (3) inpatient mortality or 30-day hospice referral. MEASURES: We estimated the average effect comparing patients who were and were not treated by CHCT. We estimated propensity scores using an ensemble super learner (random forest, XGBoost, generalised additive model and multivariate adaptive regression splines) and augmented inverse probability weighting. RESULTS: There were 98 585 patients with COVID-19. The majority were followed by CHCT (n=80 067, 81.2%). Patients followed by CHCT were older (mean age 43.9 vs 41.6 years, p<0.001) and more comorbid with COmorbidity Point Score, V.2, score ≥65 (1.7% vs 1.1%, p<0.001). Unadjusted analyses showed more COVID-19-related emergency department visits (9.5% vs 8.5%, p<0.001) and hospitalisations (3.9% vs 3.2%, p<0.001) in patients followed by CHCT but lower inpatient death or 30-day hospice referral (0.3% vs 0.5%, p<0.001). After weighting, there were higher rates of COVID-19-related emergency department visits (estimated intervention effect -0.8%, 95% CI -1.4% to -0.3%) and hospitalisation (-0.5%, 95% CI -0.9% to -0.1%) but lower inpatient mortality or 30-day hospice referral (-0.5%, 95% CI -0.7% to -0.3%) in patients followed by CHCT. CONCLUSIONS: Despite CHCT following older patients with higher comorbidity burden, there appeared to be a protective effect. Patients followed by CHCT were more likely to present to acute care and less likely to die inpatient.

Training the next generation of delivery science researchers: 10-year experience of a post-doctoral research fellowship program within an integrated care system.

Introduction: Learning health systems require a workforce of researchers trained in the methods of identifying and overcoming barriers to effective, evidence-based care. Most existing postdoctoral training programs, such as NIH-funded postdoctoral T32 awards, support basic and epidemiological science with very limited focus on rigorous delivery science methods for improving care. In this report, we present the 10-year experience of developing and implementing a Delivery Science postdoctoral fellowship embedded within an integrated health care delivery system. Methods: In 2012, the Kaiser Permanente Northern California Division of Research designed and implemented a 2-year postdoctoral Delivery Science Fellowship research training program to foster research expertise in identifying and addressing barriers to evidence-based care within health care delivery systems. Results: Since 2014, 20 fellows have completed the program. Ten fellows had PhD-level scientific training, and 10 fellows had clinical doctorates (eg, MD, RN/PhD, PharmD). Fellowship alumni have graduated to faculty research positions at academic institutions (9), and research or clinical organizations (4). Seven alumni now hold positions in Kaiser Permanente's clinical operations or medical group (7). Conclusions: This delivery science fellowship program has succeeded in training graduates to address delivery science problems from both research and operational perspectives. In the next 10 years, additional goals of the program will be to expand its reach (eg, by developing joint research training models in collaboration with clinical fellowships) and strengthen mechanisms to support transition from fellowship to the workforce, especially for researchers from underrepresented groups.

Changes in COVID-19 Vaccine Intent Among a Diverse Population of Older Adults, June 2021-February 2022.

Introduction COVID-19 vaccination rates remain suboptimal in the United States. Clinicians and policymakers need to better understand how likely vaccine-hesitant individuals are to ultimately accept vaccination and what is associated with such changes. This study's aims were to 1) describe changes between vaccine intentions and actual uptake from June 2021 through February 2022, and 2) identify modifiable factors associated with vaccine uptake among those with initial hesitancy. Methods This cohort study included a stratified random sample of adults aged 65 years and older in an integrated health care system. The survey, conducted June through August 2021, elicited intent and perceptions regarding COVID-19 vaccination. Subsequent vaccine uptake through February 2022 was analyzed using electronic health records. Results Of 1195 individuals surveyed, 66% responded; 213 reported not yet having received a COVID-19 vaccine and were further analyzed. At baseline, most individuals said they would definitely not (42%) or probably not (5%) get the COVID-19 vaccine or were not sure (26%). During follow-up, 61 individuals (29%) were vaccinated, including 19% of those who initially said they would definitely not be vaccinated. Among vaccine-hesitant individuals, the rate of vaccination was highest for those who initially considered COVID-19 less dangerous than the vaccine (46%) or named short-term side effects (36%) as their most important concern. Conclusions COVID-19 vaccine intent among older adults was malleable during the pandemic's second year, even among those who initially said they would definitely not be vaccinated. Vaccine uptake could be enhanced by increasing awareness of COVID-19 risks and by addressing vaccine side effects.

Development of a healthcare system COVID Hotspotting Score in California: an observational study with prospective validation.

OBJECTIVE: To examine the value of health systems data as indicators of emerging COVID-19 activity. DESIGN: Observational study of health system indicators for the COVID Hotspotting Score (CHOTS) with prospective validation. SETTING AND PARTICIPANTS: An integrated healthcare delivery system in Northern California including 21 hospitals and 4.5 million members. MAIN OUTCOME MEASURES: The CHOTS incorporated 10 variables including four major (cough/cold calls, emails, new positive COVID-19 tests, COVID-19 hospital census) and six minor (COVID-19 calls, respiratory infection and COVID-19 routine and urgent visits, and respiratory viral testing) indicators assessed with change point detection and slope metrics. We quantified cross-correlations lagged by 7-42 days between CHOTS and standardised COVID-19 hospital census using observational data from 1 April to 31 May 2020 and two waves of prospective data through 21 March 2021. RESULTS: Through 30 September 2020, peak cross-correlation between CHOTS and COVID-19 hospital census occurred with a 28-day lag at 0.78; at 42 days, the correlation was 0.69. Lagged correlation between medical centre CHOTS and their COVID-19 census was highest at 42 days for one facility (0.63), at 35 days for nine facilities (0.52-0.73), at 28 days for eight facilities (0.28-0.74) and at 14 days for two facilities (0.73-0.78). The strongest correlation for individual indicators was 0.94 (COVID-19 census) and 0.90 (new positive COVID-19 tests) lagged 1-14 days and 0.83 for COVID-19 calls and urgent clinic visits lagged 14-28 days. Cross-correlation was similar (0.73) with a 35-day lag using prospective validation from 1 October 2020 to 21 March 2021. CONCLUSIONS: Passively collected health system indicators were strongly correlated with forthcoming COVID-19 hospital census up to 6 weeks before three successive COVID-19 waves. These tools could inform communities, health systems and public health officials to identify, prepare for and mitigate emerging COVID-19 activity.

Racial Disparities in COVID-19 Testing and Outcomes : Retrospective Cohort Study in an Integrated Health System.

BACKGROUND: Racial disparities exist in outcomes after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. OBJECTIVE: To evaluate the contribution of race/ethnicity in SARS-CoV-2 testing, infection, and outcomes. DESIGN: Retrospective cohort study (1 February 2020 to 31 May 2020). SETTING: Integrated health care delivery system in Northern California. PARTICIPANTS: Adult health plan members. MEASUREMENTS: Age, sex, neighborhood deprivation index, comorbid conditions, acute physiology indices, and race/ethnicity; SARS-CoV-2 testing and incidence of positive test results; and hospitalization, illness severity, and mortality. RESULTS: Among 3 481 716 eligible members, 42.0% were White, 6.4% African American, 19.9% Hispanic, and 18.6% Asian; 13.0% were of other or unknown race. Of eligible members, 91 212 (2.6%) were tested for SARS-CoV-2 infection and 3686 had positive results (overall incidence, 105.9 per 100 000 persons; by racial group, White, 55.1; African American, 123.1; Hispanic, 219.6; Asian, 111.7; other/unknown, 79.3). African American persons had the highest unadjusted testing and mortality rates, White persons had the lowest testing rates, and those with other or unknown race had the lowest mortality rates. Compared with White persons, adjusted testing rates among non-White persons were marginally higher, but infection rates were significantly higher; adjusted odds ratios [aORs] for African American persons, Hispanic persons, Asian persons, and persons of other/unknown race were 2.01 (95% CI, 1.75 to 2.31), 3.93 (CI, 3.59 to 4.30), 2.19 (CI, 1.98 to 2.42), and 1.57 (CI, 1.38 to 1.78), respectively. Geographic analyses showed that infections clustered in areas with higher proportions of non-White persons. Compared with White persons, adjusted hospitalization rates for African American persons, Hispanic persons, Asian persons, and persons of other/unknown race were 1.47 (CI, 1.03 to 2.09), 1.42 (CI, 1.11 to 1.82), 1.47 (CI, 1.13 to 1.92), and 1.03 (CI, 0.72 to 1.46), respectively. Adjusted analyses showed no racial differences in inpatient mortality or total mortality during the study period. For testing, comorbid conditions made the greatest relative contribution to model explanatory power (77.9%); race only accounted for 8.1%. Likelihood of infection was largely due to race (80.3%). For other outcomes, age was most important; race only contributed 4.5% for hospitalization, 12.8% for admission illness severity, 2.3% for in-hospital death, and 0.4% for any death. LIMITATION: The study involved an insured population in a highly integrated health system. CONCLUSION: Race was the most important predictor of SARS-CoV-2 infection. After infection, race was associated with increased hospitalization risk but not mortality. PRIMARY FUNDING SOURCE: The Permanente Medical Group, Inc.

Suppression of Adipogenesis by 5-Hydroxy-3,6,7,8,3',4'-Hexamethoxyflavone from Orange Peel in 3T3-L1 Cells.

We reported previously that hydroxylated polymethoxyflavones (HPMFs) effectively suppressed obesity in high-fat-induced mouse. In this study, we further investigated the molecular mechanism of action of 5-hydroxy-3,6,7,8,3',4'-hexamethoxyflavone (5-OH-HxMF), one of major HPMFs in orange peel. Treatment of 5-OH-HxMF effectively inhibited lipid accumulation by 55-60% in a dose-dependent manner. The 5-OH-HxMF attenuated adipogenesis through downregulating adipogenesis-related transcription factors such as peroxisome proliferator-activated receptor gamma (PPARγ) and CCAAT/enhancer-binding proteins (C/EBPs), as well as downstream target fatty acid synthase and acetyl-CoA carboxylase (ACC). 5-OH-HxMF activated adenosine monophosphate-activated protein kinase signaling and silent mating type information regulation 1 (SIRTUIN 1 or SIRT1) in 3T3-L1 adipocytes to decrease lipid accumulation. In addition, the inhibition rate of lipid accumulation was compared between 5-OH-HxMF and 3,5,6,7,8,3',4'-heptamethoxyflavone (HpMF). 5-OH-HxMF inhibited lipid accumulation 15-20% more than HpMF did, indicating that hydroxyl group at position 5 can be a key factor in the suppression of adipogenesis.

Human amygdala activation by the sound produced during dental treatment: A fMRI study.

During dental treatments, patients may experience negative emotions associated with the procedure. This study was conducted with the aim of using functional magnetic resonance imaging (fMRI) to visualize cerebral cortical stimulation among dental patients in response to auditory stimuli produced by ultrasonic scaling and power suction equipment. Subjects (n = 7) aged 23-35 years were recruited for this study. All were right-handed and underwent clinical pure-tone audiometry testing to reveal a normal hearing threshold below 20 dB hearing level (HL). As part of the study, subjects initially underwent a dental calculus removal treatment. During the treatment, subjects were exposed to ultrasonic auditory stimuli originating from the scaling handpiece and salivary suction instruments. After dental treatment, subjects were imaged with fMRI while being exposed to recordings of the noise from the same dental instrument so that cerebral cortical stimulation in response to aversive auditory stimulation could be observed. The independent sample confirmatory t-test was used. Subjects also showed stimulation in the amygdala and prefrontal cortex, indicating that the ultrasonic auditory stimuli elicited an unpleasant response in the subjects. Patients experienced unpleasant sensations caused by contact stimuli in the treatment procedure. In addition, this study has demonstrated that aversive auditory stimuli such as sounds from the ultrasonic scaling handpiece also cause aversive emotions. This study was indicated by observed stimulation of the auditory cortex as well as the amygdala, indicating that noise from the ultrasonic scaling handpiece was perceived as an aversive auditory stimulus by the subjects. Subjects can experience unpleasant sensations caused by the sounds from the ultrasonic scaling handpiece based on their auditory stimuli.

Geranyl flavonoid derivatives from the fresh leaves of Artocarpus communis and their anti-inflammatory activity.

Breadfruit (Artocarpus communis) is a widely distributed crop in tropical and subtropical regions of the world. It is used in Southeast Asia and India to treat several inflammatory disorders. The aim of this study was to investigate the presence of anti-inflammatory flavonoids in A. communis leaves. Three new geranyl flavonoids, arcommunol C (1), arcommunol D (3), and 5'-geranyl-3,4,2',4'-tetrahydroxychalcone (5), together with four known compounds, prostratol (2), arcommunol E (4), 3'-geranyl-3,4,2',4'-tetrahydroxydihydrochalcone (6), and 3'-geranyl-3,4,2',4'-tetrahydroxychalcone (7), were isolated from the leaves of A. communis. Compound 4 was isolated for the first time from natural sources. The anti-inflammatory activity of the isolated compounds (1-7) was evaluated by determining their inhibitory activity on the production of proinflammatory mediators in lipopolysaccharide (LPS)-activated RAW 264.7 murine macrophage cells. Compounds 2, 3, and 4 suppressed the LPS-induced production of nitric oxide (NO) in RAW 264.7 cells with IC50 values of 8.13 ± 0.17, 18.45 ± 2.15, and 22.74 ± 1.74 µM, respectively. Furthermore, 2 decreased lipopolysaccharide (LPS)-mediated induction of protein expressions of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) in RAW 264.7 cells. It was also found that 2 suppressed LPS-induced phosphorylation of JNK and p38 mitogen-activated protein kinase (MAPK) signaling.

Effects of micronization on the physico-chemical properties of peels of three root and tuber crops.

BACKGROUND: The aim of this study was to investigate the effect of micronization on the physicochemical properties of the peels of root and tuber crops, including yam (Dioscorea alata L.), taro (Colocasia esculenta L.) and sweet potato (Ipomea batatas L.). Two continuous milling sections, including hammer milling and ball milling, were applied to three samples to obtain micro-sized particles of root and tuber peels. The micronization by ball-milling treatment for 10 h was carried out to investigate the distribution of particle sizes and the changes in physiochemical properties. RESULTS: The results indicate that the peels of three crops appeared to be significantly decreased in particle size after 10 h of ball-milling treatment. Moreover, the ball-milling treatments resulted in the redistribution of fiber components from insoluble fiber to soluble fiber. The micronization treatments decreased the bulk density but increased the solubility and water-holding capacities of the micronized peels. CONCLUSION: Our findings suggested that micronization treatments can improve functional properties of the fiber components of micronized peels, which provide a good source of dietary fiber in food applications.