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.

Development and Validation of an Obstetric Comorbidity Risk Score for Clinical Use.

Background: A comorbidity summary score may support early and systematic identification of women at high risk for adverse obstetric outcomes. The objective of this study was to conduct the initial development and validation of an obstetrics comorbidity risk score for automated implementation in the electronic health record (EHR) for clinical use. Methods: The score was developed and validated using EHR data for a retrospective cohort of pregnancies with delivery between 2010 and 2018 at Kaiser Permanente Northern California, an integrated health care system. The outcome used for model development consisted of adverse obstetric events from delivery hospitalization (e.g., eclampsia, hemorrhage, death). Candidate predictors included maternal age, parity, multiple gestation, and any maternal diagnoses assigned in health care encounters in the 12 months before admission for delivery. We used penalized regression for variable selection, logistic regression to fit the model, and internal validation for model evaluation. We also evaluated prenatal model performance at 18 weeks of pregnancy. Results: The development cohort (n = 227,405 pregnancies) had an outcome rate of 3.8% and the validation cohort (n = 41,683) had an outcome rate of 2.9%. Of 276 candidate predictors, 37 were included in the final model. The final model had a validation c-statistic of 0.72 (95% confidence interval [CI] 0.70-0.73). When evaluated at 18 weeks of pregnancy, discrimination was modestly diminished (c-statistic 0.68 [95% CI 0.67-0.70]). Conclusions: The obstetric comorbidity score demonstrated good discrimination for adverse obstetric outcomes. After additional appropriate validation, the score can be automated in the EHR to support early identification of high-risk women and assist efforts to ensure risk-appropriate maternal care.

Assessing the clinical impact of CYP2C9 pharmacogenetic variation on phenytoin prescribing practice and patient response in an integrated health system.

OBJECTIVE: To assess the impact of CYP2C9 variation on phenytoin patient response and clinician prescribing practice where genotype was unknown during treatment. METHODS: A retrospective analysis of Resource on Genetic Epidemiology Research on Adult Health and Aging cohort participants who filled a phenytoin prescription between 1996 and 2017. We used laboratory test results, medication dispensing records, and medical notes to identify associations of CYP2C9 genotype with phenytoin blood concentration, neurologic side effects, and medication dispensing patterns reflecting clinician prescribing practice and patient response. RESULTS: Among 993 participants, we identified 69% extensive, 20% high-intermediate, 10% low-intermediate, and 2% poor metabolizers based on CYP2C9 genotypes. Compared with extensive metabolizer genotype, low-intermediate/poor metabolizer genotype was associated with increased dose-adjusted phenytoin blood concentration [21.3 pg/mL, 95% confidence interval (CI): 13.6-29.0 pg/mL; P < 0.01] and increased risk of neurologic side effects (hazard ratio: 2.40, 95% CI: 1.24-4.64; P < 0.01). Decreased function CYP2C9 genotypes were associated with medication dispensing patterns indicating dose decrease, use of alternative anticonvulsants, and worse adherence, although these associations varied by treatment indication for phenytoin. CONCLUSION: CYP2C9 variation was associated with clinically meaningful differences in clinician prescribing practice and patient response, with potential implications for healthcare utilization and treatment efficacy.

The Impact of Pharmacy-specific Predictors on the Performance of 30-Day Readmission Risk Prediction Models.

RESEARCH OBJECTIVE: Pharmacists are an expensive and limited resource in the hospital and outpatient setting. A pharmacist can spend up to 25% of their day planning. Time spent planning is time not spent delivering an intervention. A readmission risk adjustment model has potential to be used as a universal outcome-based prioritization tool to help pharmacists plan their interventions more efficiently. Pharmacy-specific predictors have not been used in the constructs of current readmission risk models. We assessed the impact of adding pharmacy-specific predictors on performance of readmission risk prediction models. STUDY DESIGN: We used an observational retrospective cohort study design to assess whether pharmacy-specific predictors such as an aggregate pharmacy score and drug classes would improve the prediction of 30-day readmission. A model of age, sex, length of stay, and admission category predictors was used as the reference model. We added predictor variables in sequential models to evaluate the incremental effect of additional predictors on the performance of the reference. We used logistic regression to regress the outcomes on predictors in our derivation dataset. We derived and internally validated our models through a 50:50 split validation of our dataset. POPULATION STUDIED: Our study population (n=350,810) was of adult admissions at hospitals in a large integrated health care delivery system. PRINCIPAL FINDINGS: Individually, the aggregate pharmacy score and drug classes caused a nearly identical but moderate increase in model performance over the reference. As a single predictor, the comorbidity burden score caused the greatest increase in model performance when added to the reference. Adding the severity of illness score, comorbidity burden score and the aggregate pharmacy score to the reference caused a cumulative increase in model performance with good discrimination (c statistic, 0.712; Nagelkerke R, 0.112). The best performing model included all predictors: severity of illness score, comorbidity burden score, aggregate pharmacy score, diagnosis groupings, and drug subgroups. CONCLUSIONS: Adding the aggregate pharmacy score to the reference model significantly increased the c statistic but was out-performed by the comorbidity burden score model in predicting readmission. The need for a universal prioritization tool for pharmacists may therefore be potentially met with the comorbidity burden score model. However, the aggregate pharmacy score and drug class models still out-performed current Medicare readmission risk adjustment models. IMPLICATIONS FOR POLICY OR PRACTICE: Pharmacists have a great role in preventing readmission, and therefore can potentially use one of our models: comorbidity burden score model, aggregate pharmacy score model, drug class model or complex model (a combination of all 5 major predictors) to prioritize their interventions while exceeding Medicare performance measures on readmission. The choice of model to use should be based on the availability of these predictors in the health care system.

Control of stair ascent and descent with a powered transfemoral prosthesis.

This paper presents a finite state-based control system for a powered transfemoral prosthesis that provides stair ascent and descent capability. The control system was implemented on a powered prosthesis and evaluated by a unilateral, transfemoral amputee subject. The ability of the powered prosthesis to provide stair ascent and descent capability was assessed by comparing the gait kinematics, as recorded by a motion capture system, with the kinematics provided by a passive prosthesis, in addition to those recorded from a set of healthy subjects. The results indicate that the powered prosthesis provides gait kinematics that are considerably more representative of healthy gait, relative to the passive prosthesis, for both stair ascent and descent.

A running controller for a powered transfemoral prosthesis.

This paper describes a running controller for a powered knee and ankle prosthesis. The running controller was implemented on a powered prosthesis prototype and evaluated by a transfemoral amputee subject running on a treadmill at a speed of 2.25 m/s (5.0 mph). The ability of the prosthesis and controller to provide the salient features of a running gait was assessed by comparing the kinematics of running provided by the powered prosthesis to the averaged kinematics of five healthy subjects running at the same speed. This comparison indicates that the powered prosthesis and running controller are able to provide essential features of a healthy running gait.

Immunomodulation of murine collagen-induced arthritis by N, N-dimethylglycine and a preparation of Perna canaliculus.

BACKGROUND: Rheumatoid arthritis (RA) and its accepted animal model, murine collagen-induced arthritis (CIA), are classic autoimmune inflammatory diseases which require proinflammatory cytokine production for pathogenesis. We and others have previously used N, N-dimethylglycine (DMG) and extracts from the New Zealand green-lipped mussel Perna canaliculus (Perna) as potent immunomodulators to modify ongoing immune and/or inflammatory responses. METHODS: In our initial studies, we treated lipopolysaccahride (LPS) stimulated THP-1 monocytes in vitro with increasing concentrations of Perna extract or DMG. Additionally, we treated rat peripheral blood neutrophils with increasing concentrations of Perna extract and measured superoxide burst. In subsequent in vivo experiments, CIA was induced by administration of type II collagen; rats were prophylactically treated with either Perna or DMG, and then followed for disease severity. Finally, to test whether Perna and/or DMG could block or inhibit an ongoing pathologic disease process, we induced CIA in mice and treated them therapeutically with either of the two immunomodulators. RESULTS: Following LPS stimulation of THP-1 monocytes, we observed dose-dependent reductions in TNF-alpha and IL-12p40 production in Perna treated cultures. DMG treatment, however, showed significant increases in both of these cytokines in the range of 0.001-1 microM. We also demonstrate that in vitro neutrophil superoxide burst activity is dose-dependently reduced in the presence of Perna. Significant reductions in disease incidence, onset, and severity of CIA in rats were noted following prophylactic treatment with either of the two immunomodulators. More importantly, amelioration of mouse CIA was observed following therapeutic administration of Perna. In contrast, DMG appeared to have little effect in mice and may act in a species-specific manner. CONCLUSION: These data suggest that Perna, and perhaps DMG, may be useful supplements to the treatment of RA in humans.

Effects of conjugated linoleic acid supplementation on blood lipids and adiposity of rats fed diets rich in saturated versus unsaturated fat.

Conjugated linoleic acid (CLA) may decrease adiposity and improve blood lipid profiles under some conditions. The goal of this study was to determine the effects of CLA supplementation on blood lipid profiles and adiposity of rats fed a diet containing a primarily saturated fat versus a diet containing a primarily unsaturated fat. Twenty-eight male Sprague-Dawley rats were randomly assigned to one of four diets containing coconut oil, coconut oil with CLA, corn oil or corn oil with CLA. After 28 days, blood was collected and serum concentrations of total cholesterol (TC), HDL-cholesterol (HDL-C), and triacylglycerols (TG) were assessed. Food intake, body weights, and epididymal fat pads were measured. No significant differences (p>0.05) were noted among groups for amount of food consumed, weight gained, food efficiency ratio or serum TG concentrations. TC concentrations were lower (p<0.05) in the CLA-supplemented rats that were fed coconut oil but not those consuming corn oil. Serum HDL-C was lower (p<0.05) in rats consuming corn oil but was not significantly different (p>0.05) for CLA supplemented groups. Epididymal fat pads weighed significantly more (p<0.05) in the coconut oil fed group compared to the corn oil fed group, but there was no significant difference (p>0.05) between the corn oil and coconut oil + CLA group. Overall, this study suggests that CLA is more beneficial for control of blood lipids and adiposity when supplemented to a diet rich in saturated versus unsaturated fat.