Shared longitudinal health records for clinical and population health

The ability of a health information exchange (HIE) to consolidate information, collected from multiple, disparate information systems, into a single, person-centric health record can provide a comprehensive and longitudinal representation of an individual's medical history. Shared, longitudinal health records can be leveraged to enhance the delivery of individual clinical care and provide opportunities to improve health outcomes at the population level. This chapter describes the clinical benefits imparted by the shared health record (SHR) component an HIE infrastructure. It also characterizes the potential public health benefits of the aggregate level, population health indicators calculated, stored, and distributed by a health management information system (HMIS) component. Tools for visualizing health indicators from the HMIS, including disease surveillance systems developed during the COVID-19 pandemic, are also described. Postpandemic components such as the SHR and HMIS will likely play critical roles in strengthening health information infrastructures in states and nations. © 2023 Elsevier Inc. All rights reserved.

A Randomized, Double-Blind, Placebo-Controlled Phase II Study to Evaluate the Efficacy and Safety of Ivarmacitinib (SHR0302) in Adult Patients with Moderate to Severe Alopecia Areata.

BACKGROUND: Alopecia areata (AA) is a CD8+ T cell mediated autoimmune disease characterized by non-scarring hair loss. Ivarmacitinib, a selective oral Janus kinase 1 (JAK1) inhibitor, may interrupt certain cytokine signaling implicated in the pathogenesis of AA. OBJECTIVE: To evaluate the efficacy and safety of ivarmacitinib in adult AA patients who have ≥25% scalp hair loss. METHODS: Eligible patients were randomized 1:1:1:1 to receive ivarmacitinib 2 mg, 4 mg, or 8 mg QD or placebo for 24 weeks. The primary endpoint was percentage change from baseline in Severity of Alopecia Tool (SALT) score at week 24. RESULTS: A total of 94 patients were randomized. At week 24, the least squares mean (LSM) difference in percentage change from baseline in SALT score for ivarmacitinib 2 mg,4 mg, 8 mg, and placebo groups were -30.51% (90% confidence interval [CI]: -45.25, -15.76), -56.11% (90% CI: -70.28, -41.95), -51.01% (90% CI: -65.20, -36.82) and -19.87% (90% CI: -33.99, -5.75), respectively. Two SAEs, follicular lymphoma, and COVID-19 pneumonia were reported. LIMITATIONS: Small sample size limits the generalizability of the results. CONCLUSION: Treatment with ivarmacitinib 4 mg and 8 mg doses in moderate and severe AA patients for 24 weeks was efficacious and generally tolerated.

Quantifying Social Interventions for Combating COVID-19 via a Symmetry-Based Model.

The COVID-19 pandemic has revealed new features in terms of substantial changes in rates of infection, cure, and death as a result of social interventions, which significantly challenges traditional SEIR-type models. In this paper we developed a symmetry-based model for quantifying social interventions for combating COVID-19. We found that three key order parameters, separating degree (S) for susceptible populations, healing degree (H) for mild cases, and rescuing degree (R) for severe cases, all display logistic dynamics, establishing a novel dynamic model named SHR. Furthermore, we discovered two evolutionary patterns of healing degree with a universal power law in 23 areas in the first wave. Remarkably, the model yielded a quantitative evaluation of the dynamic back-to-zero policy in the third wave in Beijing using 12 datasets of different sizes. In conclusion, the SHR model constitutes a rational basis by which we can understand this complex epidemic and policymakers can carry out sustainable anti-epidemic measures to minimize its impact.

Fall of viral and bacterial pneumonia hospitalizations following COVID-19 pandemic mitigation strategies: a central Italian Region retrospective study.

Community-Acquired Pneumonia (CAP) represents one of the first causes of hospitalization and death in the elderly all over the world and weighs heavily on public health system. Since the beginning of the COVID-19 (CoronaVirus Disease-19) pandemic, everybody's behavior was forced to change, as the result of a global lockdown strategy and the obligation of using personal protection equipment (PPE). We aimed to evaluate how the mitigation strategies adopted to fight SARS-CoV-2 (Severe Acute Respiratory Coronavirus Syndrome 2) infection have influenced hospitalizations due to CAP in two different Local Health Boards (LHBs) of central Italy. We considered two main periods of observation: before and after the national start of lockdown, in two Abruzzo's LHBs. We analyzed 19,558 hospital discharge records of bacterial and viral CAP. Excluding SARS-CoV2 infection, a significant decrease in CAP hospitalizations was observed. Through the analysis of Diagnosis Related Group (DRG) values, we highlighted a significant saving of founds for the Regional Health Service. The enactment of social distancing measures to contain COVID-19 spread, brought down admissions for bacterial and viral pneumonia. Our study emphasizes that costs for hospitalizations due to CAP could be drastically reduced by mask wearing and social distancing.

Sacubitril/Valsartan and Ivabradine Attenuate Left Ventricular Remodelling and Dysfunction in Spontaneously Hypertensive Rats: Different Interactions with the Renin-Angiotensin-Aldosterone System.

This study investigated whether sacubitril/valsartan and ivabradine are able to prevent left ventricular (LV) fibrotic remodelling and dysfunction in a rat experimental model of spontaneous hypertension (spontaneously hypertensive rats, SHRs) and whether this potential protection is associated with RAAS alterations. Five groups of three-month-old male Wistar rats and SHRs were treated for six weeks as follows: untreated Wistar controls, Wistar plus sacubitril/valsartan, SHR, SHR plus sacubitril/valsartan, and SHR plus ivabradine. The SHRs developed a systolic blood pressure (SBP) increase, LV hypertrophy and fibrosis, and LV systolic and diastolic dysfunction. However, no changes in serum RAAS were observed in SHRs compared with the controls. Elevated SBP in SHRs was decreased by sacubitril/valsartan but not by ivabradine, and only sacubitril/valsartan attenuated LV hypertrophy. Both sacubitril/valsartan and ivabradine reduced LV collagen content and attenuated LV systolic and diastolic dysfunction. Sacubitril/valsartan increased the serum levels of angiotensin (Ang) II, Ang III, Ang IV, Ang 1-5, Ang 1-7, and aldosterone, while ivabradine did not affect the RAAS. We conclude that the SHR is a normal-to-low serum RAAS model of experimental hypertension. While the protection of the hypertensive heart in SHRs by sacubitril/valsartan may be related to an Ang II blockade and the protective Ang 1-7, the benefits of ivabradine were not associated with RAAS modulation.

Angiotensin System Modulations in Spontaneously Hypertensive Rats and Consequences on Erythrocyte Properties; Action of MLN-4760 and Zofenopril.

Various pathologies (COVID-19 including) are associated with abnormalities in erythrocyte properties. Hypertension represents an unfavorable condition for erythrocyte quality and is the most prevalent risk factor in COVID-19 patients. ACE2 downregulation that is typical of these patients can further deteriorate cardiovascular health; however, its consequences on erythrocyte properties are not known yet. The aim was to investigate the effect of ACE2 inhibition and the potential beneficial effect of zofenopril on erythrocytes in spontaneously hypertensive rats. ACE2 inhibition induced by MLN-4760 (1 mg/kg/day for 2 weeks) led to deterioration of erythrocyte morphology and osmotic resistance, but plasma markers of oxidative stress, erythrocyte deformability, nitric oxide production and Na,K-ATPase activity were not significantly affected. Zofenopril administration (10 mg/kg/day, initiated after 4-day-lasting ACE2 inhibition) resulted in unexpected increase in angiotensin II plasma levels in both control and ACE-inhibited spontaneously hypertensive rats, but in normalization of osmotic resistance in ACE2-inhibited rats. The overall effect of zofenopril on erythrocyte qualities could be evaluated as beneficial.

Spontaneously Hypertensive Rat substrains show differences in model traits for addiction risk and cocaine self-administration: Implications for a novel rat reduced complexity cross.

Forward genetic mapping of F2 crosses between closely related substrains of inbred rodents - referred to as a reduced complexity cross (RCC) - is a relatively new strategy for accelerating the pace of gene discovery for complex traits, such as drug addiction. RCCs to date were generated in mice, but rats are thought to be optimal for addiction genetic studies. Based on past literature, one inbred Spontaneously Hypertensive Rat substrain, SHR/NCrl, is predicted to exhibit a distinct behavioral profile as it relates to cocaine self-administration traits relative to another substrain, SHR/NHsd. Direct substrain comparisons are a necessary first step before implementing an RCC. We evaluated model traits for cocaine addiction risk and cocaine self-administration behaviors using a longitudinal within-subjects design. Impulsive-like and compulsive-like traits were greater in SHR/NCrl than SHR/NHsd, as were reactivity to sucrose reward, sensitivity to acute psychostimulant effects of cocaine, and cocaine use studied under fixed-ratio and tandem schedules of cocaine self-administration. Compulsive-like behavior correlated with the acute psychostimulant effects of cocaine, which in turn correlated with cocaine taking under the tandem schedule. Compulsive-like behavior also was the best predictor of cocaine seeking responses. Heritability estimates indicated that 22 %-40 % of the variances for the above phenotypes can be explained by additive genetic factors, providing sufficient genetic variance to conduct genetic mapping in F2 crosses of SHR/NCrl and SHR/NHsd. These results provide compelling support for using an RCC approach in SHR substrains to uncover candidate genes and variants that are of relevance to cocaine use disorders.

Contrasting Roles of Ang II and ACEA in the Regulation of IL10 and IL1ß Gene Expression in Primary SHR Astroglial Cultures.

Angiotensin (Ang) II is well-known to have potent pro-oxidant and pro-inflammatory effects in the brain. Extensive crosstalk between the primary Ang II receptor, Ang type 1 receptor (AT1R), and the cannabinoid type 1 receptor (CB1R) has been demonstrated by various groups in the last decade. Since activation of glial CB1R has been demonstrated to play a key role in the resolution of inflammatory states, we investigated the role of Ang II (100 nM) and/or ACEA (10 nM), a potent CB1R-specific agonist in the regulation of inflammatory markers in astrocytes from spontaneously hypertensive rats (SHR) and Wistar rats. Astrocytes were cultured from brainstems and cerebellums of SHR and Wistar rats and assayed for IL1ß and IL10 gene expression and secreted fraction, in treated and non-treated cells, by employing qPCR and ELISA, respectively. mRNA expression of both IL10 and IL1ß were significantly elevated in untreated brainstem and cerebellar astrocytes isolated from SHR when compared to Wistar astrocytes. No changes were observed in the secreted fraction. While ACEA-treatment resulted in a significant increase in IL10 gene expression in Wistar brainstem astrocytes (Log2FC ≥ 1, p < 0.05), its effect in SHR brainstem astrocytes was diminished. Ang II treatment resulted in a strong inhibitory effect on IL10 gene expression in astrocytes from both brain regions of SHR and Wistar rats (Log2FC ≤ -1, p < 0.05), and an increase in IL1ß gene expression in brainstem astrocytes from both strains (Log2FC ≥ 1, p < 0.05). Co-treatment of Ang II and ACEA resulted in neutralization of Ang II-mediated effect in Wistar brainstem and cerebellar astrocytes, but not SHR astrocytes. Neither Ang II nor ACEA resulted in any significant changes in IL10 or IL1ß secreted proteins. These data suggest that Ang II and ACEA have opposing roles in the regulation of inflammatory gene signature in astrocytes isolated from SHR and Wistar rats. This however does not translate into changes in their secreted fractions.