Impact of pharmacist participation in the patient care team on value-based health measures.

PURPOSE: To evaluate whether pharmacist engagement on the interdisciplinary team leads to improved performance on diabetes-related quality measures. METHODS: This was a retrospective observational study of patients seen in primary care and specialty clinics from October 2014 to October 2020. Patients were included if they had a visit with a physician, nurse practitioner, physician's assistant, or clinical pharmacist practitioner (CPP) within the study period and had a diagnosis of diabetes. The intervention group included patients with at least one visit with a CPP, while the control group consisted of patients who were exclusively managed by non-CPP providers. The primary outcome of this study was the median change in glycosylated hemoglobin (HbA1c) from baseline to follow-up at 3, 6, and 12 months. The secondary outcome was the probability of achieving the HbA1c targets of <7% and <8% at 3, 6, and 12 months. RESULTS: Patients referred to a CPP had higher HbA1c levels at baseline and were more likely to have concomitant hypertension (P < 0.01). Patients seen by a CPP had 0.31%, 0.41%, and 0.44% greater reductions in HbA1c compared to patients in the control group at 3, 6, and 12 months, respectively (P < 0.01). Patients managed by a CPP were also more likely to achieve the identified HbA1c targets of <7% and <8%. CONCLUSION: Patients referred to a CPP were more complex, but had greater reductions in HbA1c and were more likely to achieve HbA1c goals included in the organization's quality measures. This study demonstrates the value of pharmacists in improving patient care and their role in supporting an organization's achievement of value-based quality measures.

Clinical Utility of Midregional Proadrenomedullin in Patients with COVID-19.

OBJECTIVE: The aim of the study was to assess the role of midregional proadrenomedullin (MR-proADM) in patients with COVID-19. METHODS: We included 110 patients hospitalized for COVID-19. Biochemical biomarkers, including MR-proADM, were measured at admission. The association of plasma MR-proADM levels with COVID-19 severity, defined as a requirement for mechanical ventilation or in-hospital mortality, was evaluated. RESULTS: Patients showed increased levels of MR-proADM. In addition, MR-proADM was higher in patients who died during hospitalization than in patients who survived (median, 2.59 nmol/L; interquartile range, 2.3-2.95 vs median, 0.82 nmol/L; interquartile range, 0.57-1.03; P <.0001). Receiver operating characteristic curve analysis showed good accuracy of MR-proADM for predicting mortality. A MR-proADM value of 1.73 nmol/L was established as the best cutoff value, with 90% sensitivity and 95% specificity (P <.0001). CONCLUSION: We found that MR-proADM could represent a prognostic biomarker of COVID-19.

Role of plasma angiotensin II and angiotensin-converting enzyme 2 levels on prognosis and mortality in hypertensive patients with COVID-19.

Introduction: SARS-CoV-2 requires angiotensin-converting enzyme 2 (ACE2) to enter the cell. In our study, we aimed to investigate the role of angiotensin-converting enzyme 2 and angiotensin II plasma levels on prognosis and mortality in patients with isolated hypertension, patients with chronic diseases in addition to hypertension and patients with COVID-19 without comorbidities, in accordance with the use of renin-angiotensin-aldosterone system inhibitor. Materials & methods: In the study, patients diagnosed with COVID-19 were divided into three groups. Angiotensin II and ACE2 levels were compared by comorbidities, antihypertensive drugs used, intensive care hospitalization and termination of patients. The relationship between angiotensin II and ACE2 levels and service and intensive care times was investigated. Findings: A total of 218 patients were enrolled in our study, including 68 patients diagnosed with COVID-19 without comorbidities, 33 patients diagnosed with isolated hypertension and 117 patients with other chronic diseases in addition to hypertension. There was no statistically significant difference between the comorbid disease groups between angiotensin II and ACE2 levels of the patients enrolled in the study. The rate of patients admitted to the intensive care unit was 17.9%, and the mortality rate was 11.5%. Results: In our study, we did not obtain significant findings regarding angiotensin II and ACE2 levels on presentation that can be used in prognosis and mortality of COVID-19 patients and development of future treatment methods.

Angiotensin II receptor blocker intake associates with reduced markers of inflammatory activation and decreased mortality in patients with cardiovascular comorbidities and COVID-19 disease.

AIMS: Patients with cardiovascular comorbidities have a significantly increased risk for a critical course of COVID-19. As the SARS-CoV2 virus enters cells via the angiotensin-converting enzyme receptor II (ACE2), drugs which interact with the renin angiotensin aldosterone system (RAAS) were suspected to influence disease severity. METHODS AND RESULTS: We analyzed 1946 consecutive patients with cardiovascular comorbidities or hypertension enrolled in one of the largest European COVID-19 registries, the Lean European Open Survey on SARS-CoV-2 (LEOSS) registry. Here, we show that angiotensin II receptor blocker intake is associated with decreased mortality in patients with COVID-19 [OR 0.75 (95% CI 0,59-0.96; p = 0.013)]. This effect was mainly driven by patients, who presented in an early phase of COVID-19 at baseline [OR 0,64 (95% CI 0,43-0,96; p = 0.029)]. Kaplan-Meier analysis revealed a significantly lower incidence of death in patients on an angiotensin receptor blocker (ARB) (n = 33/318;10,4%) compared to patients using an angiotensin-converting enzyme inhibitor (ACEi) (n = 60/348;17,2%) or patients who received neither an ACE-inhibitor nor an ARB at baseline in the uncomplicated phase (n = 90/466; 19,3%; p<0.034). Patients taking an ARB were significantly less frequently reaching the mortality predicting threshold for leukocytes (p<0.001), neutrophils (p = 0.002) and the inflammatory markers CRP (p = 0.021), procalcitonin (p = 0.001) and IL-6 (p = 0.049). ACE2 expression levels in human lung samples were not altered in patients taking RAAS modulators. CONCLUSION: These data suggest a beneficial effect of ARBs on disease severity in patients with cardiovascular comorbidities and COVID-19, which is linked to dampened systemic inflammatory activity.

CXCL10 levels at hospital admission predict COVID-19 outcome: hierarchical assessment of 53 putative inflammatory biomarkers in an observational study.

BACKGROUND: Host inflammation contributes to determine whether SARS-CoV-2 infection causes mild or life-threatening disease. Tools are needed for early risk assessment. METHODS: We studied in 111 COVID-19 patients prospectively followed at a single reference Hospital fifty-three potential biomarkers including alarmins, cytokines, adipocytokines and growth factors, humoral innate immune and neuroendocrine molecules and regulators of iron metabolism. Biomarkers at hospital admission together with age, degree of hypoxia, neutrophil to lymphocyte ratio (NLR), lactate dehydrogenase (LDH), C-reactive protein (CRP) and creatinine were analysed within a data-driven approach to classify patients with respect to survival and ICU outcomes. Classification and regression tree (CART) models were used to identify prognostic biomarkers. RESULTS: Among the fifty-three potential biomarkers, the classification tree analysis selected CXCL10 at hospital admission, in combination with NLR and time from onset, as the best predictor of ICU transfer (AUC [95% CI] = 0.8374 [0.6233-0.8435]), while it was selected alone to predict death (AUC [95% CI] = 0.7334 [0.7547-0.9201]). CXCL10 concentration abated in COVID-19 survivors after healing and discharge from the hospital. CONCLUSIONS: CXCL10 results from a data-driven analysis, that accounts for presence of confounding factors, as the most robust predictive biomarker of patient outcome in COVID-19.

Clinical characteristics of COVID-19 patients in three consecutive generations of spread in Zhejiang, China.

OBJECTIVES: The aim was to determine the clinical characteristics of COVID-19 patients because the SARS-CoV-2 virus continues to circulate in the population. METHODS: This is a retrospective, multicentre, cohort study. Adult COVID-19 cases from four hospitals in Zhejiang were enrolled and clustered into three groups based on epidemiological history. First-generation patients had a travel history to Hubei within 14 days before disease onset; second-generation patients had a contact history with first-generation patients; third-generation patients had a contact history with second-generation patients. Demographic, clinical characteristics, clinical outcomes and duration of viral shedding were analysed. RESULTS: A total of 171 patients were enrolled, with 83, 44 and 44 patients in the first-, second-, and third-generation, respectively. Compared with the first and second generations, third-generation patients were older (61.3 vs. 48.3 and 44.0 years, p < 0.001) and had more coexisting conditions (56.8% vs. 36.1% and 27.3%, p 0.013). At 7 ± 1 days from illness onset, third-generation patients had lower lymphocyte (0.6 vs. 0.8 and 0.8 × 109/L, p 0.007), higher C-reactive protein (29.7 vs. 17.1 and 13.8 mg/L, p 0.018) and D-dimer (1066 vs. 412.5 and 549 µg/L, p 0.002) and more lesions involving the pulmonary lobes (lobes ≥5, 81.8% vs. 53.0% and 34.1%, p < 0.001). The proportions of third-generation patients developing severe illness (72.7% vs. 32.5% and 27.3%, p < 0.001), critical illness (38.6% vs. 10.8% and 6.8%, p < 0.001) and receiving endotracheal intubation (20.5% vs. 3.6% and 2.3%, p 0.002) were higher than in the other two groups. DISCUSSION: Third-generation patients were older, had more underlying comorbidities and had a higher proportion of severe or critical illness than first- and second-generation patients.

Serum ACE2, Angiotensin II, and Aldosterone Levels Are Unchanged in Patients With COVID-19.

BACKGROUND: The role of the renin-angiotensin-aldosterone system (RAAS) in coronavirus disease 2019 (COVID-19) is controversially discussed. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) enters host cells by binding to angiotensin-converting enzyme 2 (ACE2) and activity of the RAAS may affect susceptibility to SARS-CoV-2 infection and outcome of patients with COVID-19. METHODS: In this prospective single-center study, we determined the serum levels of ACE2, angiotensin II, and aldosterone in patients with COVID-19 compared with control patients presenting with similar symptoms in the emergency unit. RESULTS: We analyzed serum samples from 24 SARS-CoV-2 positive and 61 SARS-CoV-2 negative patients. SARS-CoV-2 positive and control patients did not differ in baseline patients characteristics, symptoms, and clinical presentation. Mean serum concentrations of ACE2, angiotensin II, and aldosterone did not differ between the SARS-CoV-2 positive and the control group. In line with this, serum potassium as surrogate parameter for RAAS activity and blood pressure were similar in both groups. CONCLUSIONS: In summary, we did not find evidence for altered RAAS activity including angiotensin II, aldosterone, or potassium levels, and blood pressure in patients with COVID-19. CLINICAL TRIALS REGISTRATION: Trial Number DRKS00021206.

Development of neutralizing antibody responses against SARS-CoV-2 in COVID-19 patients.

The novel coronavirus severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and coronavirus disease 2019 (COVID-19) are new global problems. The understanding of the host immune response in COVID-19 and its implications in the development of therapeutic agents are new challenges. Here, we evaluated the development of immunoglobulin G (IgG) and neutralizing (Nt) antibodies in symptomatic hospitalized COVID-19 patients. We followed up 117 COVID-19 confirmed patients from a reference health center for COVID-19 during the epidemic in Santiago de Chile. One and two sequential blood samples from 117 to 68 cases were, respectively, obtained to evaluate the immune response. Immunofluorescence and neutralization assays in Vero E6 cells with a Chilean SARS-CoV-2 strain were performed. Out of the 68 patients, 44% were women and 56% men, and the most frequent comorbidities were hypertension (47.7%) and diabetes (27.4%). The most frequent symptoms or signs related to COVID-19 were dyspnea, cough, fever, myalgia, and headache. In all the study population, 76.1% and 60.7% of patients were positive for IgG and Nt antibodies in the first blood sample. All patients except one were positive for IgG and Nt antibodies in the second sample. IgG and Nt antibodies positivity increased significantly according to the disease evolution periods. Higher Nt antibody titers were observed in the first sample in patients under 60 years of age. Obese and diabetic patients had no increase in Nt antibodies, unlike normal weight and diabetes-free patients. Both hypertensive and normotensive patients showed a significant increase in Nt antibodies. These results show an early and robust immune response against SARS-CoV-2 infection during severe COVID-19.

Pattern of liver function and clinical profile in COVID-19: A cross-sectional study of 91 patients.

BACKGROUND: - COVID-19 caused by SARS-CoV-2 leads to myriad range of organ involvement including liver dysfunction. AIM: To analyse the liver function in patients with COVID-19 and their association with respect to age, sex, severity of disease and clinical features. MATERIALS AND METHODS: This study was a cross-sectional study done at Rajendra Institute of Medical Sciences, Ranchi. 91 patients admitted with confirmed SARS-CoV-2 infection were included in this study and divided into asymptomatic, mild, moderate and severe groups. Liver function tests were compared among different severity groups. RESULTS: Of 91 patients with COVID-19, 70 (76.9%) had abnormal liver function. Aspartate transaminase (AST), alanine transaminase (ALT), alkaline phosphatase (ALP), total bilirubin levels was 1-2 × ULN in 33(36.3%), 34(37.3%), 12(13.2%), 6(6.6%) cases and >2 × ULN in 20(22%), 18(19.8%), 7(7.7%) and 2 (2.2%) cases respectively. Mean AST and ALP levels among different severity groups of COVID-19 was statistically significant (p < 0.05) whereas mean ALT and total bilirubin levels was statistically non-significant (p > 0.05). There was no statistical difference between males and females with regard to abnormal liver function. Liver injury was seen in 64.3% cases of hypertension and 73.3% cases of diabetes. Fever, myalgia, headache and breathlessness were found to be correlated significantly with severity of disease. CONCLUSION: Liver injury is common in SARS-CoV-2 infection and is more prevalent in the severe disease group. Aspartate transaminase and alkaline phosphatase are better indicators of covid-19 induced liver injury than alanine transaminase and total bilirubin.

Hematologic changes predict clinical outcome in recovered patients with COVID-19.

2019 coronavirus disease (COVID-19) presents as a newly recognized pneumonia that has brought about a global pandemic and is increasingly considered as a systemic illness. We investigated the clinical and laboratory features of recovered COVID-19 patients without pre-existing hematologic diseases at Wuhan No. 1 Hospital. Fifty-nine male and 68 female Chinese patients were included with the median age at 64 years in the present study. Eosinopenia (37.80%), monocytosis (51.97%), lymphocytopenia (25.20%), and anemia (51.97%) were the most common hematologic findings in our cohort, particularly in severe or critically ill COVID-19. The levels of changes in leukocytes, neutrophils, lymphocytes, monocytes, eosinophils, basophils, platelets, hemoglobin levels, mean corpuscular volume (MCV), and mean cell hemoglobin concentration (MCHC) are overall associated with lung involvement, oxygen demand, and disease activity. However, changes of eosinophils (end hospitalization-baseline) (coefficients = 10.32; 95% CI = 1.03-19.60, P = 0.03) and basophils (Max - Min) (coefficients = 71.43; 95% CI = 8.55-134.31, P = 0.03) were independent predictors of delayed recovery in the hospital by the multivariate analysis in this recovered population. A variety of hematologic changes are associated with the severity and clinical outcome of recovered COVID-19 patients, which warrants further exploration of their underlying mechanisms.

High prevalence of diabetes and other comorbidities in hospitalized patients with COVID-19 in Delhi, India, and their association with outcomes.

BACKGROUND AND AIMS: To study the prevalence and impact of diabetes mellitus and other comorbidities among hospitalized patients with COVID-19. METHODS: In a prospective, observational study including consecutive adults hospitalized with COVID-19, clinical outcomes and inflammatory markers were compared in those with and without diabetes. Participants were classified as having mild or severe COVID-19 disease using the WHO ordinal scale. RESULTS: 401 patients (125 females) with median age of 54 years (range 19-92) were evaluated. Of them 189 (47.1%) had pre-existing diabetes and21 (5.2%) had new-onset hyperglycaemia. Overall, 344 (85.8%) and 57 (14.2%) cases had mild and severe COVID-19 disease respectively. The group with diabetes had a higher proportion of severe cases (20.1% vs 9%, p-0.002), mortality (6.3 vs 1.4%, p-0.015), ICU admission (24.3 vs 12.3%, p-0.002), and oxygen requirement (53.4 vs 28.3%, p < 0.001). Baseline Hba1c (n = 331) correlated significantly with outcome severity scores (r 0.136, p-0.013) and 12/15 (80%) of those who succumbed had diabetes. Hypertension, coronary artery disease, and chronic kidney disease were present in 164 (40.9%), 35 (8.7%) and 12 (2.99%) patients respectively. Hypertension was associated with a higher proportion of severe cases, mortality, ICU admission and oxygen administration. CONCLUSIONS: We report a high prevalence of diabetes in a hospitalized COVID-19 population. Patients with diabetes or hypertension had more severe disease and greater mortality.

Furin Protease: From SARS CoV-2 to Anthrax, Diabetes, and Hypertension.

Furin is a protease that is ubiquitous in mammalian metabolism. One of the innovations that make sudden acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) more infectious than its ancestor viruses is the addition of a furin cleavage site. Conditions associated with elevated furin levels, including diabetes, obesity, and hypertension, overlap greatly with vulnerability to the severe form of coronavirus disease 2019 (COVID-19). We suggest that diet and lifestyle modifications that reduce the associated comorbidities may prevent the development of severe COVID-19 by, in part, lowering circulating furin levels. Likewise, natural and pharmaceutical inhibitors of furin may be candidate prophylactic interventions or, if used early in the COVID-19, may prevent the development of critical symptoms.

Blood Test Results of Pregnant COVID-19 Patients: An Updated Case-Control Study.

Background: Coronavirus disease (COVID-19) is a current global public health emergency. However, current research on the blood test results of pregnant women with COVID-19 is insufficient. Methods: A case-control study was carried out based on clinical blood test results. Pregnant COVID-19 patients, pregnant COVID-19 patients with diabetes, and pregnant COVID-19 patients with hypertension, were assessed in this study. Also, 120 controls were matched by age, parity, fetus number, and presence of chronic disease. T-tests, Chi-square tests, Wilcoxon signed-rank tests, and Kruskal-Wallis tests were used to compare data from the blood tests and liver function indices among the selected groups. Results: Between January 24 and March 14, 2020, 60 pregnant COVID-19 patients delivered at the Maternal and Child Health Hospital of Hubei Province. The average maternal age of pregnant COVID-19 patients was 30.97 years and the mean gestational period was 37.87 weeks. 71.67% (43/60) of pregnant COVID-19 patients gave birth by cesarean delivery. In total, 21.67% (13/60) were diagnosed with diabetes and 18.33% (11/60) were diagnosed with hypertension during pregnancy. Compared to controls, pregnant COVID-19 patients showed significantly lower numbers of blood lymphocytes and higher numbers of neutrophils, as well as higher levels of C-reactive protein and total bilirubin. Among the three groups, pregnant COVID-19 patients with diabetes had significantly higher levels of neutrophils and lower levels of total protein. Aspartate transaminase levels were higher in pregnant COVID-19 patients with hypertension than in pregnant COVID-19 patients with no comorbidities and controls with hypertension. Interpretations: Blood and liver function indices indicate that chronic complications, including hypertension and diabetes, could increase the risk of inflammation and liver injury in pregnant COVID-19 patients.

Implications of AB0 blood group in hypertensive patients with covid-19.

BACKGROUND: Hypertension is the most frequent co-morbidity in patients with covid-19 infection, and we might speculate that a specific blood group could play a key role in the clinical outcome of hypertensive patients with covid-19. METHODS: In this prospective study, we compared 0 vs. non-0 blood group in hypertensive patients with covid-19 infection. In these patients, we evaluated inflammatory and thrombotic status, cardiac injury, and death events. RESULTS: Patients in non-0 (n = 92) vs. 0 blood group (n = 72) had significantly different values of activated pro-thrombin time, D-dimer, and thrombotic indexes as Von Willebrand factor and Factor VIII (p < 0.05). Furthermore, patients in non-0 vs. 0 blood group had higher rate of cardiac injury (10 (13.9%) vs. 27 (29.3%)) and death, (6 (8.3%) vs. 18 (19.6%)), (p < 0.05). At the multivariate analysis, Interleukin-6 (1.118, CI 95% 1.067-1.171) and non-0 blood group (2.574, CI 95% 1.207-5.490) were independent predictors of cardiac injury in hypertensive patients with covid-19. D-dimer (1.082, CI 95% 1.027-1.140), Interleukin-6 (1.216, CI 95% 1.082-1.367) and non-0 blood group (3.706, CI 95% 1.223-11.235) were independent predictors of deaths events in hypertensive patients with covid-19. CONCLUSIONS: Taken together, our data indicate that non-0 covid-19 hypertensive patients have significantly higher values of pro-thrombotic indexes, as well as higher rate of cardiac injury and deaths compared to 0 patients. Moreover, AB0 blood type influences worse prognosis in hypertensive patients with covid-19 infection.

Blood routine test in mild and common 2019 coronavirus (COVID-19) patients.

The new 2019 coronavirus disease (COVID-19), according to the World Health Organization (WHO), has been characterized as a pandemic. As more is being discovered about this virus, we aim to report findings of the complete blood count (CBC) of COVID-19 patients. This would serve in providing physicians with important knowledge on the changes that can be expected from the CBC of mild and normal COVID-19 patients. A total of 208 mild and common patients were admitted at the Dongnan Hospital located in the city of Xiaogan, Hubei, China. The CBCs of these patients, following a confirmed diagnosis of COVID-19, were retrospectively analyzed and a significant P<0.05 was found after a full statistical analysis was conducted using the Statistical Package for the Social Sciences (IBM SPSS). CBC analysis revealed changes in the levels of red blood cells (RBCs), hemoglobin (HGB), hematocrit (HCT), mean corpuscular volume (MCV), and C-reactive protein (CRP). Clinicians should expect similar findings when dealing with the new COVID-19.

Fenofibrate increases the amount of sulfatide which seems beneficial against Covid-19.

Fenofibrate, which is a PPAR-alfpha agonist, increases the level of sulfatide. In this letter we hypothesize on the background of various findings that this is beneficial against COVID-19. Fenofibrate has been used for decades against hypercholesterolemia and has no serious side effects. Therefore, a trial giving fenofibrate to patients with corona virus infection is recommended.

COVID-19 in people with diabetes: understanding the reasons for worse outcomes.

Since the initial COVID-19 outbreak in China, much attention has focused on people with diabetes because of poor prognosis in those with the infection. Initial reports were mainly on people with type 2 diabetes, although recent surveys have shown that individuals with type 1 diabetes are also at risk of severe COVID-19. The reason for worse prognosis in people with diabetes is likely to be multifactorial, thus reflecting the syndromic nature of diabetes. Age, sex, ethnicity, comorbidities such as hypertension and cardiovascular disease, obesity, and a pro-inflammatory and pro-coagulative state all probably contribute to the risk of worse outcomes. Glucose-lowering agents and anti-viral treatments can modulate the risk, but limitations to their use and potential interactions with COVID-19 treatments should be carefully assessed. Finally, severe acute respiratory syndrome coronavirus 2 infection itself might represent a worsening factor for people with diabetes, as it can precipitate acute metabolic complications through direct negative effects on ß-cell function. These effects on ß-cell function might also cause diabetic ketoacidosis in individuals with diabetes, hyperglycaemia at hospital admission in individuals with unknown history of diabetes, and potentially new-onset diabetes.

Clinical features in 52 patients with COVID-19 who have increased leukocyte count: a retrospective analysis.

Recent reports have showed that a proportion of patients with Coronavirus Disease 2019 (COVID-19) presented elevated leukocyte count. Clinical data about these patients is scarce. We aimed to evaluate the clinical findings of patients with COVID-19 who have increased leukocyte at admission. We retrospectively collected the clinical data on the 52 patients who have increased leukocyte count at admission from the 619 patients with confirmed COVID-19 who had pneumonia with abnormal features on chest CT scan in Renmin Hospital of Wuhan University in Wuhan, China, from February 3 to March 3, 2020. The mean age of the 52 patients with increased leukocyte count was 64.7 (SD 11.4) years, 32 (61.5%) were men and 47 (90.4%) had fever. Compared with the patients with non-increased leukocyte count, the patients with increased leukocyte count were significantly older (P < 0.01), were more likely to have underlying chronic diseases (P < 0.01), more likely to develop critically illness (P < 0.01), more likely to admit to an ICU (P < 0.01), more likely to receive mechanical ventilation (P < 0.01), had higher rate of death (P < 0.01) and the blood levels of neutrophil count and the serum concentrations of CRP and IL-6 were significantly increased, (P < 0.01). The older patients with COVID-19 who had underlying chronic disorders are more likely to develop leukocytosis. These patients are more likely to develop critical illness, with a high admission to an ICU and a high mortality rate.