Contextualising adverse events of special interest to characterise the baseline incidence rates in 24 million patients with COVID-19 across 26 databases: a multinational retrospective cohort study.

Background: Adverse events of special interest (AESIs) were pre-specified to be monitored for the COVID-19 vaccines. Some AESIs are not only associated with the vaccines, but with COVID-19. Our aim was to characterise the incidence rates of AESIs following SARS-CoV-2 infection in patients and compare these to historical rates in the general population. Methods: A multi-national cohort study with data from primary care, electronic health records, and insurance claims mapped to a common data model. This study's evidence was collected between Jan 1, 2017 and the conclusion of each database (which ranged from Jul 2020 to May 2022). The 16 pre-specified prevalent AESIs were: acute myocardial infarction, anaphylaxis, appendicitis, Bell's palsy, deep vein thrombosis, disseminated intravascular coagulation, encephalomyelitis, Guillain- Barré syndrome, haemorrhagic stroke, non-haemorrhagic stroke, immune thrombocytopenia, myocarditis/pericarditis, narcolepsy, pulmonary embolism, transverse myelitis, and thrombosis with thrombocytopenia. Age-sex standardised incidence rate ratios (SIR) were estimated to compare post-COVID-19 to pre-pandemic rates in each of the databases. Findings: Substantial heterogeneity by age was seen for AESI rates, with some clearly increasing with age but others following the opposite trend. Similarly, differences were also observed across databases for same health outcome and age-sex strata. All studied AESIs appeared consistently more common in the post-COVID-19 compared to the historical cohorts, with related meta-analytic SIRs ranging from 1.32 (1.05 to 1.66) for narcolepsy to 11.70 (10.10 to 13.70) for pulmonary embolism. Interpretation: Our findings suggest all AESIs are more common after COVID-19 than in the general population. Thromboembolic events were particularly common, and over 10-fold more so. More research is needed to contextualise post-COVID-19 complications in the longer term. Funding: None.

Evaluation of Stress Response in Middle-Aged Male Diabetic Hypertensive Patients.

CONTEXT: Stress triggers a cascade of reactions that alter the organism's dynamic steady state. There is a scarcity of interventional studies that show cortisol variability upon stress over time in groups of patients with chronic noncommunicable diseases and comorbidities. OBJECTIVE: We aimed to examine salivary cortisol changes in the cognitive stress response of patients with hypertension and diabetes mellitus (HT&DM) and patients with hypertension (HT) and to determine differences between them. METHODS: The study was conducted using a stress test of solving an arithmetic task in 62 patients with HT&DM and HT who were being treated in the outpatient clinic of the Medical Pharmacology and Clinical Pharmacology Department in Istanbul University, Istanbul Medical Faculty Hospital. RESULTS: There was no statistically significant difference between the HT&DM and HT groups for systolic blood pressure (SBP) and diastolic blood pressure (DBP) values (P = .331 and P = .058). When measured by repeated ANOVA, salivary cortisol level [F (1.842, 60) = 8.771, P < .0001], SBP [F (2.185, 60) = 12.080, P < .0001], DBP [F (2.793, 60) = 6.043, P = .001], and heart rate [F (2.073, 60) = 13.259, P < .0001] were statistically significant for the main effect (time), while the effect of the group × time interaction factor was statistically not significant (P = .773; P = .751; P = .713 and P = .506, respectively). CONCLUSION: The arithmetic problem-solving task used with the HT&DM and HT patients was useful as an acute stress test in the laboratory environment. There was no statistically significant difference for group × time interaction factor between the HT&DM and HT groups; however, the salivary cortisol and BP values increased significantly after acute stress within each group.

Evaluation of Risk Factors Associated With Antihypertensive Treatment Success Employing Data Mining Techniques.

OBJECTIVE: This study aimed to evaluate the effects of potential risk factors on antihypertensive treatment success. METHODS: Patients with hypertension who were treated with antihypertensive medications were included in this study. Data from the last visit were analyzed retrospectively for each patient. To evaluate the predictive models for antihypertensive treatment success, data mining algorithms (logistic regression, decision tree, random forest, and artificial neural network) using 5-fold cross-validation were applied. Additionally, study parameters between patients with controlled and uncontrolled hypertension were statistically compared and multiple regression analyses were conducted for secondary endpoints. RESULTS: The data of 592 patients were included in the analysis. The overall blood pressure control rate was 44%. The performance of random forest algorithm (accuracy = 97.46%, precision = 97.08%, F1 score = 97.04%) was slightly higher than other data mining algorithms including logistic regression (accuracy = 87.31%, precision = 86.21%, F1 score = 85.74%), decision tree (accuracy = 76.94%, precision = 70.64%, F1 score = 76.54%), and artificial neural network (accuracy = 86.47%, precision = 83.85%, F1 score = 84.86%). The top 5 important categorical variables (predictive correlation value) contributed the most to the prediction of antihypertensive treatment success were use of calcium channel blocker (-0.18), number of antihypertensive medications (0.18), female gender (0.10), alcohol use (-0.09) and attendance at regular follow up visits (0.09), respectively. The top 5 numerical variables contributed the most to the prediction of antihypertensive treatment success were blood urea nitrogen (-0.12), glucose (-0.12), hemoglobin A1c (-0.12), uric acid (-0.09) and creatinine (-0.07), respectively. According to the decision tree model; age, gender, regular attendance at follow-up visits, and diabetes status were identified as the most critical patterns for stratifying the patients. CONCLUSION: Data mining algorithms have the potential to produce predictive models for screening the antihypertensive treatment success. Further research on larger populations and longitudinal datasets are required to improve the models.

Early Effects of Low Molecular Weight Heparin Therapy with Soft-Mist Inhaler for COVID-19-Induced Hypoxemia: A Phase IIb Trial.

In COVID-19-induced acute respiratory distress syndrome, the lungs are incapable of filling with sufficient air, leading to hypoxemia that results in high mortality among hospitalized patients. In clinical trials, low-molecular-weight heparin was administered via a specially designed soft-mist inhaler device in an investigator initiated, single-center, open-label, phase-IIb clinical trial. Patients with evidently worse clinical presentations were classed as the "Device Group"; 40 patients were given low-molecular-weight heparin via a soft mist inhaler at a dose of 4000 IU per administration, twice a day. The Control Group, also made up of 40 patients, received the standard therapy. The predetermined severity of hypoxemia and the peripheral oxygen saturation of patients were measured on the 1st and 10th days of treatment. The improvement was particularly striking in cases of severe hypoxemia. In the 10-day treatment, low-molecular-weight heparin was shown to significantly improve breathing capability when delivered via a soft-mist inhaler.

Traditional Chinese medicine practices used in COVID-19 (Sars-cov 2/Coronavirus-19) treatment in clinic and their effects on the cardiovascular system.

OBJECTIVE: The aim of this study was to evaluate the effectiveness of plants used in the formulations of traditional Chinese medicine (TCM), which were also used in clinical trials to treat patients with the novel coronavirus COVID-19, and to assess their effects on the cardiovascular system. METHODS: A literature review of PubMed, ResearchGate, ScienceDirect, the Cochrane Library, and TCM monographs was conducted and the effects of the plants on the cardiovascular system and the mechanisms of action in COVID-19 treatment were evaluated. RESULTS: The mechanism of action, cardiovascular effects, and possible toxicity of 10 plants frequently found in TCM formulations that were used in the clinical treatment of COVID-19 were examined. CONCLUSION: TCM formulations that had been originally developed for earlier viral diseases have been used in COVID-19 treatment. Despite the effectiveness seen in laboratory and animal studies with the most commonly used plants in these formulations, the clinical studies are currently insufficient according to standard operating procedures. More clinical studies are needed to understand the safe clinical use of traditional plants.

Efficacy and Safety of S-Amlodipine 2.5 and 5 mg/d in Hypertensive Patients Who Were Treatment-Naive or Previously Received Antihypertensive Monotherapy.

The aim of the present study was to evaluate the efficacy and safety of S-amlodipine 2.5 and 5 mg/d in patients with hypertension who were treatment-naive or previously received antihypertensive monotherapy. During the 8-week treatment period, all patients received S-amlodipine 2.5 mg/d for the first 4 weeks, followed by S-amlodipine 5 mg/d for the second 4 weeks. For efficacy assessments, ambulatory and office blood pressure (BP) measurements were performed during the baseline, fourth-week, and eighth-week visits. For safety assessments, all adverse events and abnormal laboratory findings were recorded. This study is registered with ClinicalTrials.gov (NCT03038451). Of 43 patients evaluated at the screening visit, 33 were enrolled. In the treatment-naive arm, significant reductions in both office and ambulatory systolic BP (SBP) and diastolic BP (DBP) were observed with S-amlodipine 2.5 mg/d and additional significant reductions were achieved with dose titration (S-amlodipine 5 mg/d). At the end of the study, the rate of the treatment-naive patients with BP under control (SBP/DBP <140/90 mm Hg) was 53% with S-amlodipine 2.5 mg and increased to 78% with S-amlodipine 5 mg. For the noninferiority evaluation, S-amlodipine 2.5 and 5 mg/d treatments were generally noninferior to both office and ambulatory BP levels achieved with the medications that the patients received before participating in the study. Five nonserious adverse events likely to be associated with the study drug were observed. No serious adverse event was encountered. Consequently, S-amlodipine can be suggested as an effective and safe treatment option for patients with hypertension.

Hypertension and valsartan.

Hypertension, which is pointed to be the most frequent cause of death in the World and in Turkey and defined by the World Health Organization as global health crisis and the prominent risk factor for cardiovascular diseases, is a problem threatening public health. Renin-angiotensin system (RAS) plays an important role in pathophysiology and in turn treatment of the disease. The drugs suppressing RAS are recommended both for monotherapy and combinations. Together with the blood pressure lowering effects and positive contributions of this group of drugs to the cardiovascular and renal process have been proved by clinical studies. In this review, the recent developments about the hypertension treatment were summarized and the place of valsartan molecule, being an angiotensin receptor blocker in hypertension treatment, was examined in the light of the studies in which the effectiveness, tolerability and safety of valsartan were evaluated.

[The future of renin inhibition]. / Renin inhibisyonunun gelecegi.

Although antihypertensive drugs currently used provide significant decreases in blood pressure and improve clinical results, cardiovascular morbidity and mortality are not sufficiently decreased; therefore, there is still a need for new approaches to the treatment of hypertension and related cardiovascular diseases. However, when a new blood-pressure lowering therapy is introduced, the question of whether this will be superior over other drug classes in terms of its advantages in hypertensive patients is frequently asked. In 1898, Tigerstedt and Bergman discovered "renin" as a consequence of an observation of blood-pressure elevation following the injection of rabbit renal extracts to rabbits; however, the first member of the renin system pharmacology, ACE inhibitors, could be developed in 1970's. This was followed by the development of angiotensin-receptor blockers (ARB) and, during the last 30 years, it has been shown that the pharmacologic blockage of renin-angiotensin system (RAS) improves the prognosis in hypertensive patients. It has been shown that renin system is the key system in the treatment of hypertension and related comorbidities and that the drugs which target renin system, such as ACE inhibitors and ARB, reduce the cardiovascular events to a large extent. In contrast, as the inhibition of angiotensin II (Ang II) production and effect prevents the negative feedback which helps Ang II to inhibit the renin release from the kidney, elevated Ang II levels suggest that renin enzyme, which can be considered to be the center of renin system, can be the optimal tool in the treatment. Aliskiren, which is the first oral direct renin inhibitor developed based on these ideas, was approved by the FDA in March 2007. During all this period, clinical studies have shown that aliskiren is as efficient as other antihypertensive drugs, and preclinical studies have shown that, in genetically modified rats, aliskiren is efficient in healing the cardiovascular damage associated with Ang II. The fact that the plasma renin activity (PRA), which increases with other antihypertensive therapies and is associated with increased cardiovascular complications, decreases with the use of direct renin inhibitors raises the question as to whether aliskiren may provide additional benefit in reducing cardiovascular morbidity and mortality. The ASPIRE HIGHER program designed to find an answer to this question includes several studies which investigate how aliskiren impacts the clinical results. The studies AVOID, ALOFT and ALLAY, which were completed within the ASPIRE HIGHER program, showed that aliskiren had beneficial effects for surrogate markers of cardiovascular and renal diseases, while AGELESS study showed that, in elderly with systolic hypertension, aliskiren (150 or 300 mg) provided a higher blood pressure lowering compared to ramipril (5 or 10 mg). In addition, many studies included in this program are ongoing and the results of these studies will provide more information about direct renin inhibition. Potential effects of RAS in cognitive functions and the functions of its different components such as angiotensin and AT4 receptor are the topics which are still awaiting answers.

The effects of losartan and immobilization stress on heart rate variability and plasma corticosterone levels in rats.

In this study, the effects of losartan, an angiotensin II receptor antagonist, on heart rate variability and the changes of plasma corticosterone levels caused by immobilization stress were investigated. Losartan (3 mg/kg, p.o.) significantly prevented increases in plasma corticosterone levels in both losartan+acute stress and losartan+chronic stress groups. But, losartan did not prevent the diminution of the power of heart rate variability caused by stress. Our results supported the idea that the renin-angiotensin system is also involved in the stress- induced cardiovascular response, besides the autonomic nervous system. But, the effects of losartan on heart rate variability remained controversial.