Early Start of Oral Clarithromycin Is Associated with Better Outcome in COVID-19 of Moderate Severity: The ACHIEVE Open-Label Single-Arm Trial.

INTRODUCTION: The anti-inflammatory effect of macrolides prompted the study of oral clarithromycin in moderate COVID-19. METHODS: An open-label non-randomized trial in 90 patients with COVID-19 of moderate severity was conducted between May and October 2020. The primary endpoint was defined at the end of treatment (EOT) as no need for hospital re-admission and no progression into lower respiratory tract infection (LRTI) for patients with upper respiratory tract infection and as at least 50% decrease of the respiratory symptoms score without progression into severe respiratory failure (SRF) for patients with LRTI. Viral load, biomarkers, the function of mononuclear cells and safety were assessed. RESULTS: The primary endpoint was attained in 86.7% of patients treated with clarithromycin (95% CIs 78.1-92.2%); this was 91.7% and 81.4% among patients starting clarithromycin the first 5 days from symptoms onset or later (odds ratio after multivariate analysis 6.62; p 0.030). The responses were better for patients infected by non-B1.1 variants. Clarithromycin use was associated with decreases in circulating C-reactive protein, tumour necrosis factor-alpha and interleukin (IL)-6; by increase of production of interferon-gamma and decrease of production of interleukin-6 by mononuclear cells; and by suppression of SARS-CoV-2 viral load. No safety concerns were reported. CONCLUSIONS: Early clarithromycin treatment provides most of the clinical improvement in moderate COVID-19. TRIAL REGISTRATION: ClinicalTrials.gov, NCT04398004.

An open label trial of anakinra to prevent respiratory failure in COVID-19.

Background: It was studied if early suPAR-guided anakinra treatment can prevent severe respiratory failure (SRF) of COVID-19. Methods: A total of 130 patients with suPAR ≥6 ng/ml were assigned to subcutaneous anakinra 100 mg once daily for 10 days. Primary outcome was SRF incidence by day 14 defined as any respiratory ratio below 150 mmHg necessitating mechanical or non-invasive ventilation. Main secondary outcomes were 30-day mortality and inflammatory mediators; 28-day WHO-CPS was explored. Propensity-matched standard-of care comparators were studied. Results: 22.3% with anakinra treatment and 59.2% comparators (hazard ratio, 0.30; 95% CI, 0.20-0.46) progressed into SRF; 30-day mortality was 11.5% and 22.3% respectively (hazard ratio 0.49; 95% CI 0.25-0.97). Anakinra was associated with decrease in circulating interleukin (IL)-6, sCD163 and sIL2-R; IL-10/IL-6 ratio on day 7 was inversely associated with SOFA score; patients were allocated to less severe WHO-CPS strata. Conclusions: Early suPAR-guided anakinra decreased SRF and restored the pro-/anti-inflammatory balance. Funding: This study was funded by the Hellenic Institute for the Study of Sepsis, Technomar Shipping Inc, Swedish Orphan Biovitrum, and the Horizon 2020 Framework Programme. Clinical trial number: NCT04357366.

People infected with the SARS-CoV-2 virus, which causes COVID-19, can develop severe respiratory failure and require a ventilator to keep breathing, but this does not happen to every infected individual. Measuring a blood protein called suPAR (soluble urokinase plasminogen activator receptor) may help identify patients at the greatest risk of developing severe respiratory failure and requiring a ventilator. Previous investigations have suggested that measuring suPAR can identify pneumonia patients at highest risk for developing respiratory failure. The protein can be measured by taking a blood sample, and its levels provide a snapshot of how the body's immune system is reacting to infection, and of how it may respond to treatment. Anakinra is a drug that forms part of a class of medications called interleukin antagonists. It is commonly prescribed alone or in combination with other medications to reduce pain and swelling associated with rheumatoid arthritis. Kyriazopoulou et al. investigated whether treating COVID-19 patients who had developed pneumonia with anakinra could prevent the use of a ventilator and lower the risk of death. The findings show that treating COVID-19 patients with an injection of 100 milligrams of anakinra for ten days may be an effective approach because the drug combats inflammation. Kyriazopoulou et al. examined various markers of the immune response and discovered that anakinra was able to improve immune function, protecting a significant number of patients from going on a ventilator. The drug was also found to be safe and cause no significant adverse side effects. Administering anakinra decreased of the risk of progression into severe respiratory failure by 70%, and reduced death rates significantly. These results suggest that it may be beneficial to use suPAR as an early biomarker for identifying those individuals at highest risk for severe respiratory failure, and then treat them with anakinra. While the findings are promising, they must be validated in larger studies.

Automated pulse wave velocity assessment using a professional oscillometric office blood pressure monitor.

Carotid-femoral pulse wave velocity (cfPWV) is the gold standard method for assessing arterial stiffness. This study evaluated automated brachial-ankle PWV (baPWV) taken by a professional oscillometric blood pressure monitor (Microlife WatchBP Office Vascular) versus reference cfPWV (Complior device). Subjects recruited from a hypertension outpatient clinic had duplicate baPWV and cfPWV measurements (randomized crossover design) and carotid ultrasonography. Of 102 subjects recruited, 101 had valid baPWV measurements. Four subjects were excluded and 97 were analyzed (age 58.3 ± 11.4 years, men 70%, hypertensives 76%, diabetics 17%, cardiovascular disease 10%, smokers 23%). The mean difference between baPWV (13.1 ± 1.8 m/s) and cfPWV (9.1 ± 1.8 m/s) was 4.0 ± 1.4 m/s (P < .01) with close association between them (r = 0.70, P < .01). baPWV and cfPWV were correlated with age (r 0.54/0.49 respectively), systolic blood pressure (0.45/0.50), carotid intima-media thickness (0.31/0.44), and carotid distensibility coefficient (-0.47/-0.34) (all P < .05; no difference between the two methods, z test). There was reasonable agreement (77%) between the two methods in identifying subjects at the top quartile of their distributions (kappa 0.39, P < .01). The areas under the receiver operating characteristic curves for the identification of carotid plaques were comparable for cfPWV and baPWV (0.79 and 0.74 respectively, P = NS). Automated baPWV measurement by a professional oscillometric blood pressure monitor is feasible and observer-independent. baPWV values differ from those by cfPWV, yet they are closely correlated, have reasonable agreement in detecting increased arterial stiffness and give similar associations with carotid stiffness and atherosclerosis.

Validation of the InBody BPBIO250 oscillometric blood pressure monitor for professional office use in general population according to the Association for the Advancement of Medical Instrumentation/European Society of Hypertension/International Organization for Standardization Universal Standard.

OBJECTIVE: The aim of this study was to evaluate the accuracy of the InBody BPBIO250 oscillometric upper-arm professional office blood pressure (BP) monitor in general population according to the Association for the Advancement of Medical Instrumentation/European Society of Hypertension/International Organization for Standardization (AAMI/ESH/ISO) Universal Standard (ISO 81060-2:2018). METHODS: Subjects were recruited to fulfil the age, gender, BP, and cuff distribution criteria of the AAMI/ESH/ISO Universal Standard in general population using the same arm sequential BP measurement method. Two cuffs of the test device were used for arm circumference 22-32 (medium) and 32-42 cm (large). RESULTS: Ninety-seven subjects were recruited and 88 were analyzed. For validation criterion 1, the mean ± SD of the differences between the test device and reference BP readings was 1.9 ± 5.9/0.9 ± 4.9 mmHg (systolic/diastolic). For criterion 2, the SD of the averaged BP differences between the test device and reference BP per subject was 4.78/4.31 mmHg (systolic/diastolic). CONCLUSION: The InBody BPBIO250 professional oscillometric device for office BP measurement fulfilled all the requirements of the AAMI/ESH/ISO Universal Standard (ISO 81060-2:2018) in general population and can be recommended for clinical use.

Validation of the InBody BP170 oscillometric home blood pressure monitor in general population according to the Association for the Advancement of Medical Instrumentation/European Society of Hypertension/International Organization for Standardization Universal Standard.

OBJECTIVE: To evaluate the accuracy of the InBody BP170 oscillometric upper-arm home blood pressure (BP) monitor in general population according to the Association for the Advancement of Medical Instrumentation/European Society of Hypertension/International Organization for Standardization (AAMI/ESH/ISO) Universal Standard (ISO 81060-2:2018). METHODS: Subjects were recruited to fulfill the age, gender, BP and cuff distribution criteria of the AAMI/ESH/ISO Universal Standard in general population using the same arm sequential BP measurement method. Two cuffs of the test device were used for arm circumference 22-32 (medium) and 32-42 cm (large). RESULTS: One-hundred five subjects were recruited and 88 were analyzed. For validation Criterion 1, the mean ± SD of the differences between the test device and reference BP readings was 0.9 ± 6.9/0.5 ± 5.5 mmHg (systolic/diastolic). For Criterion 2, the SD of the averaged BP differences between the test device and reference BP per subject was 5.77/4.80 mmHg (systolic/diastolic). CONCLUSION: The InBody BP170 oscillometric home BP monitor fulfilled all the requirements of the AAMI/ESH/ISO Universal Standard (ISO 81060-2:2018) in general population and can be recommended for clinical use.

Diagnostic accuracy of a novel cuffless self-blood pressure monitor for atrial fibrillation screening in the elderly.

Blood pressure (BP) monitors equipped with atrial fibrillation (AF) detection algorithm are attractive screening tools for AF in elderly hypertensives. This study assessed the diagnostic accuracy of a novel cuffless pocket-size self-BP monitor (Freescan, Maisense) equipped with an AF detection algorithm, which displays results for the detection of "AF" or "Arrhythmia" during routine BP measurement. Subjects aged >65 years or 60-65 years with hypertension, diabetes, or cardiovascular disease were subjected to BP measurements using the Freescan device with simultaneous continuous Holter electrocardiography (ECG) monitoring. Readings with device notification "Instability" (29%) or "Error" (20%) were discarded. Data from 136 subjects with five valid Freescan BP measurements were analyzed (age 73.8 ± 7.1 years, males 63%, treated hypertensives 88%, AF in ECG 21%). Analysis of 680 Freescan readings vs ECG revealed specificity 99%, sensitivity 67%, and diagnostic accuracy 93% for AF diagnosis. When the "Arrhythmia" notification was considered as AF diagnosis, the sensitivity was improved (93%, 96%, and 93%, respectively). Analysis of AF diagnosis in subjects (diagnosis defined as at least three of five readings indicating "AF" or "Arrhythmia") revealed specificity, sensitivity, and diagnostic accuracy for AF detection at 94%, 100%, and 95%, respectively. These data suggest that the Freescan cuffless device could be used as a useful screening tool for AF detection during routine self-measurement of BP in the elderly.

Unattended versus attended automated office blood pressure: Systematic review and meta-analysis of studies using the same methodology for both methods.

There is increasing interest in unattended automated office blood pressure (OBP) measurement, which gives lower blood pressure values than the conventional auscultatory OBP. Whether unattended automated OBP differs from standardized attended automated OBP performed using the same device and measurement protocol remains uncertain. A systematic review and meta-analysis of studies (aggregate data) comparing unattended vs attended automated OBP using the same device and measurement protocol (conditions, number of measurements, visits) was performed. Ten eligible studies (n = 1004, weighted age 60.8 ± 4.2 [SD] years, 55% males) were analyzed. Unattended OBP (pooled systolic/diastolic 133.9 [95% CI: 129.7, 138]/80.6 [95% CI: 77, 84.2] mm Hg) did not differ from attended OBP (135.3 [95% CI: 130.9, 139.6]/81 [95% CI: 77.6, 84.3] mm Hg); pooled systolic OBP difference -1.3, 95% CI: -4.3, 1.7 mm Hg and diastolic -0.4, 95% CI: -1.2, 0.3 mm Hg. Nine of ten studies achieved high quality score and no publication bias was identified. Meta-regression analysis did not reveal any effect of age, gender, or attended systolic OBP on the unattended-attended systolic OBP difference (P = NS for all). However, there was a trend toward higher attended than unattended OBP at higher OBP levels. These data suggest that, when the same device and measurement protocol are used, attended automated OBP provides similar blood pressure values as unattended automated OBP. Although unattended automated OBP is theoretically advantageous as it ensures that standardized conditions and measurement protocol are used, attended automated OBP, if carefully performed, appears to be a reasonable and practical alternative.