Hard Clinical Outcomes Research Articles

Characterization of sleep-disordered breathing in children with Duchenne muscular dystrophy by the American Academy of Sleep Medicine criteria vs disease-specific criteria: what are the differences?

Individuals with Duchenne muscular dystrophy (DMD) frequently develop sleep-disordered breathing. Noninvasive ventilation is often prescribed for sleep-disordered breathing treatment based on the American Academy of Sleep Medicine (AASM) criteria. In 2018, DMD disease-specific criteria for sleep-disordered breathing were established. Our study aimed to examine the clinical interpretation differences using these different criteria. We performed a multicenter, retrospective chart review of children with DMD followed at The Hospital for Sick Children, Toronto, Canada, and Rady Children's Hospital, San Diego, California, who underwent polysomnography from August 1, 2012, to February 29, 2020. Baseline characteristics and polysomnography data were summarized using descriptive statistics. Agreement for the diagnosis of sleep-disordered breathing evaluated by kappa statistics and sensitivity/specificity analysis was assessed. One hundred five male children with DMD (mean ± SD age: 12.1 ± 3.8 years; body mass index z score: 0.2 ± 2.3) were included. The proportions of children with DMD that met at least 1 AASM criterion and at least 1 DMD criterion were 45.7% and 67.6%, respectively. We found that 32.4% of children met neither AASM nor DMD criteria. Overall agreement between AASM and DMD criteria was moderate (k = 0.57). There was almost perfect agreement in sleep apnea diagnosis (k = 0.90); however, there was only slight agreement in hypoventilation diagnosis (k = 0.12) between AASM and DMD criteria. There were more children with DMD diagnosed with nocturnal hypoventilation and prescribed noninvasive ventilation using DMD criteria compared with AASM criteria. Future studies should address whether the prescription of noninvasive ventilation for children with DMD based on both criteria is associated with different clinical outcomes. Hurvitz MS, Sunkonkit K, Massicotte C, Li R, Bhattacharjee R, Amin R. Characterization of sleep-disordered breathing in children with Duchenne muscular dystrophy by the American Academy of Sleep Medicine criteria vs disease-specific criteria: what are the differences? J Clin Sleep Med. 2022;18(2):609-615.

The Susceptibility of Healthy People to COVID-19 Infection and the Role of ACE2

The COVID-19 virus has caused many deaths of people worldwide since the pandemic began. However, no definitive treatment for this infection has been discovered so far. It has been shown that comorbidities such as diabetes, hypertension and cardiovascular diseases are associated with an increased risk of SARS-COV-2 infection. Interestingly, SARS-COV-2, like SARS-COV, uses the ACE2 gene to enter the host cell. Also, changes or imbalance in ACE2.ACE can affect SARS-COV-2 susceptibility, related outcomes and mortality. Regarding the crucial role of ACE2 protein in COVID-19 infection, the effect of different factors such as age, BMI, physical activity levels, nutritional status, altitude, as well as blood group was assessed on the level of this protein. Further, to our knowledge, no study has been conducted to examine factors that increase or decrease the risk of COVID-19 and its related severity and outcome in normal subjects emphasizing the pivotal role of ACE2. Therefore, the primary purpose of this study was to investigate the involved mechanisms of ACE2 protein and other risk factors causing infection in different situations and finally, to introduce a safe, accurate, and cost-effective approach to prevent SARS-COV-2 infection and hard clinical outcomes in normal subjects.

Therapeutic Drug Monitoring Strategies for Envarsus in De Novo Kidney Transplant Patients Using Population Modelling and Simulations.

Tacrolimus, the cornerstone of transplantation immunosuppression, is a narrow therapeutic index drug with a low and highly variable bioavailability. Therapeutic drug monitoring based on trough level assessment is mandatory in order to target a personalised exposure and avoid both rejection and toxicity. Population pharmacokinetic (POPPK) models might be a useful tool for improving early attainment of target range by guiding initial doses until steady state is reached and trough levels can be reliably used as surrogate marker of exposure. Here we present the first POPPK for predicting the initial doses of the once-daily prolonged release tacrolimus Envarsus (LCPT) in adult kidney recipients. The model was developed exploiting the data from a recent pharmacokinetic randomised clinical study, in which 69 de novo kidney recipients, 33 of whom treated with LCPT, underwent an intensive blood sampling strategy for tacrolimus including four complete pharmacokinetic profiles. The complex and prolonged absorption of LCPT is well described by the three-phase model that incorporates body weight and CYP3A5 genotype as significant covariates accounting for a great proportion of the inter-patient variability: in particular, CYP3A5*1/*3 expressors had a 66% higher LCPT clearance. We have then generated by simulation a personalised dosing strategy based on the model that could improve the early attainment of therapeutic trough levels by almost doubling the proportion of patients within target range (69.3% compared to 36.1% with the standard body weight-based approach) on post-transplantation day4 and significantly reduce the proportion of overexposed patients at risk of toxicity. A POPPK model was successfully developed for LCPT in de novo kidney recipients. The model could guide a personalised dosing strategy early after transplantation. For the model to be translated into clinical practice, its beneficial impact of earlier attainment of therapeutic trough levels should be demonstrated on hard clinical outcomes in further studies.

Anabolic hormones and heart failure with preserved ejection fraction: looking for Ariadne's thread.

Heart failure with preserved ejection fraction (HFpEF) is a complex clinical syndrome that accounts for more than half of all heart failure patients. Identification, early diagnosis and management of patients are still complex, and no targeted treatment is available, since all tested drugs were not able to lower hard clinical outcomes. A multi-hormonal deficiency syndrome has been described in HFpEF patients suggesting that different hormones may represent new biomarkers of the disease, but their clinical utility is still debated. The natriuretic peptides are the cornerstone biomarker in heart failure, predicting cardiovascular death and heart failure hospitalization. Testosterone and DHEA-S deficiencies have been reported in HFpEF and associated with right ventricular impairment and diastolic dysfunction. IGFBP-1/IGF-1 axis correlates with echocardiographic parameters of HFpEF patients and with several prognostic biomarkers including NT-proBNP and C reactive protein. Low triiodothyronine syndrome is frequently found in HFpEF and thyroid hormones should represent a potential biomarker of risk stratification and prognosis.

Protecting children from tobacco-related harm in private vehicles

Protecting children from tobacco-related harm in private vehicles

Comparative safety of percutaneous ventricular assist device and intra-aortic balloon pump in acute myocardial infarction-induced cardiogenic shock

BackgroundThe relative safety of percutaneous left ventricular assist device (pVAD) and intra-aortic balloon pump (IABP) in patients with cardiogenic shock after acute myocardial infarction remain unknown.MethodsMultiple databases were searched to...

Closed loop stimulation in heart failure patients with severe chronotropic incompetence: responder versus non-responders

Abstract Funding Acknowledgements Type of funding sources: Private company. Main funding source(s): Biotronik SE & Co. KG Woermannkehre 1 12359 Berlin Background The prevalence of chronotropic incompetence (CI) in heart failure (HF) population is high and negatively impacts prognosis. Rate-adaptive pacing (RAP) is an important treatment option for CI. However, only a proportion of HF patients treated with cardiac resynchronisation therapy (CRT) devices benefit from accelerometer-based RAP in terms of exercise tolerance, functional capacity, and quality of life (QoL). Further research is needed to identify patient characteristics predicting positive response to RAP, and to evaluate performance of alternative sensors such as closed loop stimulation (CLS) driven by cardiac impedance measurements. An optimal outcome measure is represented by ventilatory efficiency (VE) slope during cardio-pulmonary exercise test (CPX) because of superior prognostic value. Purpose The purpose of the BIO|Create pilot study was to assess the benefit of CLS in CRT patients with CI. In this predefined subanalysis, we identify predictors of positive response to CLS (reduction of VE slope by ≥5%) and compare study outcomes in responders vs non-responders. Methods The study enrolled CRT patients with NYHA class II or III and severe CI (<75% of age-predicted maximum heart rate [HR] or <50% of HR reserve utilised at end-exercise). Patients were randomised to DDD-CLS mode or to DDD pacing at 40 beats/min for 1 month, followed by crossover for another month. At 1- and 2-month follow-ups, exercise tolerance was assessed by treadmill CPX, functional capacity by 6-min walk test, and QoL by the EQ-5D-5L and Minnesota Living with HF (MLHFQ) questionnaires. Results Among 17 patients with full follow-up datasets, 8 (47%) were responders to CLS. Compared to non-responders, responders had larger left ventricular (LV) ejection fraction at baseline (46 ± 3 vs 36 ± 9 %; p = 0.0070), smaller end-diastolic (121 ± 34 vs 181 ± 41 ml; p = 0.0085) and end-systolic (65 ± 23 vs 114 ± 39 ml; p = 0.0076) LV volumes, and were predominantly in NYHA class II (p = 0.0498). For study outcomes, the mean difference between DDD-CLS and DDD-40 modes in responders vs non-responders was - 6.1 (-16.4%) vs +2.7 (+6.8%) for VE slope (both p < 0.05), +0.5 vs -0.2 ml/min (O2 uptake efficiency slope), +1.3 vs -0.3 ml/kg/min (peak O2 uptake), +1.4 vs -0.75 mmHg (end-exercise end-tidal CO2), 16 vs 7 m (6-min walk distance), 0.08 vs 0.06 (EQ-5D-5L index), 1.9 vs 0 (EQ-5D-5L scale), and -2.5 vs +1.75 (MLHFQ). Conclusions For the first time, predictors for positive outcome of RAP in CRT patients have been identified. Patients with less advanced HF were responders to RAP driven by CLS principle. In addition, a consistent increase in exercise and functional capacity and QoL in these patients could be achieved. In contrast, patients with advanced HF experienced worse exercise capacity and QoL during RAP, suggesting caution if RAP is desirable due to CI. Further clinical research is needed to evaluate if positive response to RAP can improve hard clinical outcomes.

Atrial Fibrillation Burden and Clinical Outcomes in HeartFailure: The CASTLE-AF Trial.

This subanalysis of the CASTLE-AF (Catheter Ablation vs. Standard Conventional Treatment in Patients With LV Dysfunction and AF) trial aimed to address the association between atrial fibrillation (AF) recurrence, AF burden, and hard clinical outcomes in heart failure (HF) patients with AF. The CASTLE-AF trial demonstrated the benefit of CA compared to pharmacological treatment in decreasing mortality and CV hospitalizations in patients with AF and HFrEF. However, the impact of AF recurrence and AF burden after ablation on long-term treatment benefit remains unknown. The CASTLE-AF protocol randomized 363 patients with coexisting HF and AF in a multicenter prospective controlled fashion to catheter ablation (n=179) versus pharmacological therapy (n=184). Two hundred eighty patients were included in this subanalysis (as-treated), 128 of them underwent ablation and 152 received pharmacological treatment. All patients had implanted dual chamber or biventricular implantable defibrillators with activated home monitoring capabilities. The individual AF burden was calculated as the percentage of the atrial arrhythmia time per day. AF burden at baseline was not predictive of the primary endpoint (p=0.473) or all-cause mortality (p=0.446). AF recurrence (defined as any episode >30 s) did not show any relationship with the primary endpoints of mortality and occurrence of HF, irrespective of the treatment arm. An AF burden below 50% after 6months of catheter ablation, was associated with a significant decrease in primary composite outcome (hazard ratio [HR]: 0.33; 95% confidence interval [CI]: 0.15 to 0.71; p=0.014) and all-cause mortality (HR: 0.23; 95% CI: 0.07 to 0.71; p=0.031). The risk of the primary endpoint or mortality was directly related to a low (<50%) or high (≥50%) AF burden at 6months post-ablation. AF burden at 6months was predictive of hard clinical outcomes in HF patients with AF. The first recurrent atrial tachyarrhythmia episode >30s after ablation was not associated with improvement in mortality andhospitalization for HF. (Catheter Ablation vs. Standard Conventional Treatment in Patients With LV DysfunctionandAF [CASTLE-AF]; NCT00643188).

Effects of Hospital-Based Comprehensive Medication Reviews Including Postdischarge Follow-up on Older Patients’ Use of Health Care

Suboptimal use of medications is a leading cause of health care-related harm. Medication reviews improve medication use, but evidence of the possible benefit of inpatient medication review for hard clinical outcomes after discharge is scarce. To study the effects of hospital-based comprehensive medication reviews (CMRs), including postdischarge follow-up of older patients' use of health care resources, compared with only hospital-based reviews and usual care. The Medication Reviews Bridging Healthcare trial is a cluster randomized crossover trial that was conducted in 8 wards with multiprofessional teams at 4 hospitals in Sweden from February 6, 2017, to October 19, 2018, with 12 months of follow-up completed December 6, 2019. The study was prespecified in the trial protocol. Outcome assessors were blinded to treatment allocation. In total, 2644 patients aged 65 years or older who had been admitted to 1 of the study wards for at least 1 day were included. Data from the modified intention-to-treat population were analyzed from December 10, 2019, to September 9, 2020. Each ward participated in the trial for 6 consecutive 8-week periods. The wards were randomized to provide 1 of 3 treatments during each period: CMR, CMR plus postdischarge follow-up, and usual care without a clinical pharmacist. The primary outcome measure was the incidence of unplanned hospital visits (admissions plus emergency department visits) within 12 months. Secondary outcomes included medication-related admissions, visits with primary care clinicians, time to first unplanned hospital visit, mortality, and costs of hospital-based care. Of the 2644 participants, 7 withdrew after inclusion, leaving 2637 for analysis (1357 female [51.5%]; median age, 81 [interquartile range, 74-87] years; median number of medications, 9 [interquartile range, 5-13]). In the modified intention-to-treat analysis, 922 patients received CMR, 823 received CMR plus postdischarge follow-up, and 892 received usual care. The crude incidence rate of unplanned hospital visits was 1.77 per patient-year in the total study population. The primary outcome did not differ between the intervention groups and usual care (adjusted rate ratio, 1.04 [95% CI, 0.89-1.22] for CMR and 1.15 [95% CI, 0.98-1.34] for CMR plus postdischarge follow-up). However, CMR plus postdischarge follow-up was associated with an increased incidence of emergency department visits within 12 months (adjusted rate ratio, 1.29; 95% CI, 1.05-1.59) compared with usual care. There were no differences between treatment groups regarding other secondary outcomes. In this study of older hospitalized patients, CMR plus postdischarge follow-up did not decrease the incidence of unplanned hospital visits. The findings do not support the performance of hospital-based CMRs as conducted in this trial. Alternative forms of medication reviews that aim to improve older patients' health outcomes should be considered and subjected to randomized clinical trials. ClinicalTrials.gov Identifier: NCT02986425.

Routine Oxygen Therapy Does Not Improve Health-Related Quality of Life in Patients With Acute Myocardial Infarction-Insights From the Randomized DETO2X-AMI Trial.

Background: After decades of ubiquitous oxygen therapy in all patients with acute myocardial infarction (MI), recent guidelines are more restrictive based on lack of efficacy in contemporary trials evaluating hard clinical outcomes in patients without hypoxemia at baseline. However, no evidence regarding treatment effects on health-related quality of life (HRQoL) exists. In this study, we investigated the impact of routine oxygen supplementation on HRQoL 6–8 weeks after hospitalization with acute MI. Secondary objectives included analyses of MI subtypes, further adjustment for infarct size, and oxygen saturation at baseline and 1-year follow-up.Methods: In the DETermination of the role of Oxygen in suspected Acute Myocardial Infarction (DETO2X-AMI) trial, 6,629 normoxemic patients with suspected MI were randomized to oxygen at 6 L/min for 6–12 h or ambient air. In this prespecified analysis, patients younger than 75 years of age with confirmed MI who had available HRQoL data by European Quality of Life Five Dimensions questionnaire (EQ-5D) in the national registry were included. Primary endpoint was the EQ-5D index assessed by multivariate linear regression at 6–10 weeks after MI occurrence.Results: A total of 3,086 patients (median age 64, 22% female) were eligible, 1,518 allocated to oxygen and 1,568 to ambient air. We found no statistically significant effect of oxygen therapy on EQ-5D index (−0.01; 95% CI: −0.03–0.01; p = 0.23) or EQ-VAS score (−0.57; 95% CI: −1.88–0.75; p = 0.40) compared to ambient air after 6–10 weeks. Furthermore, no significant difference was observed between the treatment groups in EQ-5D dimensions. Results remained consistent across MI subtypes and at 1-year follow-up, including further adjustment for infarct size or oxygen saturation at baseline.Conclusions: Routine oxygen therapy provided to normoxemic patients with acute MI did not improve HRQoL up to 1 year after MI occurrence.Clinical Trial Registration: ClinicalTrials.gov number, NCT01787110.

Screening for Atrial Fibrillation in the Older Population

Atrial fibrillation (AF) is a major cause of preventable strokes. Screening asymptomatic individuals for AF may increase anticoagulant use for stroke prevention. To evaluate 2 home-based AF screening interventions. This multicenter randomized clinical trial recruited individuals from primary care practices aged 75 years or older with hypertension and without known AF. From April 5, 2015, to March 26, 2019, 856 participants were enrolled from 48 practices. The control group received standard care (routine clinical follow-up plus a pulse check and heart auscultation at baseline and 6 months). The screening group received a 2-week continuous electrocardiographic (cECG) patch monitor to wear at baseline and at 3 months, in addition to standard care. The screening group also received automated home blood pressure (BP) machines with oscillometric AF screening capability to use twice-daily during the cECG monitoring periods. With intention-to-screen analysis, the primary outcome was AF detected by cECG monitoring or clinically within 6 months. Secondary outcomes included anticoagulant use, device adherence, and AF detection by BP monitors. Of the 856 participants, 487 were women (56.9%); mean (SD) age was 80.0 (4.0) years. Median cECG wear time was 27.4 of 28 days (interquartile range [IQR], 18.4-28.0 days). In the primary analysis, AF was detected in 23 of 434 participants (5.3%) in the screening group vs 2 of 422 (0.5%) in the control group (relative risk, 11.2; 95% CI, 2.7-47.1; P = .001; absolute difference, 4.8%; 95% CI, 2.6%-7.0%; P < .001; number needed to screen, 21). Of those with cECG-detected AF, median total time spent in AF was 6.3 hours (IQR, 4.2-14.0 hours; range 1.3 hours-28 days), and median duration of the longest AF episode was 5.7 hours (IQR, 2.9-12.9 hours). Anticoagulation was initiated in 15 of 20 patients (75.0%) with cECG-detected AF. By 6 months, anticoagulant therapy had been prescribed for 18 of 434 participants (4.1%) in the screening group vs 4 of 422 (0.9%) in the control group (relative risk, 4.4; 95% CI, 1.5-12.8; P = .007; absolute difference, 3.2%; 95% CI, 1.1%-5.3%; P = .003). Twice-daily AF screening using the home BP monitor had a sensitivity of 35.0% (95% CI, 15.4%-59.2%), specificity of 81.0% (95% CI, 76.7%-84.8%), positive predictive value of 8.9% (95% CI, 4.9%-15.5%), and negative predictive value of 95.9% (95% CI, 94.5%-97.0%). Adverse skin reactions requiring premature discontinuation of cECG monitoring occurred in 5 of 434 participants (1.2%). In this randomized clinical trial, among older community-dwelling individuals with hypertension, AF screening with a wearable cECG monitor was well tolerated, increased AF detection 10-fold, and prompted initiation of anticoagulant therapy in most cases. Compared with continuous ECG, intermittent oscillometric screening with a BP monitor was an inferior strategy for detecting paroxysmal AF. Large trials with hard clinical outcomes are now needed to evaluate the potential benefits and harms of AF screening. ClinicalTrials.gov Identifier: NCT02392754.

Functional Assessment of Coronary Artery Lesions-Old and New Kids on the Block.

Angiography is inaccurate in assessing functional significance of coronary lesions, and often stenoses deemed severe on angiographic assessment do not restrict coronary blood flow at rest or with maximal dilatation. Angiography-guided revascularization has not shown improvement in hard clinical outcomes in stable ischemic heart disease (SIHD). Most current guidelines for SIHD recommend invasive functional assessment of lesions to guide revascularization if prior evidence of ischemia is not available. There has been several recent advances and development of novel methods in this arena. Various contemporary clinical trials have been undertaken for validation of these indices. Here we review the physiological basis, tools, techniques, and evidence base for various invasive (resting as well as hyperemic) and noninvasive methods for functional assessment of coronary lesions. Left main stenosis, bifurcation lesions, serial stenosis, and acute coronary syndrome each causes unique disequilibrium that may affect measurements and require special considerations for accurate functional assessment.

Ultra-processed foods and human health: What do we already know and what will further research tell us?

Ultra-processed foods and human health: What do we already know and what will further research tell us?

Clinical outcomes in a primary-level non-communicable disease programme for Syrian refugees and the host population in Jordan: A cohort analysis using routine data.

BackgroundLittle is known about the content or quality of non-communicable disease (NCD) care in humanitarian settings. Since 2014, Médecins Sans Frontières (MSF) has provided primary-level NCD services in Irbid, Jordan, targeting Syrian refugees and vulnerable Jordanians who struggle to access NCD care through the overburdened national health system. This retrospective cohort study explored programme and patient-level patterns in achievement of blood pressure and glycaemic control, patterns in treatment interruption, and the factors associated with these patterns.Methods and findingsThe MSF multidisciplinary, primary-level NCD programme provided facility-based care for cardiovascular disease, diabetes, and chronic respiratory disease using context-adapted guidelines and generic medications. Generalist physicians managed patients with the support of family medicine specialists, nurses, health educators, pharmacists, and psychosocial and home care teams. Among the 5,045 patients enrolled between December 2014 and December 2017, 4,044 eligible adult patients were included in our analysis, of whom 72% (2,913) had hypertension and 63% (2,546) had type II diabetes. Using visits as the unit of analysis, we plotted the following on a monthly basis: mean blood pressure among hypertensive patients, mean fasting blood glucose and HbA1c among type II diabetic patients, the proportion of each group achieving control, mean days of delayed appointment attendance, and the proportion of patients experiencing a treatment interruption. Results are presented from programmatic and patient perspectives (using months since programme initiation and months since cohort entry/diagnosis, respectively). General linear mixed models explored factors associated with clinical control and with treatment interruption. Mean age was 58.5 years, and 60.1% (2,432) were women. Within the programme’s first 6 months, mean systolic blood pressure decreased by 12.4 mm Hg from 143.9 mm Hg (95% CI 140.9 to 146.9) to 131.5 mm Hg (95% CI 130.2 to 132.9) among hypertensive patients, while fasting glucose improved by 1.12 mmol/l, from 10.75 mmol/l (95% CI 10.04 to 11.47) to 9.63 mmol/l (95% CI 9.22 to 10.04), among type II diabetic patients. The probability of achieving treatment target in a visit was 63%–75% by end of 2017, improving with programme maturation but with notable seasonable variation. The probability of experiencing a treatment interruption declined as the programme matured and with patients’ length of time in the programme. Routine operational data proved useful in evaluating a humanitarian programme in a real-world setting, but were somewhat limited in terms of data quality and completeness. We used intermediate clinical outcomes proven to be strongly associated with hard clinical outcomes (such as death), since we had neither the data nor statistical power to measure hard outcomes.ConclusionsGood treatment outcomes and reasonable rates of treatment interruption were achieved in a multidisciplinary, primary-level NCD programme in Jordan. Our approach to using continuous programmatic data may be a feasible way for humanitarian organisations to account for the complex and dynamic nature of interventions in unstable humanitarian settings when undertaking routine monitoring and evaluation. We suggest that frequency of patient contact could be reduced without negatively impacting patient outcomes and that season should be taken into account in analysing programme performance.

The role of liver steatosis as measured with transient elastography and transaminases on hard clinical outcomes in patients with COVID-19.

Liver injury has been widely described in patients with Coronavirus disease 2019 (COVID-19). We aimed to study the effect of liver biochemistry alterations, previous liver disease, and the value of liver elastography on hard clinical outcomes in COVID-19 patients. We conducted a single-center prospective observational study in 370 consecutive patients admitted for polymerase chain reaction (PCR)-confirmed COVID-19 pneumonia. Clinical and laboratory data were collected at baseline and liver parameters and clinical events recorded during follow-up. Transient elastography [with Controlled Attenuation Parameter (CAP) measurements] was performed at admission in 98 patients. All patients were followed up until day 28 or death. The two main outcomes of the study were 28-day mortality and the occurrence of the composite endpoint intensive care unit (ICU) admission and/or death. Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels were elevated at admission in 130 patients (35%) and 167 (45%) patients, respectively. Overall, 14.6% of patients presented the composite endpoint ICU and/or death. Neither ALT elevations, prior liver disease, liver stiffness nor liver steatosis (assessed with CAP) had any effect on outcomes. However, patients with abnormal baseline AST had a higher occurrence of the composite ICU/death (21% versus 9.5%, p = 0.002). Patients ⩾65 years and with an AST level > 50 U/ml at admission had a significantly higher risk of ICU and/or death than those with AST ⩽ 50 U/ml (50% versus 13.3%, p < 0.001). In conclusion, mild liver damage is prevalent in COVID-19 patients, but neither ALT elevation nor liver steatosis influenced hard clinical outcomes. Elevated baseline AST is a strong predictor of hard outcomes, especially in patients ⩾65 years.

Enoxaparin dose impacts blood cell phenotypes during mild SARS-CoV-2 infection: the observational single-center study.

Coronavirus disease 2019 (COVID-19) is associated with various hemostatic abnormalities requiring constant search for better delicate antithrombotic management in these high-risk patients. The choice and the optimal dose of anticoagulant is important, but unclear, especially for mild COVID-19. Enoxaparin has been tested in several COVID trials with mixed results regarding hard clinical outcomes including mortality. We analyzed clinical, laboratory data and changes in platelets, erythrocytes and leukocytes by scanning electron microscopy on admission and at hospital discharge in patients with confirmed COVID-19 treated with enoxaparin (n = 31) and matched healthy controls (n = 32) in a retrospective observational study. The data were triaged by enoxaparin dose comparing 40 mg/daily prophylactic enoxaparin dose (PED) with 80 mg/daily therapeutic (TED) regimens. All patients experienced mild disease, none required pulmonary support, and all survived. The impact of enoxaparin dose was prominent for platelets and erythrocytes, but less evident for leukocytes. PED was associated with significant platelet activation, diminished numbers of silent nonactive discoid cells, and increased number and size of platelet microaggregates with leukocyte involvement. In contrast, TED did not cause extra platelet activation, while circulating platelet microaggregates were smaller and lacking leukocytes in their construction. PED caused significant increase of erythrocyte-platelet aggregates formation, and numerically higher proportion of circulating echinocytes. TED was associated with significant decrease of rouleaux sludge formation compared to only some trend after PED. Changes in leukocytes were less dependent on enoxaparin dose. However, PED has been associated with enhanced aggregate formation in 7 out of 10 patients, while trap net formation has been decreased in 17 out of 21 TED patients. We conclude that over hospital stay TED was superior to PED in patients with mild COVID-19. The inability of PED to adequately protect major circulating blood cells is probably due to enhanced clearance or/and diminished bioavailability of enoxaparin during COVID. These retrospective observational small sample size data may be relevant to better understanding of the mixed results in controlled outcome-driven trials exploring optimal COVID-19 anticoagulant strategies.

To Retrograde Autologous Prime or Not?

To Retrograde Autologous Prime or Not?

Blood pressure telemonitoring and remote counseling of hypertensive patients: pros and cons

Home blood pressure monitoring (HBPM) is strongly recommended by current guidelines as an effective out-of-office diagnostic and monitoring tool in patients with hypertension (HTN). However, there are personal, cultural, logistic difficulties owing to low effectiveness of HBPM. These put HBPM at a disadvantage in routine clinical practice. As such, telehealth solutions are of special interest nowadays, particularly blood pressure telemonitoring (BPTM) with or without remote counseling. BPTM might become something of digital assistant in the long-term patients’ follow-up and it fits well into the practice of continuity of medical care. The purpose of this review is to highlight not only the benefits of BPTM, but important discrepancies that may impede its widespread implementation in everyday clinical work. Critical comments address the lack of long-term, high-quality studies, absence of hard clinical outcomes and uncertainty on the best technical performance.

Abstract 13660: Initial Revascularization in Chronic Coronary Syndromes With Myocardial Ischemia

Introduction: Ischemic heart disease is the leading cause of death worldwide. It is unknown whether initial revascularization using percutaneous coronary intervention (PCI) or coronary artery bypass graft surgery (CABG) plus optimal medical therapy (OMT) in patients with chronic coronary syndromes (CCS), obstructive coronary artery disease (CAD) and myocardial ischemia improves hard clinical outcomes compared to OMT alone. Hypothesis: In CCS patients with obstructive CAD and documented myocardial ischemia, initial revascularization plus OMT does not reduce death or nonfatal myocardial infarction (MI) compared to OMT alone. Methods: We searched Ovid Medline, Embase, Scopus, and Cochrane Library databases from inception to March 2020 for randomized controlled trials (RCTs) of PCI or CABG and OMT vs OMT alone for CCS patients in whom stents and statins were used in more than 50% of patients. Random-effects models were used to estimate average treatment effects across trials. The co-primary outcomes were all-cause death and nonfatal MI at 5 years. Results: Six RCTs were identified that randomized 10,020 CCS patients. At 5 years, among 5,025 CCS patients assigned to revascularization plus OMT, there were 492 deaths (9.8%) compared to 482 deaths among 4,995 patients (9.6%) assigned to OMT (OR, 1.01, 95% CI: 0.88-1.16; P=0.87). There were 521 nonfatal MIs (10.3%) in those assigned to revascularization plus OMT compared with 593 MIs (11.9%) in those assigned to OMT arms (OR, 0.78, 95% CI: 0.58-1.05; P=0.10). In subgroup analysis, nonfatal MI was not reduced by PCI plus OMT (OR, 0.95, 95% CI: 0.74-1.23, P=0.71) but was significantly reduced in studies of CABG plus OMT compared to OMT alone (OR, 0.38, 95% CI: 0.23-0.64, P&lt;0.001). The overall effect of CABG on reducing nonfatal MI was significantly greater than that of PCI (P=0.002). Conclusions: In patients with CCS and myocardial ischemia, initial revascularization with PCI or CABG plus OMT was not associated with a reduction in death at 5 years compared to OMT alone. CABG plus OMT reduced nonfatal MI compared to OMT alone whereas PCI did not. These findings suggest important differences in MI outcomes between those who undergo CABG vs. PCI, but no overall difference in mortality compared with OMT alone.

Evidence-Based Policy Making for Public Health Interventions in Cardiovascular Diseases: Formally Assessing the Feasibility of Clinical Trials.

Implementation of prevention policies has often been impeded or delayed due to the lack of randomized controlled trials (RCTs) with hard clinical outcomes (eg, incident disease, mortality). Despite the prominent role of RCTs in health care, it may not always be feasible to conduct RCTs of public health interventions with hard outcomes due to logistical and ethical considerations. RCTs may also lack external validity and have limited generalizability. Currently, there is insufficient guidance for policymakers charged with establishing evidence-based policy to determine whether an RCT with hard outcomes is needed before policy recommendations. In this context, the purpose of this article is to assess, in a case study, the feasibility of conducting an RCT of the oft-cited issue of sodium reduction on cardiovascular outcomes and then propose a framework for decision-making, which includes an assessment of the feasibility of conducting an RCT with hard clinical outcomes when such trials are unavailable. We designed and assessed the feasibility of potential individual- and cluster-randomized trials of sodium reduction on cardiovascular outcomes. Based on our assumptions, a trial using any of the designs considered would require tens of thousands of participants and cost hundreds of millions of dollars, which is prohibitively expensive. Our estimates may be conservative given several key challenges, such as the unknown costs of sustaining a long-term difference in sodium intake, the effect of differential cotreatment with antihypertensive medications, and long lag time to clinical outcomes. Thus, it would be extraordinarily difficult to conduct such a trial, and despite the high costs, would still be at substantial risk for a spuriously null result. A robust framework, such as the one we developed, should be used to guide policymakers when establishing evidence-based public health interventions in the absence of trials with hard clinical outcomes.