Clinical Characteristics and Risk Factors of Respiratory Failure in a Cohort of Young Patients Requiring Hospital Admission with SARS-CoV2 Infection in Spain: Results of the Multicenter SEMI-COVID-19 Registry

BackgroundAge is a risk factor for COVID severity. Most studies performed in hospitalized patients with SARS-CoV2 infection have shown an over-representation of older patients and consequently few have properly defined COVID-19 in younger patients who require hospital admission. The aim of the present study was to analyze the clinical characteristics and risk factors for the development of respiratory failure among young (18 to 50 years) hospitalized patients with COVID-19.MethodsThis retrospective nationwide cohort study included hospitalized patients from 18 to 50 years old with confirmed COVID-19 between March 1, 2020, and July 2, 2020. All patient data were obtained from the SEMI-COVID Registry. Respiratory failure was defined as the ratio of partial pressure of arterial oxygen to fraction of inspired oxygen (PaO2/FiO2 ratio) ≤200 mmHg or the need for mechanical ventilation and/or high-flow nasal cannula or the presence of acute respiratory distress syndrome.ResultsDuring the recruitment period, 15,034 patients were included in the SEMI-COVID-19 Registry, of whom 2327 (15.4%) were younger than 50 years. Respiratory failure developed in 343 (14.7%), while mortality occurred in 2.3%. Patients with respiratory failure showed a higher incidence of major adverse cardiac events (44 (13%) vs 14 (0.8%), p<0.001), venous thrombosis (23 (6.7%) vs 14 (0.8%), p<0.001), mortality (43 (12.5%) vs 7 (0.4%), p<0.001), and longer hospital stay (15 (9–24) vs 6 (4–9), p<0.001), than the remaining patients. In multivariate analysis, variables associated with the development of respiratory failure were obesity (odds ratio (OR), 2.42; 95% confidence interval (95% CI), 1.71 to 3.43; p<0.0001), alcohol abuse (OR, 2.40; 95% CI, 1.26 to 4.58; p=0.0076), sleep apnea syndrome (SAHS) (OR, 2.22; 95% CI, 1.07 to 3.43; p=0.032), Charlson index ≥1 (OR, 1.77; 95% CI, 1.25 to 2.52; p=0.0013), fever (OR, 1.58; 95% CI, 1.13 to 2.22; p=0.0075), lymphocytes ≤1100 cells/μL (OR, 1.67; 95% CI, 1.18 to 2.37; p=0.0033), LDH >320 U/I (OR, 1.69; 95% CI, 1.18 to 2.42; p=0.0039), AST >35 mg/dL (OR, 1.74; 95% CI, 1.2 to 2.52; p=0.003), sodium <135 mmol/L (OR, 2.32; 95% CI, 1.24 to 4.33; p=0.0079), and C-reactive protein >8 mg/dL (OR, 2.42; 95% CI, 1.72 to 3.41; p<0.0001).ConclusionsYoung patients with COVID-19 requiring hospital admission showed a notable incidence of respiratory failure. Obesity, SAHS, alcohol abuse, and certain laboratory parameters were independently associated with the development of this complication. Patients who suffered respiratory failure had a higher mortality and a higher incidence of major cardiac events, venous thrombosis, and hospital stay.Supplementary InformationThe online version contains supplementary material available at 10.1007/s11606-021-07066-z.KEY WORDS: SARS-CoV2, COVID-19, young, respiratory failure, obesity, hyponatremia     

Beneficial and Harmful Effects of Monoclonal Antibodies for the Treatment and Prophylaxis of COVID-19: Systematic Review and Meta-Analysis

BackgroundWe systematically assessed beneficial and harmful effects of monoclonal antibodies for coronavirus disease 2019 (COVID-19) treatment, and prophylaxis in individuals exposed to severe acute respiratory syndrome coronavirus 2.MethodsWe searched 5 engines and 3 registries until November 3, 2021 for randomized controlled trials evaluating monoclonal antibodies vs control in hospitalized or non-hospitalized adults with COVID-19, or as prophylaxis. Primary outcomes were all-cause mortality, COVID-19-related death, and serious adverse events; hospitalization for non-hospitalized; and development of symptomatic COVID-19 for prophylaxis. Inverse variance random effects models were used for meta-analyses. Grading of Recommendations, Assessment, Development, and Evaluations methodology was used to assess certainty of evidence.ResultsTwenty-seven randomized controlled trials were included: 20 in hospitalized patients (n = 8253), 5 in non-hospitalized patients (n = 2922), and 2 in prophylaxis (n = 2680). In hospitalized patients, monoclonal antibodies slightly reduced mechanical ventilation (relative risk [RR] 0.74; 95% confidence interval [CI], 0.60-0.9; I² = 20%, low certainty of evidence) and bacteremia (RR 0.77; 95% CI, 0.64-0.92; I² = 7%, low certainty of evidence); evidence was very uncertain about the effect on adverse events (RR 1.31; 95% CI, 1.02-1.67; I² = 77%, very low certainty of evidence). In non-hospitalized patients, monoclonal antibodies reduced hospitalizations (RR 0.30; 95% CI, 0.17-0.53; I² = 0%, high certainty of evidence) and may slightly reduce serious adverse events (RR 0.47; 95% CI, 0.22-1.01; I² = 33%, low certainty of evidence). In prophylaxis studies, monoclonal antibodies probably reduced viral load slightly (mean difference ?0.8 log₁₀; 95% CI, ?1.21 to ?0.39, moderate certainty of evidence). There were no effects on other outcomes.ConclusionsMonoclonal antibodies had limited effects on most of the outcomes in COVID-19 patients, and when used as prophylaxis. Additional data are needed to determine their efficacy and safety.     

Acute kidney injury in hospitalized patients with COVID-19: A Portuguese cohort

IntroductionThe incidence of acute kidney injury (AKI) in coronavirus disease 2019 (COVID-19) patients ranges from 0.5% to 35% and has been associated with worse prognosis. The purpose of this study was to evaluate the incidence, severity, duration, risk factors and prognosis of AKI in hospitalized patients with COVID-19.MethodsWe conducted a retrospective single-center analysis of 192 hospitalized COVID-19 patients from March to May of 2020. AKI was diagnosed using the Kidney Disease Improving Global Outcome (KDIGO) classification based on serum creatinine (SCr) criteria. Persistent and transient AKI were defined according to the Acute Disease Quality Initiative (ADQI) workgroup definitions.ResultsIn this cohort of COVID-19 patients, 55.2% developed AKI (n = 106). The majority of AKI patients had persistent AKI (n = 64, 60.4%). Overall, in-hospital mortality was 18.2% (n = 35) and was higher in AKI patients (28.3% vs. 5.9%, p < 0.001, unadjusted OR 6.03 (2.22–16.37), p < 0.001). In this multivariate analysis, older age (adjusted OR 1.07 (95% CI 1.02–1.11), p = 0.004), lower Hb level (adjusted OR 0.78 (95% CI 0.60–0.98), p = 0.035), duration of AKI (adjusted OR 7.34 for persistent AKI (95% CI 2.37–22.72), p = 0.001) and severity of AKI (adjusted OR 2.65 per increase in KDIGO stage (95% CI 1.32–5.33), p = 0.006) were independent predictors of mortality.ConclusionAKI was frequent in hospitalized patients with COVID-19. Persistent AKI and higher severity of AKI were independent predictors of in-hospital mortality.     

Incidence of acute pulmonary embolism in COVID-19 patients: Systematic review and meta-analysis.

BackgroundAcute pulmonary embolism (PE) has been described as a frequent and prognostically relevant complication of COVID-19 infection.AimWe performed a systematic review and meta-analysis of the in-hospital incidence of acute PE among COVID-19 patients based on studies published within four months of COVID-19 outbreak.Material and MethodsSystematic Reviews and Meta-Analyses (PRISMA) guidelines were followed in abstracting data and assessing validity. We searched Medline, Scopus and Web of Science to locate all articles published up to August 1, 2020 reporting the incidence of acute PE (or lung thrombosis) in COVID-19 patients. The pooled in-hospital incidence of acute PE among COVID-19 patients was calculated using a random effects model and presenting the related 95% confidence interval (CI). Statistical heterogeneity was measured using the Higgins I² statistic.ResultsWe analysed data from 7178 COVID-19 patients [mean age 60.4 years] included in twenty-three studies. Among patients hospitalized in general wards and intensive care unit (ICU), the pooled in-hospital incidence of PE (or lung thrombosis) was 14.7% of cases (95% CI: 9.9–21.3%, I²=95.0%, p<0.0001) and 23.4% (95% CI:16.7–31.8%, I2=88.7%, p<0.0001), respectively. Segmental/sub-segmental pulmonary arteries were more frequently involved compared to main/lobar arteries (6.8% vs18.8%, p<0.001). Computer tomography pulmonary angiogram (CTPA) was used only in 35.3% of patients with COVID-19 infection across six studies.ConclusionsThe in-hospital incidence of acute PE among COVID-19 patients is higher in ICU patients compared to those hospitalized in general wards. CTPA was rarely used suggesting a potential underestimation of PE cases.     

Short- and long-term cardiovascular outcomes in insulin-treated versus non-insulin-treated diabetes mellitus patients after percutaneous coronary intervention: A systematic review and meta-analysis

AimsThis study aims to assess differences in severity of short-term (<1 year) and long-term (≥1 year) adverse CV outcomes after PCI in insulin-treated vs. non-insulin-treated diabetes mellitus (DM) patients.MethodsA systematic search on Pubmed and Embase led to the incorporation of 29 studies that compared post-percutaneous coronary interventional outcomes in insulin-treated and non-insulin-treated diabetes mellitus. Diabetes mellitus (type 2) was defined as fasting blood glucose (FBG) level of >7.0 mmol/L or with an oral glucose tolerance test (OGTT) level of >11.1 mmol/L at least on two separate occasions. Adverse CV outcomes were assessed in insulin-treated and non-insulin-treated DM after the PCI procedure considered for the analyses were mortality, MACE, TLR, TVR, MI, stent thrombosis, target lesion failure (TLF), and need for-post PCI CABG. Data were pooled and analyzed using Review Manager 5.3, and risk ratios (RR) with respective 95% confidence intervals (CI) were calculated.The statistical analyses were carried out by Review Manager v.5.3, and the data were pooled using a random-effects model. Risk ratios (RRs) with 95% confidence intervals (CI) were reported along with forest plots. The chi-square test was performed to assess for differences between the subgroups. Heterogeneity across studies was evaluated using Higgins I² statistics. Visual inspection of the funnel plot and Begg's regression test were used to assess publication bias.ResultsA total of 40,527 patients (11742 in the Insulin-treated diabetes mellitus group and 28785 in the non-insulin-treated DM group) who underwent PCI were included. The pooled analysis of short-term follow up outcomes preceding PCI demonstrated a significantly higher risk of mortality (RR = 1.75 [1.24,2.47]; p = 0.002), MI (RR = 1.81[1.14,2.87]; p = 0.01], stent thrombosis (RR = 1.63[1.13, 2.35]; p = 0.009) and target lesion revascularization (TLR) (RR = 1.29[1.02,1.63]; p = 0.03) in insulin-treated DM patients. Similarly, analysis of long-term follow-up studies depicted a significantly higher risk mortality (RR = 1.55 [1.22, 1.97]; p = 0.0003), MI (RR = 1.63 [1.35, 1.97]; p=<0.00001), MACE (R = 1.47 [1.31, 1.65]; p=<0.00001), stent thrombosis (RR = 1.54 [1.19,1.99]; p = 0.001), TLR (RR = 1.40 [1.18, 1.66]; p = 0.0001), target vessel revascularization (TVR) (RR = 1.35 [1.11, 1.64]; p = 0.003) in insulin-treated DM group after PCI versus non-insulin-treated DM patients.ConclusionDespite a tremendous technical success rate of multi-vessel stenting, people living with diabetes who were being treated with insulin had higher long-term, and short-term mortality rates, MI, TLR, TVR, and stroke compared to people living with diabetes who were being treated with means other than insulin and are more prone to detrimental cardiovascular outcomes.     

Effectiveness of tocilizumab in the treatment of hospitalized adults COVID-19: A systematic review and meta-analysis

Background:Since December 2019, the coronavirus disease (COVID-19) has spread worldwide, leading to a global health threat. This study aimed to investigate the effectiveness of tocilizumab in COVID-19 patients.Methods:We systematically searched PubMed, EMBASE, the Cochrane Central Register of Controlled Trials, and World Health Organization International Clinical Trials Registry Platform to March 10, 2021 for randomized controlled trials in which patients were randomly assigned to receive tocilizumab plus usual care or usual care alone in hospitalized adults with COVID-19. A random-effects meta-analysis model was used to pool studies. All data analyses were performed using Review Manager version 5.4.Results:Eleven studies with 6579 patients were included in our meta-analysis, of which 3406 and 3173 were assigned to tocilizumab and control groups, respectively. Tocilizumab significantly reduced the 28 to 30-day mortality (relative risk [RR] = 0.89, 95% confidence interval [CI] 0.80-0.99, P = .04), incidence of mechanical ventilation (MV) (RR = 0.79, 95% CI 0.71-0.89, P < .001), composite outcome of MV or death (RR = 0.81, 95% CI 0.72-0.90, P < .001), time-to-hospital discharge (hazard ratio = 1.30, 95% CI 1.16-1.45, P < .001), intensive care unit admission (RR = 0.64, 95% CI 0.47-0.88, P = .006), serious infection (RR = 0.61, 95% CI 0.40-0.94, P = .02), and number of serious adverse events (RR = 0.64, 95% CI 0.47-0.86, P = .004).Conclusion:Tocilizumab reduced short-term mortality, incidence of MV, composite outcome of death or MV, intensive care unit admission, serious infection, serious adverse events, and time-to-hospital discharge in hospitalized COVID-19 patients. Further studies are required to determine the optimal dose.     

Effect of foetal exposure to famine on the risk of nonalcoholic fatty liver disease in adulthood: A systematic review and meta-analysis

ObjectiveThe risk of metabolic disease in adulthood is not only attributed to an unhealthy lifestyle after birth but also to famine exposure during the foetal period. This systematic review and meta-analysis aimed to evaluate the effects of foetal exposure to famine as a risk factor for developing nonalcoholic fatty liver disease (NAFLD) in adulthood.MethodsStudies were retrieved from PubMed, Embase, Cochrane Library, Web of Science, China National Knowledge Infrastructure (CNKI), and Wanfang databases to evaluate the effect of foetal exposure to famine on the risk of nonalcoholic fatty liver disease in adulthood.ResultsSix studies involving 90,582 subjects were included in this meta-analysis. Foetal exposure to famine was associated with an increased risk of NAFLD(RR = 1.17, 95% CI: 1.08–1.27, P < 0.0001). Exposure to famine during the foetal period significantly increased the incidence of NAFLD in women (RR = 1.27, 95% CI: 1.16–1.40, P <0.00001), while similar results were not observed in the male subgroup (RR =0.99, 95% CI: 0.89–1.11, P = 0.88). Foetal exposure to famine was associated with the risk of mild NAFLD (RR = 1.17, 95% CI: 1.02–1.33, P = 0.02) and moderate to severe NAFLD (RR = 1.51, 95% CI: 1.16–1.98, P = 0.002).ConclusionsFoetal exposure to famine is associated with an increased risk of NAFLD in adulthood. Women with NAFLD and moderate to severe NAFLD have a more robust association with foetal exposure to famine.     

Factors associated with survival in older patients affected by COVID-19: A retrospective cohort study

AimMortality is high in Coronavirus disease 2019 patients with pre-existing comorbidities and advanced age. Associated complications have added to the negative prognosis. Nevertheless, many have fully recovered, even among the most fragile. Factors associated with their survival was investigated.MethodsRetrospective study of patients aged ≥90 years admitted for COVID-19 to the Internal Medicine wards of two hospitals in Lombardy, Italy.ResultsAmong 34 patients with SARS-CoV-2 pneumonia, 33 (97.1%) had respiratory failure. Eighteen patients (52.9%) survived and 16 (47.1%) died during hospital stay. Survivors compared to deceased had a significantly longer hospitalization (19 vs. 10 days respectively; p = 0.02), a better PaO2:FiO2 ratio (241 vs. 171 respectively; p = 0.003), higher lymphocyte counts (p = 0.01) and lower serum LDH levels (p < 0.001) at admission. At multivariate analysis only higher PaO2:FiO2 was associated with survival (OR 1.06 [95%CI 1.0–1.03]; p = 0.02). Kaplan-Meier analysis showed a significant difference in event-free survival between patients treated or not with LMWH (p < 0.0001) and between those treated or not with beta-blockers (p = 0.008). Cox regression, performed in the subgroup of patients who received LMWH, did not show significant difference for sex (HR 2.7 [95% CI 0.53–14.3], p = 0.23), CCI (HR 0.7 [95% CI 0.37–1.45], p = 0.38), PaO2:FiO2 ratio (HR 0.98 [95% CI 0.97–1.0], p = 0.07), corticosteroid therapy (HR 0.99 [95% CI 0.22–4.5], p = 0.99) and beta-blocker therapy (HR 2.8 [95% CI 0.56–14,7], p = 0.21).ConclusionsDespite higher mortality in elderly, treatment with LMWH and betablockers might be associated with better survival. Dedicated studies are required to confirm our result.     

Statin use and the risk of CVD events,stroke, and all-cause mortality in patients with diabetes: A systematic review and meta-analysis

AimsConsidering the lack of evidence on statin use and the risk of cardiovascular disease (CVD) in patients with diabetes in primary and secondary prevention, this study aimed to evaluate the effect of statin use in individuals with diabetes for primary and secondary prevention.Data synthesisThe MEDLINE, Web of Science, Embase, ClinicalTrials.gov, and Cochrane Central Register for Controlled Trials databases were searched. We included studies that assessed the effect of statin use in individuals with diabetes for at least 1 year. The outcomes included CVD, all-cause mortality, and stroke. A total of 24 studies including 2,152,137 patients with diabetes were included in the meta-analysis. Compared with statin non-users, patients who received statins showed a lower risk of CVD events (primary prevention: risk ratio [RR] = 0.80, 95% confidence interval [CI] 0.69–0.94, P = 0.006; secondary prevention: RR = 0.75, 95% CI 0.65–0.87, P < 0.0001). No association was observed between statin and non-statin users and the risk of all-cause mortality. The pooled results also revealed that statin use reduced the risk of ischemic stroke in patients with diabetes (primary prevention: RR = 0.83, 95% CI 0.70–0.97, P = 0.020; secondary prevention: RR = 0.74, 95% CI 0.63–0.85, P < 0.0001).ConclusionsStatin use significantly reduced the risk of CVD events and stroke, but not all-cause mortality, in individuals with diabetes undergoing both primary and secondary prevention. More data are required to verify the effects of statins in patients with diabetes.Systematic review registrationPROSPERO CRD42021281132.     

Safety and Efficacy of Colchicine in Patients With Coronary Artery Disease: A Systematic Review and Meta-Analysis

BackgroundGiven current evidence, the use of colchicine for the prevention of adverse cardiovascular events in patients with coronary artery disease (CAD) remains controversial.MethodsMultiple databases were queried to identify studies comparing the safety and efficacy of colchicine in patients with acute coronary syndrome (ACS) or stable angina. The relative risk (RR) of major adverse cardiovascular events (MACE) and gastrointestinal (GI) adverse events were calculated using a random-effect model.ResultsSix clinical trials comprising a total of 5820 patients were identified. The pooled RR of MACE (0.64, 95% confidence interval (CI) 0.36–1.14, p = 0.13), ACS (0.62, 95% CI 0.27–1.41, p = 0.25), cardiac arrest (0.74, 95% CI 0.26–2.14, p = 0.58), stent restenosis (0.71, 95% CI 0.41–1.23, p = 0.22) and mortality (0.95, 95% CI 0.63–1.42, p = 0.79) with colchicine was not significantly different from placebo or control groups. The overall RR of revascularization (0.53, 95% CI 0.34–0.83, p = 0.005) and stroke (0.26, 95% CI 0.11–0.62, p = 0.002) was significantly lower while the net RR of GI adverse events was significantly higher (HR 2.66, 95% CI 1.21–5.87, p = 0.02) in the colchicine group. Propensity matched cohort, sensitivity and subgroup analysis based on adjusted MACE and dosages of colchicine all mirrored the overall results.ConclusionIn patients with CAD presenting with an acute coronary syndrome or stable angina, colchicine might offer no significant reduction in MACE and could potentially be harmful due to a significantly higher risk of GI-related adverse events.     

Hepatocellular liver injury in hospitalized patients affected by COVID-19: Presence of different risk factors at different time points

BackgroundPrevalence and clinical impact of increased liver function tests in patients affected by Coronavirus disease 2019 (COVID-19) is controversial.AimsThis observational study evaluates the prevalence of transaminases elevation in hospitalized patients affected by COVID-19 and investigates the presence of factors associated with hepatocellular injury and with mortality.MethodsData of 292 adult patients with confirmed COVID-19 admitted to the Ente Ospedaliero Cantonale (Switzerland) were retrospectively analyzed.ResultsTransaminases were increased in about one-third of patients on hospital admission and two-thirds of patients during the hospital stay. On hospital admission, transaminases were more commonly elevated in younger patients, who also reported elevated C reactive protein and a higher degree of respiratory failure. Independent factors associated with abnormal transaminases during hospitalization were drugs, in particular paracetamol (OR=2.67; 95% CI=1.38–5.18; p = 0.004) and remdesivir (OR=5.16; 95% CI=1.10–24.26; p = 0.04). Mortality was independently associated to age (OR = 1.09; 95% CI=1.05–1.13; p<0.001), admission to intensive care unit (OR=5.22; 95% CI=2.28–11.90; p<0.001) and alkaline phosphatase peak (OR=1.01; 95% CI=1.00- 1.01; p = 0.01).ConclusionsOn hospital admission, factors associated with liver damage were linked to demographic and clinical characteristics (age, inflammation and hypoxia) while, during hospitalization, drug treatment was related to development and progression of hepatocellular damage. Mortality was associated with alkaline phosphate peak value.     

Diabetes as a risk factor for greater COVID-19 severity and in-hospital death: A meta-analysis of observational studies

AimsTo estimate the prevalence of established diabetes and its association with the clinical severity and in-hospital mortality associated with COVID-19.Data synthesisWe systematically searched PubMed, Scopus and Web of Science, from 1st January 2020 to 15th May 2020, for observational studies of patients admitted to hospital with COVID-19. Meta-analysis was performed using random-effects modeling. A total of 83 eligible studies with 78,874 hospitalized patients with laboratory-confirmed COVID-19 were included. The pooled prevalence of established diabetes was 14.34% (95% CI 12.62–16.06%). However, the prevalence of diabetes was higher in non-Asian vs. Asian countries (23.34% [95% CI 16.40–30.28] vs. 11.06% [95% CI 9.73–12.39]), and in patients aged ≥60 years vs. those aged <60 years (23.30% [95% CI 19.65–26.94] vs. 8.79% [95% CI 7.56–10.02]). Pre-existing diabetes was associated with an approximate twofold higher risk of having severe/critical COVID-19 illness (n = 22 studies; random-effects odds ratio 2.10, 95% CI 1.71–2.57; I² = 41.5%) and ~threefold increased risk of in-hospital mortality (n = 15 studies; random-effects odds ratio 2.68, 95% CI 2.09–3.44; I² = 46.7%). Funnel plots and Egger's tests did not reveal any significant publication bias.ConclusionsPre-existing diabetes is significantly associated with greater risk of severe/critical illness and in-hospital mortality in patients admitted to hospital with COVID-19.     

COVID-19 in real world: Survival and medical costs of hospitalized patients in Brazil´s first wave

ObjectiveTo evaluate survival and direct medical costs of patients admitted in private hospitals with COVID-19 during the first wave.MethodsA retrospective, observational study analyzing survival and the economic data retrieved on hospitalized patients with COVID-19. Data from March 2020 to December 2020. The direct cost of hospitalization was estimated using the microcosting method with each individual hospitalization.Results342 cases were evaluated. Median age of 61.0 (95% CI 57.0‒65.0). 194 (56.7%) were men. The mortality rate was higher in the female sex (p = 0.0037), ICU (p < 0.001), mechanical ventilation (p<0.001) and elderly groups. 143 (41.8%) patients were admitted to the ICU (95% CI 36.6%–47.1%), of which 60 (41.9%) required MV (95% CI 34.0%–50.0%). Global LOS presented median of 6.7 days (95% CI 6.0–7.2). Mean costs were US$ 7,060,00 (95% CI 5,300.94–8,819,00) for each patient. Mean cost for patients discharged alive and patients deceased was US$ 5,475.53 (95% CI 3,692.91–7,258.14) and US$ 12,955.19 (95% CI 8,106.61–17,803.76), respectively (p < 0.001).ConclusionsPatients admitted with COVID-19 in these private hospitals point to great economic impact, mainly in the elderly and high-risk patients. It is key to better understand such costs in order to be prepared to make wise decisions during the current and future global health emergencies.     

Randomized Blinded Placebo-Controlled Trials of Renal Sympathetic Denervation for Hypertension: A Meta-Analysis

BackgroundThe efficacy of renal denervation has been controversial, but the procedure has now undergone several placebo-controlled trials. New placebo-controlled trial data has recently emerged, with longer follow-up of one trial and the full report of another trial (which constitutes 27% of the total placebo-controlled trial data). We therefore sought to evaluate the effect of renal denervation on ambulatory and office blood pressures in patients with hypertension.MethodsWe systematically identified all blinded placebo-controlled randomized trials of catheter-based renal denervation for hypertension. The primary efficacy outcome was ambulatory systolic blood pressure change relative to placebo. A random-effects meta-analysis was performed.Results6 studies randomizing 1232 patients were eligible. 713 patients were randomized to renal denervation and 519 to placebo. Renal denervation significantly reduced ambulatory systolic blood pressure (−3.52 mmHg; 95% CI −4.94 to −2.09; p < 0.0001), ambulatory diastolic blood pressure (−1.93 mmHg; 95% CI −3.04 to −0.83, p = 0.0006), office systolic blood pressure size (−5.10 mmHg; 95% CI −7.31 to −2.90, p < 0.0001) and office diastolic pressure (effect size −3.11 mmHg; 95% CI −4.43 to −1.78, p < 0.0001). Adverse events were rare and not more common with denervation.ConclusionsThe totality of blinded, randomized placebo-controlled data shows that renal denervation is safe and provides genuine reduction in blood pressure for at least 6 months post-procedure. If this effect continues in the long term, renal denervation might provide a life-long 10% relative risk reduction in major adverse cardiac events and 7.5% relative risk reduction in all-cause mortality.     

Causal associations between COVID-19 and atrial fibrillation: A bidirectional Mendelian randomization study

Background and aimsObservational studies showed that coronavirus disease (2019) (COVID-19) attacks universally and its most menacing progression uniquely endangers the elderly with cardiovascular disease (CVD). The causal association between COVID-19 infection or its severity and susceptibility of atrial fibrillation (AF) remains unknown.Methods and resultsThe bidirectional causal relationship between COVID-19 (including COVID-19, hospitalized COVID-19 compared with not hospitalized COVID-19, hospitalized COVID-19 compared with the general population, and severe COVID-19) and AF are determined by using two-sample Mendelian randomization (MR) analysis. Genetically predicted severe COVID-19 was not significantly associated with the risk of AF [odds ratio (OR), 1.037; 95% confidence interval (CI), 1.005–1.071; P = 0.023, q = 0.115]. In addition, genetically predicted AF was also not causally associated with severe COVID-19 (OR, 0.993; 95% CI, 0.888–1.111; P = 0.905, q = 0.905). There was no evidence to support the association between genetically determined COVID-19 and the risk of AF (OR, 1.111; 95% CI, 0.971–1.272; P = 0.127, q = 0.318), and vice versa (OR, 1.016; 95% CI, 0.976–1.058; P = 0.430, q = 0.851). Besides, no significant association was observed for hospitalized COVID-19 with AF. MR-Egger analysis indicated no evidence of directional pleiotropy.ConclusionOverall, this MR study provides no clear evidence that COVID-19 is causally associated with the risk of AF.     

Status of hospital infection prevention practices in Thailand in the era of COVID-19: Results from a national survey

BackgroundA 2014 study assessed infection prevention (IP) practices in Thai hospitals for catheter-associated urinary tract infection (CAUTI), central line-associated bloodstream infection (CLABSI), and ventilator-associated pneumonia (VAP). This study compares current IP practices to results obtained in 2014.MethodsBetween February 1, 2021 and August 31, 2021, we resurveyed Thai hospitals regarding practices to prevent CAUTI, CLABSI, and VAP. We also assessed COVID-19 impact and healthcare worker burnout and coping strategies. We distributed 100 surveys to a convenience sample of infection preventionists.ResultsResponse rate: 100%. One-third (31%) of hospitals reported excellent leadership support for infection control (ie, responses of “good” or “excellent” to one survey question). Some prevention practices increased between 2014 vs 2021 (CAUTI: catheter reminder/stop-order/nurse-initiated discontinuation [50.0% vs 70.0%, P < .001]; condom catheters [36.3% vs 51.0%, P = .01]; ultrasound bladder scanner [4.7% vs 12.0%, P = .03]; CLABSI: chlorhexidine gluconate insertion site antisepsis [73.6% vs 85.0%, P = .03]; maximum sterile barrier precautions [63.2% vs 80.0%, P = .003]; VAP: selective digestive tract decontamination [26.9% vs 40.0%, P = .02]). Antimicrobial catheter use decreased since 2014 (10.4% vs 3.0%, P < .001). Many other practices remain suboptimal. COVID-19 challenges: staff shortages (71%), financial hardships (67%). Only 46% of infection preventionists felt safe working during COVID-19.ConclusionsMore national strategic support is needed for IP programs to prevent CAUTI, CLABSI, VAP and healthcare worker well-being in Thailand during the COVID-19 pandemic.     

Joint effect of heart failure and coronary artery disease on the risk of death during hospitalization for COVID-19

Aimsheart failure (HF) and coronary artery disease (CAD) are independent predictors of death in patients with COVID-19. The adverse prognostic impact of the combination of HF and CAD in these patients is unclear.Methods and resultswe analysed data from 954 consecutive patients hospitalized for SARS-CoV-2 in five Italian Hospitals from February 23 to May 22, 2020. The study was a systematic prospective data collection according to a pre-specified protocol. All-cause mortality during hospitalization was the outcome measure.Mean duration of hospitalization was 33 days. Mortality was 11% in the total population and 7.4% in the group without evidence of HF or CAD (reference group). Mortality was 11.6% in the group with CAD and without HF (odds ratio [OR]: 1.6, p = 0.120), 15.5% in the group with HF and without CAD (OR: 2.3, p = 0.032), and 35.6% in the group with CAD and HF (OR: 6.9, p<0.0001).The risk of mortality in patients with CAD and HF combined was consistently higher than the sum of risks related to either disorder, resulting in a significant synergistic effect (p<0.0001) of the two conditions. Age-adjusted attributable proportion due to interaction was 64%. Adjusting for the simultaneous effects of age, hypotension, and lymphocyte count did not significantly lower attributable proportion which persisted statistically significant (p = 0.0360).ConclusionThe combination of HF and CAD exerts a marked detrimental impact on the risk of mortality in hospitalized patients with COVID-19, which is independent on other adverse prognostic markers.     

Safety and efficacy of anticoagulant monotherapy in atrial fibrillation and stable coronary artery disease: A systematic review and meta-analysis

BackgroundAdjunctive use of oral anticoagulant (OAC) and antiplatelet therapy (APT) in patients with stable coronary artery disease (CAD) and nonvalvular atrial fibrillation (AF) is a challenge of daily practice.MethodsA comprehensive literature search of databases was performed to identify studies comparing the safety and efficacy of OAC monotherapy and combined therapy (OAC plus single (S) APT). Events including major adverse cardiovascular events (MACE), all-cause mortality, stroke and major bleeding were analyzed.ResultsSeven articles comprising 11,070 subjects were identified. Combined therapy was associated with a significantly higher risk of major bleeding (pooled hazard ratio (HR) of 1.62, 95% CI 1.40–1.86, p=<0.0001) compared to the OAC monotherapy. There was no significant difference between the two comparison arms in terms of MACE (HR 1.14; 95% CI 0.97–1.34, p = 0.11), stroke (HR 1.05; 95% CI 0.77–1.43, p = 0.78) and all-cause mortality (HR 1.15; 95% CI 0.94–1.40, p = 0.16). Stratified analysis by inclusion of only patients with coronary stents attenuated the safety effect of monotherapy. Subgroup analysis based on the study design, type of OAC, major bleeding criteria and APT revealed findings consistent with the pooled HR. The combined therapy group had a 19% and 38% higher risk of MACE in studies with a history of MI (p = 0.03) and with the use of rivaroxaban (p = 0.02), respectively.ConclusionOAC monotherapy might have a lower incidence of major bleeding events with no higher overall risk of MACE, ischemic stroke and all-cause mortality compared to the combined therapy group.     

Metabolically unhealthy phenotype in normal weight population and risk of mortality and major adverse cardiac events: A meta-analysis of 41 prospective cohort studies

Background and aimsIt is still debatable whether metabolic status in normal weight population increases the risk of mortality (all-cause mortality (ACM), cardiovascular mortality (CVM)) and major adverse cardiac events (MACE) as compared to the obese population. Therefore, this meta-analysis aims to evaluate the association of the metabolically unhealthy normal weight (MUH-NW) phenotype with all-cause mortality, cardiovascular mortality, and MACE in comparison to metabolically healthy obesity (MH-O), along with the association of metabolically unhealthy obesity (MUH-O) phenotype regarding the same outcomes compared to MUH-NW.MethodsA systematic literature search was conducted using online databases from inception to June 20, 2022, to comprehensively search all prospective cohort studies comprising three variables including adults aged ≥18 years, obesity and four metabolic phenotypes, and interest outcomes (ACM, CVM, and MACE).ResultsForty-one prospective cohort studies with a total of 4,028,750 participants was included in this study. Compared to MH-O, MUH-NW had a substantially higher risk of ACM (RR = 1.47 (95%CI = 1.32–1.64); P < 0.001; I² = 89.8%,P-heterogeneity<0.001), CVM (RR = 2.37 (95%CI = 1.97–2.86); P < 0.001; I² = 83.7%,P-heterogeneity<0.001), and MACE (RR = 1.73 (95%CI = 1.49–2.00); P < 0.001; I² = 74.3%,P-heterogeneity<0.001). Moreover, MUH-O did not have a significantly elevated risk of ACM (RR = 0.97 (95%CI = 0.82–1.15); P = 0.736; I² = 98.3%,P-heterogeneity<0.001), CVM (RR = 0.96 (95%CI = 0.88–1.05); P = 0.394; I² = 77.0%,P-heterogeneity<0.001), and MACE (RR = 0.95 (95%CI = 0.80–1.13); P = 0.570; I² = 92.2%,P-heterogeneity<0.001) compared to MUH-NW.ConclusionIn conclusion, MUH-NW was superior but not inferior to MH-O and MUH-O in terms of increased risk of interest outcomes, refuting the notion that normal weight population is a benign condition. Hence, in normal weight population, metabolic screening is highly suggested to measure the baseline of obesity and metabolic phenotypes, thus preventing the risk of CVD and mortality in the future.     

Efficacy and safety of Lianhuaqingwen for mild or moderate coronavirus disease 2019: A meta-analysis of randomized controlled trials

Background: Coronavirus disease 2019 (COVID-19) is an emerging and rapidly evolving disease, with no recommended effective anti-coronavirus treatments. Traditional Chinese Medicine (TCM) has been widely used to treat COVID-19 in China, and the most used one is Lianhuaqingwen (LH). This study aimed to assess the efficacy and safety of LH combined with usual treatment vs usual treatment alone in treating mild or moderate COVID-19 by a meta-analysis of randomized controlled trials (RCTs).Methods and analysis: We systematically searched the Medline (OVID), Embase, the Cochrane Library, and 4 Chinese databases from inception to July 2020 to include the RCTs that evaluated the efficacy and safety of LH in combination with usual treatment vs usual treatment for mild or moderate COVID-19. A meta-analysis was performed to calculate the risk ratio (RR) and 95% confidence interval (CI) for binary outcomes and mean difference (MD) for continuous outcomes.Results: A total of 5 RCTs with 824 individuals with mild or moderate COVID 19 were included. Compared with the usual treatment alone, LH in combination with usual treatment significantly improved the overall clinical efficacy (RR = 2.39, 95% CI 1.61–3.55), increased the rate of recovery of chest computed tomographic manifestations (RR = 1.80, 95% CI 1.08–3.01), reduced the rate of conversion to severe cases (RR = 0.47, 95% CI 0.29–0.74), shorten the duration of fever (MD = −1.00, 95% CI −1.17 to −0.84). Moreover, LH in combination with usual treatment did not increase the occurrence of the adverse event compared to usual treatment alone.Conclusion: Our meta-analysis of RCTs indicated that LH in combination with usual treatment may improve the clinical efficacy in patients with mild or moderate COVID-19 without increasing adverse events. However, given the limitations and poor quality of included trials in this study, further large-sample RCTs or high-quality real-world studies are needed to confirm our conclusions.