Editor's Choice - Systematic Review and Meta-Analysis of Contemporary Abdominal Aortic Aneurysm Growth Rates.

OBJECTIVE: To evaluate the contemporary growth rate of small abdominal aortic aneurysms (AAAs) in view of recent epidemiological changes, such as decreasing smoking rates and establishment of population screening programmes. DATA SOURCES: MEDLINE, CENTRAL, PsycINFO, Web of Science Core Collection, and OpenGrey databases. REVIEW METHODS: Systematic review following the PRISMA guidelines. In October 2021, databases were queried for studies reporting on AAA growth rates published from 2015 onwards. The primary outcome was contemporary AAA growth rates in mm/year. Data were pooled in a random effects model meta-analysis, and heterogeneity was assessed through the I2 statistic. GRADE assessment of the findings was performed. The protocol was published in PROSPERO (CRD42022297404). RESULTS: Of 8 717 titles identified, 43 studies and 28 277 patients were included: 1 241 patients from randomised controlled trials (RCTs), 23 941 from clinical observational studies, and 3 095 from radiological or translational research studies. The mean AAA growth rate was 2.38 mm/year (95% CI 2.16 - 2.60 mm/year; GRADE = low), with meta-regression analysis adjusted for baseline diameter showing an increase of 0.08 mm/year (95% CI 0.024 - 0.137 mm/year; p = .005) for each millimetre of increased baseline diameter. When analysed by study type, the growth rate estimated from RCTs was 1.88 mm/year (95% CI 1.69 - 2.06 mm/year; GRADE = high), while it was 2.31 mm/year (95% CI 1.95 - 2.67 mm/year; GRADE = moderate) from clinical observational studies, and 2.85 mm/year (95% CI 2.44 - 3.26 mm/year; GRADE = low) from translational and radiology based studies (p < .001). Heterogeneity was high, and small study publication bias was present (p = .003), with 27 studies presenting a moderate to high risk of bias. The estimated growth rate from low risk studies was 2.09 mm/year (95% CI 1.87 - 2.32; GRADE = high). CONCLUSION: This study estimated a contemporaneous AAA growth rate of 2.38 mm/year, being unable to demonstrate any clinically meaningful AAA growth rate reduction concomitant with changed AAA epidemiology. This suggests that the RESCAN recommendations on small AAA surveillance are still valid. However, sub-analysis results from RCTs and high quality study data indicate potential lower AAA growth rates of 1.88 - 2.09 mm/year, findings that should be validated in a high quality prospective registry.

Preoperative statin therapy for adults undergoing cardiac surgery.

BACKGROUND: Despite significant advances in surgical techniques and perioperative care, people undertaking cardiac surgery due to cardiovascular disease are more prone to the development of postoperative adverse events. Statins (5-hydroxy-3-methylglutaryl-co-enzyme A (HMG-CoA) reductase inhibitors) are well-known for their anti-inflammatory and antioxidant effects and are established for primary and secondary prevention of coronary artery disease. In addition, statins are thought to have clinical benefits in perioperative outcomes in people undergoing cardiac surgery. This review is an update of a review that was first published in 2012 and updated in 2015. OBJECTIVES: To evaluate the benefits and harms of preoperative statin therapy in adults undergoing cardiac surgery compared to standard of care or placebo. SEARCH METHODS: We performed a search of the Cochrane Central Register of Controlled Trials (CENTRAL) (Issue 9, 2023), Ovid MEDLINE (1980 to 14 September 2023), and Ovid Embase (1980 to 2023 (week 36)). We applied no language restrictions. SELECTION CRITERIA: We included all randomised controlled trials (RCTs) comparing any statin treatment before cardiac surgery, for any given duration and dose, versus no preoperative statin therapy (standard of care) or placebo. We excluded trials without a registered trial protocol and trials without approval by an institutional ethics committee. DATA COLLECTION AND ANALYSIS: We used standard Cochrane methodology. Primary outcomes were short-term mortality and major adverse cardiovascular events. Secondary outcomes were myocardial infarction, atrial fibrillation, stroke, renal failure, length of intensive care unit (ICU) stay, length of hospital stay and adverse effects related to statin therapy. We reported effect measures as risk ratios (RRs) or mean differences (MDs) with corresponding 95% confidence intervals (CIs). We used the RoB 1 tool to assess the risk of bias in included trials, and GRADE to assess the certainty of the evidence. MAIN RESULTS: We identified eight RCTs (five new to this review) including 5592 participants. Pooled analysis showed that statin treatment before surgery may result in little to no difference in the risk of postoperative short-term mortality (RR 1.36, 95% CI 0.72 to 2.59; I2 = 0%; 6 RCTs, 5260 participants; low-certainty evidence; note 2 RCTs reported 0 events in both groups so RR calculated from 4 RCTs with 5143 participants). We are very uncertain about the effect of statins on major adverse cardiovascular events (RR 0.93, 95% CI 0.77 to 1.13; 1 RCT, 2406 participants; very low-certainty evidence). Statins probably result in little to no difference in myocardial infarction (RR 0.88, 95% CI 0.73 to 1.06; I2 = 0%; 5 RCTs, 4645 participants; moderate-certainty evidence), may result in little to no difference in atrial fibrillation (RR 0.87, 95% CI 0.72 to 1.05; I2 = 60%; 8 RCTs, 5592 participants; low-certainty evidence), and may result in little to no difference in stroke (RR 1.47, 95% CI 0.90 to 2.40; I2 = 0%; 4 RCTs, 5143 participants; low-certainty evidence). We are very uncertain about the effect of statins on renal failure (RR 1.04, 95% CI 0.80 to 1.34; I2 = 57%; 4 RCTs, 4728 participants; very low-certainty evidence). Additionally, statins probably result in little to no difference in length of ICU stay (MD 1.40 hours, 95% CI -1.62 to 4.41; I2 = 43%; 3 RCTs, 4528 participants; moderate-certainty evidence) and overall hospital stay (MD -0.31 days, 95% CI -0.64 to 0.03; I2 = 84%; 5 RCTs, 4788 participants; moderate-certainty evidence). No study had any individual risk of bias domain classified as high. However, two studies were at high risk of bias overall given the classification of unclear risk of bias in three domains. AUTHORS' CONCLUSIONS: In this updated Cochrane review, we found no evidence that statin use in the perioperative period of elective cardiac surgery was associated with any clinical benefit or worsening, when compared with placebo or standard of care. Compared with placebo or standard of care, statin use probably results in little to no difference in MIs, length of ICU stay and overall hospital stay; and may make little to no difference to mortality, atrial fibrillation and stroke. We are very uncertain about the effects of statins on major harmful cardiac events and renal failure. The certainty of the evidence validating this finding varied from moderate to very low, depending on the outcome. Future trials should focus on assessing the impact of statin therapy on mortality and major adverse cardiovascular events.

Clinical Outcomes of Anticoagulated Patients With Atrial Fibrillation After Falls or Head Injury: Insights From RE-LY.

BACKGROUND: Falls are always a concern regarding the balance of risk/benefit in patients with atrial fibrillation treated with anticoagulants. In this analysis, we aimed to evaluate the outcomes of patients that had a fall/head injury reported in the RE-LY clinical trial (Randomized Evaluation of Long-Term Anticoagulation Therapy) and to explore the safety of dabigatran (a nonvitamin K antagonist oral anticoagulant). METHODS: We performed a post hoc retrospective analysis of intracranial hemorrhage and major bleeding outcomes in the RE-LY trial with 18 113 individuals with atrial fibrillation, according to the status occurrence of falls (or head injury) reported as adverse events. Multivariate Cox regression models were used to provide adjusted hazard ratio (HR) and 95% CI. RESULTS: In the study, 974 falls or head injury events were reported among 716 patients (4%). These patients were older and had more frequently comorbidities such as diabetes, previous stroke, or coronary artery disease. Patients with fall had a higher risk of major bleeding (HR, 2.41 [95% CI, 1.90-3.05]), intracranial hemorrhage (HR, 1.69 [95% CI, 1.35-2.13]), and mortality (HR, 3.91 [95% CI, 2.51-6.10]) compared to those who did not have reported falls or head injury. Among patients who had falls, those allocated to dabigatran showed a lower intracranial hemorrhage risk (HR, 0.42 [95% CI, 0.18-0.98]) compared with warfarin. CONCLUSIONS: In this population, the risk of falls is important and confers a worse prognosis, increasing intracranial hemorrhage, and major bleeding. Patients who fell and were under dabigatran was associated with lower intracranial hemorrhage risk than those anticoagulated with warfarin, but the analysis was merely exploratory.

Impact of Selective Serotonin-Reuptake Inhibitors in Hemorrhagic Risk in Anticoagulated Patients Taking Non-Vitamin K Antagonist Anticoagulants: A Systematic Review and Meta-analysis.

BACKGROUND: Studies show an increase in hemorrhagic risk related to selective serotonin-reuptake inhibitors (SSRIs) alone, but also in association with vitamin K antagonists (VKAs). Non-VKA anticoagulants (NOACs) can be a good substitute to VKAs, but the correlation between them and SSRIs is not well studied. Therefore, we conducted a systematic review to evaluate the risk of major bleeding associated with concomitant use of SSRIs and NOACs. METHODS: MEDLINE, Cochrane Central Register of Controlled Trials (CENTRAL), Web of Science, and PubMed databases were searched, in September 2022, for longitudinal studies evaluating SSRIs' impact on hemorrhagic risk in anticoagulated patients taking NOACs compared with a control group taking non-SSRI medication instead or no antidepressants at all. The outcome of interest was major bleeding. The quality of the included studies was assessed using the ROBINS-I tool. We performed a random-effects meta-analysis to estimate the pooled RRs with 95% confidence intervals (CIs), and heterogeneity was evaluated using the I2 statistic. RESULTS: Eight studies were included in the meta-analysis. From a population of 279,540 anticoagulated patients taking NOACs, the ones taking SSRIs concomitantly were associated with a higher risk of major bleeding (relative risk, 1.33; 95% CI, 1.06-1.66; I2 = 60%). However, the subgroup analysis of cohort studies did not achieve statistical significance (relative risk, 1.05; 95% CI, 0.94-1.66). CONCLUSIONS: The findings show that SSRIs are associated with a greater hemorrhagic risk in patients anticoagulated with NOACs; however, our confidence is reduced because of nonstatistically significant results from more robust studies, as cohort studies.

Incidence, Risk Factors, and Prognostic Impact of Type Ib Endoleak Following Endovascular Repair for Abdominal Aortic Aneurysm: Scoping Review.

OBJECTIVE: The primary objectives of this scoping review were to assess the rate of and risk factors for type Ib endoleak and to evaluate the extent of the evidence base that links type Ib endoleak to short and long term outcomes in patients undergoing endovascular aneurysm repair (EVAR) for abdominal aortic aneurysm (AAA). METHODS: Potentially eligible studies were searched in the Cochrane Central Register of Controlled Trials, MEDLINE, Web of Science Core Collection, SciELO Citation Index, Russian Science Citation Index, and KCI-Korean Journal Database. A scoping review was performed according to PRISMA extension for Scoping Reviews. RESULTS: A total of 27 articles (four prospective registries and 23 retrospective cohort studies) dealing with type Ib endoleak were included in the final analysis. The number of patients reported on was 7 197, with follow up ranging between 12 months and 93 months. The reported frequency of type Ib endoleak in patients treated with EVAR ranged from 0% to 8%, Patient and or procedure related factors associated with risk of type Ib endoleak were (1) common iliac artery (CIA) diameter ˃ 18 mm requiring use of flared stent graft limbs (FLs) ˃ 20 mm, (2) length of CIA landing zone ˂ 20 mm, (3) marked iliac tortuosity, and (4) large initial AAA diameter. Depending on the study, 50 - 100% of type Ib endoleaks were corrected by endovascular means, with a reported immediate technical success of 100% in the studies providing this information. CONCLUSION: Type Ib endoleak after EVAR has been reported to occur in 0 - 8% of cases. Several anatomical features, including CIA diameter ˃ 18 mm or requiring the use of FLs ˃ 20 mm, length of CIA landing zone ˂ 20 mm, marked iliac tortuosity, and large initial AAA diameter, could increase the risk of type Ib endoleak and may require alternative therapeutic options and or more stringent follow up. Therefore, this updated scoping review provides a comprehensive summary of the frequency, risk factors, prognosis, and treatment of type Ib endoleaks, and has identified knowledge gaps in the literature to guide further studies.

The effect of catheter-based sham renal denervation in hypertension: systematic review and meta-analysis.

BACKGROUND: Renal denervation (RDN) has emerged in recent years as a possible treatment for hypertension. The first sham-controlled trial showed a small magnitude and non-significant in the blood pressure (BP) lowering effect, also due to a substantial decrease of BP in sham arm. Considering this, we aimed to quantify the magnitude of BP decrease within the sham arm of Randomized Controlled Trials (RCT) with RDN in patients with hypertension. METHODS: Electronic databases were searched since inception until January 2022 for randomized sham-controlled trials which assessed the efficacy in lowering BP of the sham intervention for catheter-based RDN in adult patients with hypertension. The outcomes were change in ambulatory/office systolic and diastolic BP. RESULTS: A total of 9 RCT were included in the analysis enrolling a total of 674 patients. Sham intervention showed a decrease in all evaluated outcomes. Office systolic BP had a reduction of -5.52 mmHg [95%CI -7.91, -3.13] and office diastolic BP of -2.13 mmHg [95%CI -3.08, -1.17]. Sham procedure for RDN also showed a reduction of -3.41 mmHg [95%CI -5.08, -1.75] in ambulatory systolic BP and - 2.44 mmHg [95%CI -3.31, -1.57] in ambulatory diastolic BP. CONCLUSION: Despite recent data indicating that RDN might be an effective treatment for patients with resistant hypertension when compared to a sham intervention, our results indicate that the sham intervention for RDN also has a significant effect on lowering Office and Ambulatory (24-h) Blood Pressure in adult patients with hypertension. This highlights that BP itself might be sensitive to placebo-like effect and also brings further difficulties in establishing the BP lowering efficacy of invasive interventions due to the magnitude of the sham effect.

Data monitoring committees in pediatric randomized controlled trials registered in ClinicalTrials.gov.

BACKGROUND: Data monitoring committees advise on clinical trial conduct through appraisal of emerging data to ensure participant safety and scientific integrity. While consideration of their use is recommended for trials performed with vulnerable populations, previous research has shown that data monitoring committees are reported infrequently in publications of pediatric randomized controlled trials. We aimed to assess the frequency of reported data monitoring committee adoption in ClinicalTrials.gov registry records and to examine the influence of key trial characteristics. METHODS: We conducted a cross-sectional data analysis of all randomized controlled trials performed exclusively in a pediatric population and registered in ClinicalTrials.gov between 2008 and 2021. We used the Access to Aggregate Content of ClinicalTrials.gov database to retrieve publicly available information on trial characteristics and data on safety results. Abstracted data included reported trial design and conduct parameters, population and intervention characteristics, reasons for prematurely halting, serious adverse events, and mortality outcomes. We performed descriptive analyses on the collected data and explored the influence of clinical, methodological, and operational trial characteristics on the reported adoption of data monitoring committees. RESULTS: We identified 13,928 pediatric randomized controlled trial records, of which 39.7% reported adopting a data monitoring committee, 49.0% reported not adopting a data monitoring committee, and 11.3% did not answer on this item. While the number of registered pediatric trials has been increasing since 2008, we found no clear time trend in the reported adoption of data monitoring committees. Data monitoring committees were more common in multicenter trials (50.6% vs 36.9% for single-center), multinational trials (60.2% vs 38.7% for single-country), National Institutes of Health-funded (60.3% vs 40.1% for industry-funded or 37.5% for other funders), and placebo-controlled (47.6% vs 37.5% for other types of control groups). Data monitoring committees were also more common among trials enrolling younger participants, trials employing blinding techniques, and larger trials. Data monitoring committees were more common in trials with at least one serious adverse event (52.6% vs 38.4% for those without) as well as for trials with reported deaths (70.3% vs 38.9% for trials without reported deaths). In all, 4.9% were listed as halted prematurely, most often due to low accrual rates. Trials with a data monitoring committee were more often halted for reasons related to scientific data than trials without a data monitoring committee (15.7% vs 7.3%). CONCLUSION: According to registry records, the use of data monitoring committees in pediatric randomized controlled trials was more frequent than previously reported in reviews of published trial reports. The use of data monitoring committees varied across key clinical and trial characteristics based on which their use is recommended. Data monitoring committees may still be underutilized in pediatric trials, and reporting of this item could be improved.

Atrial fibrillation risk on Parkinson's disease - a systematic review and meta-analysis.

The association of Parkinson's Disease (PD) with atrial fibrillation (AF) is not well established and previous studies' results were heterogeneous. This review aimed to evaluate if patients with PD are at increased risk of having AF. MEDLINE, Cochrane Central Register of Controlled Trials (CENTRAL), and Web of Science, were searched from inception May 2021. Two reviewers independently selected observational studies with data allowing to estimate the risk of atrial fibrillation in PD patients compared with no-PD controls. Pooled estimates Odds Ratio (OR) and 95% confidence intervals (CIs) were derived through meta-analysis. Heterogeneity was assessed using I2 test. The risk of bias of individual studies was evaluated using the ROBINS-I tool. The study protocol was registered at PROSPERO: CRD42020216572. Seven studies were included: five case-control studies and two cohort studies. Three of the studies included were a population-based study. No significant difference was detected between PD and controls regarding atrial fibrillation (OR 1.10, 95% CI 0.81 to 1.49). Early PD present a significant higher risk of AF (OR 1.55, 95% CI 1.00 to 2.40, I2 98%). The overall risk of bias was serious, with only two studies being considered as having moderate risk. The best evidence available do not support that there is an increased risk of AF in PD patients. Further studies are needed to better conclude if there is a relation between AF and PD.

Direct oral anticoagulants vs vitamin K antagonist on dementia risk in atrial fibrillation: systematic review with meta-analysis.

Oral anticoagulation significantly reduces the incidence of dementia in atrial fibrillation patients. However, this protective effect has not been compared between Direct Oral Anticoagulants (DOAC) and Vitamin K antagonists' anticoagulants (VKA). We conducted an electronic search for potentially eligible studies through the bibliographic databases MEDLINE, CENTRAL, ClinicalTrials.gov, EMBASE and Web of Science. The outcome of interest was dementia. Random-effects meta-analysis was performed. Nine observational studies were included and 1,175,609 atrial fibrillation patients were enrolled. DOAC therapy was associated with a significant reduction when compared with patients under VKA therapy (hazard ratio 0.89; 95% confidence interval 0.80-0.99). The grade of confidence of our results was very low due to the risk of bias. DOAC therapy is associated with a significant decrease in the risk of dementia when compared with VKA therapy. However, the low certainty of the evidence along with the paucityof clinical trials dedicated to answering this important question underscores a need for global clinical research initiatives.

Myocardial infarction and viral triggers: what do we know by now?

Myocardial infarction (MI) is an acute clinical manifestation ischaemic heart disease, which is the leading cause of death worldwide. Infections also have an important burden worldwide, with lower respiratory infections being the worldwide leading cause of death due to communicable diseases. The relationship of MI with viral respiratory infections (including influenza and SARS-CoV-2) as a trigger has been well documented with significant associations. These infections can lead to Type 1 MI, where inflammation and vascular dysfunction, as well as the increased prothrombotic environment lead to atherothrombosis. Type 2 MI may also occur due to an imbalance of oxygen/blood supply and myocardial demand (hypoxaemia, fever, and tachycardia). The data from randomized controlled trials showing a potential benefit of influenza vaccination in coronary artery disease patients should not be ignored. This can be considered a further argument for the association of viral infections (influenza in particular) and MI.

A systematic review and meta-analysis of the incidence of acute aortic dissections in population-based studies.

OBJECTIVE: To perform a systematic review and meta-analysis of all population-based studies reporting on incidence of acute aortic dissections (AADs). METHODS: We searched the MEDLINE, EMBASE, CENTRAL, and Open Grey databases from inception to August 2020 for population-based studies reporting on the incidence of AAD. A systematic review was conducted following the PRISMA guidelines using a registered protocol (CRD42020204007). Data were pooled using a random effects model of proportions using Freeman-Tukey double arcsine transformation. The main outcome was the incidence of AAD. Secondary outcomes were incidence type A aortic dissections (TAAD) and type B aortic dissections (TBAD), the incidence of aortic dissection repair and medical management, and the incidence of in-hospital mortality. In addition, we estimated the proportion of aortic dissection repair and mortality (in hospital, overall and specific mortality according to subtype) among patients with AAD. RESULTS: Thirty-three studies were included. The pooled incidence of AADs was 4.8 per 100,000 individuals/year (95% confidence interval [CI], 3.6-6.1). The incidence of TAAD was 3.0 per 100,000/year (95% CI, 1.8-4.4) and the incidence of TBAD was 1.6 per 100,000/year (95% CI, 1.1-2.2). The incidence of AAD needing repair was 1.4 per 100,000/year (95% CI, 1.0-2.0) (or 1.4 [95% CI, 1.2-1.7] for TAAD and 0.4 [95% CI, 0.2-0.7] for TBAD). The incidence of medically managed AAD was 3.4 per 100,000/year (95% CI, 2.4-4.5). The incidence of in-hospital death owing to AAD was 1.3 per 100,000 individuals/year (95% CI, 0.9-1.9), 1.0 (95% CI, 0.6-1.4; I2 = 97%) for TAAD, and 0.3 for TBAD (95% CI, 0.2-0.4; I2 = 96%). CONCLUSIONS: A global estimate regarding the incidence rate of AADs was achieved. The incidence of AAD varied significantly between study designs and geographical regions. More accurate information on AAD epidemiology is crucial for public health decisions, clinical understanding, and healthcare management.

Systematic Review and Meta-analysis of Physician Modified Endografts for Treatment of Thoraco-Abdominal and Complex Abdominal Aortic Aneurysms.

OBJECTIVE: To perform a systematic review and meta-analysis of the outcomes of physician modified endografts (PMEG) for the treatment of thoraco-abdominal (TAAA) and complex abdominal aortic aneurysms (C-AAA). DATA SOURCES: MEDLINE, CENTRAL, Web of Science Core Collection, Scielo, and Open Grey. REVIEW METHODS: The databases were searched from inception to July 2021 for studies reporting on outcomes of PMEGs for TAAA or C-AAA repair. A systematic review was conducted (protocol CRD42021267856) and data were pooled using a random effects model of proportions. The outcomes analysed were major adverse events at 30 days (30 day mortality, myocardial infarction, respiratory failure requiring prolonged ventilation [> 24 hours or re-intubation], renal failure requiring dialysis, bowel ischaemia requiring surgery, major stroke, or definitive paraplegia); technical success; 30 day mortality; ruptures; spinal cord ischaemia; endoleaks; re-interventions; and target vessel patency. RESULTS: Twenty studies were included. Overall study quality assessment was found to be low. Overall, 909 PMEGs were reported and analysed. Regarding aneurysm location (n = 867), 222 patients had extent I - III TAAAs and 645 had C-AAA or extent IV TAAA. Regarding presentation, 14 studies reported whether the patients were treated in an elective or urgent setting (n = 782). Overall, 500 (63.9%) patients were treated in an elective setting and 282 (36.1%) in an urgent setting. Major adverse events (at 30 days) occurred in 15.5% of patients (95% confidence interval [CI] 10.8 - 20.8; I2 = 63%, 135/832 cases): 11.6% (95% CI 8.1 - 15.7; I2 = 0%, 23/280 cases) for elective patients and 24.6% for urgent (95% CI 14.1 - 36.6; I2 = 65%, 50/192 cases). Overall technical success was 97.2% (95% CI 95.4 - 98.7; I2 = 0%, 587/611 cases): 98.0% (95% CI 92.1 - 100; I2 = 0%, 106/113cases) for extent I - III TAAAs and 99.4% (95% CI 97.5 - 100; I2 = 0%, 317/324 cases) for C-AAA and extent IV TAAAs. Regarding technique, technical success was 96.1% for fenestrated endovascular repair (FEVAR; 95% CI 93.2 - 98.4; I2 = 0%, 313/329 cases) and 99.8% for FEVAR/branched endovascular repair (95% CI 99.8 - 100; I2 = 0%, 17/18 cases). CONCLUSION: Physician modified fenestrated or branched grafts for endovascular aortic repair seem feasible and safe in the short term. However, the quality of the available data is low, which highlights the need for better and more accurate data regarding this technique.

Systematic reviews and meta-analysis published in indexed Portuguese medical journals: time trends and critical appraisal.

INTRODUCTION: Over the last years, the number of systematic reviews published is steadily increasing due to the global interest in this type of evidence synthesis. However, little is known about the characteristics of this research published in Portuguese medical journals. This study aims to evaluate the publication trends and overall quality of these systematic reviews. MATERIAL AND METHODS: This was a methodological study. We aimed the most visible Portuguese medical journals indexed in MEDLINE. Systematic reviews were identified through an electronic search (through PUBMED). We included systematic reviews published up to August 2020. Systematic reviews selection and data extraction were done independently by three authors. The overall quality critical appraisal using the A MeaSurement Tool to Assess systematic Reviews (AMSTAR-2) was independently assessed by three authors. Disagreements were solved by consensus. RESULTS: Sixty-six systematic reviews published in 5 Portuguese medical journals were included. Most (n = 53; 80.3%) were systematic reviews without meta-analysis. Up to 2010 there was a steady increase in the number of systematic reviews published, followed by a period of great variability of publication, ranging from 1 to 10 in a given year. According to the systematic reviews' typology, most have been predominantly conducted to assess the effectiveness/efficacy of health interventions (n = 27; 40.9%). General and Internal Medicine (n = 20; 30.3%) was the most addressed field. Most systematic reviews (n = 46; 69.7%) were rated as being of "critically low-quality". CONCLUSIONS: There were consistent flaws in the methodological quality report of the systematic reviews included, particularly in establishing a prior protocol and not assessing the potential impact of the risk of bias on the results. Through the years, the number of systematic reviews published increased, yet their quality is suboptimal. There is a need to improve the reporting of systematic reviews in Portuguese medical journals, which can be achieved by better adherence to quality checklists/tools.

Low risk of haematomas with intramuscular vaccines in anticoagulated patients: a systematic review with meta-analysis.

INTRODUCTION: The summary of product characteristics of vaccines administered intramuscularly, including the vaccine for coronavirus SARS-CoV-2 (COVID-19) and Influenza, warned for risks of bleeding in patients treated with oral anticoagulants. We aimed to estimate the incidence of major bleeding events in this setting and to compare these risks against other vaccination routes. METHODS: This systematic review included all prospective and retrospective studies enrolling anticoagulated patients that received intramuscular vaccination, published until December 2020 in CENTRAL, MEDLINE and EMBASE. The outcomes of interest were major bleeding and haematoma related with vaccination. The incidence of the outcomes was estimated through a random-effects meta-analysis using the Freeman-Turkey transformation. The results are expressed in percentages, with 95%-confidence intervals (95%CI), limited between 0 and 100%. When studies compared intramuscular vaccination vs. other route, the data were compared and pooled using random-effects meta-analysis. Risk ratios (RR) with 95%CI were reported. RESULTS: Overall 16 studies with 642 patients were included. No major bleeding event was reported. The pooled incidence of haematomas following vaccination (mostly against Influenza) in patients treated with oral anticoagulants (mostly warfarin; no data with DOACs / NOACs) was 0.46% (95%CI 0-1.53%). Three studies evaluated the intramuscular vs. subcutaneous route of vaccination. Intramuscular vaccines did not increase the risk of haematoma (RR 0.53, 95%CI 0.10-2.82) compared with subcutaneous route. CONCLUSIONS: Intramuscular vaccination in anticoagulated patients is safe with very low incidence of haematomas and the best available evidence suggests that using the intramuscular route does not increase the risk of haematomas compared with the subcutaneous route.

The sham effect of invasive interventions in chronic coronary syndromes: a systematic review and meta-analysis.

BACKGROUND: Some patients with chronic coronary syndromes undergo invasive procedures but the efficacy of such interventions remains to be robustly established by randomised sham-controlled trials (RCTs). PURPOSE: To determine the sham effect in patients with chronic coronary syndromes enrolled in RCTs by performing a systematic review and meta-analysis. METHODS: In April 2022, we performed a literature search for published patient-blind RCTs (CENTRAL, MEDLINE®, PsycINFO, and reference lists) with sham procedures, reporting the pre-post effects in the invasive sham arm among patients with Canadian cardiovascular society (CCS) angina or angina equivalents. RESULTS: 16 RCTs were included with 546 patients in the sham arm. Pooled results showed that sham interventions were associated with: improvement of 7% (95% CI 2-11%; I2 = 0%) in exercise time; decrease of 0.78 (95% CI - 1.10 to - 0.47; I2 = 75%) in CCS angina class; decrease of 53% (95% CI 24-71%; I2 = 96%) and 25% (95% CI 20-29%; I2 = 0%) in anginal episodes and nitroglycerine (NTG) use, respectively. Pooled results also showed an improvement in the physical functioning, angina frequency, treatment satisfaction, and disease perception domains of the Seattle Angina Questionnaire (SAQ). CONCLUSION: Sham interventions in patients with chronic coronary syndromes were associated with a significant decrease in anginal episodes, NTG use, and CCS angina class and increased SAQ quality of life and exercise time. These results highlight the need for previous non sham-controlled trials to be interpreted with caution, and the importance of new invasive interventions to be evaluated versus a sham procedure.

Cardiovascular and Respiratory Safety of Sedation Strategies Used in Transesophageal Echocardiography: A Systematic Review Incorporating Network Meta-Analysis.

TRANSESOPHAGEAL ECHOCARDIOGRAPHY (TEE) is carried out in various clinical settings, with an increasing importance, and sedation usually is required to perform it. Several sedative agents are available, and the authors aimed to compare the cardiovascular and respiratory safety of the strategies used for sedation in TEE through a systematic review with network meta-analysis (NMA). The MEDLINE, CENTRAL, EMBASE, and PsycInfo databases were searched in December 2020 for randomized clinical trials (RCTs) comparing sedation strategies for patients undergoing TEE. The authors assessed variations in systolic blood pressure (SBP), heart rate (HR), and peripheral oxygen saturation (SpO2), along with the incidences of hypotension, bradycardia, and desaturation. A random-effect meta-analysis was performed. Nine RCTs (N = 881 patients) with 20 active arms (5 dexmedetomidine; 4 propofol; 4 midazolam; 3 midazolam + opioid; 2 ketamine + propofol; 1 midazolam + ondansetron; 1 midazolam + metoclopramide) and 1 placebo arm were included. Dexmedetomidine was associated with decreases in SBP (mean difference [MD] = -18.78 mmHg; 95% CI [-26.27 to -11.28]) and HR (MD = -11.15 beats/min; 95% CI [-16.15 to -6.15]). Dexmedetomidine significantly reduced the HR compared with ketamine + propofol (-16.90 beats/min; 95% CI: -33.21 to -0.58]) and midazolam + opioid (-24.15 beats/min; 95% CI: -42.67 to -5.63). Midazolam was found to reduce SBP (-12.09 mmHg; 95% CI: -20.43 to -3.74) and was shown to reduce SpO2 compared with the placebo (-1.00%; 95% CI -1.74 to -0.26). Based on the NMA, the drugs with a higher likelihood of decreasing both SBP and HR were dexmedetomidine and midazolam. All of the drugs led to a small decrease (only statistically significant for midazolam) in SpO2, with the systematic use of supplemental O2 in some trials. The risks of hypotension, bradycardia, or desaturation were not significantly different among the evaluated drugs.

Cardiovascular and cerebrovascular risk markers in Parkinson's disease: Results from a case-control study.

BACKGROUND: The relationship between Parkinson's disease (PD) and cardiovascular and cerebrovascular disease is not yet well established. Recent data suggest an increased risk of myocardial infarction and stroke in PD patients. Therefore, we designed a study to assess surrogate markers of cardiovascular and cerebrovascular risk in PD. METHODS: We conducted a case-control study comparing PD patients recruited from a Movement Disorders Unit with controls randomly invited from a primary healthcare center. All participants underwent a detailed clinical evaluation, including medical history, physical assessment, carotid ultrasound, blood and urine analysis, and 24-h ambulatory blood pressure monitoring. The primary outcome was the carotid intima-media thickness (CIMT). RESULTS: We included 102 participants in each study arm. No significant difference was found in the CIMT among groups (MD: 0.01, 95% CI: -0.02, 0.04). Carotid plaques were more frequent in PD patients (OR: 1.90, 95% CI: 1.02, 3.55), although the lipid profile was more favorable in this group (LDL MD: -18.75; 95% CI: -10.69, -26.81). Nocturnal systolic blood pressure was significantly higher in PD patients (MD: 4.37, 95% CI: 0.27, 8.47) and more than half of the PD patients were non-dippers or reverse dippers (OR: 1.83, 95% CI: 1.04, 3.20). CONCLUSION: We did not find a difference in CIMT between PD and controls. A higher frequency of carotid plaques and abnormal dipper profile supports the hypothesis that PD patients are not protected from cardiovascular and cerebrovascular disease.

The Risk of Mortality Associated With Opioid Use in Patients With Acute Heart Failure: Systematic Review and Meta-analysis.

AIMS: The impact of opioids in acute heart failure (AHF) is unclear. This systematic review with meta-analysis aimed to evaluate the mortality risk associated with opioid use in AHF. METHODS AND RESULTS: An electronic search was performed in MEDLINE, CENTRAL, Web of Science Core Collection, and SCIELO (December 2019) for randomized controlled trials and observational studies evaluating the impact of opioids in in-hospital and 30-day mortality in patients with AHF. Data were screened, extracted, and appraised by 2 independent reviewers. A random-effects meta-analysis to estimate the pooled odds ratios (OR) with 95% confidence intervals (CI) was performed and heterogeneity was evaluated using the I2 statistics. Six observational retrospective studies with 151,735 participants were included. Pooled results showed a statistical significant association between morphine and in-hospital mortality (OR 1.78; 95% CI 1.01-3.13; I2 = 92%; 6 studies) and 30-day mortality (OR 1.56; 95% CI 1.14-2.15; I2 = 0; 2 studies). Both outcomes were rated as having a serious risk of bias and had a very low Grading of Recommendation, Assessment, Development, and Evaluation evidence. CONCLUSIONS: Opioids seem to be associated with an increased risk of short-term mortality in AHF patients; however, the confidence in the estimated effect is very low, which highlights the need of further research to evaluate this question.

Thrombotic Complications in Patients with COVID-19: Pathophysiological Mechanisms, Diagnosis, and Treatment.

INTRODUCTION: Emerging evidence points to an association between severe clinical presentation of COVID-19 and increased risk of thromboembolism. One-third of patients hospitalized due to severe COVID-19 develops macrovascular thrombotic complications, including venous thromboembolism, myocardial injury/infarction and stroke. Concurrently, the autopsy series indicate multiorgan damage pattern consistent with microvascular injury. PROPHYLAXIS, DIAGNOSIS AND TREATMENT: COVID-19 associated coagulopathy has distinct features, including markedly elevated D-dimers concentration with nearly normal activated partial thromboplastin time, prothrombin time and platelet count. The diagnosis may be challenging due to overlapping features between pulmonary embolism and severe COVID-19 disease, such as dyspnoea, high concentration of D-dimers, right ventricle with dysfunction or enlargement, and acute respiratory distress syndrome. Both macro- and microvascular complications are associated with an increased risk of in-hospital mortality. Therefore, early recognition of coagulation abnormalities among hospitalized COVID-19 patients are critical measures to identify patients with poor prognosis, guide antithrombotic prophylaxis or treatment, and improve patients' clinical outcomes. RECOMMENDATIONS FOR CLINICIANS: Most of the guidelines and consensus documents published on behalf of professional societies focused on thrombosis and hemostasis advocate the use of anticoagulants in all patients hospitalized with COVID-19, as well as 2-6 weeks post hospital discharge in the absence of contraindications. However, since there is no guidance for deciding the intensity and duration of anticoagulation, the decision-making process should be made in individual-case basis. CONCLUSIONS: Here, we review the mechanistic relationships between inflammation and thrombosis, discuss the macrovascular and microvascular complications and summarize the prophylaxis, diagnosis and treatment of thromboembolism in patients affected by COVID-19.

Anticoagulation after typical atrial flutter ablation: Systematic review and meta-analysis.

BACKGROUND: Cavotricuspid isthmus (CTI) ablation in typical atrial flutter (AFL) restores sinus rhythm in 95% of patients, which may lead to the discontinuation of oral anticoagulation during follow-up. Therefore, we aimed to systematically review the clinical impact of oral anticoagulation in the incidence of thromboembolic events (TE) after typical AFL ablation. METHODS: We searched for controlled studies evaluating the impact of anticoagulation in the incidence of TE in patients submitted to AFL ablation in MEDLINE, CENTRAL, PsycINFO database (June/2021). The primary outcome was TE events (ischemic stroke or systemic embolism). A meta-analysis was performed deriving risk ratios (RR) and 95% confidence intervals (CI). Statistical heterogeneity was measured through I2 metric. The confidence in the evidence was appraised with Grading of Recommendations Assessment, Development and Evaluation (GRADE) framework. RESULTS: Eight observational studies with 4870 patients were included. TE events were not significantly reduced (RR 1.18, 95% CI 0.59-2.36; n = 4870; GRADE very low). A meta-regression showed that for each 10% increase in the prevalence of previous AF in the studied population, anticoagulation reduced TE risk in 32%. There were no significant differences regarding bleeding events (RR 2.16, 95% CI 0.43-10.97, I2  = 0%; GRADE low), but there was a lower all-cause mortality (RR 0.24, 95% CI 0.17-0.32, GRADE low). CONCLUSION: The best available evidence lacks robustness and the data did not definitely associate anticoagulation after typical AFL ablation with reduced TE.