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Background Current evidence from randomized controlled trials on statins for primary prevention of cardiovascular disease (CVD) in older people, especially those aged > 75 years, is still lacking. We conducted a systematic review and meta-analysis of observational studies to extend the current evidence about the association of statin use in older people primary prevention group with risk of CVD and mortality. Methods PubMed, Scopus, and Embase were searched from inception until March 18, 2021. We included observational studies (cohort or nested case-control) that compared statin use vs non-use for primary prevention of CVD in older people aged ≥ 65 years; provided that each of them reported the risk estimate on at least one of the following primary outcomes: all cause-mortality, CVD death, myocardial infarction (MI), and stroke. Risk estimates of each relevant outcome were pooled as a hazard ratio (HR) with a 95% confidence interval (CI) using the random-effects meta-analysis model. The quality of the evidence was rated using the GRADE approach. Results Ten observational studies (9 cohorts and one case-control study; n = 815,667) fulfilled our criteria. The overall combined estimate suggested that statin therapy was associated with a significantly lower risk of all-cause mortality (HR: 0.86 [95% CI 0.79 to 0.93]), CVD death (HR: 0.80 [95% CI 0.78 to 0.81]), and stroke (HR: 0.85 [95% CI 0.76 to 0.94]) and a non-significant association with risk of MI (HR 0.74 [95% CI 0.53 to 1.02]). The beneficial association of statins with the risk of all-cause mortality remained significant even at higher ages (> 75 years old; HR 0.88 [95% CI 0.81 to 0.96]) and in both men (HR: 0.75 [95% CI: 0.74 to 0.76]) and women (HR 0.85 [95% CI 0.72 to 0.99]). However, this association with the risk of all-cause mortality remained significant only in those with diabetes mellitus (DM) (HR 0.82 [95% CI 0.68 to 0.98]) but not in those without DM. The level of evidence of all the primary outcomes was rated as “very low.” Conclusions Statin therapy in older people (aged ≥ 65 years) without CVD was associated with a 14%, 20%, and 15% lower risk of all-cause mortality, CVD death, and stroke, respectively. The beneficial association with the risk of all-cause mortality remained significant even at higher ages (> 75 years old), in both men and women, and in individuals with DM, but not in those without DM. These observational findings support the need for trials to test the benefits of statins in those above 75 years of age.

There has been less volume of literature focusing on the Immune-related Hematological Adverse Drug Events (Hem-irAEs) of Immune Checkpoint Inhibitors (ICPis) in cancer patients. Furthermore, there has been no consensus about the management of hematological toxicity from immunotherapy in the recently published practice guidelines by the European Society for Medical Oncology (ESMO). We conducted a systematic review of case reports/series to describe the diagnosis and management of potentially rare and unrecognized Hem-irAEs. We searched Medline, OVID, Web of Science for eligible articles. Data were extracted on patient characteristics, Hem-irAEs, and management strategies. We performed quality assessment using the Pierson-5 evaluation scheme and causality assessment using the Naranjo scale. Our search retrieved 49 articles that described 118 cases. The majority of patients had melanoma (57.6%) and lung cancer (26.3%). The most common Hem-irAEs reported with ICPis (such as nivolumab, ipilimumab, and pembrolizumab) were thrombocytopenia, hemolytic and aplastic anemias. Less reported adverse events included agranulocytosis and neutropenia. Steroids were commonly used to treat these adverse events with frequent success. Other used strategies included intravenous immunoglobulins (IVIG), rituximab, and transfusion of blood components. The findings of this review provide more insights into the diagnosis and management of the rarely reported Hem-irAEs of ICPis.

ObjectiveThe adherence to public health recommendations to control COVID-19 spread is influenced by public knowledge, attitudes and practices (KAP). We performed this cross-sectional study to assess the levels and determinants of public KAP towards COVID-19 in a large, multinational sample.DesignCross-sectional study (survey).SettingThe questionnaire was distributed to potential respondents via online platforms.Participants71 890 individuals from 22 countries.MethodsWe formulated a four-section questionnaire in English, followed by validation and translation into seven languages. The questionnaire was distributed (May to June 2020) and each participant received a score for each KAP section.ResultsOverall, the participants had fair knowledge (mean score: 19.24±3.59) and attitudes (3.72±2.31) and good practices (12.12±1.83) regarding COVID-19. About 92% reported moderate to high compliance with national lockdown. However, significant gaps were observed: only 68.2% knew that infected individuals may be asymptomatic; 45.4% believed that antibiotics are an effective treatment; and 55.4% stated that a vaccine has been developed (at the time of data collection). 71.9% believed or were uncertain that COVID-19 is a global conspiracy; 36.8% and 51% were afraid of contacting doctors and Chinese people, respectively. Further, 66.4% reported the pandemic had moderate to high negative effects on their mental health. Female gender, higher education and urban residents had significantly (p≤0.001) higher knowledge and practice scores. Further, we observed significant correlations between all KAP scores.ConclusionsAlthough the public have fair/good knowledge and practices regarding COVID-19, significant gaps should be addressed. Future awareness efforts should target less advantaged groups and future studies should develop new strategies to tackle COVID-19 negative mental health effects.

Regularly updated data on stroke and its pathological types, including data on their incidence, prevalence, mortality, disability, risk factors, and epidemiological trends, are important for evidence-based stroke care planning and resource allocation. The Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) aims to provide a standardised and comprehensive measurement of these metrics at global, regional, and national levels. We applied GBD 2019 analytical tools to calculate stroke incidence, prevalence, mortality, disability-adjusted life-years (DALYs), and the population attributable fraction (PAF) of DALYs (with corresponding 95% uncertainty intervals [UIs]) associated with 19 risk factors, for 204 countries and territories from 1990 to 2019. These estimates were provided for ischaemic stroke, intracerebral haemorrhage, subarachnoid haemorrhage, and all strokes combined, and stratified by sex, age group, and World Bank country income level. In 2019, there were 12·2 million (95% UI 11·0–13·6) incident cases of stroke, 101 million (93·2–111) prevalent cases of stroke, 143 million (133–153) DALYs due to stroke, and 6·55 million (6·00–7·02) deaths from stroke. Globally, stroke remained the second-leading cause of death (11·6% [10·8–12·2] of total deaths) and the third-leading cause of death and disability combined (5·7% [5·1–6·2] of total DALYs) in 2019. From 1990 to 2019, the absolute number of incident strokes increased by 70·0% (67·0–73·0), prevalent strokes increased by 85·0% (83·0–88·0), deaths from stroke increased by 43·0% (31·0–55·0), and DALYs due to stroke increased by 32·0% (22·0–42·0). During the same period, age-standardised rates of stroke incidence decreased by 17·0% (15·0–18·0), mortality decreased by 36·0% (31·0–42·0), prevalence decreased by 6·0% (5·0–7·0), and DALYs decreased by 36·0% (31·0–42·0). However, among people younger than 70 years, prevalence rates increased by 22·0% (21·0–24·0) and incidence rates increased by 15·0% (12·0–18·0). In 2019, the age-standardised stroke-related mortality rate was 3·6 (3·5–3·8) times higher in the World Bank low-income group than in the World Bank high-income group, and the age-standardised stroke-related DALY rate was 3·7 (3·5–3·9) times higher in the low-income group than the high-income group. Ischaemic stroke constituted 62·4% of all incident strokes in 2019 (7·63 million [6·57–8·96]), while intracerebral haemorrhage constituted 27·9% (3·41 million [2·97–3·91]) and subarachnoid haemorrhage constituted 9·7% (1·18 million [1·01–1·39]). In 2019, the five leading risk factors for stroke were high systolic blood pressure (contributing to 79·6 million [67·7–90·8] DALYs or 55·5% [48·2–62·0] of total stroke DALYs), high body-mass index (34·9 million [22·3–48·6] DALYs or 24·3% [15·7–33·2]), high fasting plasma glucose (28·9 million [19·8–41·5] DALYs or 20·2% [13·8–29·1]), ambient particulate matter pollution (28·7 million [23·4–33·4] DALYs or 20·1% [16·6–23·0]), and smoking (25·3 million [22·6–28·2] DALYs or 17·6% [16·4–19·0]). The annual number of strokes and deaths due to stroke increased substantially from 1990 to 2019, despite substantial reductions in age-standardised rates, particularly among people older than 70 years. The highest age-standardised stroke-related mortality and DALY rates were in the World Bank low-income group. The fastest-growing risk factor for stroke between 1990 and 2019 was high body-mass index. Without urgent implementation of effective primary prevention strategies, the stroke burden will probably continue to grow across the world, particularly in low-income countries. Bill & Melinda Gates Foundation.

Cyclophosphamide (CP) is a well-known antineoplastic agent; however, its clinical use can be associated with various organ toxicities. Evening primrose oil (EPO) contains several phytoconstituents with potent anti-oxidant and anti-inflammatory activities. This experimental study was performed to investigate the chemoprotective effects of EPO in the liver and pancreas of CP-intoxicated mice. Thirty-two albino mice were randomly divided into 4 equal groups: group I received saline (control mice), group II were treated with CP at 100 mg/kg/day for two subsequent days, and groups III and VI were treated with 5 and 10 mg/kg/day bw EPO, respectively for 14 days, followed by two doses of CP at the 15th and 16th days of the experiment. Then, mice were sacrificed and histopathological examinations, biochemical studies, and DNA laddering tests were conducted for hepatic and pancreatic tissues. Cyclophosphamide-intoxicated mice showed significant increases (p < 0.05) in the serum levels of liver enzymes, pancreatic amylase and tissue levels of malondialdehyde, and TNF-α, as well as a significant decrease (p < 0.05) in the serum insulin level. In addition, both hepatic and pancreatic tissues showed disturbed tissue architecture, hydropic degeneration, congested vessels, and inflammatory infiltrates, as well as increased DNA fragmentation. In a dose-dependent manner, pretreatment with EPO was associated with significant improvements (p < 0.05) in all biochemical parameters and significant amelioration of histopathological alterations and DNA fragmentation in CP-intoxicated mice. Pretreatment with EPO showed significant antioxidant, anti-inflammatory, and genoprotective effects against the toxic effects of CP in mice hepatic and pancreatic tissues.

Objective: Systematic reviews are increasingly used as sources of evidence in clinical cardiology guidelines. In the present study, we aimed to assess the quality of published systematic reviews in high impact cardiology journals. Methods: We searched PubMed for systematic reviews published between 2010 and 2019 in five general cardiology journals with the highest impact factor (according to Clarivate Analytics 2019). We extracted data on eligibility criteria, methodological characteristics, bias assessments, and sources of funding. Further, we assessed the quality of retrieved reviews using the AMSTAR tool. Results: A total of 352 systematic reviews were assessed. The AMSTAR quality score was low or critically low in 71% (95% CI: 65.7–75.4) of the assessed reviews. Sixty-four reviews (18.2%, 95% CI: 14.5–22.6) registered/published their protocol. Only 221 reviews (62.8%, 95% CI: 57.6–67.7) reported adherence to the EQUATOR checklists, 208 reviews (58.4%, 95% CI: 53.9–64.1) assessed the risk of bias in the included studies, and 177 reviews (52.3%, 95% CI: 45.1–55.5) assessed the risk of publication bias in their primary outcome analysis. The primary outcome was statistically significant in 274 (79.6%, 95% CI: 75.1–83.6) and had statistical heterogeneity in 167 (48.5%, 95% CI: 43.3–53.8) reviews. The use and sources of external funding was not disclosed in 87 reviews (24.7%, 95% CI: 20.5–29.5). Data analysis showed that the existence of publication bias was significantly associated with statistical heterogeneity of the primary outcome and that complex design, larger sample size, and higher AMSTAR quality score were associated with higher citation metrics. Conclusion: Our analysis uncovered widespread gaps in conducting and reporting systematic reviews in cardiology. These findings highlight the importance of rigorous editorial and peer review policies in systematic review publishing, as well as education of the investigators and clinicians on the synthesis and interpretation of evidence.

Background: While the prevalence of rheumatic heart disease (RHD) in Egypt is relatively high, data on the awareness of Egyptians about the cause of RHD are lacking. Methods: Using a pre-tested questionnaire, we performed a multicenter survey of outpatients attending 15 university hospitals across Egypt. Results: A total of 6958 participants were interviewed. Most subjects (81.7%) reported a previous experience of sore throat. Seeking treatment, most patients (69.3%) consulted a medical professional, while the others relied on self/peer medication. Individuals consulting a physician received antibiotics more frequently than those who did not (89.1 vs. 38.7%; OR: 12.4, 95% CI 10.8–14.1). The median RHD knowledge score in our sample was 4 (IQR = 6). While most subjects (56.3%) claimed knowledge of the complications of an untreated sore throat, only a third (34%) were aware of the association between sore throat and RHD. In a multivariate analysis, older age (Mean Difference [MD]: 1.58, 95% CI 1.37–1.79), female gender (MD: 0.89, 95% CI 0.75–1.04), higher education (MD: 1.10, 95% CI 0.90–1.30), and being interviewed outside Cairo (MD: 0.67, 95% CI 0.51–0.82) were significant predictors of knowledge about RHD. Conclusion: The current study showed low levels of awareness on the cause of RHD among Egyptians and highlights a pressing need for interventions to address this public knowledge gap.

Background: Valve-in-Valve transcatheter aortic valve implantation (ViV-TAVI) is a growing alternative for redo-surgery in patients with degenerated surgical valves. To our knowledge, data are lacking on the determinants on ViV-TAVI procedural success in patients with degenerated surgical valves. Methods: All consecutive patients undergoing ViV-TAVI for degenerated surgical valves at the Cleveland Clinic were analyzed. Data were extracted from our patient registry on baseline patient characteristics, echocardiographic parameters, and procedural details. To identify possible predictors of ViV-TAVI procedural success, we employed a multivariate logistic regression model. Results: A total of 186 patients who underwent ViV-TAVI were analyzed, with procedural success (VARC-2 device success and absence of periprocedural MACCE) reported in 165 (88.7%) patients. Patients with successful ViV-TAVI were significantly younger and had more frequent utilization of the transfemoral access than those with failed procedure. Other baseline and procedural characteristics were comparable between both groups. In terms of echocardiographic parameters, the procedural success group had a significantly lower AV peak pressure gradient (62.1 ± 24.7 vs. 74.1 ± 34.6 mmHg; p = 0.04) and lower incidence of moderate-to-severe aortic regurgitation [AR] (30.4 vs. 55%; p = 0.04). However, no significant differences between both groups were noted in terms of AV mean pressure gradient and left ventricular measurements. In multivariate analysis, lower AV peak pressure gradient (OR = 0.97, 95% CI: 0.95–0.99) and absence of moderate-to-severe AR (OR = 0.65, 95% CI: 0.44–0.95) at baseline emerged as independent predictors of ViV-TAVI procedural success. Conclusion: Valve-in-Valve TAVI for degenerated surgical valves is a feasible approach with high success rates, especially in those with lower AV peak pressure gradient and absence of moderate-to-severe AR. Studies with larger sample size and longer follow-up are required to further characterize the predictors of ViV-TAVI success and other clinical outcomes.

Data on the association between annular size and transcatheter aortic valve implantation (TAVI) outcomes beyond 1 year are limited. The present study assessed the association between the aortic annulus size and TAVI clinical and hemodynamic outcomes at 3 years of follow-up. Patients were classified according to the aortic annulus size as having small, intermediate, and large annuli (size <400, 400 to 574, and ≥575 mm2, respectively). The co-primary endpoints were all-cause mortality and heart failure hospitalization. Further, the changes in hemodynamic outcomes over the follow-up period (median 37, interquartile range: 26 to 45 months) were assessed. The present analysis included 850 patients, with 182 patients (21.4%), 538 patients (63.3%), and 130 patients (15.3%) in the small, intermediate, and large-sized aortic annulus groups, respectively. The groups had comparable age and pre-TAVI pressure gradients; however, patients with small annuli had higher Society of Thoracic Surgeons risk scores. Adjusted Cox regression analysis showed that compared to patients with intermediate-sized annuli, patients with small and large annuli had similar all-cause mortality (hazard ratio [HR] = 1.11, 95% confidence interval [CI] 0.72 to 1.69 and HR = 0.74, 95% CI 0.48 to 1.16, respectively) and heart failure hospitalization rates (HR = 0.96, 95% CI 0.55 to 1.69 and HR = 1.26, 95% CI 0.73 to 2.17, respectively). However, patients with small annuli had consistently higher mean and peak pressure gradients and a higher risk of patient-prosthesis mismatch. The risks of moderate-to-severe regurgitation and structural valve deterioration were similar between the three groups. In conclusion, although patients with small annuli had higher transvalvular gradients, there was no significant association between the aortic annulus size and TAVI clinical outcomes at 3 years of follow-up. Future studies should compare the performance of transcatheter valve types in patients with different aortic annulus sizes. [Display omitted]