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Background: Angiotensin converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) are known to increase the expression of angiotensin converting enzyme 2 receptor, which has been shown to be the receptor for the acute severe respiratory syndrome coronavirus 2 (SARS-CoV-2)., Areas of Uncertainty: Based on these observations, speculations raised the concerns that ACEIs/ARBs users would be more susceptible to SARS-CoV-2 infection and would be at higher risk for severe COVID-19 disease and death. Therefore, we systematically reviewed the literature and performed a meta-analysis of the association between prior use of ACEIs and ARBs and mortality due to COVID-19 disease., Data Sources: A comprehensive search of several databases from November 2019 to June 18, 2020 was conducted. The databases included Ovid MEDLINE(R) and Epub Ahead of Print, In-Process and Other Non-Indexed Citations and Daily, Ovid Embase, Ovid Cochrane Central Register of Controlled Trials, Ovid Cochrane Database of Systematic Reviews, Web of Science, and Scopus. Medrxiv.org was also searched for unpublished data., Therapeutic Advances: Nine studies with a total of 18,833 patients infected with SARS-CoV-2 met our eligibility criteria. Prior use of ACEIs and/or ARBs was associated with reduced mortality among SARS-CoV-2-infected patients, with a pooled adjusted relative risk (aRR) from 6 studies of 0.63, 95% confidence interval (CI) (0.42-0.94) (I 2 = 65%). Three studies reported separately on ACEIs or ARBs and their association with survival among SARS-CoV-2-infected patients, with a pooled adjusted relative risk of 0.78, 95% CI (0.58-1.04) (I 2 = 0%) and 0.97, 95% CI (0.73-1.30) (I 2 = 0%) respectively. The results of sensitivity analyses were consistent with the main analysis., Conclusion: Our meta-analysis suggests that use of ACEIs/ARBs is associated with a decreased risk of death among SARS-CoV-2-infected patients. This finding provides a reassurance to the public not to stop prescribed ACEIs/ARBs because of fear of severe COVID-19., Competing Interests: The authors have no conflicts of interest to declare., (Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.)

Hospitalized patients are likely to have chronic illnesses and are at an increased risk of mortality due to infection caused by MDR bacteria. We aimed to identify carbapenem-resistant genes carrying Klebsiella pneumoniae ( K. pneumoniae ) isolates and their risk factors recovered from adult patients with comorbidities. A cross-sectional study was carried out between April 2021 and December 2021 at King Abdullah Hospital (KAH) in Bisha province, Saudi Arabia. Seventy-one multi-drug resistant K. pneumoniae recovered from clinical samples and screened for carbapenemase genes of bla OXA-48-like, bla NDM-1, bla KPC, bla VIM, and bla IMP. Of 71 MDR K. pneumoniae examined, 47 (66.2%) isolates harbored various carbapenemase genes. The most prevalent single resistance gene was bla OXA-48-like (62.5%; n = 25), and 33.3% of them were recovered from sputum isolates. The bla NDM-1 gene was detected in 12 (30.0%) isolates, and eight of them were recovered from urine (n = 4) and blood (n = 4). Two (5.0%) single bla KPC genes were recovered from the sputum (n = 1) and blood (n = 1) isolates. In contrast, no bla IMP- and bla VIM-carrying isolates were detected. The co-existence of two resistance genes between bla OXA-48-like and bla NDM-1 was found in six strains, whereas only one strain was found to be produced in the three genes of bla NDM-1, bla KPC, and bla OXA-48-like. There were statistically significant associations between the presence of carbapenem-gene-carrying K. pneumoniae and patients' gender (χ2(1) = 5.94, p = 0.015), intensive care unit admission (χ2(1) = 7.649, p = 0.002), and chronic obstructive pulmonary disease (χ2(1) = 4.851, p = 0.028). The study highlighted the existence of carbapenemase-producing K. pneumoniae , particularly bla OXA-48-like and bla NDM-1, in patients with comorbidities. Our findings emphasize the importance of the molecular characterization of resistance-determinant-carrying bacterial pathogens as a part of infection control and prevention in hospital settings.

Objective: To systematically review the literature and to estimate the risk of chloroquine (CQ) and hydroxychloroquine (HCQ) cardiac toxicity in patients with coronavirus disease 2019 (COVID-19)., Methods: We searched multiple data sources including PubMed/MEDLINE, Ovid Embase, Ovid EBM Reviews, Scopus, and Web of Science and medrxiv.org from November 2019 through May 27, 2020. We included studies that enrolled patients with COVID-19 treated with CQ or HCQ, with or without azithromycin, and reported on cardiac toxic effects. We performed a meta-analysis using the arcsine transformation of the different incidences., Results: A total of 19 studies with a total of 5652 patients were included. The pooled incidence of torsades de pointes arrhythmia, ventricular tachycardia, or cardiac arrest was 3 per 1000 (95% CI, 0-21; I 2 =96%) in 18 studies with 3725 patients. Among 13 studies of 4334 patients, the pooled incidence of discontinuation of CQ or HCQ due to prolonged QTc or arrhythmias was 5% (95% CI, 1-11; I 2 =98%). The pooled incidence of change in QTc from baseline of 60 milliseconds or more or QTc of 500 milliseconds or more was 9% (95% CI, 3-17; I 2 =97%). Mean or median age, coronary artery disease, hypertension, diabetes, concomitant QT-prolonging medications, intensive care unit admission, and severity of illness in the study populations explained between-studies heterogeneity., Conclusion: Treatment of patients with COVID-19 with CQ or HCQ is associated with an important risk of drug-induced QT prolongation and relatively higher incidence of torsades de pointes, ventricular tachycardia, or cardiac arrest. Therefore, these agents should not be used routinely in the management of COVID-19 disease. Patients with COVID-19 who are treated with antimalarials for other indications should be adequately monitored., (© 2020 Mayo Foundation for Medical Education and Research. Published by Elsevier Inc.)

Background: SARS-CoV-2 infects its target cells via angiotensin converting enzyme 2 receptor, a membrane-bound protein found on the surface of many human cells. Treatment with angiotensin converting enzyme inhibitors (ACEI) or angiotensin receptors blockers (ARB) has been shown to increase angiotensin converting enzyme 2 expression by up to 5-fold., Areas of Uncertainty: These findings coupled with observations of the high prevalence and mortality among SARS-CoV-2-infected patients with underlying cardiovascular disease have led to a speculation that ACEIs/ARBs may predispose to higher risk of being infected with SARS-CoV-2. Therefore, we systematically reviewed the literature and performed a meta-analysis of the association between prior use of ACEIs and ARBs and the risk of SARS-CoV-2 infection or hospitalization due to COVID-19 disease., Data Sources: We searched Ovid MEDLINE(R) and Epub Ahead of Print, In-Process & Other Non-Indexed Citations and Daily, Ovid Embase, Ovid Cochrane Central Register of Controlled Trials, Ovid Cochrane Database of Systematic Reviews, Web of Science, Scopus, and Medrxiv.org preprint server until June 18, 2020., Therapeutic Advances: Ten studies (6 cohorts and 4 case control) that enrolled a total of 23,892 patients and 853,369 controls were eligible for inclusion in our meta-analysis. One study was excluded from the analysis because of high risk of bias. Prior use of ACEIs was not associated with an increased risk of acquiring SARS-CoV-2 or hospitalization due to COVID-19 disease, odds ratio 0.98, 95% confidence interval (0.91-1.05), I2 = 15%. Similarly, prior use of ARBs was not associated with an increased risk of acquiring SARS-CoV-2, odds ratio 1.04, 95% confidence interval (0.98-1.10), I2 = 0%., Conclusion: Cumulative evidence suggests that prior use of ACEIs or ARBs is not associated with a higher risk of COVID-19 or hospitalization due to COVID-19 disease. Our results provide a reassurance to the public not to discontinue prescribed ACEIs/ARBs because of fear of COVID-19., Competing Interests: The authors have no conflicts of interest to declare., (Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.)

Objective: To investigate the association between fluoroquinolones use and development of aortopathy., Methods: A systematic review and meta-analysis was conducted following PRISMA and MOOSE guidelines for reporting systematic reviews of observational studies. Multiple databases were searched and two authors independently screened studies for eligibility. Newcastle Ottawa scale was used to assessed the quality of included studies. Primary outcome of interest was development of aortic aneurysm or dissection among fluoroquinolones users in comparison to non-users. An inverse variance model meta-analysis was used to pool odds ratio or hazards ratio from included studies to calculate the overall effect estimate. Pre specified subgroups analyses were also conducted to explore sources of heterogeneity., Results: Three observational studies that enrolled 941,639 subjects met the inclusion criteria and were included in the final analysis. All studies were of a good methodological quality. Current use of fluoroquinolones, defined as within 60 days from development of the primary outcome, was associated with significantly elevated risk of developing aortic aneurysm and/or dissection in comparison to controls, (OR = 2.04; 95% CI [1.67, 2.48]). There was only a mild degree of between study heterogeneity, I 2  = 33%. The association remains robust among all subgroups analyses., Conclusion: Our findings indicate that current fluoroquinolone use was significantly associated with increased risk of aortic aneurysm and dissection. Health care providers need to be aware of this serious association and use fluoroquinolones judiciously in order to minimize the risk of the serious sequela of aortopathy., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Infective endocarditis (IE) is associated with significant serious adverse outcomes including death. IE usually presents with diverse clinical picture and syndromic diagnoses including heart failure, stroke, and peripheral embolization. Given variable, vague, and syndromic presentations, the diagnosis of IE may be delayed for days to weeks. Maintaining a high index of suspicion among clinicians is the key to early recognition of the disease and prompt initiation of antimicrobial therapy to prevent IE-associated mortality and morbidity. Blood culture and echocardiography remain essential tools in the diagnosis of infective endocarditis. However, advances in molecular techniques, serology testing, computed tomography scan, and nuclear medicine have led to growth in the available tools that may aid in early diagnosis of infective endocarditis. Antimicrobial agents are the mainstay of IE therapy; however, as many as 50% of endocarditis cases will undergo valve surgery, even on an urgent or emergent basis.

Statins are essential medications in the management of patients with clinical atherosclerotic cardiovascular disease, and have been supported by numerous clinical trials. Emerging evidence suggests that adding ezetimibe to statin therapy is associated with a net benefit and improved hard clinical outcomes, particularly in patients with significantly elevated atherosclerotic cardiovascular disease risk and elevated low-density lipoprotein cholesterol levels., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Background : Population-based studies are the gold standard to understand the burden of different diseases, plan health care policy and resource allocation, and provide an accurate estimate of disease several disease indices including mortality. However, population-based studies are difficult to undertake in a resource-limited situation where no robust data bases and disease registries are available. Therefore, hospital-based cohorts may be used to inform about the community health. Objectives: We sought to study the pattern of disease causing admission, hospital stay, and outcomes of medical admissions to King Abdullah Hospital in Bisha in order to inform clinicians, public health professionals, and policymakers about the current status of diseases within the community in Bisha. Methods: This is a cross-sectional study including all adult patients aged above 18 years who were admitted to King Abdullah Hospital in Bisha, Assir region, to medical services including general internal medicine, general cardiology, nephrology, gastroenterology, rheumatology, and neurology during the study period between 1 June 2015 and 31 May 2016. Common causes of hospital admission, outcomes of hospitalization, and length of stay were estimated and the data were presented as frequency and percentage for categorical valve and mean and standard deviation for continuous variables. Results : Cardiovascular diseases including stroke are considered the leading cause of hospital admission in a teaching community hospital in Bisha, Assir region. Diabetes mellitus and hypertension are prevalent comorbidities among hospitalized patients. Majority of admitted patients have improved and discharged home (83.3%). However, 6.7% were transferred to another facility, 4.1% have left against medical advice, and 5.9% died. Conclusion : Health-related data bases and disease registries are urgently needed to precisely estimate the burden of cardiovascular disease in Assir region in Saudi Arabia. Lifestyle changes, healthy diet, aggressive management of hypertension and diabetes within the community, and allocating necessary resources are urgently to combat the growing burden of cardiovascular disease.

Background: The 2013 American College of Cardiology/American Heart Association blood cholesterol guideline recommends high-intensity statin therapy among certain groups of patients, but full implementation of the guideline has not yet been satisfactory. We aimed to investigate the temporal trends and predictors of high-intensity statin therapy among veterans who had been treated with percutaneous coronary intervention (PCI) and followed up by cardiologists within the Veterans Health Administrative system., Methods and Results: A retrospective cohort study was conducted at the Veterans Health Administrative system including all patients >18 years old who had their PCI procedure between October 2010 and September 2016. National Veterans Health Administrative databases were used to retrieve study participant's demographics, comorbid conditions, statin type and dose within 90 days before and after the PCI procedure. There were 48 862 patients who underwent a PCI procedure during the study period. High-intensity statin use at 90 days post-PCI rose from 23% in 2010 to 37% before release of the 2013 American College of Cardiology/American Heart Association cholesterol guideline, then rose sharply to 80% by 2016. The projected 10-year risk of arteriosclerotic cardiovascular disease events among our study population was projected to be ≈1841 fewer if the cohort had received high-intensity statin therapy versus moderate-intensity statin., Conclusions: By 2016, the 2013 American College of Cardiology/American Heart Association blood cholesterol guideline was well implemented among veterans who had a PCI procedure in the Veterans Health Administrative system, suggesting systems of care can be improved to increase rates of high-intensity statin initiation., (© 2018 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.)

Aims: Total occlusion (TO) of the culprit artery usually presents with ST-elevation myocardial infarction. A subset of patients with TO present as non-ST segment elevation myocardial infarction (NSTEMI) without classic ST-elevation on the electrocardiogram. This may lead to delay in identification of these patients and further management. We performed a meta-analysis to estimate the difference in outcomes between totally occluded and non-occluded culprit arteries in patients with NSTEMI., Methods and Results: Our literature search yielded seven studies with 40 777 patients. The outcomes assessed were clinical presentation (Killip class), left ventricular ejection fraction, time to angiography, major cardiac adverse events (MACE) and all-cause mortality. The generic inverse or Mantel-Haenszel method was used to pool relevant outcomes and the mean difference (MD) or relative risk (RR) was calculated. A total of 10 415 (25.5%) patients had an occluded culprit artery with a predominant infero-lateral distribution (40% right coronary and 33% left circumflex artery). There was an increased risk of both MACE (short-term RR: 1.41; CI: 1.17, 1.70; P = 0.0003; I2 = 26%; medium- to long-term RR: 1.32; CI: 1.11, 1.56; P = 0.001; I2 = 25%) and all-cause mortality (short-term RR: 1.67; CI: 1.31, 2.13; P < 0.0001; I2 = 41%; medium to long-term RR: 1.42; CI: 1.08, 1.86; P = 0.01; I2 = 32%) with TO of the culprit artery., Conclusion: Our meta-analysis suggests that patients with NSTEMI who demonstrate a totally occluded culprit vessel on coronary angiography are at higher risk of mortality and major adverse cardiac events. Better risk stratification tools are needed to identify such high-risk acute coronary syndrome patients to facilitate earlier revascularization and potentially to improve outcomes., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2017. For permissions, please email: journals.permissions@oup.com.)

Background: The scarcity of familial hypercholesterolemia (FH) cases reported in Saudi Arabia might be indicative of a lack of awareness of this common genetic disease among physicians., Objective: To assess physicians' awareness, practice, and knowledge of FH in Saudi Arabia., Methods: This is a cross-sectional study conducted among physicians at four tertiary hospitals in Riyadh, Saudi Arabia between March 2016 and May 2016 using a self-administered questionnaire., Results: A total of 294 physicians completed the survey (response rate 90.1%). Overall, 92.9% of the participants have poor knowledge of FH while only 7.1% have acceptable knowledge. The majority (68.7%) of physicians rated their familiarity with FH as average or above average, and these had higher mean knowledge scores than participants with self-reported below average familiarity (mean 3.4 versus 2.6) (P < 0.001). Consultant physicians were 4.2 times more likely to be familiar with FH than residents or registrars (OR = 4.2, 95% CI = 1.9-9.1, P < 0.001). Physicians who currently managed FH patients had higher mean knowledge scores compared to those without FH patients in their care (3.5 versus 2.9) (P = 0.006). In addition, there were statistically significant differences between physicians' mean knowledge scores and their ages, levels of training, and years in practice. Moreover, a substantial deficit was identified in the awareness of various clinical algorithms to diagnose patients with FH, cascade screening, specialist lipid services, and the existence of statin alternatives, such as proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors., Conclusion: A substantial deficit was found in the awareness, knowledge, practice, and detection of FH among physicians in Saudi Arabia. Extensive educational programs are required to raise physician awareness and implement best practices; only then can the impact of these interventions on FH management and patient outcome be assessed.

Purpose of the Review: Community-acquired pneumonia (CAP) is still associated with a large burden and causes significant morbidity and mortality. Besides universal vaccination and antibiotic treatment, statins as adjunctive therapy may also have a beneficial role in the prevention and treatment of CAP. Our goal from this review is to discuss the epidemiology of CAP, and role of statins as adjunctive therapy in the development of CAP., Recent Findings: Statins are lipid-lowering medications characterized by their ability to control hypercholesterolemia in addition to other pleiotropic effects that could explain their role in the pathogenesis of CAP. While most observational studies have shown that statins reduce risk of pneumonia in the general population, patients with diabetes, and recently in patients with myocardial infarction, no randomized controlled trial (RCT) to date has been conducted to assess the efficacy of statins to prevent development of CAP. Given the paucity of robust randomized evidence to assess statin use and the development of CAP, and considering conflicting results of the observational studies, we are not in favor of initiation of statins for either the prevention or treatment of CAP.

Purpose of the Review: Infective endocarditis (IE) is a serious disease with significant morbidity and mortality. Valve surgery is fundamental in the standard of care of selected IE patients. Indeed, valve surgery can be a lifesaving procedure in critically ill endocarditis patients. Our goal from this review is to discuss the indications of surgery in IE population and international cardiac societies' guideline recommendations., Recent Findings: Though IE is an uncommon disease, its incidence is noted to be on rise in some parts of the world, and the disease is expected to continue to be a major health problem. Antimicrobials remain the mainstay of IE therapy, but as many as 50% of endocarditis patients will undergo surgical intervention. Heart failure most commonly from acute valvular insufficiency, uncontrolled and persistent infection, and recurrent embolic events are the major indications for valve surgery in IE population. Heart failure is by far the most common indication for surgery in IE patients. Despite the fact that many IE patients will require surgical interventions, most of the international societies' recommendations to perform valve surgery are based on observational studies or experts' opinion. Surgery plays a major role in the management of IE patients, and it is most commonly performed in patients with heart failure, persistent or uncontrolled infection, and recurrent emboli. Most of the current evidence supporting surgical intervention in IE patients is based on observational studies and experts' opinion. Randomized clinical trials are urgently needed to guide surgical therapy in IE.

Background: The eastern Mediterranean region is comprised of 22 countries: Afghanistan, Bahrain, Djibouti, Egypt, Iran, Iraq, Jordan, Kuwait, Lebanon, Libya, Morocco, Oman, Pakistan, Palestine, Qatar, Saudi Arabia, Somalia, Sudan, Syria, Tunisia, the United Arab Emirates, and Yemen. Since our Global Burden of Disease Study 2010 (GBD 2010), the region has faced unrest as a result of revolutions, wars, and the so-called Arab uprisings. The objective of this study was to present the burden of diseases, injuries, and risk factors in the eastern Mediterranean region as of 2013., Methods: GBD 2013 includes an annual assessment covering 188 countries from 1990 to 2013. The study covers 306 diseases and injuries, 1233 sequelae, and 79 risk factors. Our GBD 2013 analyses included the addition of new data through updated systematic reviews and through the contribution of unpublished data sources from collaborators, an updated version of modelling software, and several improvements in our methods. In this systematic analysis, we use data from GBD 2013 to analyse the burden of disease and injuries in the eastern Mediterranean region specifically., Findings: The leading cause of death in the region in 2013 was ischaemic heart disease (90·3 deaths per 100 000 people), which increased by 17·2% since 1990. However, diarrhoeal diseases were the leading cause of death in Somalia (186·7 deaths per 100 000 people) in 2013, which decreased by 26·9% since 1990. The leading cause of disability-adjusted life-years (DALYs) was ischaemic heart disease for males and lower respiratory infection for females. High blood pressure was the leading risk factor for DALYs in 2013, with an increase of 83·3% since 1990. Risk factors for DALYs varied by country. In low-income countries, childhood wasting was the leading cause of DALYs in Afghanistan, Somalia, and Yemen, whereas unsafe sex was the leading cause in Djibouti. Non-communicable risk factors were the leading cause of DALYs in high-income and middle-income countries in the region. DALY risk factors varied by age, with child and maternal malnutrition affecting the younger age groups (aged 28 days to 4 years), whereas high bodyweight and systolic blood pressure affected older people (aged 60-80 years). The proportion of DALYs attributed to high body-mass index increased from 3·7% to 7·5% between 1990 and 2013. Burden of mental health problems and drug use increased. Most increases in DALYs, especially from non-communicable diseases, were due to population growth. The crises in Egypt, Yemen, Libya, and Syria have resulted in a reduction in life expectancy; life expectancy in Syria would have been 5 years higher than that recorded for females and 6 years higher for males had the crisis not occurred., Interpretation: Our study shows that the eastern Mediterranean region is going through a crucial health phase. The Arab uprisings and the wars that followed, coupled with ageing and population growth, will have a major impact on the region's health and resources. The region has historically seen improvements in life expectancy and other health indicators, even under stress. However, the current situation will cause deteriorating health conditions for many countries and for many years and will have an impact on the region and the rest of the world. Based on our findings, we call for increased investment in health in the region in addition to reducing the conflicts., Funding: Bill & Melinda Gates Foundation., (Copyright © 2016 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY license. Published by Elsevier Ltd.. All rights reserved.)

Capecitabine is an orally administered chemotherapeutic agent that is metabolized at the tumor site to 5-fluorouracil and thought to be without significant cardiac toxicity. We report a rare case of takotsubo cardiomyopathy that is thought to be related to capecitabine where the patient presented with chest pain, and ST elevation within 48 hours of capecitabine therapy. Workup included cardiac catheterization and coronary angiogram that showed nonobstructive coronary artery disease and anteroapical left ventricular wall motion abnormality with left ventricular ejection fraction of 35%. The drug was stopped, and the patient was treated with beta-blocker and angiotensin-converting enzymes inhibitor. Six weeks later, she had a repeat echocardiogram that was normal. Capecitabine-related cardiomyopathy seems to be very rare because only 5 cases have been reported in the literature (including our case). The condition has to be anticipated and treated to prevent the serious consequence of cardiac dysfunction. All reported cases have eventually recovered after stopping capecitabine.

Background: Disagreement among many underpowered studies has led to an equivocal understanding of the efficacy of the 5-HT3 antagonist ondansetron in preventing the consequences of sympathectomy after subarachnoid anesthesia. The authors assessed the efficacy of ondansetron with respect to the overall quality and statistical power of the meta-analyses., Methods: The authors used a standard and a newer method of meta-analysis, trial sequential analysis (TSA), to estimate adjusted CIs based on how much information has been accrued. They also used random-effects meta-analyses techniques, small trial bias assessment, selection models, sensitivity analyses, and the Grading of Recommendations on Assessment, Development, and Evaluation system. These results from the aforementioned techniques were compared, and importance of consideration of these factors was discussed., Results: Fourteen randomized placebo-controlled trials (1,045 subjects) were identified and analyzed. By using conventional meta-analyses, the authors determined that ondansetron was associated with reduction in the incidence of hypotension (relative risk = 0.62 [95% CI, 0.46 to 0.83], P = 0.001; TSA-adjusted CI, 0.34 to 1.12; I = 60%, P = 0.002) and bradycardia (relative risk = 0.44 [95% CI, 0.26 to 0.73], P = 0.001; TSA-adjusted CI, 0.05 to 3.85; I = 0%, P = 0.84). However, the authors found indications of bias among these trials. TSAs demonstrated that the meta-analysis lacked adequate information size and did not achieve statistical significance when adjusted for sparse data and repetitive testing. The Grading of Recommendations on Assessment, Development, and Evaluation system showed that the results had low to very low quality of evidence., Conclusions: The analyses fail to confirm evidence that ondansetron reduces the incidence of hypotension and bradycardia after subarachnoid anesthesia due to the risk of bias and information sizes less than the required. As results from meta-analysis are given significant weight, it is important to carefully evaluate the quality of the evidence that is input.

Background: The Global Burden of Disease, Injuries, and Risk Factor study 2013 (GBD 2013) is the first of a series of annual updates of the GBD. Risk factor quantification, particularly of modifiable risk factors, can help to identify emerging threats to population health and opportunities for prevention. The GBD 2013 provides a timely opportunity to update the comparative risk assessment with new data for exposure, relative risks, and evidence on the appropriate counterfactual risk distribution., Methods: Attributable deaths, years of life lost, years lived with disability, and disability-adjusted life-years (DALYs) have been estimated for 79 risks or clusters of risks using the GBD 2010 methods. Risk-outcome pairs meeting explicit evidence criteria were assessed for 188 countries for the period 1990-2013 by age and sex using three inputs: risk exposure, relative risks, and the theoretical minimum risk exposure level (TMREL). Risks are organised into a hierarchy with blocks of behavioural, environmental and occupational, and metabolic risks at the first level of the hierarchy. The next level in the hierarchy includes nine clusters of related risks and two individual risks, with more detail provided at levels 3 and 4 of the hierarchy. Compared with GBD 2010, six new risk factors have been added: handwashing practices, occupational exposure to trichloroethylene, childhood wasting, childhood stunting, unsafe sex, and low glomerular filtration rate. For most risks, data for exposure were synthesised with a Bayesian meta-regression method, DisMod-MR 2.0, or spatial-temporal Gaussian process regression. Relative risks were based on meta-regressions of published cohort and intervention studies. Attributable burden for clusters of risks and all risks combined took into account evidence on the mediation of some risks such as high body-mass index (BMI) through other risks such as high systolic blood pressure and high cholesterol., Findings: All risks combined account for 57·2% (95% uncertainty interval [UI] 55·8-58·5) of deaths and 41·6% (40·1-43·0) of DALYs. Risks quantified account for 87·9% (86·5-89·3) of cardiovascular disease DALYs, ranging to a low of 0% for neonatal disorders and neglected tropical diseases and malaria. In terms of global DALYs in 2013, six risks or clusters of risks each caused more than 5% of DALYs: dietary risks accounting for 11·3 million deaths and 241·4 million DALYs, high systolic blood pressure for 10·4 million deaths and 208·1 million DALYs, child and maternal malnutrition for 1·7 million deaths and 176·9 million DALYs, tobacco smoke for 6·1 million deaths and 143·5 million DALYs, air pollution for 5·5 million deaths and 141·5 million DALYs, and high BMI for 4·4 million deaths and 134·0 million DALYs. Risk factor patterns vary across regions and countries and with time. In sub-Saharan Africa, the leading risk factors are child and maternal malnutrition, unsafe sex, and unsafe water, sanitation, and handwashing. In women, in nearly all countries in the Americas, north Africa, and the Middle East, and in many other high-income countries, high BMI is the leading risk factor, with high systolic blood pressure as the leading risk in most of Central and Eastern Europe and south and east Asia. For men, high systolic blood pressure or tobacco use are the leading risks in nearly all high-income countries, in north Africa and the Middle East, Europe, and Asia. For men and women, unsafe sex is the leading risk in a corridor from Kenya to South Africa., Interpretation: Behavioural, environmental and occupational, and metabolic risks can explain half of global mortality and more than one-third of global DALYs providing many opportunities for prevention. Of the larger risks, the attributable burden of high BMI has increased in the past 23 years. In view of the prominence of behavioural risk factors, behavioural and social science research on interventions for these risks should be strengthened. Many prevention and primary care policy options are available now to act on key risks., Funding: Bill & Melinda Gates Foundation., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Purpose: Effective intraprocedural anticoagulation is considered essential to minimize the risk of thromboembolism in catheter ablation (CA) of atrial fibrillation (AF). The effect of interrupted apixaban on intraprocedural heparin dosing requirements and levels of achieved anticoagulation with heparin has not been well studied. The purpose of the present study was to compare heparin administration and activated clotted times (ACTs) for patients undergoing CA for AF treated with interrupted apixaban before the procedure with patients on uninterrupted warfarin., Methods: Consecutive patients undergoing CA for AF treated with interrupted apixaban or uninterrupted warfarin were prospectively enrolled. Heparin administration determined by a standard protocol and normalized to patient weight and procedure duration, as well as rapidity, and degree of anticoagulation with heparin (as measured by mean ACT, peak ACT, time to ACT ≥300 s, and time to ACT ≥350 s) were compared between the groups., Results: Forty-eight patients were enrolled (25 apixaban and 23 warfarin). Heparin administered by bolus (51.3 ± 21.5 vs 27.8 ± 9.6 units/kg/h; p < 0.001) and mean heparin drip rate (25.3 ± 3.6 vs 20.7 ± 2.4 units/kg/h; p < 0.001) were significantly higher in the apixaban group compared to the warfarin group. Despite greater heparin administration, apixaban patients achieved a significantly lower mean ACT (332.3 ± 17.0 vs 384.5 ± 53.9; p < 0.001) and peak ACT (369.5 ± 22.6 vs 432.3 ± 75.8, p < 0.001) compared to the warfarin group. The time to ACT ≥350 s (66.7 ± 35.8 vs 26.9 ± 34.0; p < 0.001) was significantly longer for apixaban-treated patients. Outcome differences persisted after analysis using linear models and Cox proportional hazard regression with adjustment for propensity scores., Conclusions: A standard intraprocedural heparin protocol results in delayed and lower levels of anticoagulation as measured by the ACT for interrupted apixaban-treated patients in comparison to those on uninterrupted warfarin during CA of AF.

Recent evidence, though conflicting, suggests an association between azithromycin use and cardiovascular death. We conducted a systematic review and meta-analysis to evaluate the effect of azithromycin on risk of death. Multiple databases were searched. Authors independently screened and extracted the data from studies. Primary outcome of interest was risk of death (cardiovascular and/or noncardiovascular). Subgroup analyses were conducted to explore the source of a possible heterogeneity. Random effects model meta-analysis and hazards ratio (HR) were used to pool the data and calculate the overall effect estimate, respectively. Eight hundred twenty-eight citations, identified with 5 cohort studies that involved 2,246,178 episodes of azithromycin use, met our inclusion criteria. Azithromycin use was not associated with higher risk of death from any cause, HR = 0.99 [confidence interval (CI), 0.82-1.19], I = 54%, or cardiovascular cause, HR = 1.15 (CI, 0.66-2.00), I = 64%, but there was a moderate degree of heterogeneity. Subgroup analyses have shown no increased risk of death with azithromycin use in younger population with zero degree of heterogeneity, HR = 0.85 (CI, 0.66-1.09), I = 0%. However, current use of azithromycin (within 1-5 days of therapy) was associated with a higher risk of death among older population with mild degree of heterogeneity, HR = 1.64 (CI, 1.23-2.19), I = 4%. In summary, azithromycin use was not associated with higher risk of death particularly in younger population. Nevertheless, older population might be at higher risk of death with current use of azithromycin, and an alternative therapy should probably be considered.

Infective endocarditis (IE) is a life-threatening disease associated with serious complications. The GBD 2010 (Global Burden of Disease, Injuries, and Risk Factors) study IE expert group conducted a systematic review of IE epidemiology literature to inform estimates of the burden on IE in 21 world regions in 1990 and 2010. The disease model of IE for the GBD 2010 study included IE death and 2 sequelae: stroke and valve surgery. Several medical and science databases were searched for IE epidemiology studies in GBD high-, low-, and middle-income regions published between 1980 and 2008. The epidemiologic parameters of interest were IE incidence, proportions of IE patients who developed stroke or underwent valve surgery, and case fatality. Literature searches yielded 1,975 unique papers, of which 115 published in 10 languages were included in the systematic review. Eligible studies were population-based (17%), multicenter hospital-based (11%), and single-center hospital-based studies (71%). Population-based studies were reported from only 6 world regions. Data were missing or sparse in many low- and middle-income regions. The crude incidence of IE ranged between 1.5 and 11.6 cases per 100,000 people and was reported from 10 countries. The overall mean proportion of IE patients that developed stroke was 0.158 ± 0.091, and the mean proportion of patients that underwent valve surgery was 0.324 ± 0.188. The mean case fatality risk was 0.211 ± 0.104. A systematic review for the GBD 2010 study provided IE epidemiology estimates for many world regions, but highlighted the lack of information about IE in low- and middle-income regions. More complete knowledge of the global burden of IE will require improved IE surveillance in all world regions., (Copyright © 2014 World Heart Federation (Geneva). All rights reserved.)

Objectives: This study sought to perform a meta-analysis of randomized controlled trials comparing device closure with medical therapy in the prevention of recurrent neurological events in patients with cryptogenic stroke and patent foramen ovale., Background: The optimal strategy for secondary prevention of cryptogenic stroke with a patent foramen ovale is unclear., Methods: Several databases were searched from their inception to March 2013, which yielded 3 eligible studies. The results were pooled as per the different patient populations defined in the studies:-intention-to-treat, per-protocol, and as-treated cohorts. A generic inverse method was used based on time-to-event outcomes in a fixed-effect model. A supplementary analysis pooled the results from only 2 trials (RESPECT [Randomized Evaluation of Recurrent Stroke Comparing PFO Closure to Established Current Standard of Care Treatment] and PC Trial [Randomized Clinical Trial Comparing the Efficacy of Percutaneous Closure of Patent Foramen Ovale (PFO) With Medical Treatment in Patients With Cryptogenic Embolism]) as a similar device was used in them., Results: Our meta-analysis yielded effect-estimate hazard ratios of 0.67 (95% confidence interval [CI]: 0.44 to 1.00, I(2) = 0%) in the intention-to-treat cohort, 0.62 (95% CI: 0.40 to 0.95). I(2) = 0%) in the per-protocol cohort, and 0.61 (95% CI: 0.40 to 0.95, I(2) = 38%) in the as-treated cohort, showing beneficial effects of device closure. The results became more robust with pooled results from RESPECT and the PC Trial: The effect-estimate hazard ratios being 0.54 (95% CI: 0.29 to 1.01, I(2) = 0%), 0.48 (95% CI: 0.24 to 0.94, I(2) = 26%), and 0.42 (95% CI: 0.21 to 0.84, I(2) = 26%) in the intention-to-treat, per-protocol, and as-treated populations, respectively., Conclusions: Our meta-analysis suggests that PFO closure is beneficial as compared to medical therapy in the prevention of recurrent neurological events. This meta-analysis helps to further strengthen the role of device closure in cryptogenic stroke., (Copyright © 2013 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Aims: To examine the safety (defined as bleeding risk) and efficacy (defined as prevention of thromboembolic events) of interrupted dabigatran for peri-procedural anticoagulation in catheter ablation (CA) of atrial fibrillation (AF) in comparison with warfarin., Methods and Results: Reviewers independently searched literature databases from January 2010 through April 2013 for studies comparing the safety and efficacy of dabigatran and warfarin in CA of AF and extracted pre-defined data. The Mantel-Haenszel method was used to pool data of bleeding and thromboembolism outcomes into random and fixed effect model meta-analyses, respectively. Odds ratios (ORs), and risk difference (RD) analysis when studies reported no events in either arm, were used to generate an overall effect estimate of both outcomes. Publication bias and heterogeneity were assessed by contour funnel plot and the I(2) test, respectively. Nine citations, including 3036 patients (1073 dabigatran), met the inclusion criteria. There was no significant difference between interrupted dabigatran and warfarin therapy in CA of AF in occurrence of bleeding [dabigatran 58 (5.4%), warfarin 103 (5.2%); OR 0.92 (95% confidence interval (CI) 0.55-1.45); χ(2) = 13.03-P = 0.11; I(2) = 39%] or thromboembolism [dabigatran 5 (0.4%), warfarin 2 (0.1%); OR 2.15 (95% CI-0.58-7.98); χ(2) = 2.14, P = 0.54; I(2) = 0%; RD 0.00 (95% CI-0.00 to 0.01); χ(2) = 3.37, P = 0.81; I(2) = 0%]. Analysis of pre-defined subgroups (published articles vs. abstracts), sensitivity analyses (interrupted warfarin, USA studies, and Japanese studies) and fixed effect model analyses showed similar results. Heterogeneity was mild in the bleeding outcome analysis and zero in thromboembolism. There was no evidence of publication bias in either meta-analysis., Conclusion: Meta-analysis of currently available studies showed no significant difference in bleeding and thromboembolism between interrupted dabigatran and warfarin therapy in CA of AF. Dabigatran appears to be safe and effective for peri-procedural anticoagulation in CA of AF.

Background: Emerging epidemiological evidence suggests that statins may reduce the risk of community-acquired pneumonia (CAP) and its complications., Purpose: Performed a systematic review to address the role of statins in the prevention or treatment of CAP., Data Source: Ovid MEDLINE, Cochrane, EMBASE, ISI Web of Science, and Scopus from inception through December 2011 were searched for randomized clinical trials, cohort and case-control studies., Study Selection: Two authors independently reviewed studies that examined the role of statins in CAP., Data Extraction: Data about study characteristics, adjusted effect-estimates and quality characteristics was extracted., Data Synthesis: Eighteen studies corresponding to 21 effect-estimates (eight and 13 of which addressed the preventive and therapeutic roles of statins, respectively) were included. All studies were of good methodological quality. Random-effects meta-analyses of adjusted effect-estimates were used. Statins were associated with a lower risk of CAP, 0.84 (95% CI, 0.74-0.95), I(2) = 90.5% and a lower short-term mortality in patients with CAP, 0.68 (95% CI, 0.59-0.78), I(2) = 75.7%. Meta-regression did not identify sources of heterogeneity. A funnel plot suggested publication bias in the treatment group, which was adjusted by a novel regression method with a resultant effect-estimate of 0.85 (95% CI, 0.77-0.93). Sensitivity analyses using the rule-out approach showed that it is unlikely that the results were due to an unmeasured confounder., Conclusions: Our meta-analysis reveals a beneficial role of statins for the risk of development and mortality associated with CAP. However, the results constitute very low quality evidence as per the GRADE framework due to observational study design, heterogeneity and publication bias.

Infectious complications of cardiac surgery are often severe and life threatening. Statins having both immunomodulatory and anti-inflammatory effects were intuitively thought to influence the development of postsurgical infections. We sought to systematically examine whether any association exists between statin use and risk of infectious complications in patients undergoing cardiac surgery. We searched Ovid MEDLINE, Ovid EMBASE, Thomson Scientific Web of Science, and Elsevier Scopus from inception through February 2011 for comparative studies examining the association between statin use and risk of postoperative infections in patients undergoing cardiac surgery. We contacted a study's author for missing information. We conducted a random-effects meta-analysis of individual studies' odds ratios (adjusted for potential confounders). We identified 6 cohort studies for inclusion, 3 of which were conducted in Canada and 3 of which were conducted in the United States. Four were single-center studies, and 2 were population based. Exposure ascertainment was based on a review of admission medication list or prescription databases. Infectious outcomes were heterogeneous and included surgical site infections within 30 days, serious infections (sepsis), or any other postoperative infection. Statin use in the preoperative period was associated with a trend toward reduction in the incidence of postoperative infections in patients who underwent cardiac surgery (odds ratio, 0.81 [95% confidence interval, 0.64-1.01]; [Formula: see text]; [Formula: see text]). Heterogeneity was explained by country effect. Studies performed in Canada showed weaker associations than studies performed in the United States. This difference could not be attributed to study quality alone. We did not find good evidence to support an association between statin use and postoperative infectious complications. However, the trend toward statistical significance for this association indicates that further investigation is warranted.

Introduction: Emerging epidemiological evidence suggests that proton pump inhibitor (PPI) acid-suppression therapy is associated with an increased risk of Clostridium difficile infection (CDI)., Methods: Ovid MEDLINE, EMBASE, ISI Web of Science, and Scopus were searched from 1990 to January 2012 for analytical studies that reported an adjusted effect estimate of the association between PPI use and CDI. We performed random-effect meta-analyses. We used the GRADE framework to interpret the findings., Results: We identified 47 eligible citations (37 case-control and 14 cohort studies) with corresponding 51 effect estimates. The pooled OR was 1.65, 95% CI (1.47, 1.85), I(2) = 89.9%, with evidence of publication bias suggested by a contour funnel plot. A novel regression based method was used to adjust for publication bias and resulted in an adjusted pooled OR of 1.51 (95% CI, 1.26-1.83). In a speculative analysis that assumes that this association is based on causality, and based on published baseline CDI incidence, the risk of CDI would be very low in the general population taking PPIs with an estimated NNH of 3925 at 1 year., Conclusions: In this rigorously conducted systemic review and meta-analysis, we found very low quality evidence (GRADE class) for an association between PPI use and CDI that does not support a cause-effect relationship.

Transient osteoporosis of the hip (TOH) is a rare condition mainly affecting pregnant women in their third trimester and middle aged men. We report a case of TOH/Bone marrow edema syndrome in pregnancy with involvement of the surrounding soft tissues on magnetic resonance image, which has not been previously reported. The presence of such edema in the soft tissues may help to differentiate this condition from early avascular necrosis of the hip, and may also provide an insight into the pathogenesis of the condition. The reported patient was treated conservatively and fully recovered.

Background: Antibiotics sales without medical prescriptions are increasingly recognized as sources of antimicrobial misuse that can exacerbate the global burden of antibiotic resistance. We aimed to determine the percentage of pharmacies who sell antibiotics without medical prescriptions, examining the potential associated risks of such practice in Riyadh, Saudi Arabia, by simulation of different clinical scenarios., Methods: A cross sectional study of a quasi-random sample of pharmacies stratified by the five regions of Riyadh. Each pharmacy was visited once by two investigators who simulated having a relative with a specific clinical illness (sore throat, acute bronchitis, otitis media, acute sinusitis, diarrhea, and urinary tract infection (UTI) in childbearing aged women)., Results: A total of 327 pharmacies were visited. Antibiotics were dispensed without a medical prescription in 244 (77.6%) of 327, of which 231 (95%) were dispensed without a patient request. Simulated cases of sore throat and diarrhea resulted in an antibiotic being dispensed in (90%) of encounters, followed by UTI (75%), acute bronchitis (73%), otitis media (51%) and acute sinusitis (40%). Metronidazole (89%) and ciprofloxacin (86%) were commonly given for diarrhea and UTI, respectively, whereas amoxicillin/clavulanate was dispensed (51%) for the other simulated cases. None of the pharmacists asked about antibiotic allergy history or provided information about drug interactions. Only 23% asked about pregnancy status when dispensing antibiotics for UTI-simulated cases., Conclusions: We observed that an antibiotic could be obtained in Riyadh without a medical prescription or an evidence-based indication with associated potential clinical risks. Strict enforcement and adherence to existing regulations are warranted.

To highlight the importance of intact skin infection syndromes caused by Stenotrophomonas maltophilia, we review 17 reported cases. Skin infection syndrome presentations included metastatic cellulitis (58%), primary cellulitis (23%), and ecthyma gangrenosum (17%). Associated risk factors were hematologic malignancies and chemotherapy (94%), neutropenia (94%), presence of central venous catheter (17%), and exposure to broad-spectrum antibiotics (84%). The diagnosis was supported by cultures of skin biopsy specimens (35%), blood cultures (24%), or both (41%). Trimethoprim-sulfamethoxazole was the treatment of choice (76%), and outcomes were favorable (71%).