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1.  17 Beta-Estradiol Differentially Affects Left Ventricular and Cardiomyocyte Hypertrophy Following Myocardial Infarction and Pressure Overload 
Journal of cardiac failure  2008;14(3):245-253.
Background
We have shown previously that 17β-estradiol (E2) increases left ventricular (LV) and cardiomyocyte hypertrophy following myocardial infarction (MI). However, E2 decreases hypertrophy in pressure overload models. We hypothesized that the effect of estrogen on cardiac hypertrophy was dependent on the type of hypertrophic stimulus.
Methods
Ovariectomized wild type female mice (n=192) were given vehicle or E2 treatment followed by coronary ligation (MI), transverse aortic constriction (TAC), or sham operation. Signaling pathway activation was studied at 3, 24, and 48 hours while echocardiography and hemodynamic studies were performed at 14 days.
Results
MI induced early but transient activation of p38 and p42/44 MAPK pathways, whereas TAC induced sustained activation of both pathways. E2 had no effect on these pathways, but increased Stat3 activation following MI while decreasing Stat3 activation following TAC. MI caused LV dilation, and decreased fractional shortening (FS), that were unaltered by E2. TAC caused LV dilation, reduced FS, and increased LV mass, but in this model, E2 improved these parameters. Following MI, E2 led to increases in myocyte cross-sectional area, atrial natriuretic peptide (ANP) and β-myosin heavy chain (MHC) gene expression, but E2 diminished TAC-induced increases ANP and β-MHC gene expression.
Conclusions
These data demonstrate that the effects of E2 on LV and myocyte remodeling depend on the nature of the hypertrophic stimulus. The opposing influence of E2 on hypertrophy in these models may, in part, result from differential effects of E2 on Stat3 activation. Further work will be necessary to explore this and other potential mechanisms by which estrogen affects hypertrophy in these models.
doi:10.1016/j.cardfail.2007.10.024
PMCID: PMC4181711  PMID: 18381189
Estrogen; LV Remodeling; Myocyte Hypertrophy; Myocardial Infarction; Pressure Overload; Signal Transducer and Activator of Transcription
2.  Cardiovascular Risk Factor Burden in Africa and the Middle East: The Africa Middle East Cardiovascular Epidemiological (ACE) Study 
PLoS ONE  2014;9(8):e102830.
Background
Increased urbanization in the developing world parallels a rising burden of chronic diseases. Developing countries account for ∼80% of global cardiovascular (CV) deaths, but contribute a paucity of systematic epidemiological data on CV risk factors.
Objective
To estimate the prevalence of CV risk factors in rural and urban cohorts attending general practice clinics in the Africa and Middle East (AfME) region.
Methods
In a cross-sectional epidemiological study, the presence of CV risk factors (hypertension, diabetes mellitus (diabetes), dyslipidemia, obesity, smoking and abdominal obesity) were evaluated in stable adult outpatients attending general practice primary care clinics. A rural population was defined as isolated (>50 km or lack of easy access to commuter transportation) from urban centers.
Results
4,378 outpatients were systematically recruited from 94 clinics across 14 AfME countries. Mean age was 46±14 years and 52% of outpatients were female. A high prevalence of dyslipidemia (70%) and abdominal obesity (68%) were observed, followed by hypertension (43%) and diabetes (25%). The vast majority of outpatients (92%) had at least one modifiable CV risk factor, many (74%) had more than one, and half (53%) had 3 or more. These findings were observed in both genders and across urban and rural centers. Among outpatients with pre-existing hypertension or dyslipidemia, many were not at their target blood pressure or LDL-cholesterol goals.
Conclusion
Cardiovascular risk factors are highly prevalent among relatively young, stable outpatients attending general practice clinics across AfME. The findings support opportunistic screening for CV risk factors whenever outpatients visit a general practitioner and provide an opportunity for early identification and management of CV risk factors, including lifestyle interventions.
doi:10.1371/journal.pone.0102830
PMCID: PMC4121128  PMID: 25090638
3.  Age and clinical outcomes in patients presenting with acute coronary syndromes☆ 
Context
Elderly patients have more cardiovascular risk factors and a greater burden of ischemic disease than younger patients.
Aims
To examine the impact of age on clinical presentation and outcomes in patients presenting with acute coronary syndrome (ACS).
Methods and material
Collected data from the 2nd Gulf Registry of Acute Coronary Events (Gulf RACE-2), which is a prospective multicenter study from six adjacent Arab Middle Eastern Gulf countries. Patients were divided into 3 groups according to their age: ≤50 years, 51–70 years and >70 years and their clinical characteristics and outcomes were analyzed. Mortality was assessed at one and 12 months.
Statistical analysis used
One-way ANOVA test for continuous variables, Pearson chi-square (X2) test for categorical variables and multivariate logistic regression analysis for predictors were performed.
Results
Among 7930 consecutive ACS patients; 2755 (35%) were ≤50 years, 4110 (52%) were 51–70 years and 1065 (13%) >70 years old. The proportion of women increased with increasing age (13% among patients ≤50 years to 31% among patients > 70 years). The risk factor pattern varied with age; younger patients were more often obese, smokers and had a positive family history of CAD, whereas older patients more likely to have diabetes mellitus, hypertension, and dyslipidemia. Advancing age was associated with under-treatment evidence-based therapies. Multivariate logistic regression analysis after adjusting for relevant covariates showed that old age was independent predictors for re-ischemia (OR 1.29; 95% CI 1.03–1.60), heart failure (OR 2.8; 95% CI 2.17–3.52) and major bleeding (OR 4.02; 95% CI 1.37–11.77) and in-hospital mortality (age 51–70: OR 2.67; 95% CI 1.86–3.85, and age >70: OR 4.71; 95% CI 3.11–7.14).
Conclusion
Despite being higher risk group, elderly are less likely to receive evidence-based therapies and had worse outcomes. Guidelines adherence is highly recommended in elderly.
doi:10.1016/j.jcdr.2012.08.005
PMCID: PMC3770118  PMID: 24027372
Acute coronary syndrome; Age; Elderly
4.  Case-finding of chronic obstructive pulmonary disease with questionnaire, peak flow measurements and spirometry: a cross-sectional study 
BMC Research Notes  2014;7:241.
Background
Spirometry is commonly accepted as the gold standard for the diagnosis of COPD, but the reality remains that quality assured spirometry is not or cannot be provided universally around the globe. Adding PEF measurement to a screening questionnaire may rule out airflow limitation compatible with COPD rationalizing spirometry testing.
Methods
We conducted a cross-sectional survey in a sample of individuals 40–80 yrs. old in Dubai, UAE. They were invited to answer a short socio-demographic questionnaire including a report on current, past history of smoking, and had PEF measured, then they conducted spirometry to identify airflow limitation compatible with COPD.
Results
Overall, 525 (91.0%) participants performed PEF and spirometry (68% male, with a mean age of 59 years, 17% UAE Nationals), 24% reported smoking of different sorts. Overall, 68 participants (12.9%, 95% C.I. 10.3% to 16.1%) had airflow limitation compatible with COPD. PEFR alone identified 141participants with airflow limitation compatible with COPD, with specificity of 80% and sensitivity of 73.5%.
Conclusions
PEFR could be an easy, cheap, and non-biased tool to assist with the case-finding of COPD before confirmation with spirometry.
doi:10.1186/1756-0500-7-241
PMCID: PMC3996099  PMID: 24739210
5.  Rationale, Design, Methodology and Hospital Characteristics of the First Gulf Acute Heart Failure Registry (Gulf CARE) 
Background:
There is paucity of data on heart failure (HF) in the Gulf Middle East. The present paper describes the rationale, design, methodology and hospital characteristics of the first Gulf acute heart failure registry (Gulf CARE).
Materials and Methods:
Gulf CARE is a prospective, multicenter, multinational registry of patients >18 year of age admitted with diagnosis of acute HF (AHF). The data collected included demographics, clinical characteristics, etiology, precipitating factors, management and outcomes of patients admitted with AHF. In addition, data about hospital readmission rates, procedures and mortality at 3 months and 1-year follow-up were recorded. Hospital characteristics and care provider details were collected. Data were entered in a dedicated website using an electronic case record form.
Results:
A total of 5005 consecutive patients were enrolled from February 14, 2012 to November 13, 2012. Forty-seven hospitals in 7 Gulf States (Oman, Saudi Arabia, Yemen, Kuwait, United Gulf Emirates, Qatar and Bahrain) participated in the project. The majority of hospitals were community hospitals (46%; 22/47) followed by non-University teaching (32%; 15/47 and University hospitals (17%). Most of the hospitals had intensive or coronary care unit facilities (93%; 44/47) with 59% (28/47) having catheterization laboratory facilities. However, only 29% (14/47) had a dedicated HF clinic facility. Most patients (71%) were cared for by a cardiologist.
Conclusions:
Gulf CARE is the first prospective registry of AHF in the Middle East, intending to provide a unique insight into the demographics, etiology, management and outcomes of AHF in the Middle East. HF management in the Middle East is predominantly provided by cardiologists. The data obtained from this registry will help the local clinicians to identify the deficiencies in HF management as well as provide a platform to implement evidence based preventive and treatment strategies to reduce the burden of HF in this region.
doi:10.4103/1995-705X.132137
PMCID: PMC4062990  PMID: 24949181
Acute heart failure; gulf; heart failure; middle east
6.  Design and Rationale of Gulf locals with Acute Coronary Syndrome Events (Gulf Coast) Registry 
Objectives:
To describe the risk profile, management and one-year outcomes of patients hospitalized with acute coronary syndrome (ACS) in the Gulf region of the Middle East.
Subjects and Methods:
The Gulf locals with acute coronary syndrome events (Gulf COAST) registry is a prospective, multinational, longitudinal, observational, cohort-based registry of consecutive citizens, from the Gulf region of the Middle East, admitted from January 2012 to January 2013 to 29 hospitals with a diagnosis of ACS. Data entered online included patient demographics, cardiovascular risk profiles, past medical history, physical findings on admission, in-hospital diagnostic tests and therapeutic management, as well as one year outcomes.
Results:
3188 patients were recruited. The mean age was 60.4 ± 12.6years (range: 22-112), 2104 (66%) were males and 1084 (34%) females. The discharge diagnosis was ST-segment elevation myocardial infarction (STEMI) in 741 (23.2%), new-onset left bundle branch block myocardial infarction (LBBBMI) in 30 (0.9%), non-ST-segment elevation myocardial infarction (NSTEMI) in 1486 (46.6%) and unstable angina in 931 (29.2%). At hospital presentation, 2105 (66%), 1779 (55.8%), 1703 (53.4%) and 740 (23.2%) had history of hypertension, dyslipidemia, diabetes mellitus and active smoking, respectively.
Conclusion:
Patients with ACS in our region are young with very high risk profile. The Gulf COAST registry is an example of successful regional collaboration and will provide information on contemporary management of ACS in the region.
doi:10.2174/1874192401408010088
PMCID: PMC4197526  PMID: 25328551
Acute coronary syndromes; Gulf; Middle East; registries.
7.  Short-Term Effects of Ivabradine in Patients with Chronic Stable Ischemic Heart Disease 
Introduction:
Ivabradine is a novel selective If current inhibitor with anti-ischemic and antianginal activity.
Objectives:
To assess the effect of the selective If current inhibitor ivabradine on heart rate, angina pectoris, and functional capacity in stable patients with chronic coronary artery disease on maximally tolerated medical therapy.
Materials and Methods:
Consecutive patients from the out-patient cardiology clinic with stable coronary artery disease documented by coronary angiography were included. Patients had to be on maximally tolerated medical therapy with β-blockers, angiotensin-converting enzyme inhibitors or receptor blockers (ACE-I or ARB), antiplatelets, statins, nitrates, and anti-metabolics with a baseline heart rate of at least 70 beats per minute. All patients underwent assessment of angina (Canadian Cardiovascular Society Angina Class: CCS I to IV) and functional capacity (using a validated self-administered questionnaire), at baseline and after 4 months of ivabradine therapy.
Results:
Twenty patients were enrolled (mean age 47 ± 7 years, all male, 60% with hypertension, 30% with diabetes mellitus). Patients were on optimal medical regimen of aspirin (100%), β-blocker (100%), statins (100%), clopidogrel (90%), nitrates (35%), anti-metabolics (90%), and ACE-I or ARB (95%). At baseline, the majority of patients (90%) were in CCS class II-IV. All patients were started on ivabradine 5 mg twice daily, and in 12 patients the dose was increased to 7.5 mg twice daily. After 4 months of treatment, the heart rate was significantly reduced from an average of 82 ± 8 to 68 ± 6 bpm (P < 0.001). The reduction in heart rate was accompanied by a significant improvement in functional capacity (score 3.5 ± 0.9 to 4.7 ± 0.7, P < 0.001) and angina classification; at baseline 10% of the patients were in CCS class I compared to 50% after 4 months of therapy (P = 0.01). No symptomatic bradycardia was reported with ivabradine.
Conclusion:
The addition of ivabradine to optimal medical therapy in patients with stable coronary artery disease is associated with significant improvement in anginal symptoms and functional capacity.
doi:10.4103/1995-705X.115495
PMCID: PMC3752876  PMID: 23983908
Heart rate; ischemic heart disease; ivabradine
8.  Gender Disparities in the Presentation, Management and Outcomes of Acute Coronary Syndrome Patients: Data from the 2nd Gulf Registry of Acute Coronary Events (Gulf RACE-2) 
PLoS ONE  2013;8(2):e55508.
Background
Gender-related differences in mortality of acute coronary syndrome (ACS) have been reported. The extent and causes of these differences in the Middle-East are poorly understood. We studied to what extent difference in outcome, specifically 1-year mortality are attributable to demographic, baseline clinical differences at presentation, and management differences between female and male patients.
Methodology/Principal Findings
Baseline characteristics, treatment patterns, and 1-year mortality of 7390 ACS patients in 65 hospitals in 6 Arabian Gulf countries were evaluated during 2008–2009, as part of the 2nd Gulf Registry of Acute Coronary Events (Gulf RACE-2). Women were older (61.3±11.8 vs. 55.6±12.4; P<0.001), more overweight (BMI: 28.1±6.6 vs. 26.7±5.1; P<0.001), and more likely to have a history of hypertension, hyperlipidemia or diabetes. Fewer women than men received angiotensin-converting enzyme inhibitors (ACE), aspirin, clopidogrel, beta blockers or statins at discharge. They also underwent fewer invasive procedures including angiography (27.0% vs. 34.0%; P<0.001), percutaneous coronary intervention (PCI) (10.5% vs. 15.6%; P<0.001) and reperfusion therapy (6.9% vs. 20.2%; P<0.001) than men. Women were at higher unadjusted risk for in-hospital death (6.8% vs. 4.0%, P<0.001) and heart failure (HF) (18% vs. 11.8%, P<0.001). Both 1-month and 1-year mortality rates were higher in women than men (11% vs. 7.4% and 17.3% vs. 11.4%, respectively, P<0.001). Both baseline and management differences contributed to a worse outcome in women. Together these variables explained almost all mortality disparities.
Conclusions/Significance
Differences between genders in mortality appeared to be largely explained by differences in prognostic variables and management patterns. However, the origin of the latter differences need further study.
doi:10.1371/journal.pone.0055508
PMCID: PMC3566183  PMID: 23405162
9.  Immediate and one-year outcome of patients presenting with Acute Coronary Syndrome complicated by stroke: Findings from the 2nd Gulf Registry of Acute Coronary Events (Gulf RACE-2) 
Background
Stroke is a potential complication of acute coronary syndrome (ACS). The aim of this study was to identify the prevalence, risk factors predisposing to stroke, in-hospital and 1-year mortality among patients presenting with ACS in the Middle East.
Methods
For a period of 9 months in 2008 to 2009, 7,930 consecutive ACS patients were enrolled from 65 hospitals in 6 Middle East countries.
Results
The prevalence of in-hospital stroke following ACS was 0.70%. Most cases were ST segment elevation MI-related (STEMI) and ischemic stroke in nature. Patients with in-hospital stroke were 5 years older than patients without stroke and were more likely to have hypertension (66% vs. 47.6%, P = 0.001). There were no differences between the two groups in regards to gender, other cardiovascular risk factors, or prior cardiovascular disease. Patients with stroke were more likely to present with atypical symptoms, advanced Killip class and less likely to be treated with evidence-based therapies. Independent predictors of stroke were hypertension, advanced killip class, ACS type –STEMI and cardiogenic shock. Stroke was associated with increased risk of in-hospital (39.3% vs. 4.3%) and one-year mortality (52% vs. 12.3%).
Conclusion
There is low incidence of in-hospital stroke in Middle-Eastern patients presenting with ACS but with very high in-hospital and one-year mortality rates. Stroke patients were less likely to be appropriately treated with evidence-based therapy. Future work should be focused on reducing the risk and improving the outcome of this devastating complication.
doi:10.1186/1471-2261-12-64
PMCID: PMC3480946  PMID: 22894647
Acute coronary syndrome; Myocardial infarction; Stroke; Risk factors; Prognosis
10.  Characteristics, Management, and In-Hospital Outcomes of Diabetic Patients with Acute Coronary Syndrome in the United Arab Emirates 
The Scientific World Journal  2012;2012:698597.
We describe the baseline characteristics, management, and in-hospital outcomes of patients in the United Arab Emirates (UAE) with DM admitted with an acute coronary syndrome (ACS) and assess the influence of DM on in-hospital mortality. Data was analyzed from 1697 patients admitted to various hospitals in the UAE with a diagnosis of ACS in 2007 as part of the 1st Gulf RACE (Registry of Acute Coronary Events). Of 1697 patients enrolled, 668 (39.4%) were diabetics. Compared to patients without DM, diabetic patients were more likely to have a past history of coronary artery disease (49.1% versus 30.1%, P < 0.001), hypertension (67.2% versus 36%, P < 0.001), and prior revascularization (21% versus 11.4%, P < 0.001). They experienced more in-hospital recurrent ischemia (8.5% versus 5.1%; P = 0.004) and heart failure (20% versus 10%; P < 0.001). The mortality rate was 2.7% for diabetics and 1.6% for nondiabetics (P = 0.105). After age adjustment, in-hospital mortality increased by 3.5% per year of age (P = 0.016). This mortality was significantly higher in females than in males (P = 0.04). ACS patients with DM have different clinical characteristics and appear to have poorer outcomes.
doi:10.1100/2012/698597
PMCID: PMC3385598  PMID: 22778703
11.  Clinical Profile and Mortality of ST-Segment Elevation Myocardial Infarction Patients Receiving Thrombolytic Therapy in the Middle East 
Objective:
Little is known about thrombolytic therapy patterns in patients with ST-elevation myocardial infarction (STEMI) in the Middle East. The objective of this study was to evaluate the clinical profile and mortality of STEMI patients who arrived in hospital within 12 hours from pain onset and received thrombolytic therapy.
Patients and Methods:
This was a prospective, multinational, multi-centre, observational survey of consecutive acute coronary syndrome patients admitted to 65 hospitals in six Middle Eastern countries during the period between October 2008 and June 2009, as part of Gulf RACE-II (Registry of Acute Coronary Events). Analyses were performed using univariate statistics.
Results:
Out of 2,465 STEMI patients, 66% (n = 1,586) were thrombolysed with namely: streptokinase (43%), reteplase (44%), tenecteplase (10%), and alteplase (3%). 22.7% received no reperfusion. Median age of the study cohort was 50 (45-59) years with majority being males (91%). The overall median symptom onset-to-presentation and door-to-needle times were 165 (95- 272) minutes and 38 (24-60) minutes, respectively. Generally, patients presenting with higher GRACE risk scores were treated with newer thrombolytic agents (reteplase and tenecteplase) (P < 0.001). The use of newer thrombolytic agents was associated with a significantly lower mortality at both 1-month (0.8% vs. 1.7% vs. 4.2%; P = 0.014) and 1-year (0% vs. 1.7% vs. 3.4%; P = 0.044) compared to streptokinase use.
Conclusions:
Majority of STEMI patients from the Middle East were thrombolysed with streptokinase and reteplase in equal numbers. Nearly one-fifth of patients did not receive any reperfusion therapy. There was inappropriately long symptom-onset to hospital presentation as well as door-to-needle times. Use of newer thrombolytic agents in high risk patients was appropriate. Newer thrombolytic agents were associated with significantly lower mortality at 1-month and 1-year compared to the older agent, streptokinase.
doi:10.4103/1995-705X.99224
PMCID: PMC3424777  PMID: 22919446
Acute coronary syndrome; GRACE score; Middle East; mortality; reteplase; STEMI; streptokinase; tenecteplase; thrombolytic therapy
12.  Polyvascular Disease in Patients Presenting with Acute Coronary Syndrome: Its Predictors and Outcomes 
The Scientific World Journal  2012;2012:284851.
We evaluated prevalence and clinical outcome of polyvascular disease (PolyVD) in patients presenting with acute coronary syndrome (ACS). Data for 7689 consecutive ACS patients were collected from the 2nd Gulf Registry of Acute Coronary Events between October 2008 and June 2009. Patients were divided into 2 groups (ACS with versus without PolyVD). All-cause mortality was assessed at 1 and 12 months. Patients with PolyVD were older and more likely to have cardiovascular risk factors. On presentation, those patients were more likely to have atypical angina, high resting heart rate, high Killip class, and GRACE risk scoring. They were less likely to receive evidence-based therapies. Diabetes mellitus, renal failure, and hypertension were independent predictors for presence of PolyVD. PolyVD was associated with worse in-hospital outcomes (except for major bleedings) and all-cause mortality even after adjusting for baseline covariates. Great efforts should be directed toward primary and secondary preventive measures.
doi:10.1100/2012/284851
PMCID: PMC3259691  PMID: 22272171
13.  Prevalence, Characteristics, and In-Hospital Outcomes of Metabolic Syndrome among Patients with Acute Coronary Syndrome in the United Arab Emirates 
Objective:
To evaluate clinical profiles, management and in-hospital outcomes of acute coronary syndrome (ACS) patients with metabolic syndrome (MetS) in the United Arab Emirates (UAE).
Methods:
MetS was defined according to the criteria for its diagnosis by the International Diabetes Federation (IDF) and the American Heart Association/National Heart, Lung and Blood Institute (AHA/NHLBI). Participants were admitted to various hospitals in the UAE with a diagnosis of ACS in 2007 as part of the Gulf Registry of Acute Coronary Events (Gulf RACE) project. We compared baseline characteristics, treatment patterns, and in-hospital outcomes stratified by MetS status.
Results:
Of 1259 patients with ACS in the UAE (mean age: 52 ± 11 years, 88.8% males), the majority (n = 851, 67.6%) had MetS. MetS patients were more frequently males (86.4 vs 13.6%; P < 0.001). They were more obese (waist circumference and BMI, P < 0.001) as compared with non-MetS patients. MetS was more frequently associated with hypertension (51.1 vs 37.7%; P < 0.001) and diabetes mellitus (45.6 vs 24.3%; P < 0.001). After multivariate adjustment, certain MetS criteria rather than MetS itself were associated with higher in-hospital mortality and heart failure. Paradoxically, hypertension was associated with lower in-hospital mortality.
Conclusions:
Prevalence of MetS among patients with ACS in our study population was high. Certain MetS criteria were associated with higher in-hospital mortality and heart failure.
doi:10.2174/1874192401206010081
PMCID: PMC3414714  PMID: 22888374
acute coronary syndrome; Gulf Registry of Acute Coronary Events; metabolic syndrome; Middle East; obesity; United Arab Emirates.
14.  Weekend Versus Weekday, Morning Versus Evening Admission in Relationship to Mortality in Acute Coronary Syndrome Patients in 6 Middle Eastern Countries: Results from Gulf Race 2 Registry 
We used prospective cohort data of patients with acute coronary syndrome (ACS) to compare their management on weekdays/mornings with weekends/nights, and the possible impact of this on 1-month and 1-year mortality. Analyses were evaluated using univariate and multivariate statistics. Of the 4,616 patients admitted to hospitals with ACS, 76% were on weekdays. There were no significant differences in 1-month (odds ratio (OR), 0.88; 95% CI: 0.68-1.14) and 1-year mortality (OR, 0.88; 95% CI: 0.70-1.10), respectively, between weekday and weekend admissions. Similarly, there were no significant differences in 1-month (OR, 0.92; 95% CI: 0.73-1.15) and 1-year mortality (OR, 0.98; 95% CI: 0.80-1.20), respectively, between nights and day admissions. In conclusion, apart from lower utilization of angiography (P < .001) at weekends, there were largely no significant discrepancies in the management and care of patients admitted with ACS on weekdays and during morning hours compared with patients admitted on weekends and night hours, and the overall 30-day and 1-year mortality was similar between both the cohorts.
doi:10.2174/1874192401206010106
PMCID: PMC3447162  PMID: 23002404
Acute coronary syndrome; Weekend; Weekday; Mortality; Admission.
15.  Public Availability of Published Research Data in High-Impact Journals 
PLoS ONE  2011;6(9):e24357.
Background
There is increasing interest to make primary data from published research publicly available. We aimed to assess the current status of making research data available in highly-cited journals across the scientific literature.
Methods and Results
We reviewed the first 10 original research papers of 2009 published in the 50 original research journals with the highest impact factor. For each journal we documented the policies related to public availability and sharing of data. Of the 50 journals, 44 (88%) had a statement in their instructions to authors related to public availability and sharing of data. However, there was wide variation in journal requirements, ranging from requiring the sharing of all primary data related to the research to just including a statement in the published manuscript that data can be available on request. Of the 500 assessed papers, 149 (30%) were not subject to any data availability policy. Of the remaining 351 papers that were covered by some data availability policy, 208 papers (59%) did not fully adhere to the data availability instructions of the journals they were published in, most commonly (73%) by not publicly depositing microarray data. The other 143 papers that adhered to the data availability instructions did so by publicly depositing only the specific data type as required, making a statement of willingness to share, or actually sharing all the primary data. Overall, only 47 papers (9%) deposited full primary raw data online. None of the 149 papers not subject to data availability policies made their full primary data publicly available.
Conclusion
A substantial proportion of original research papers published in high-impact journals are either not subject to any data availability policies, or do not adhere to the data availability instructions in their respective journals. This empiric evaluation highlights opportunities for improvement.
doi:10.1371/journal.pone.0024357
PMCID: PMC3168487  PMID: 21915316
16.  Trends in the Use of Evidence-based Therapies Early in the Course of Acute Myocardial Infarction and its Influence on Short Term Patient Outcomes 
Aim:
To evaluate changes in management practices and its influence on short term hospital outcomes in patients with acute myocardial infarction (AMI) admitted during two different time periods, 2007 and 2004.
Methods and Results:
We studied AMI patients from two acute coronary syndrome registries carried out in Kuwait in 2007 and 2004. We included 1872 and 1197 patients from the 2007 and 2004 registries, respectively. When compared with 2004, patients from the 2007 registry had similar baseline clinical characteristics. In 2007 compared to 2004, during the in-hospital period, patients with AMI received significantly more statins (94% vs. 73%%, p<0.0001), Angiotensin converting enzyme (ACE) inhibitors and angiotensin receptor blockers (ARB) (70% vs. 47%, p<0.001), and Clopidogrel (38% vs. 4%, p<0.001), while beta-blockers use dropped in 2007 compared to 2004 (63% vs. 68%, p=0.0066). The rates of in-hospital mortality and recurrent ischemia were significantly lower in the 2007 cohort compared with the 2004 cohort (for mortality 2.2% vs. 3.9%, P=0.0008, for recurrent ischemia 13.7% vs. 20.4%, P=0<0.0001).Higher utilization of angiotensin converting enzyme inhibitors, angiotensin receptor blockers and statins were the main contributors to the improved in-hospital mortality and morbidity.
In Conclusion:
In the acute management of AMI, there was a significant increase in the use of statins, ACE inhibitors and Clopidogrel in 2007 compared to 2004. This was associated with a significant decrease in the in-hospital mortality and recurrent ischemia. Adherence to guidelines recommended therapies improved in-hospital outcomes.
doi:10.2174/1874192401105010171
PMCID: PMC3162191  PMID: 21886684
Acute Coronary Syndrome; Outcomes; Evidence based therapies.
17.  Clinical Characteristics and Outcomes of Patients with Acute Coronary Syndrome and Prior Coronary Artery Bypass Grafting in a Large Middle Eastern Cohort 
Background:
Acute Coronary Syndrome (ACS) can occur in patients with prior coronary artery bypass grafting (CABG). In the Gulf Registry of acute coronary events (Gulf RACE), we identified the clinical characteristics and in-hospital outcomes of these patients.
Methods:
Clinical characteristics and in-hospital outcomes for 461 ACS patients with prior CABG are compared to 7715 ACS patients without prior CABG enrolled from 64 hospitals in 6 Gulf countries over a 6-month period.
Results:
The overall incidence of ACS with prior CABG was 5.6% out of 8176 patients. The ACS with prior CABG were older (63 vs 55 years, P<0.0001), had more history of diabetes (62.3 vs 37.6%, P <0.0001), dyslipidemia (70.3 vs 29.5%, P<0.0001), and hypertension (75.7 vs 47.8%, P<0.0001) compared with the non-CABG group. They presented more frequently with dyspnea (14.8 vs 9.5%, P<0.0005), non-ST segment elevation myocardial infarction (41.4 vs 31.6%, P<0.0001) and echocardiographic evidence of left ventricular dysfunction (49.4 vs 29.8%, P<0.0001) than ACS without prior CABG. They had a complicated in-hospital course with more recurrent ischemia (13.9 vs 9.3%, P=0.0011), heart failure (24.1 vs 15.7%), and stroke (2.2 vs 0.6%) compared with those without CABG. The in-hospital mortality rate was 5.6% in the CABG group compared with 3.5% in the ACS without prior CABG group. After adjusting for confounders, prior CABG was independently associated with recurrent ischemia and shock, more in patients presenting with ST elevation than non-ST elevation ACS.
Conclusions:
Patients with ACS and prior CABG are a high-risk group with poor outcomes irrespective of their older age and comorbidities. They should be identified and treated differently to improve their outcomes.
doi:10.2174/1874192401105010196
PMCID: PMC3170976  PMID: 21915225
Acute Coronary Syndrome; Angioplasty; Comorbidity; Coronary Artery Bypass Grafting; Risk factors; Stroke.
18.  Percutaneous Coronary Interventions for Nonacute Coronary Artery Disease: A Quantitative Twenty-Year Synopsis 
Lancet  2009;373(9667):911-918.
Summary
Background
Over the last 20 years, percutaneous transluminal balloon coronary angioplasty (PTCA), bare metal stents (BMS) and drug eluting stents (DES) succeeded each other as catheter-based treatments for coronary artery disease (CAD). We present an overview of randomised trials comparing these interventions with each other and with medical therapy in patients with nonacute CAD.
Methods
We searched Medline for trials contrasting at least two of the aforementioned interventions. Outcomes of interest were death, myocardial infarction (MI), coronary artery bypass grafting (CABG), target lesion or vessel revascularisation (TLR/TVR), and any revascularisation. Random effects meta-analyses summarised head-to-head (direct) comparisons, and network meta-analyses integrated direct and indirect evidence.
Findings
61 eligible trials (25 388 patients) investigated 4 of 6 possible comparisons between the 4 interventions. No trials directly compared DES with medical therapy or PTCA. In all direct or indirect comparisons, succeeding advancements in PCI did not yield detectable improvements in deaths and MI. The risk ratio for indirect comparisons between DES and medical therapy was 0·96 (95% confidence interval: 0·60, 1·52) for death and 1·15 (0·73, 1·82) for MI. In contrast, there were sequential significant reductions in TLR/TVR with BMS compared to PTCA and with DES compared to BMS. The risk ratio for the indirect comparison between DES and PTCA for TLR/TVR was 0·30 (0·17, 0·51).
Interpretation
Sequential innovations in the catheter-based treatment of nonacute CAD showed no evidence of an impact on death or MI when compared with medical therapy.
doi:10.1016/S0140-6736(09)60319-6
PMCID: PMC2967219  PMID: 19286090
19.  Patent Foramen Ovale in Cryptogenic Stroke: Incidental or Pathogenic? 
BACKGROUND
Patent foramen ovale (PFO) is significantly associated with cryptogenic stroke (CS). However, even in patients with CS, a PFO can be an incidental finding. We sought to estimate the probability that a PFO in a patient with CS is incidental.
METHODS
A systematic search identified 23 case-control studies examining the prevalence of PFO in patients with CS versus controls with stroke of known-cause. Using simple assumptions and Bayes’ theorem we calculated the probability a PFO is incidental in patients with CS. Random effects meta-analyses estimated the odds ratio (OR) of a PFO in CS versus controls in different age populations, with or without atrial septal aneurysms (ASA), and were used to summarize across studies the probability that a PFO in CS is incidental.
RESULTS
The summary OR (95% confidence limits) for PFO in CS versus controls was 2.9 (CI 2.1, 4.0). The corresponding ORs for young and old patients (< or ≥ 55 years) were 5.1 (3.3, 7.8) and 2.0 (1.0, 3.7), respectively. The corresponding probabilities that a PFO in patients with CS is incidental were 33% (28%, 39%) in age-inclusive studies, 20% (16%, 25%) in younger patients, and 48% (34%, 66%) in older patients. These probabilities were much lower when an ASA was present.
CONCLUSIONS
In patients with otherwise CS, approximately a third of discovered PFOs are likely to be incidental, and hence not benefit from closure. This probability is sensitive to patient characteristics such as age and the presence of an ASA, suggesting the importance of patient-selection in therapeutic decision-making.
doi:10.1161/STROKEAHA.109.547828
PMCID: PMC2764355  PMID: 19443800
Patent foramen ovale; Risk factors for stroke; Secondary stroke prevention
20.  Association of prolonged QRS duration with ventricular tachyarrhythmias and sudden cardiac death in the Multicenter Automatic Defibrillator Implantation Trial II (MADIT-II) 
OBJECTIVES
We evaluated the prognostic significance of prolonged QRS duration (QRSd) relative to arrhythmic outcomes in medically- and implantable cardioverter-defibrillator (ICD)-treated patients enrolled in the Multicenter Automatic Defibrillator Implantation Trial (MADIT) II.
BACKGROUND
There is conflicting literature on the relationship between prolonged QRSd and arrhythmic events, including sudden cardiac death (SCD), in heart failure patients with or without ICDs.
METHODS
Using a Cox-proportional hazards model adjusting for ejection fraction (EF), heart failure class, and blood urea nitrogen, we estimated the association of prolonged QRSd ≥ 140 milliseconds with SCD in the medically-treated arm, and SCD or first ICD therapy for rapid ventricular tachycardia/fibrillation (VT/VF, cycle length ≤ 260 ms) in the ICD-treated arm.
RESULTS
In the medically-treated arm, prolonged QRSd was a significant independent predictor of SCD (HR 2.12 [95% CI 1.20–3.76], p = 0.01). However, in the ICD-treated arm, prolonged QRSd did not predict SCD or rapid VT/VF (HR 0.77 [95% CI 0.47–1.24], p = 0.28). The difference in the prognostic effect of prolonged QRSd in these two groups was significant (p<0.01). These results were not affected by varying the cycle length defining rapid VT/VF or the duration defining QRSd prolongation.
CONCLUSIONS
In patients with prior myocardial infarction and EF ≤ 30%, prolonged QRSd does not predict SCD/VT/VF in ICD-treated patients, but does predict SCD in medically-treated patients. This underscores the non-equivalence of VT/VF and SCD, and the need for caution in inferring risk of SCD when using non-randomized databases that include only patients with ICDs.
doi:10.1016/j.hrthm.2008.02.013
PMCID: PMC2692879  PMID: 18534364
Death; sudden; defibrillation; tachyarrhythmias; risk factors; QRS duration
21.  Competing risk and heterogeneity of treatment effect in clinical trials 
Trials  2008;9:30.
It has been demonstrated that patients enrolled in clinical trials frequently have a large degree of variation in their baseline risk for the outcome of interest. Thus, some have suggested that clinical trial results should routinely be stratified by outcome risk using risk models, since the summary results may otherwise be misleading. However, variation in competing risk is another dimension of risk heterogeneity that may also underlie treatment effect heterogeneity. Understanding the effects of competing risk heterogeneity may be especially important for pragmatic comparative effectiveness trials, which seek to include traditionally excluded patients, such as the elderly or complex patients with multiple comorbidities. Indeed, the observed effect of an intervention is dependent on the ratio of outcome risk to competing risk, and these risks – which may or may not be correlated – may vary considerably in patients enrolled in a trial. Further, the effects of competing risk on treatment effect heterogeneity can be amplified by even a small degree of treatment related harm. Stratification of trial results along both the competing and the outcome risk dimensions may be necessary if pragmatic comparative effectiveness trials are to provide the clinically useful information their advocates intend.
doi:10.1186/1745-6215-9-30
PMCID: PMC2423182  PMID: 18498644

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