Progress Toward Measles Elimination - World Health Organization Eastern Mediterranean Region, 2019-2022.

In 2015, all 22 World Health Organization Eastern Mediterranean Region (EMR) countries and areas (countries) pledged to achieve measles elimination by 2020. Despite success in several countries, most countries in the region still have not eliminated measles. This report updates a previous report and describes progress toward measles elimination in EMR during 2019-2022. During that period, estimated regional coverage with the first and second doses of a measles-containing vaccine (MCV) was 82%-83% and 76%-78%, respectively. During 2019-2022, approximately 160 million children were vaccinated during national or subnational supplementary immunization activities. Reported confirmed regional measles incidence decreased from 29.8 cases per 1 million population in 2019 to 7.4 in 2020, but then increased 68%, to 50.0 in 2022 because of challenges providing immunization services and conducting surveillance during the COVID-19 pandemic. Surveillance indicators deteriorated in 11 (50%) of the 22 EMR countries. During 2019-2022, four countries in the region were verified as having achieved measles elimination, but other countries reported immunity gaps and increased measles incidence in 2022. To achieve measles elimination in EMR, national immunization programs, especially in those countries with high measles incidence, will need to continue to recover from the COVID-19 pandemic, increase overall vaccination coverage to close immunity gaps, and maintain high-quality disease surveillance.

Comparative Efficacy of Levosimendan, Ramipril, and Sacubitril/ Valsartan in Isoproterenol-induced Experimental Heart Failure: A Hemodynamic and Molecular Approach.

OBJECTIVE: Cardiac ischemia-related myocardial damage has been considered a major reason for heart failure. We aimed to investigate the role of levosimendan (LEVO) in comparison to ramipril and sacubitril/valsartan (Sac/Val) in preventing damage associated with isoproterenol (ISO) induced myocardial infarction. METHODS: Myocardial infarction was induced by injecting subcutaneous isoproterenol (5 mg/kg once for 7 consecutive days) to establish an experimental heart failure model. Simultaneously, LEVO (1 mg/kg/day), ramipril (3mg/kg/day) and Sac/Val (68 mg/kg/day) suspension were administered orally for four weeks. RESULTS: We observed a significant correlation between ISO-induced ischemia with cardiac remodeling and alterations in myocardial architecture. LEVO, ramipril, and Sac/Val significantly prevented lipid peroxidation and damaged antioxidant enzymes like superoxide dismutase, catalase, glutathione and thioredoxin reductase. We also observed their ameliorative effects in myocardium's cardiac hypertrophy, evidenced by reduced heart weight to body weight ratio and transforming growth factor ß related collagen deposition. LEVO, ramipril, and Sac/Val also maintained cardiac biomarkers like lactate dehydrogenase, creatine kinase-MB, brain natriuretic peptide and cardiac Troponin-I, indicating reduced myocardial damage that was further demonstrated by histopathological examination. Decreased sarcoplasmic endoplasmic reticulum Ca2+ATPase2a and sodium-calcium exchanger-1 protein depletion after LEVO, ramipril, and Sac/Val administration indicated improved Ca2+ homeostasis during myocardial contractility. CONCLUSION: Our findings suggest that LEVO has comparable effects to ramipril, and Sac/Val in preventing myocardial damage via balancing oxidant-antioxidant system, decreased collagen deposition, reduced myocardial stress as well as improved Ca2+ homeostasis during myocardial contractility.

Progress Toward Measles Elimination - Eastern Mediterranean Region, 2013-2019.

In 1997, during the 41st session of the Regional Committee for the Eastern Mediterranean, the 21 countries in the World Health Organization (WHO) Eastern Mediterranean Region* (EMR) passed a resolution to eliminate† measles (1). In 2015, this goal was included as a priority in the Eastern Mediterranean Vaccine Action Plan 2016-2020 (EMVAP) (2), endorsed at the 62nd session of the Regional Committee (3). To achieve this goal, the WHO Regional Office for the Eastern Mediterranean developed a four-pronged strategy: 1) achieve ≥95% vaccination coverage with the first dose of measles-containing vaccine (MCV1) among children in every district of each country through routine immunization services; 2) achieve ≥95% vaccination coverage with a second MCV dose (MCV2) in every district of each country either through implementation of a routine 2-dose vaccination schedule or through supplementary immunization activities§ (SIAs); 3) conduct high-quality, case-based surveillance in all countries; and 4) provide optimal measles clinical case management, including dietary supplementation with vitamin A (4). This report describes progress toward measles elimination in EMR during 2013-2019 and updates a previous report (5). Estimated MCV1 coverage increased from 79% in 2013 to 82% in 2018. MCV2 coverage increased from 59% in 2013 to 74% in 2018. In addition, during 2013-2019, approximately 326.4 million children received MCV during SIAs. Reported confirmed measles incidence increased from 33.5 per 1 million persons in 2013 to 91.2 in 2018, with large outbreaks occurring in Pakistan, Somalia, and Yemen; incidence decreased to 23.3 in 2019. In 2019, the rate of discarded nonmeasles cases¶ was 5.4 per 100,000 population. To achieve measles elimination in the EMR, increased visibility of efforts to achieve the measles elimination goal is critically needed, as are sustained and predictable investments to increase MCV1 and MCV2 coverage, conduct high-quality SIAs, and reach populations at risk for not accessing immunization services or living in areas with civil strife.

Levosimendan suppresses oxidative injury, apoptotic signaling and mitochondrial degeneration in streptozotocin-induced diabetic cardiomyopathy.

Diabetic cardiomyopathy plays a major role in morbidity and mortality among cardiovascular disorder-related complications. This study was designed to explore long-term benefits of Levosimendan (LEVO) along with Ramipril and Insulin. Diabetic cardiomyopathy was induced using streptozotocin (STZ) at the dose of 25 mg/kg/body weight/day for three consecutive days in Wistar rats. Rats were randomly divided into 10 groups and treatments were started after 2 weeks of STZ administration. A gradual but severe hyperglycemia ((§§§)p < 0.001) was observed in all STZ-treated groups except those received insulin (2 U/day). LEVO alone and in combination with Ramipril and Insulin normalized (**p < 0.01) mean arterial pressure and heart rate, restored catalase, superoxide dismutase, malondialdehyde, glutathione level and also attenuated (***p < 0.001) the raised serum levels of creatine kinase-heart type, lactate dehydrogenase, tumor necrosis factor-alpha, C-reactive protein, and caspase-3 level in heart tissue altered after STZ treatment. Myofibril degeneration, mitochondrial fibrosis and vacuolization occurred after STZ treatment, were also reversed by LEVO in combination with Ramipril and Insulin. The combination of LEVO with Ramipril and Insulin improved hemodynamic functions, maintained cardiac enzymes and ameliorated myofibril damage in diabetic cardiomyopathy.

Usefulness of quantitative versus qualitative ST-segment depression for risk stratification of non-ST elevation acute coronary syndromes in contemporary clinical practice.

This aim of this study was to assess the clinical utility of quantitative ST-segment depression (STD) for refining the risk stratification of non-ST elevation acute coronary syndromes in the prospective, multinational Global Registry of Acute Coronary Events (GRACE). Quantitative measurements of STD on admission electrocardiograms were evaluated independently by a core laboratory, and their predictive value for in-hospital and cumulative 6-month mortality was examined. Although more severe STD is a marker of increased short- and long-term mortality, it is also associated with higher risk clinical features and biomarkers. Thus, after adjustment for these clinically important predictors, quantitative STD does not provide incremental prognostic value beyond simple dichotomous evaluation for the presence of STD. Furthermore, adopting quantitative instead of the prognostically proven qualitative evaluation of STD does not improve risk discrimination afforded by the validated GRACE risk models. In conclusion, the findings do not support the quantification of STD in routine clinical practice beyond simple evaluation for the presence of STD as an integral part of comprehensive risk stratification using the GRACE risk score.

Local hospital vs. core-laboratory interpretation of the admission electrocardiogram in acute coronary syndromes: increased mortality in patients with unrecognized ST-elevation myocardial infarction.

AIMS: Previous analyses suggest only modest agreement between local site and core-laboratory (core-lab) electrocardiogram (ECG) interpretation in patients with acute coronary syndromes (ACSs); however, this has not been well examined outside of clinical trial populations. METHODS AND RESULTS: Patients (n = 5277 from 51 hospitals; 4916 with 1 year vital status) participating in the Canadian ACS Registry who were hospitalized with an ACS and had an interpretable initial ECG were included in this study. Core-lab ECG interpretation was blinded to site interpretation and outcomes. There was moderate agreement between site and core-lab regarding the predominant ECG findings (kappa = 0.49). Patients with core-lab-defined ST-elevation and cardiac marker elevation (n = 1202) not classified as ST-elevation by the site were less likely to receive acetylsalicylic acid (ASA) (90 vs. 96%, P < 0.0001), heparin (91 vs. 95%, P = 0.04), and reperfusion therapy (14 vs. 76%, P < 0.0001) than patients for whom there was agreement that ST-elevation was present. After adjusting for other validated prognostic factors, site-unrecognized ST-elevation was independently associated with higher mortality (odds ratio = 2.21; 95% CI, 1.46-3.36; P < 0.001). CONCLUSIONS: In patients with ACS, there was only moderate agreement between core-lab and site interpretation of the initial ECG. Site-unrecognized ST-elevation myocardial infarction was associated with underutilization of evidence-based therapies and increased 1-year mortality.

Differences between local hospital and core laboratory interpretation of the admission electrocardiogram in patients with acute coronary syndromes and their relation to outcome.

In the prospective, multinational Global Registry of Acute Coronary Events (GRACE), patients diagnosed with non-ST-elevation acute coronary syndromes had their admission electrocardiogram independently evaluated by a central core laboratory, and its interpretation by the core laboratory and enrolling site were compared. One in 6 of these patients had clinically important features of left-bundle branch block or ST-segment deviation diagnosed by the core laboratory that were apparently not recognized at the local sites; this subgroup of patients was less likely to undergo risk stratification and revascularization. Importantly, failure to recognize these features as confirmed by the core laboratory in routine clinical practice was independently associated with higher mortality and recurrent myocardial infarction at 6 months (adjusted odds ratio 1.41, 95% confidence interval 1.01 to 1.96, p = 0.043). In conclusion, these findings underscore an urgent need to promote more accurate interpretation of electrocardiograms in contemporary clinical practice to bridge treatment gaps and improve patient outcome.

ST-segment depression in non-ST elevation acute coronary syndromes: quantitative analysis may not provide incremental prognostic value beyond comprehensive risk stratification.

BACKGROUND: It is unclear whether quantitative ST-segment assessment can improve risk stratification of unselected acute coronary syndrome (ACS) patients using the validated Global Registry of Acute Cardiac Events (GRACE) risk model. METHODS: In the prospective, multicenter, Canadian ACS Registry, the admission electrocardiogram was evaluated centrally at a blinded core laboratory. Patients with ST-elevation myocardial infarction and other electrocardiogram confounders were excluded. ST depression (ST down) was measured and summed in all leads except aVR. Patients with ST down were divided into 3 groups based on tertiles of cumulative ST down. A multivariable model was developed to examine the independent prognostic value of ST down severity after adjusting for other known prognosticators in the GRACE risk model. RESULTS: Among 2590 patients with non-ST-elevation ACS, more severe ST down was associated with advanced age, higher heart rate and Killip class, elevated creatinine, abnormal biomarkers, higher GRACE risk score, and higher 1-year mortality (all P < .001). After adjusting for these confounding prognosticators, the presence of any ST down remained independently associated with higher 1-year mortality (odds ratio 1.78, 95% CI 1.21-2.63, P = .004). However, the gradient of risk with increasing magnitude of ST down was no longer evident (adjusted odds ratios 1.77, 1.77, 1.81, for ascending tertiles of cumulative ST down, respectively). Moreover, quantitative ST down did not improve the model discrimination for 1-year mortality. The results were similar when the number of leads with ST down or the maximum magnitude of ST down was analyzed, after adjusting for tertiles of GRACE risk score or inhospital revascularization, or using the composite end point of death or myocardial (re)infarction at 1 year. CONCLUSIONS: Greater ST down is associated with other adverse prognosticators across the broad spectrum of non-ST-elevation ACS. Although the presence of any ST down is an independent predictor of 1-year mortality, its quantitative assessment is not as important as its mere presence when studied on the background of comprehensive clinical and biomarker evaluation in a nonclinical trial-based ACS population.

Short- and long-term outcomes of patients with electrocardiographic left ventricular hypertrophy after fibrinolysis for acute myocardial infarction.

There is conflicting evidence with regard to the value of electrocardiographic left ventricular hypertrophy (LVH) in myocardial infarction. Of 5,951 patients in the ASSENT-3 trial, 273 (5%) had LVH on baseline electrocardiograms and had significantly higher mortality rates at 30 days (11% vs 6%, p = 0.001) and 1 year (13% vs 8%, p = 0.007). After adjustment for differences in baseline parameters, LVH remained an independent predictor of 30-day (hazard ratio 2.3, 95% confidence interval 1.4 to 3.9) and 1-year (hazard ratio 1.8, 95% confidence interval 1.1 to 2.8) mortality rates. Thus, electrocardiographic LVH is a prognostic tool in identifying short- and long-term mortality rates in patients who have ST-elevation myocardial infarction and receive fibrinolysis.