Modification of WHO diagnostic criteria for gestational diabetes: implications for classification of hyperglycemia in pregnancy

Background: Low and medium income countries (LMICs) especially in sub-Saharan Africa face unique challenges in screening and diagnosing hyperglycaemia in pregnancy. The implications of applying the 2013 WHO modifications for assessing hyperglycaemia in pregnancy in low resource settings are not known. We evaluated the significance of these recent changes in classification of hyperglycaemia among pregnant Nigerian women.Methods: We reviewed the records of Oral glucose tolerance test conducted on 600 pregnant women at the Jos University Teaching Hospital (JUTH) between July 2012 and June 2016. The collected data were analyzed using Statistical Package for Social Sciences version 18 (SPSS Inc., Chicago, IL, USA). Test for association was done using Fisher’s exact test. P < 0.05 was set as the level of significance.Results: The results show that 15.9%, 20.2% and 15.7% of the women had GDM according to WHO (1999), IADPSG and WHO (2013) diagnostic criteria respectively while 4.8% of the women had DM in pregnancy by WHO 2013 criteria. Overall, 30.2% and 23.9% of women who were classified as GDM by WHO 1999 criteria and IADPSG criteria respectively were qualified to be classified as DM in pregnancy according to the WHO 2013 criteria.Conclusions: The recent Modifications by the WHO 2013 guideline for classifying hyperglycemia in pregnancy may create non-uniform interpretation of OGTT. The confusion in classifying hyperglycemia among pregnant women referred between health centres may become more pronounced. There is an urgent need for a streamlined globally acceptable approach to assessing and classifying hyperglycemia in pregnant women

CRT-700.05 Impella Utilization in High-Risk Percutaneous Coronary Intervention Mitigates the Risks of Procedural and Clinical Adverse Events Independent of Left Ventricular Ejection Fraction: The Protect III Study

Background: Left ventricular (LV) dysfunction is associated with an increased risk of adverse events in patients undergoing percutaneous coronary intervention (PCI). However, the impact of LV ejection fraction (LVEF) on the outcomes of Impella-supported high-risk PCI (HRPCI) is unknown. Methods: Patients enrolled in the prospective, multicenter, and observational PROTECT III study from March 2017 to March 2020 who underwent Impella-supported HRPCI at the operator’s discretion (non-cardiogenic shock). Patients were divided into three tertiles (T) based on baseline LVEF: T1 (the lowest), T2, and T3 (the highest). The primary outcome is the rate of 90-day major adverse cardiac and cerebrovascular events (MACCE), defined as the composite of all-cause death, myocardial infarction, stroke/transient ischemic attack, and repeated revascularization as adjudicated by an independent CEC. Results: Of 1237 patients, 940 with available baseline LVEF were analyzed. T1 included 353 patients (mean LVEF 19.6±4.7), T2 included 274 patients (mean LVEF 32.2±3.5), and T3 included 313 patients (mean LVEF 52.6±9.2). Patients in the higher tertiles were older, more likely to be females, presented more with acute coronary syndrome, and had more frequent left main disease. Also, severely calcified lesions and atherectomy utilization were more frequent in the higher tertiles. The rates of 90-day MACCE were comparable across all tertiles. Furthermore, PCI-related complications and 1-year mortality were also comparable (Table). After multivariable adjustment, 90-day MACCE was not significantly different between the LVEF tertiles (p=0.32). Conclusion: In patients with HRPCI supported by Impella, the rates of in-hospital adverse events, PCI-related complications, 90-day MACCE, and 1-year mortality were comparable among the different LVEF tertiles

TCT-545 Angiographic Features, Lesion, and Procedural Characteristics in Patients With Chronic Kidney Disease Undergoing Protected High-Risk Percutaneous Coronary Intervention

Background: Patients with chronic kidney disease (CKD) are at risk for accelerated atherosclerosis. There is a paucity of data regarding coronary lesion characteristics and procedural details of CKD patients, especially those on dialysis, undergoing high-risk percutaneous coronary intervention (HRPCI) with left ventricular support. Methods: We analyzed patients from the PROTECT III study who underwent Impella-supported HRPCI, stratified into 3 groups according to kidney function status based on history: 1) normal kidney function; 2) CKD not on dialysis; and 3) CKD on dialysis. Baseline characteristics, angiographic features, and procedural details were assessed. Results: The study population included 3,702 treated lesions in 1,223 patients with a mean age of 71 ± 11 years; 73% (893) were male, 68% (834) had normal kidney function (serum creatinine = 1 mg/dL [IQR: 0.9-1.2]), 23% (278) had CKD not on dialysis (serum creatinine = 1.6 mg/dL [IQR: 1.3-1.9]), and 9% (111) were on dialysis. Patients on dialysis were significantly younger and had more comorbidities, as well as a greater incidence of acute myocardial infarction as an indication for HRPCI compared with the other 2 groups (45.0 [dialysis] vs 30.1 [CKD not on dialysis] vs 36.0 [normal kidney function]; P = 0.03). There was no difference between groups in prevalence of 3-vessel disease (P = 0.63). Patients on dialysis had greater prevalence of severely calcified lesions and higher use of rotational and orbital atherectomy with greater number of passes (Table 1). Despite this, no significant differences were observed in post-PCI Thrombolysis In Myocardial Infarction flow, incidence of no-reflow, or dissection/perforation. Conclusion: In contrast to patients with normal kidney function, patients with CKD with or without dialysis treated with Impella had more comorbidities, higher prevalence of severely calcified lesions, and greater use of atherectomy with more passes. Despite the complexity of PCI, no significant differences in complications were observed. Categories: CORONARY: Complex and Higher Risk Procedures for Indicated Patients (CHIP

TCT-99 Short- and Long-Term Outcomes of Patients With Chronic Kidney Disease Undergoing Protected High-Risk Percutaneous Coronary Intervention

Background: Patients with chronic kidney disease (CKD) and concomitant multivessel coronary artery disease (CAD) with or without left ventricular dysfunction often have high surgical risk and are declined for coronary artery bypass grafting. There is little data regarding clinical outcomes in these patients undergoing high-risk PCI (HRPCI) using Impella. Methods: We analyzed patients from the PROTECT III Study who underwent Impella-supported HRPCI and stratified them into 3 groups by kidney function status based on history: 1) normal kidney function, 2) CKD without dialysis, and 3) CKD with dialysis. We compared the composite incidence of major adverse cardiac and cerebrovascular events (MACCE) rate, defined as all-cause death, myocardial infarction (MI), stroke/transient ischemic attack (TIA), and repeat revascularization at 30 and 90 days. Results: We included 1,223 patients, aged 71 ± 11 years; 73% (893) were men, 68% (834) had normal kidney function (serum creatinine [Cr] 1.1 mg/dL, IQR 0.9-1.2), 23% (278) had CKD without dialysis (Cr 1.7 mg/dL, IQR 1.3-1.9), and 9% (111) were on dialysis. Patients on dialysis were younger with more comorbidities such as diabetes, heart failure, anemia, PVD and prior stroke. HRPCI status (urgent or elective), proportion of acute MI, and mean SYNTAX scores were similar. No significant differences in MACCE were shown between groups at 30 days or 90 days (Table). Patients with normal kidney function had comparable risks of 30-day and 90-day MACCE compared with CKD patients without dialysis with Cox proportional hazards analysis, and lower risk of 90-day MACCE compared to CKD patients with dialysis. Notably, CKD patients with or without dialysis also had similar 90-day MACCE risk (Table). Conclusion: Patients with CKD and dialysis undergoing HRPCI exhibit higher risk for 90-day MACCE compared to patients with normal kidney function. CKD patients without dialysis also had higher risk of MI at 90 days. Further research is needed. Categories: CORONARY: Complex and Higher Risk Procedures for Indicated Patients (CHIP

Global, regional, and national comparative risk assessment of 79 behavioural, environmental and occupational, and metabolic risks or clusters of risks, 1990-2015: a systematic analysis for the Global Burden of Disease Study 2015

SummaryBackground The Global Burden of Diseases, Injuries, and Risk Factors Study 2015 provides an up-to-date synthesis of the evidence for risk factor exposure and the attributable burden of disease. By providing national and subnational assessments spanning the past 25 years, this study can inform debates on the importance of addressing risks in context. Methods We used the comparative risk assessment framework developed for previous iterations of the Global Burden of Disease Study to estimate attributable deaths, disability-adjusted life-years (DALYs), and trends in exposure by age group, sex, year, and geography for 79 behavioural, environmental and occupational, and metabolic risks or clusters of risks from 1990 to 2015. This study included 388 risk-outcome pairs that met World Cancer Research Fund-defined criteria for convincing or probable evidence. We extracted relative risk and exposure estimates from randomised controlled trials, cohorts, pooled cohorts, household surveys, census data, satellite data, and other sources. We used statistical models to pool data, adjust for bias, and incorporate covariates. We developed a metric that allows comparisons of exposure across risk factors—the summary exposure value. Using the counterfactual scenario of theoretical minimum risk level, we estimated the portion of deaths and DALYs that could be attributed to a given risk. We decomposed trends in attributable burden into contributions from population growth, population age structure, risk exposure, and risk-deleted cause-specific DALY rates. We characterised risk exposure in relation to a Socio-demographic Index (SDI). Findings Between 1990 and 2015, global exposure to unsafe sanitation, household air pollution, childhood underweight, childhood stunting, and smoking each decreased by more than 25%. Global exposure for several occupational risks, high body-mass index (BMI), and drug use increased by more than 25% over the same period. All risks jointly evaluated in 2015 accounted for 57·8% (95% CI 56·6–58·8) of global deaths and 41·2% (39·8–42·8) of DALYs. In 2015, the ten largest contributors to global DALYs among Level 3 risks were high systolic blood pressure (211·8 million [192·7 million to 231·1 million] global DALYs), smoking (148·6 million [134·2 million to 163·1 million]), high fasting plasma glucose (143·1 million [125·1 million to 163·5 million]), high BMI (120·1 million [83·8 million to 158·4 million]), childhood undernutrition (113·3 million [103·9 million to 123·4 million]), ambient particulate matter (103·1 million [90·8 million to 115·1 million]), high total cholesterol (88·7 million [74·6 million to 105·7 million]), household air pollution (85·6 million [66·7 million to 106·1 million]), alcohol use (85·0 million [77·2 million to 93·0 million]), and diets high in sodium (83·0 million [49·3 million to 127·5 million]). From 1990 to 2015, attributable DALYs declined for micronutrient deficiencies, childhood undernutrition, unsafe sanitation and water, and household air pollution; reductions in risk-deleted DALY rates rather than reductions in exposure drove these declines. Rising exposure contributed to notable increases in attributable DALYs from high BMI, high fasting plasma glucose, occupational carcinogens, and drug use. Environmental risks and childhood undernutrition declined steadily with SDI; low physical activity, high BMI, and high fasting plasma glucose increased with SDI. In 119 countries, metabolic risks, such as high BMI and fasting plasma glucose, contributed the most attributable DALYs in 2015. Regionally, smoking still ranked among the leading five risk factors for attributable DALYs in 109 countries; childhood underweight and unsafe sex remained primary drivers of early death and disability in much of sub-Saharan Africa. Interpretation Declines in some key environmental risks have contributed to declines in critical infectious diseases. Some risks appear to be invariant to SDI. Increasing risks, including high BMI, high fasting plasma glucose, drug use, and some occupational exposures, contribute to rising burden from some conditions, but also provide opportunities for intervention. Some highly preventable risks, such as smoking, remain major causes of attributable DALYs, even as exposure is declining. Public policy makers need to pay attention to the risks that are increasingly major contributors to global burden. Funding Bill & Melinda Gates Foundation

Antimicrobial resistance among migrants in Europe: a systematic review and meta-analysis

BACKGROUND: Rates of antimicrobial resistance (AMR) are rising globally and there is concern that increased migration is contributing to the burden of antibiotic resistance in Europe. However, the effect of migration on the burden of AMR in Europe has not yet been comprehensively examined. Therefore, we did a systematic review and meta-analysis to identify and synthesise data for AMR carriage or infection in migrants to Europe to examine differences in patterns of AMR across migrant groups and in different settings. METHODS: For this systematic review and meta-analysis, we searched MEDLINE, Embase, PubMed, and Scopus with no language restrictions from Jan 1, 2000, to Jan 18, 2017, for primary data from observational studies reporting antibacterial resistance in common bacterial pathogens among migrants to 21 European Union-15 and European Economic Area countries. To be eligible for inclusion, studies had to report data on carriage or infection with laboratory-confirmed antibiotic-resistant organisms in migrant populations. We extracted data from eligible studies and assessed quality using piloted, standardised forms. We did not examine drug resistance in tuberculosis and excluded articles solely reporting on this parameter. We also excluded articles in which migrant status was determined by ethnicity, country of birth of participants' parents, or was not defined, and articles in which data were not disaggregated by migrant status. Outcomes were carriage of or infection with antibiotic-resistant organisms. We used random-effects models to calculate the pooled prevalence of each outcome. The study protocol is registered with PROSPERO, number CRD42016043681. FINDINGS: We identified 2274 articles, of which 23 observational studies reporting on antibiotic resistance in 2319 migrants were included. The pooled prevalence of any AMR carriage or AMR infection in migrants was 25·4% (95% CI 19·1-31·8; I2 =98%), including meticillin-resistant Staphylococcus aureus (7·8%, 4·8-10·7; I2 =92%) and antibiotic-resistant Gram-negative bacteria (27·2%, 17·6-36·8; I2 =94%). The pooled prevalence of any AMR carriage or infection was higher in refugees and asylum seekers (33·0%, 18·3-47·6; I2 =98%) than in other migrant groups (6·6%, 1·8-11·3; I2 =92%). The pooled prevalence of antibiotic-resistant organisms was slightly higher in high-migrant community settings (33·1%, 11·1-55·1; I2 =96%) than in migrants in hospitals (24·3%, 16·1-32·6; I2 =98%). We did not find evidence of high rates of transmission of AMR from migrant to host populations. INTERPRETATION: Migrants are exposed to conditions favouring the emergence of drug resistance during transit and in host countries in Europe. Increased antibiotic resistance among refugees and asylum seekers and in high-migrant community settings (such as refugee camps and detention facilities) highlights the need for improved living conditions, access to health care, and initiatives to facilitate detection of and appropriate high-quality treatment for antibiotic-resistant infections during transit and in host countries. Protocols for the prevention and control of infection and for antibiotic surveillance need to be integrated in all aspects of health care, which should be accessible for all migrant groups, and should target determinants of AMR before, during, and after migration. FUNDING: UK National Institute for Health Research Imperial Biomedical Research Centre, Imperial College Healthcare Charity, the Wellcome Trust, and UK National Institute for Health Research Health Protection Research Unit in Healthcare-associated Infections and Antimictobial Resistance at Imperial College London

Evaluation of nine candidate genes in patients with normal tension glaucoma: a case control study

<p>Abstract</p> <p>Background</p> <p>Normal tension glaucoma is a major subtype of glaucoma, associated with intraocular pressures that are within the statistically normal range of the population. Monogenic forms following classical inheritance patterns are rare in this glaucoma subtype. Instead, multigenic inheritance is proposed for the majority of cases. The present study tested common sequence variants in candidate genes for association with normal tension glaucoma in the German population.</p> <p>Methods</p> <p>Ninety-eight SNPs were selected to tag the common genetic variation in nine genes, namely OPTN (optineurin), RDX (radixin), SNX16 (sorting nexin 16), OPA1 (optic atrophy 1), MFN1 (mitofusin 1), MFN2 (mitofusin 2), PARL (presenilin associated, rhomboid-like), SOD2 (superoxide dismutase 2, mitochondrial) and CYP1B1 (cytochrome P450, family 1, subfamily B, polypeptide 1). These SNPs were genotyped in 285 cases and 282 fully evaluated matched controls. Statistical analyses comprised single polymorphism association as well as haplogroup based association testing.</p> <p>Results</p> <p>Results suggested that genetic variation in five of the candidate genes (RDX, SNX16, OPA1, SOD2 and CYP1B1) is unlikely to confer major risk to develop normal tension glaucoma in the German population. In contrast, we observed a trend towards association of single SNPs in OPTN, MFN1, MFN2 and PARL. The SNPs of OPTN, MFN2 and PARL were further analysed by multimarker haplotype-based association testing. We identified a risk haplotype being more frequent in patients and a vice versa situation for the complementary protective haplotype in each of the three genes.</p> <p>Conclusion</p> <p>Common variants of OPTN, PARL, MFN1 and MFN2 should be analysed in other cohorts to confirm their involvement in normal tension glaucoma.</p

The Tumor Suppressor Gene, RASSF1A, Is Essential for Protection against Inflammation -Induced Injury

10.1371/journal.pone.0075483PLoS ONE810-POLN