Viral methyltranferases (MTase) are involved in the third step of the mRNA‐capping process, transferring a methyl group from S‐adenosyl‐l‐methionine (SAM) to the capped mRNA. MTases are classified ...into two groups: (guanine‐N7)‐methyltransferases (N7MTases), which add a methyl group onto the N7 atom of guanine, and (nucleoside‐2′‐O‐)‐methyltransferases (2′OMTases), which add a methyl group to a ribose hydroxyl. The MTases of two flaviviruses, Meaban and Yokose viruses, have been overexpressed, purified and crystallized in complex with SAM. Characterization of the crystals together with details of preliminary X‐ray diffraction data collection (at 2.8 and 2.7 Å resolution, respectively) are reported here. The sequence homology relative to Dengue virus 2′OMTase and the structural conservation of specific residues in the putative active sites suggest that both enzymes belong to the 2′OMTase subgroup.
Associations between socioeconomic status (SES) and risk factors for noncommunicable diseases (NCD-RFs) may differ in populations at different stages of the epidemiological transition. We assessed ...the social patterning of NCD-RFs in a study including populations with different levels of socioeconomic development.
Data on SES, smoking, physical activity, body mass index, blood pressure, cholesterol and glucose were available from the Modeling the Epidemiologic Transition Study (METS), with about 500 participants aged 25-45 in each of five sites (Ghana, South Africa, Jamaica, Seychelles, United States).
The prevalence of NCD-RFs differed between these populations from five countries (e.g., lower prevalence of smoking, obesity and hypertension in rural Ghana) and by sex (e.g., higher prevalence of smoking and physical activity in men and of obesity in women in most populations). Smoking and physical activity were associated with low SES in most populations. The associations of SES with obesity, hypertension, cholesterol and elevated blood glucose differed by population, sex, and SES indicator. For example, the prevalence of elevated blood glucose tended to be associated with low education, but not with wealth, in Seychelles and USA. The association of SES with obesity and cholesterol was direct in some populations but inverse in others.
In conclusion, the distribution of NCD-RFs was socially patterned in these populations at different stages of the epidemiological transition, but associations between SES and NCD-RFs differed substantially according to risk factor, population, sex, and SES indicator. These findings emphasize the need to assess and integrate the social patterning of NCD-RFs in NCD prevention and control programs in LMICs.
Background
The WHO surgical safety checklist (SSC) is known to prevent postoperative complications; however, strategies for effective implementation are unclear. In addition to cultural and ...organizational barriers faced by high-income countries, resource-constrained settings face scarcity of durable and consumable goods. We used the SSC to better understand barriers to improvement at a trauma hospital in Battambang, Cambodia.
Methods
We introduced the SSC and trained data collectors to observe surgical staff performing the checklist. Members of the research team observed cases and data collection. After 3 months, we modified the data collection tool to focus on infection prevention and elicit more accurate responses.
Results
Over 16 months we recorded data on 695 operations (304 cases using the first tool and 391 cases with the modified tool). The first tool identified five items as being in high compliance, which were then excluded from further assessment. Two items—instrument sterility confirmation and sponge counting—were identified as being misinterpreted by the data collectors’ tool. These items were reworded to capture objective assessment of task completion. Confirmation of instrument sterility was initially never performed but rectified to >95% compliance; sponge counting and prophylactic antibiotic administration were consistently underperformed.
Conclusions
Staff complied with communication elements of the SSC and quickly adopted process improvements. The wording of our data collection tool affected interpretation of compliance with standards. Material resources are not the primary barrier to checklist implementation in this setting, and future work should focus on clarification of protocols and objective confirmation of tasks.
Globally, Africans and African Americans experience a disproportionate burden of type 2 diabetes, compared to other race and ethnic groups. The aim of the study was to examine the association of ...plasma glucose with indices of glucose metabolism in young adults of African origin from 5 different countries.
We identified participants from the Modeling the Epidemiologic Transition Study, an international study of weight change and cardiovascular disease (CVD) risk in five populations of African origin: USA (US), Jamaica, Ghana, South Africa, and Seychelles. For the current study, we included 667 participants (34.8 ± 6.3 years), with measures of plasma glucose, insulin, leptin, and adiponectin, as well as moderate and vigorous physical activity (MVPA, minutes/day min/day), daily sedentary time (min/day), anthropometrics, and body composition.
Among the 282 men, body mass index (BMI) ranged from 22.1 to 29.6 kg/m(2) in men and from 25.8 to 34.8 kg/m(2) in 385 women. MVPA ranged from 26.2 to 47.1 min/day in men, and from 14.3 to 27.3 min/day in women and correlated with adiposity (BMI, waist size, and % body fat) only among US males after controlling for age. Plasma glucose ranged from 4.6 ± 0.8 mmol/L in the South African men to 5.8 mmol/L US men, while the overall prevalence for diabetes was very low, except in the US men and women (6.7 and 12 %, respectively). Using multivariate linear regression, glucose was associated with BMI, age, sex, smoking hypertension, daily sedentary time but not daily MVPA.
Obesity, metabolic risk, and other potential determinants vary significantly between populations at differing stages of the epidemiologic transition, requiring tailored public health policies to address local population characteristics.
Sepsis mortality is reported to be high worldwide, however recently the attributable fraction of mortality due to sepsis (AFsepsis) has been questioned. If improvements in treatment options are to be ...evaluated, it is important to know what proportion of deaths are potentially preventable or modifiable after a sepsis episode. The aim of the study was to establish the fraction of deaths directly related to the sepsis episode on the general wards and emergency departments.
839 patients were recruited over the two 24-h periods in 2016 and 2017. 521 patients fulfilled SEPSIS-3 criteria. 166 patients (32.4%) with sepsis and 56 patients (17.6%) without sepsis died within 90 days. Out of the 166 sepsis deaths 12 (7.2%) could have been directly related to sepsis, 28 (16.9%) possibly related and 96 (57.8%) were not related to sepsis. Overall AFsepsis was 24.1%. Upon analysis of the 40 deaths likely to be attributable to sepsis, we found that 31 patients (77.5%) had the Clinical Frailty Score ≥ 6, 28 (70%) had existing DNA-CPR order and 17 had limitations of care orders (42.5%).
Abstract 4054
Poster Board III-989
Many clinical situations are associated with the development of iron deficiency which can adversely affect energy level, physical activity, cardiovascular function, ...cognition, and immune responses. Oral iron, which is the primary treatment for iron deficiency, is limited by poor tolerability due to gastrointestinal (GI) side effects and resulting problems with compliance. In addition, in many patients it is not easily absorbed and does not replace iron stores rapidly enough to meet iron losses. Blood transfusions may be avoided in these patients with the use of intravenous (IV) iron. Whereas other forms of IV iron require multiple doses for complete replacement, LMWID may be administered as a total dose infusion, typically over a 4 to 6 hour period. LMWID (INFeD) is the preferred iron dextran due to the lower incidence of reported adverse reactions in the literature as compared to high (H) MWID, (DexFerrum). Numerous clinical studies of IV iron suggest that 1000 mg is an adequate dose for many patients. Our clinical practice routinely administers LMWID as a 1 g infusion over 1 hour without pre-medication. We summarize our experience with the safety and efficacy of this method of administration.
Data were collected for consecutive adult patients with iron deficiency who were treated with 1 gram of LMWID from August 2008 to May 2009. To avoid confounding variables patients who received erythropoiesis stimulating agents or chemotherapy were excluded from the analysis. Age, gender, height, weight, diagnosis, tests of iron status (serum ferritin, total iron binding capacity, serum iron, and percent transferrin saturation), hemoglobin (Hb), history of multiple drug allergies and/or iron allergies, dose of iron dextran, infusion rate, number of transfusions, and signs or reports of adverse reactions were recorded. As clinically important hypophosphatemia (serum phosphate <2mg/dL) has been reported with several IV iron preparations, we examined pre- and post-infusion phosphate levels.
189 consecutive iron deficient patients (84% female, 76% white, mean age = 51 years, mean weight = 85 Kg) were included in the analysis, 15.9% of whom had multiple drug allergies (≥ 2). The most common diagnoses were: menorrhagia, chronic kidney disease, angiodysplasia, pregnancy, GI bleed, and gastric bypass; 19% of patients had multiple diagnoses. A total of 224 1-gram doses were administered over a median infusion time of 63 minutes (interquartile range 60-66 min). No pre-medication was administered except for 1 dose of methylprednisolone prior to the test dose in each of 2 patients: one with a previous reaction to HMWID, and one with drug allergies. Following administration of LMWID, there was a significant increase from baseline in Hb of 1.2 g/dL (p <0.0001, 95% confidence interval CI: 1.0 to 1.4) with a median follow-up time of 3 weeks. A follow-up time of ≥ 4 weeks was associated with a greater increase in Hb than < 4 weeks (1.5 vs 1.0 g/dL, p=0.013). One patient required a transfusion following severe GI bleeding secondary to angiodysplasia. Nineteen patients (10.1%) experienced 33 adverse events (AEs). The AEs were considered treatment-related in12 patients (6.3%). The most common AEs were back pain (2.6%), headache (2.1%), and nausea (1.6%). AEs were mostly transient and resolved without therapy. Five (2.6%) patients were treated for minor reactions (3 patients received 125 milligrams of methylprednisolone during or immediately following the infusion, and 2 patients received acetaminophen). There were no serious AEs, and only 1 patient discontinued treatment due to an AE (hives). The only demographic factor that was independently associated with an increased likelihood of experiencing an AE was drug allergies. Patients with a history of > 2 drug allergies were 4.3 times more likely to experience any kind of AE than other patients (95% CI: 1.1 to 16.3, p=0.031). Mean change from baseline phosphate level was 0.0 mg/dL (95% CI: -0.1 to 0.2, p=0.537) at a median follow-up time of two weeks. No patient developed hypophosphatemia.
Our single center experience found IV administration of 1 gram of LMWID over 1 hour is a safe and effective treatment for patients with iron deficiency with the advantages of shorter treatment period, assured compliance, and a lower incidence of side effects than oral iron. Future prospective, randomized studies will help confirm these findings.
Off Label Use: The total dose infusion of low molecular weight iron dextran, although widely used, is an off label method of administration of intravenous iron. Pappadakis:Watson Laboratories: Employment. Dahl:Watson Laboratories: Employment.
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