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BACKGROUND: Features of the dyslipidemic pattern reported with the use of antiretroviral therapy predict enhanced postprandial lipemia, which is an emerging cardiovascular disease risk factor. OBJECTIVE: We evaluated the postprandial response to a physiologic, meal-based challenge in HIV-positive subjects without hyperlipidemia. DESIGN: We measured hourly lipid, lipoprotein, glucose, and insulin concentrations during a 13-h period in 25 nonwhite patients (13 women, 12 men): 13 receiving a protease inhibitor (PI)-based regimen (6 nelfinavir and 7 indinavir) and 12 receiving a nonnucleoside reverse transcriptase inhibitor (NNRTI)-based regimen (6 efavirenz and 6 nevirapine). RESULTS: Mean fasting HDL-cholesterol concentrations were lower in HIV patients than in healthy subjects without HIV infection matched for age, sex, and ethnicity (z score: -0.81 +/- 0.9; P = 0.0001). Fasting triacylglycerol concentrations were not significantly different between HIV-infected patients and healthy subjects but were higher in PI-treated than in NNRTI-treated patients [median (interquartile range): 144 (110-191) and 89 (62-135) mg/dL; P = 0.007]. Average daylong triacylglycerol concentrations, but not incremental concentrations, were higher in the PI group than in the NNRTI group [205% (185-248%) and 125% (78-191%); P < 0.05]. For all HIV-positive patients, the fractional triacylglycerol increase was lower after breakfast than after lunch (20 +/- 18% and 42 +/- 40%, respectively; P < 0.04). Insulin concentrations were higher in PI-treated than in NNRTI-treated patients [22.6 (13.1-29.8) and 11.8 (7.1-19.1) microU/mL; P = 0.01] and increased in both groups in response to each meal, whereas glucose concentrations increased only after breakfast. CONCLUSIONS: Despite baseline differences, incremental triacylglycerol and insulin responses to a physiologic caloric load among HIV-positive patients were not significantly affected by differences in the type of antiretroviral therapy. Copyright © 2005 American Society for Clinical Nutrition [ABSTRACT FROM AUTHOR]

Background: Little information is available about HDL subpopulations during dietary changes. Objective: The objective was to investigate the effect of reductions in total and saturated fat intakes on HDL subpopulations. Design: Multiracial, young and elderly men and women (n = 103) participating in the double-blind, randomized DELTA (Dietary Effects on Lipoproteins and Thrombogenic Activities) Study consumed 3 different diets, each for 8 wk: an average American diet (AAD: 34.3% total fat, 15.0% saturated fat), the American Heart Association Step I diet (28.6% total fat, 9.0% saturated fat), and a diet low in saturated fat (25.3% total fat, 6.1% saturated fat). Results: HDL2-cholesterol concentrations, by differential precipitation, decreased (P < 0.001) in a stepwise fashion after the reduction of total and saturated fat: 0.58 +/= 0.21, 0.53 +/= 0.19, and 0.48 +/= 0.18 mmol/L with the AAD, Step I, and low-fat diets, respectively. HDL3 cholesterol decreased (P < 0.01) less: 0.76 +/= 0.13, 0.73 +/= 0.12, and 0.72 +/= 0.11 mmol/L with the AAD, Step I, and low-fat diets, respectively. As measured by nondenaturing gradient gel electrophoresis, the larger-size HDL2b subpopulation decreased with the reduction in dietary fat, and a corresponding relative increase was seen for the smaller-sized HDL3a, 36, and 3c subpopulations (P < 0.01). HDL2-cholesterol concentrations correlated negatively with serum triacylglycerol concentrations on all 3 diets: r = -0.46, -0.37, and -0.45 with the AAD, Step I, and low-fat diets, respectively (P < 0.0001). A similar negative correlation was seen for HDL2b, whereas HDL3a. 36, and 3c correlated positively with triacylglycerol concentrations. Diet-induced changes in serum triacylglycerol were negatively correlated with changes in HDL2 and HDL2b cholesterol. Conclusions: A reduction in dietary total and saturated fat decreased both large (HDL2 and HDL2b) and small, dense HDL subpopulations, although decreases in HDL2 and HDL2b were most pronounced. Copyright (c) 1999 American Society for Clinical Nutrition [ABSTRACT FROM AUTHOR]

Digital technologies are creating new ways for visitors to engage with cemeteries. This article presents research into the development of digital cemetery technologies, or cemtech , to understand how they are reimagining memorial spaces. Through a systematic review of examples of cemtech in online records, academic literature, patents, and trade publications, we developed a typology of cemtech according to four characteristics: application type, technical components, target users, and development status. Analysis of the application types resulted in five higher-level themes of functionality or operation- Wayfinding , Narrativizing , Presencing , Emplacing, and Repurposing- which we discuss. This typology and thematic analysis help to identify and understand the development of cemetery technology design trajectories and how they reimagine possibilities for cemetery use and experience.

Lipoprotein(a) [Lp(a)] has two main proteins, apoB100 and apo(a). High levels of Lp(a) confer an increased risk for atherosclerotic cardiovascular disease. Most people have two circulating isoforms of apo(a) differing in their molecular mass, determined by the number of Kringle IV Type 2 repeats. Previous studies report a strong inverse relationship between Lp(a) levels and apo(a) isoform sizes. The roles of Lp(a) production and fractional clearance and how ancestry affects this relationship remain incompletely defined. We therefore examined the relationships of apo(a) size with Lp(a) levels and both apo(a) fractional clearance rates (FCR) and production rates (PR) in 32 individuals not on lipid-lowering treatment. We determined plasma Lp(a) levels and apo(a) isoform sizes, and used the relative expression of the two isoforms to calculate a "weighted isoform size" (wIS). Stable isotope studies were performed, using D3-leucine, to determine the apo(a) FCR and PR. As expected, plasma Lp(a) concentrations were inversely correlated with wIS (R 2  = 0.27; P = 0.002). The wIS had a modest positive correlation with apo(a) FCR (R 2  = 0.10, P = 0.08), and a negative correlation with apo(a) PR (R 2  = 0.11; P = 0.06). The relationship between wIS and PR became significant when we controlled for self-reported race and ethnicity (SRRE) (R 2  = 0.24, P = 0.03); controlling for SRRE did not affect the relationship between wIS and FCR. Apo(a) wIS plays a role in both FCR and PR; however, adjusting for SRRE strengthens the correlation between wIS and PR, suggesting an effect of ancestry., Competing Interests: Conflict of interest The authors declare that they have no conflicts of interest with the contents of this article, (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Completion rates among adolescents who initiate the human papillomavirus (HPV) vaccine 3-dose series are low. SMS text message vaccine reminders are effective, but less is known about the best types for HPV series completion or the ability to assess and target vaccine decision-making stage., Objective: The aim of this study is to compare the effectiveness of HPV vaccine series completion in minority adolescents who received precision and educational versus conventional SMS text message reminders., Methods: Enrolled parents of adolescents aged 9-17 years who received the first HPV vaccine dose at 1 of the 4 academic-affiliated community health clinics in New York City were randomized 1:1 to 1 of the 2 parallel, unblinded arms: precision SMS text messages (which included stage-targeted educational information, next dose due date, and site-specific walk-in hours) or conventional SMS text messages without educational information. Randomization was stratified according to gender, age, and language. The primary outcome was series completion within 12 months. In post hoc analysis, enrollees were compared with concurrent nonenrollees and historical controls., Results: Overall, 956 parents were enrolled in the study. The precision (475 families) and conventional (481 families) SMS text message arms had similarly high series completion rates (344/475, 72.4% vs 364/481, 75.7%). A total of 42 days after the first dose, two-thirds of families, not initially in the preparation stage, moved to preparation or vaccinated stage. Those in either SMS text message arm had significantly higher completion rates than nonenrollees (708/1503, 47.1% vs 679/1503, 45.17%; P<.001). Even after removing those needing only 2 HPV doses, adolescents receiving any SMS text messages had higher completion rates than historical controls (337/2823, 11.93% vs 981/2823, 34.75%; P<.001). A population-wide effect was seen from 2014 to 2016, above historical trends., Conclusions: SMS text message reminders led to timely HPV vaccine series completion in a low-income, urban, minority study population and also led to population-wide effects. Educational information did not provide an added benefit to this population., Trial Registration: ClinicalTrials.gov NCT02236273; https://clinicaltrials.gov/ct2/show/NCT02236273., (©Chelsea S Wynn, Marina Catallozzi, Chelsea A Kolff, Stephen Holleran, Dodi Meyer, Rajasekhar Ramakrishnan, Melissa S Stockwell. Originally published in JMIR mHealth and uHealth (https://mhealth.jmir.org), 27.12.2021.)

Background: Immunization reminders in electronic health records (EHR) provide clinical decision support (CDS) that can reduce missed immunization opportunities. Little is known about using CDS rules from a regional immunization information system (IIS) to power local EHR immunization reminders., Objective: This study aimed to assess the impact of EHR reminders using regional IIS CDS-provided rules on receipt of immunizations in a low-income, urban population for both routine immunizations and those recommended for patients with chronic medical conditions (CMCs)., Methods: We built an EHR-based immunization reminder using the open-source resource used by the New York City IIS in which we overlaid logic regarding immunizations needed for CMCs. Using a randomized cluster-cross-over pragmatic clinical trial in four academic-affiliated clinics, we compared captured immunization opportunities during patient visits when the reminder was "on" versus "off" for the primary immunization series, school-age boosters, and adolescents. We also assessed coverage of CMC-specific immunizations. Up-to-date immunization was measured by end of quarter. Rates were compared using chi square tests., Results: Overall, 15,343 unique patients were seen for 26,647 visits. The alert significantly impacted captured opportunities to complete the primary series in both well-child and acute care visits (57.6% on vs. 54.3% off, p  = 0.001, and 15.3% on vs. 10.1% off, p  = 0.02, respectively), among most age groups, and several immunization types. Captured opportunities for CMC-specific immunizations remained low regardless of alert status. The alert did not have an effect on up-to-date immunization overall (89.1 vs. 88.3%)., Conclusion: CDS in this population improved captured immunization opportunities. Baseline high rates may have blunted an up-to-date population effect. Converting Centers for Disease Control and Prevention (CDC) rules to generate sufficiently sensitive and specific alerts for CMC-specific immunizations proved challenging, and the alert did not have an impact on CMC-specific immunizations, potentially highlighting need for more work in this area., Competing Interests: A.M.H. received support from the Pfizer Medical Education Group for an unrelated investigator-initiated study; M.S.S. was a coinvestigator but received no financial support. Other authors have no conflicts of interest to disclose., (Thieme. All rights reserved.)

Naltrexone/bupropion (NB) is a US Food and Drug Administration-approved antiobesity medication. Clinical trials have shown variable weight loss, with responders and non-responders. NB is believed to act on central dopaminergic pathways to suppress appetite. The Taq1A polymorphism near DRD2 (rs1800497) is associated with the density of striatal dopamine D2 receptors, with individuals carrying the A allele (AA or AG; termed A1+) having 30%-40% fewer dopamine binding sites than those who do not carry the A allele (GG; termed A1-). We performed a pilot study to assess the association of the rs1800497 ANKK1 c.2137G > A (p.Glu713Lys) variant with weight loss with NB treatment in 33 subjects. Mean (SD) weight loss was 5.9% (3.2%) for the A1+ genotype group (n = 15) and 4.2% (4.2%) for the A1- genotype group (n = 18). The mean weight loss for the A1+ genotype group was significantly greater than the predefined clinically significant 4% weight-loss target (one-sample t-test, P = .035), whereas the mean weight loss for the A1- genotype group was not (P = .85). Individuals with the A1+ genotype appear to respond better to NB than A1- individuals., (© 2020 John Wiley & Sons Ltd.)

Background: In 1996 and in 2006, Palestine initiated salt iodization and multiple micronutrient fortification of wheat flour, respectively as a strategy to prevent deficiencies of these nutrients. In 2009, we assessed the impact of these interventions on the health and nutritional status of schoolchildren residing in the West Bank., Methods: We surveyed a sample of 22 schools run by the UN Relief and Works Agency for Palestine Refugees in the Near East (UNRWA) and the Palestinian Government. We randomly selected students from the first (mean age 6.7 years [SD 0.5]), sixth (11.8 years [0.6]), and ninth grades (14.8 years [0.6]). Data were obtained from 1484 (99%) of 1500 students planned for enrollment., Results: Our results suggest that iodine intake appears adequate and there was essentially no iodine deficiency. As to the status of other micronutrients, the main nutritional micronutrient risks for schoolchildren in the West Bank continue to be low serum levels of iron, zinc, and vitamin B-12; folate levels were seemingly high. The overall prevalence of anemia was 9.6%, but there were pockets of anemia in certain districts. Almost 42% of the anemia in our sample was explained by iron deficiency. There were significant differences in iron deficiency between girls and boys, 29.5% vs. 15.7%, respectively ( p  = 0.0001). There were no cases of lead toxicity in the studied sample., Conclusions: Wheat flour and salt fortification has had a major influence on improving the micronutrient status of Palestinian children, for some but not all micronutrients. The recommended key blood and biochemical parameters to be incorporated in the surveillance system are iron, zinc, and vitamin B12., Competing Interests: Competing interestsThe authors declare that they have no competing interests., (© The Author(s) 2020.)

Changing weather conditions have heightened the risk of growth of mycotoxigenic molds on crops and various agricultural commodities. Mycotoxins, which are linked to carcinogenic and nephrotoxic effects in animals and humans, have been traditionally analyzed by immunoassays, gas, and LC techniques with spectrophotometric detectors. This review discusses the current techniques and challenges in commercial settings associated with the analysis of mycotoxins in unique matrices such as animal feeds, herbal products, and dietary supplements containing botanicals. Because of the advantages and growing acceptance of LC-tandem MS (MS/MS) over traditional approaches, discussion is mainly based on LC-MS/MS-based approaches. Considering the impact of sample preparation on accuracy of quantitative results, discussion about pros and cons of recently introduced sample preparation techniques is integrated with analytical methods. A section of the review explains the importance and availability of reference materials for mycotoxins. The present discussion provides good insight into the current challenges and developments during mycotoxin analysis of feed and botanicals and addresses the need for researchers in terms of an official MS-based method.

Objective- Apo (apolipoprotein) CIII inhibits lipoprotein lipase (LpL)-mediated lipolysis of VLDL (very-low-density lipoprotein) triglyceride (TG) and decreases hepatic uptake of VLDL remnants. The discovery that 5% of Lancaster Old Order Amish are heterozygous for the APOC3 R19X null mutation provided the opportunity to determine the effects of a naturally occurring reduction in apo CIII levels on the metabolism of atherogenic containing lipoproteins. Approach and Results- We conducted stable isotope studies of VLDL-TG and apoB100 in 5 individuals heterozygous for the null mutation APOC3 R19X (CT) and their unaffected (CC) siblings. Fractional clearance rates and production rates of VLDL-TG and apoB100 in VLDL, IDL (intermediate-density lipoprotein), LDL, apo CIII, and apo CII were determined. Affected (CT) individuals had 49% reduction in plasma apo CIII levels compared with CCs ( P<0.01) and reduced plasma levels of TG (35%, P<0.02), VLDL-TG (45%, P<0.02), and VLDL-apoB100 (36%, P<0.05). These changes were because of higher fractional clearance rates of VLDL-TG and VLDL-apoB100 with no differences in production rates. CTs had higher rates of the conversion of VLDL remnants to LDL compared with CCs. In contrast, rates of direct removal of VLDL remnants did not differ between the groups. As a result, the flux of apoB100 from VLDL to LDL was not reduced, and the plasma levels of LDL-cholesterol and LDL-apoB100 were not lower in the CT group. Apo CIII production rate was lower in CTs compared with CCs, whereas apo CII production rate was not different between the 2 groups. The fractional clearance rates of both apo CIII and apo CII were higher in CTs than CCs. Conclusions- These studies demonstrate that 50% reductions in plasma apo CIII, in otherwise healthy subjects, results in a significantly higher rate of conversion of VLDL to LDL, with little effect on direct hepatic uptake of VLDL. When put in the context of studies demonstrating significant protection from cardiovascular events in individuals with loss of function variants in the APOC3 gene, our results provide strong evidence that therapies which increase the efficiency of conversion of VLDL to LDL, thereby reducing remnant concentrations, should reduce the risk of cardiovascular disease.

Elevated lipoprotein (a) [Lp(a)] levels increase the risk for CVD. Novel treatments that decrease LDL cholesterol (LDL-C) have also shown promise for reducing Lp(a) levels. Mipomersen, an antisense oligonucleotide that inhibits apoB synthesis, is approved for the treatment of homozygous familial hypercholesterolemia. It decreases plasma levels of LDL-C by 25% to 39% and lowers levels of Lp(a) by 21% to 39%. We examined the mechanisms for Lp(a) lowering during mipomersen treatment. We enrolled 14 healthy volunteers who received weekly placebo injections for 3 weeks followed by weekly injections of mipomersen for 7 weeks. Stable isotope kinetic studies were performed using deuterated leucine at the end of the placebo and mipomersen treatment periods. The fractional catabolic rate (FCR) of Lp(a) was determined from the enrichment of a leucine-containing peptide specific to apo(a) by LC/MS. The production rate (PR) of Lp(a) was calculated from the product of Lp(a) FCR and Lp(a) concentration (converted to pool size). In a diverse population, mipomersen reduced plasma Lp(a) levels by 21%. In the overall study group, mipomersen treatment resulted in a 27% increase in the FCR of Lp(a) with no significant change in PR. However, there was heterogeneity in the response to mipomersen therapy, and changes in both FCRs and PRs affected the degree of change in Lp(a) concentrations. Mipomersen treatment decreases Lp(a) plasma levels mainly by increasing the FCR of Lp(a), although changes in Lp(a) PR were significant predictors of reductions in Lp(a) levels in some subjects., (Copyright © 2018 by the American Society for Biochemistry and Molecular Biology, Inc.)

Objective: Lp(a) [lipoprotein (a)] is composed of apoB (apolipoprotein B) and apo(a) [apolipoprotein (a)] and is an independent risk factor for cardiovascular disease and aortic stenosis. In clinical trials, anacetrapib, a CETP (cholesteryl ester transfer protein) inhibitor, causes significant reductions in plasma Lp(a) levels. We conducted an exploratory study to examine the mechanism for Lp(a) lowering by anacetrapib., Approach and Results: We enrolled 39 participants in a fixed-sequence, double-blind study of the effects of anacetrapib on the metabolism of apoB and high-density lipoproteins. Twenty-nine patients were randomized to atorvastatin 20 mg/d, plus placebo for 4 weeks, and then atorvastatin plus anacetrapib (100 mg/d) for 8 weeks. The other 10 subjects were randomized to double placebo for 4 weeks followed by placebo plus anacetrapib for 8 weeks. We examined the mechanisms of Lp(a) lowering in a subset of 12 subjects having both Lp(a) levels >20 nmol/L and more than a 15% reduction in Lp(a) by the end of anacetrapib treatment. We performed stable isotope kinetic studies using 2 H 3 -leucine at the end of each treatment to measure apo(a) fractional catabolic rate and production rate. Median baseline Lp(a) levels were 21.5 nmol/L (interquartile range, 9.9-108.1 nmol/L) in the complete cohort (39 subjects) and 52.9 nmol/L (interquartile range, 38.4-121.3 nmol/L) in the subset selected for kinetic studies. Anacetrapib treatment lowered Lp(a) by 34.1% ( P ≤0.001) and 39.6% in the complete and subset cohort, respectively. The decreases in Lp(a) levels were because of a 41% reduction in the apo(a) production rate, with no effects on apo(a) fractional catabolic rate., Conclusions: Anacetrapib reduces Lp(a) levels by decreasing its production., Clinical Trial Registration: URL: http://www.clinicaltrials.gov. Unique identifier: NCT00990808., (© 2017 The Authors.)

Cholesteryl ester transfer protein (CETP) mediates the transfer of HDL cholesteryl esters for triglyceride (TG) in VLDL/LDL. CETP inhibition, with anacetrapib, increases HDL-cholesterol, reduces LDL-cholesterol, and lowers TG levels. This study describes the mechanisms responsible for TG lowering by examining the kinetics of VLDL-TG, apoC-II, apoC-III, and apoE. Mildly hypercholesterolemic subjects were randomized to either placebo (N = 10) or atorvastatin 20 mg/qd (N = 29) for 4 weeks (period 1) followed by 8 weeks of anacetrapib, 100 mg/qd (period 2). Following each period, subjects underwent stable isotope metabolic studies to determine the fractional catabolic rates (FCRs) and production rates (PRs) of VLDL-TG and plasma apoC-II, apoC-III, and apoE. Anacetrapib reduced the VLDL-TG pool on a statin background due to an increased VLDL-TG FCR (29%; P = 0.002). Despite an increased VLDL-TG FCR following anacetrapib monotherapy (41%; P = 0.11), the VLDL-TG pool was unchanged due to an increase in the VLDL-TG PR (39%; P = 0.014). apoC-II, apoC-III, and apoE pool sizes increased following anacetrapib; however, the mechanisms responsible for these changes differed by treatment group. Anacetrapib increased the VLDL-TG FCR by enhancing the lipolytic potential of VLDL, which lowered the VLDL-TG pool on atorvastatin background. There was no change in the VLDL-TG pool in subjects treated with anacetrapib monotherapy due to an accompanying increase in the VLDL-TG PR., (Copyright © 2017 by the American Society for Biochemistry and Molecular Biology, Inc.)

Background: Alirocumab, a monoclonal antibody to proprotein convertase subtilisin/kexin type 9 (PCSK9), lowers plasma low-density lipoprotein (LDL) cholesterol and apolipoprotein B100 (apoB). Although studies in mice and cells have identified increased hepatic LDL receptors as the basis for LDL lowering by PCSK9 inhibitors, there have been no human studies characterizing the effects of PCSK9 inhibitors on lipoprotein metabolism. In particular, it is not known whether inhibition of PCSK9 has any effects on very low-density lipoprotein or intermediate-density lipoprotein (IDL) metabolism. Inhibition of PCSK9 also results in reductions of plasma lipoprotein (a) levels. The regulation of plasma Lp(a) levels, including the role of LDL receptors in the clearance of Lp(a), is poorly defined, and no mechanistic studies of the Lp(a) lowering by alirocumab in humans have been published to date., Methods: Eighteen (10 F, 8 mol/L) participants completed a placebo-controlled, 2-period study. They received 2 doses of placebo, 2 weeks apart, followed by 5 doses of 150 mg of alirocumab, 2 weeks apart. At the end of each period, fractional clearance rates (FCRs) and production rates (PRs) of apoB and apo(a) were determined. In 10 participants, postprandial triglycerides and apoB48 levels were measured., Results: Alirocumab reduced ultracentrifugally isolated LDL-C by 55.1%, LDL-apoB by 56.3%, and plasma Lp(a) by 18.7%. The fall in LDL-apoB was caused by an 80.4% increase in LDL-apoB FCR and a 23.9% reduction in LDL-apoB PR. The latter was due to a 46.1% increase in IDL-apoB FCR coupled with a 27.2% decrease in conversion of IDL to LDL. The FCR of apo(a) tended to increase (24.6%) without any change in apo(a) PR. Alirocumab had no effects on FCRs or PRs of very low-density lipoproteins-apoB and very low-density lipoproteins triglycerides or on postprandial plasma triglycerides or apoB48 concentrations., Conclusions: Alirocumab decreased LDL-C and LDL-apoB by increasing IDL- and LDL-apoB FCRs and decreasing LDL-apoB PR. These results are consistent with increases in LDL receptors available to clear IDL and LDL from blood during PCSK9 inhibition. The increase in apo(a) FCR during alirocumab treatment suggests that increased LDL receptors may also play a role in the reduction of plasma Lp(a)., Clinical Trial Registration: URL: http://www.clinicaltrials.gov. Unique identifier: NCT01959971., Competing Interests: Disclosures Gissette Reyes-Soffer: Research Support (Sanofi; Merck Inc.) Consultant (Merck) Marianna Pavlyha, Colleen Ngai, Tiffany Thomas, Stephen Holleran, Rajasekhar Ramakrishnan, Wahida Karmally, Renu Nandakumar, Nelson Fontanez, Joseph Obunike, Santica M. Marcovina, Alice Lichtenstein, Nirupa Rachel Matthan: None James Matta, Frederic Becue, Franck Poitiers, Brian Swanson, Lisa Cowan, Howard K. Surks: Employment (Sanofi) Magali Maroccia: Employment (contractor to Sanofi) William J. Sasiela: Employment (Regeneron Pharmaceuticals, Inc.) Henry N. Ginsberg: Research Support (Merck; Sanofi and Regeneron; Amgen), Consultant/Advisory Board (Amgen; AstraZeneca; Bristol Myers Squibb; GlaxoSmithKline; Ionis; Janssen; Kowa; Merck; Novartis; Sanofi; Regeneron; Pfizer; Resverlogix)., (© 2016 The Authors.)

Introduction: The human papillomavirus (HPV) vaccine was introduced for female adolescents prior to male adolescents. Understanding coverage patterns related to gender-specific recommendations and factors associated with early adoption and timely completion may be important for future vaccines., Methods: Retrospective analysis of HPV vaccine initiation (one or more dose) and completion (three or more doses) patterns in adolescents aged 11-18 years using 2009-2013 New York Citywide Immunization Registry data. Log binomial models assessed patient-specific (age, insurance) and practice-specific (facility type, number of adolescents, poverty level) variables on early adoption (within 1 year of recommendation) and timely completion (within 12 months) by gender., Results: Of 1,494,767 adolescents, 50.2% were male, 57.5% were vaccinated in private practices, 58.7% in practices with more adolescents, and 48.8% in highest poverty locations. More female (54.0%) than male (33.5%) adolescents initiated vaccination (p<0.001). Of those, 56.1% received three or more doses, 34.1% within 12 months (30.0% male, 36.8% female, p<0.001). In 2009-2012, the proportion of still-eligible male adolescents who newly initiated increased from 0.1% to 17.0%; rates for female adolescents increased from 15.4% to 17.3%. Vaccination initiation within 1 year of gender-specific recommendations was similar (27.4% female, 27.3% male). For both genders, the uninsured were less likely to have early adoption and timely completion. Being publicly insured was associated with early adoption in both genders, but with timely completion in male adolescents only. Being seen in a public facility and in a practice with more adolescents was also associated with early adoption., Conclusions: Changing HPV vaccine recommendations had minimal cross-gender impact. Early adoption and timely completion patterns were mostly similar across genders., (Copyright © 2016 American Journal of Preventive Medicine. Published by Elsevier Inc. All rights reserved.)

Objective: To assess the impact of exchange of immunization information between an immunization information system (IIS) and an electronic health record on up-to-date rates, overimmunization, and immunization record completeness for low-income, urban children and adolescents., Methods: The New York City Department of Health maintains a population-based IIS, the Citywide Immunization Registry (CIR). Five community clinics in New York City implemented direct linkage of immunization data from the CIR to their local electronic health record. We compared immunization status and overimmunization in children and adolescents 19 to 35 month, 7 to 10 year, and 13 to 17 year-olds with provider visits in the 6-month period before data exchange implementation (2009; n = 6452) versus 6-months post-implementation (2010; n = 6124). We also assessed immunization record completeness with and without addition of CIR data for 8548 children and adolescents with visits in 2012-2013., Results: Up-to-date status increased from before to after implementation from 75.0% to 81.6% (absolute difference, 6.6%; 95% confidence interval [CI], 5.2% to 8.1%) and was significant for all age groups. The percentage overimmunized decreased from 8.8% to 4.7% (absolute difference, -4.1%; 95% CI, -7.8% to -0.3%) and was significant for adolescents (16.4% vs 1.2%; absolute difference, -15.2%; 95% CI, -26.7 to -3.6). Up-to-date status for those seen in 2012 to 2013 was higher when IIS data were added (74.6% vs 59.5%)., Conclusions: This study demonstrates that data exchange can improve child and adolescent immunization status. Development of the technology to support such exchange and continued focus on local, state, and federal policies to support such exchanges are needed., (Copyright © 2016 by the American Academy of Pediatrics.)

Background: The coexistence of underweight and overweight (double burden) remains a major problem in many developing countries. Little is known about the factors associated with the double burden of malnutrition in Palestinian children., Objective: To assess factors associated with undernutrition and overnutrition in 1500 schoolchildren aged 5 to 16 years, in the West Bank., Methods: We surveyed a sample of 22 schools run by the United Nations Relief and Works Agency for Palestine Refugees in the Near East (UNRWA) and the Palestinian government. Binary logistic regression was used to examine the factors associated with malnutrition. The hunger index, a composite score from 8 questions, was used to measure food insecurity., Results: In the 1484 children enrolled in UNRWA and government schools in the West Bank, the prevalence of stunting was 7% and underweight 3%. Around 12% of students were overweight and 6% obese. The hunger index was negatively associated with height for age. Factors associated with being underweight were male sex, mother being unemployed, and households not having enough food to eat for at least 2 days in the previous month. Factors associated with obesity were older age and time spent watching television. When overweight and obesity were combined in the analysis, they were inversely associated with increasing number of days spent playing sports., Conclusion: Our results show that the important nutritional risks for school-age children in the West Bank would seem to be the simultaneous occurrence of undernutrition and obesity. The study highlights the need to balance obesity management and prevention with interventions to tackle undernutrition., (© The Author(s) 2016.)

Objective: Anacetrapib (ANA), an inhibitor of cholesteryl ester transfer protein (CETP) activity, increases plasma concentrations of high-density lipoprotein cholesterol (HDL-C), apolipoprotein A-I (apoA)-I, apoA-II, and CETP. The mechanisms responsible for these treatment-related increases in apolipoproteins and plasma CETP are unknown. We performed a randomized, placebo (PBO)-controlled, double-blind, fixed-sequence study to examine the effects of ANA on the metabolism of HDL apoA-I and apoA-II and plasma CETP., Approach and Results: Twenty-nine participants received atorvastatin (ATV) 20 mg/d plus PBO for 4 weeks, followed by ATV plus ANA 100 mg/d for 8 weeks (ATV-ANA). Ten participants received double PBO for 4 weeks followed by PBO plus ANA for 8 weeks (PBO-ANA). At the end of each treatment, we examined the kinetics of HDL apoA-I, HDL apoA-II, and plasma CETP after D3-leucine administration as well as 2D gel analysis of HDL subspecies. In the combined ATV-ANA and PBO-ANA groups, ANA treatment increased plasma HDL-C (63.0%; P<0.001) and apoA-I levels (29.5%; P<0.001). These increases were associated with reductions in HDL apoA-I fractional clearance rate (18.2%; P=0.002) without changes in production rate. Although the apoA-II levels increased by 12.6% (P<0.001), we could not discern significant changes in either apoA-II fractional clearance rate or production rate. CETP levels increased 102% (P<0.001) on ANA because of a significant reduction in the fractional clearance rate of CETP (57.6%, P<0.001) with no change in CETP production rate., Conclusions: ANA treatment increases HDL apoA-I and CETP levels by decreasing the fractional clearance rate of each protein., (© 2016 American Heart Association, Inc.)

Mipomersen is a 20mer antisense oligonucleotide (ASO) that inhibits apolipoprotein B (apoB) synthesis; its low-density lipoprotein (LDL)-lowering effects should therefore result from reduced secretion of very-low-density lipoprotein (VLDL). We enrolled 17 healthy volunteers who received placebo injections weekly for 3 weeks followed by mipomersen weekly for 7 to 9 weeks. Stable isotopes were used after each treatment to determine fractional catabolic rates and production rates of apoB in VLDL, IDL (intermediate-density lipoprotein), and LDL, and of triglycerides in VLDL. Mipomersen significantly reduced apoB in VLDL, IDL, and LDL, which was associated with increases in fractional catabolic rates of VLDL and LDL apoB and reductions in production rates of IDL and LDL apoB. Unexpectedly, the production rates of VLDL apoB and VLDL triglycerides were unaffected. Small interfering RNA-mediated knockdown of apoB expression in human liver cells demonstrated preservation of apoB secretion across a range of apoB synthesis. Titrated ASO knockdown of apoB mRNA in chow-fed mice preserved both apoB and triglyceride secretion. In contrast, titrated ASO knockdown of apoB mRNA in high-fat-fed mice resulted in stepwise reductions in both apoB and triglyceride secretion. Mipomersen lowered all apoB lipoproteins without reducing the production rate of either VLDL apoB or triglyceride. Our human data are consistent with long-standing models of posttranscriptional and posttranslational regulation of apoB secretion and are supported by in vitro and in vivo experiments. Targeting apoB synthesis may lower levels of apoB lipoproteins without necessarily reducing VLDL secretion, thereby lowering the risk of steatosis associated with this therapeutic strategy., (Copyright © 2016, American Association for the Advancement of Science.)

Background: Individuals treated with the cholesteryl ester transfer protein (CETP) inhibitor anacetrapib exhibit a reduction in both LDL cholesterol and apolipoprotein B (ApoB) in response to monotherapy or combination therapy with a statin. It is not clear how anacetrapib exerts these effects; therefore, the goal of this study was to determine the kinetic mechanism responsible for the reduction in LDL and ApoB in response to anacetrapib., Methods: We performed a trial of the effects of anacetrapib on ApoB kinetics. Mildly hypercholesterolemic subjects were randomized to background treatment of either placebo (n = 10) or 20 mg atorvastatin (ATV) (n = 29) for 4 weeks. All subjects then added 100 mg anacetrapib to background treatment for 8 weeks. Following each study period, subjects underwent a metabolic study to determine the LDL-ApoB-100 and proprotein convertase subtilisin/kexin type 9 (PCSK9) production rate (PR) and fractional catabolic rate (FCR)., Results: Anacetrapib markedly reduced the LDL-ApoB-100 pool size (PS) in both the placebo and ATV groups. These changes in PS resulted from substantial increases in LDL-ApoB-100 FCRs in both groups. Anacetrapib had no effect on LDL-ApoB-100 PRs in either treatment group. Moreover, there were no changes in the PCSK9 PS, FCR, or PR in either group. Anacetrapib treatment was associated with considerable increases in the LDL triglyceride/cholesterol ratio and LDL size by NMR., Conclusion: These data indicate that anacetrapib, given alone or in combination with a statin, reduces LDL-ApoB-100 levels by increasing the rate of ApoB-100 fractional clearance., Trial Registration: ClinicalTrials.gov NCT00990808., Funding: Merck & Co. Inc., Kenilworth, New Jersey, USA. Additional support for instrumentation was obtained from the National Center for Advancing Translational Sciences (UL1TR000003 and UL1TR000040).

Background: Influenza vaccination coverage is low, especially among low-income populations. Most doses are generally administered early in the influenza season, yet sustained vaccination efforts are crucial for achieving optimal coverage. The impact of text message influenza vaccination reminders was recently demonstrated in a low-income population. Little is known about their effect on children with delayed influenza vaccination or the most effective message type., Purpose: To determine the impact of educational plus interactive text message reminders on influenza vaccination of urban low-income children unvaccinated by late fall., Design: Randomized controlled trial., Setting/participants: Parents of 5,462 children aged 6 months-17 years from four academically affiliated pediatric clinics who were unvaccinated by mid-November 2011., Intervention: Eligible parents were stratified by their child's age and pediatric clinic site and randomized using a 1:1:1 allocation to educational plus interactive text message reminders, educational-only text message reminders, or usual care. Using an immunization registry-linked text messaging system, parents of intervention children received up to seven weekly text message reminders. One of the messages sent to parents in the educational plus interactive text message arm allowed selection of more information about influenza and influenza vaccination., Main Outcome Measures: Influenza vaccination by March 31, 2012. Data were collected and analyzed between 2012 and 2014., Results: Most children were publicly insured and Spanish speaking. Baseline demographics were similar between groups. More children of parents in the educational plus interactive text message arm were vaccinated (38.5%) versus those in the educational-only text message (35.3%; difference=3.3%, 95% CI=0.02%, 6.5%; relative risk ratio (RRR)=1.09, 95% CI=1.002, 1.19) and usual care (34.8%; difference=3.8%, 95% CI=0.6%, 7.0%; RRR=1.11, 95% CI=1.02-1.21) arms., Conclusions: Text message reminders with embedded educational information and options for interactivity have a small positive effect on influenza vaccination of urban, low-income, minority children who remain unvaccinated by late fall., (Copyright © 2015 American Journal of Preventive Medicine. Published by Elsevier Inc. All rights reserved.)

Objective: To determine the impact of a vaccination reminder in an electronic health record supplemented with data from an immunization information system (IIS)., Methods: A noninterruptive influenza vaccination reminder, based on a real-time query of hospital and city IIS, was used at 4 urban, academically affiliated clinics serving a low-income population. Using a randomized cluster-crossover design, each study site had "on" and "off" period during the fall and winter of 2011-2012. Influenza vaccination during a clinic visit was assessed for 6-month to 17-year-old patients. To assess sustainability, the reminder was active at all sites during the 2012-2013 season., Results: In the 2011-2012 season, 8481 unique non-up-to-date children had visits. Slightly more non-up-to-date children seen when the reminder was 'on' were vaccinated than when 'off' (76.2% vs 73.8%; P = .027). Effects were seen in the winter (67.9% vs 62.2%; P = .005), not fall (76.8% vs 76.5%). The reminder also increased documentation of the reason for vaccine non-administration (68.1% vs 41.5%; P < .0001). During the 2011-2012 season, the reminder displayed for 8630 unique visits, and clinicians interacted with it in 83.1% of cases where patients required vaccination. During the 2012-2013 season, it displayed for 22 248 unique visits; clinicians interacted with it in 84.8% of cases., Conclusions: An IIS-linked influenza vaccination reminder increased vaccination later in the winter when fewer vaccine doses are usually given. Although the reminder did not require clinicians to interact with it, they frequently did; utilization did not wane over time., (Copyright © 2015 by the American Academy of Pediatrics.)

Background: Hormonal status influences haemostatic factors including fibrinogen, factor VII and plasminogen activator inhibitor (PAI-1), and concentrations differ among men, premenopausal and postmenopausal women. This study examines how phases of the menstrual cycle influence variability of fibrinogen, factor VII and PAI-1., Design: We studied 103 subjects (39 premenopausal women, 18 postmenopausal women and 46 men) during three, randomized, 8-week energy- and nutrient-controlled experimental diets in the Dietary Effects on Lipids and Thrombogenic Activity (DELTA) Study. Fasting blood samples were collected weekly during the last 4 weeks of each diet period, and haemostatic factors were quantified. Two linear mixed-effects models were used for fibrinogen, factor VII and PAI-1: one to estimate and compare group-specific components of variance, and the other to estimate additional fixed effects representing cyclical functions of day of menstrual cycle in premenopausal women., Results: Systematic cyclical variation with day of menstrual cycle was observed for fibrinogen (P < 0.0001), factor VII (P = 0.0012) and PAI-1 (P = 0.0024) in premenopausal women. However, the amplitude of cycling was small relative to the total magnitude of intra-individual variability. In addition, the intra-individual variance and corresponding coefficient of variation observed in premenopausal women did not differ from postmenopausal women and men., Conclusions: The variability in haemostatic factors in premenopausal women is no greater than for postmenopausal women or men. Consequently, premenopausal women can be included in studies investigating haemostatic factor responses without controlling for stage of menstrual cycle., (© 2014 Stichting European Society for Clinical Investigation Journal Foundation.)

Objective: To examine whether periadolescent children demonstrate the significant racial/ethnic differences in body fatness relative to BMI and in the prevalence and relationship of body composition to risk factors for type 2 diabetes (T2DM) as in adults., Design and Methods: Family history of obesity and T2DM, anthropometry, insulin sensitivity and secretory capacity, lipids, and cytokines (IL-6, CRP, TNF-α, and adiponectin) were examined in a cohort of 994 middle school students (47% male, 53%, female; 12% African American, 14% East Asian, 13% South Asian, 9% Caucasian, 44% Hispanic, and 8% other)., Results: Fractional body fat content was significantly greater at any BMI among South Asians. There were racial/ethnic specific differences in lipid profiles, insulin secretory capacity, insulin sensitivity, and inflammatory markers corrected for body fatness that are similar to those seen in adults. Family history of T2DM was associated with lower insulin secretory capacity while family history of obesity was more associated with insulin resistance., Conclusions: Children show some of the same racial/ethnic differences in risk factors for adiposity-related comorbidities as adults. BMI and waist circumference cutoffs to identify children at-risk for adiposity-related comorbidities should be adjusted by racial/ethnic group as well as other variables such as birthweight and family history., (Copyright © 2013 The Obesity Society.)