Comparative Effectiveness of Umeclidinium/Vilanterol versus Indacaterol/Glycopyrronium on Moderate-to-Severe Exacerbations in Patients with Chronic Obstructive Pulmonary Disease in Clinical Practice in England.

Purpose: Chronic obstructive pulmonary disease (COPD) exacerbations are associated with significant morbidity and mortality and increased economic healthcare burden for patients with COPD. Long-acting muscarinic antagonist (LAMA)/long-acting ß2-agonist (LABA) dual therapy is recommended for patients receiving mono-bronchodilator therapy who experience exacerbations or ongoing breathlessness. This study compared two single-inhaler LAMA/LABA dual therapies, umeclidinium/vilanterol (UMEC/VI) and indacaterol/glycopyrronium (IND/GLY), on moderate-to-severe exacerbation rates in patients with COPD in England. Patients and Methods: This retrospective cohort study used linked primary care electronic health record data (Clinical Practice Research Datalink-Aurum) and secondary care data (Hospital Episode Statistics) to assess outcomes for patients with COPD who had a first prescription for single-inhaler UMEC/VI or IND/GLY (index date) between 1 January 2015 and 30 September 2019 (indexing period). Analyses compared UMEC/VI and IND/GLY on moderate-to-severe, moderate, and severe exacerbations, healthcare resource utilization (HCRU), and direct costs at 6, 12, 18, and 24 months, and time-to-first on-treatment exacerbation up to 24 months post-index date. Following inverse probability of treatment weighting (IPTW), non-inferiority and superiority of UMEC/VI versus IND/GLY were assessed. Results: In total, 12,031 patients were included, of whom 8753 (72.8%) were prescribed UMEC/VI and 3278 (27.2%) IND/GLY. After IPTW, for moderate-to-severe exacerbations, weighted rate ratios were <1 at 6, 12, and 18 months and equal to 1 at 24 months for UMEC/VI; around the null value for moderate exacerbations and <1 at all timepoints for severe exacerbations. UMEC/VI showed lower HCRU incidence rates than IND/GLY for all-cause Accident and Emergency visits and COPD-related inpatient stays and associated all-cause costs at 6 months post-indexing. Time-to-triple therapy was similar for both treatments. Conclusion: UMEC/VI demonstrated non-inferiority to IND/GLY in moderate-to-severe exacerbation reduction at 6, 12 and 18 months. These results support previous findings demonstrating similarity between UMEC/VI and IND/GLY on reduction of moderate-to-severe exacerbations.

Comparison of Rescue Medication Prescriptions in Patients with Chronic Obstructive Pulmonary Disease Receiving Umeclidinium/Vilanterol versus Tiotropium Bromide/Olodaterol in Routine Clinical Practice in England.

Purpose: Routinely collected healthcare data on the comparative effectiveness of the long-acting muscarinic antagonist/long-acting ß2-agonist combination umeclidinium/vilanterol (UMEC/VI) versus tiotropium bromide/olodaterol (TIO/OLO) for chronic obstructive pulmonary disease (COPD) is limited. This study compared rescue medication prescriptions in patients with COPD in England receiving UMEC/VI versus TIO/OLO. Patients and Methods: This retrospective cohort study used primary care data from the Clinical Practice Research Datalink Aurum database linked with secondary care administrative data from Hospital Episode Statistics. Patients with a COPD diagnosis at age ≥35 years were included (indexed) following initiation of single-inhaler UMEC/VI or TIO/OLO between July 1, 2015, and September 30, 2019. Outcomes included the number of rescue medication prescriptions at 12-months (primary), and at 6-, 18- and 24-months (secondary), adherence at 6-, 12-, 18- and 24-months post-index, defined as proportion of days covered ≥80% (secondary), and time-to-initiation of triple therapy (exploratory). Inverse probability of treatment weighting (IPTW) was used to balance potential confounding baseline characteristics. Superiority of UMEC/VI versus TIO/OLO for the primary outcome of rescue medication prescriptions was assessed using an intention-to-treat analysis with a p-value < 0.05. Results: In total, 8603 patients were eligible (UMEC/VI: n = 6536; TIO/OLO: n = 2067). Following IPTW, covariates were well balanced across groups. Patients initiating UMEC/VI had statistically significantly fewer (mean [standard deviation]; p-value) rescue medication prescriptions versus TIO/OLO in both the unweighted (4.84 [4.78] vs 5.68 [5.00]; p < 0.001) and weighted comparison (4.91 [4.81] vs 5.48 [5.02]; p = 0.0032) at 12 months; consistent results were seen at all timepoints. Adherence was numerically higher for TIO/OLO versus UMEC/VI at all timepoints. Time-to-triple therapy was similar between treatment groups. Conclusion: UMEC/VI was superior to TIO/OLO in reducing rescue medication prescriptions at 12 months after treatment initiation in a primary care cohort in England, potentially suggesting improvements in symptom control with UMEC/VI compared with TIO/OLO.

Comparative Effectiveness of Umeclidinium/Vilanterol versus Inhaled Corticosteroid/Long-Acting ß2-Agonist in Patients with Chronic Obstructive Pulmonary Disease in a Primary Care Setting in England.

Purpose: To compare adherence to once-daily umeclidinium/vilanterol (UMEC/VI), a long-acting muscarinic antagonist/long-acting ß2-agonist (LAMA/LABA), and twice-daily inhaled corticosteroids (ICS)/LABA single-inhaler dual therapy in patients with chronic obstructive pulmonary disease (COPD) in a primary care cohort in England. Patients and Methods: Active comparator, new-user, retrospective cohort study using CPRD-Aurum primary care data and linked Hospital Episode Statistics secondary care administrative data. Patients without exacerbations in the previous year were indexed on first/earliest prescription date of once-daily UMEC/VI or twice-daily ICS/LABA as initial maintenance therapy between July 2014-September 2019. Primary outcome: medication adherence at 12 months post-index, defined as proportion of days covered (PDC) ≥80%. PDC represented proportion of time over the treatment duration that the patient was theoretically in possession of the medication. Secondary outcomes: adherence at 6, 18, and 24 months post-index, time-to-triple therapy, time-to-first on-treatment COPD exacerbation, COPD-related and all-cause healthcare resource utilization (HCRU), and direct health-care costs. A propensity score was generated and inverse probability of treatment weighting (IPTW) was used to balance potential confounders. Superiority was defined as >0% difference between treatment groups. Results: In total, 6815 eligible patients were included (UMEC/VI:1623; ICS/LABA:5192). At 12 months post-index, weighted odds of a patient being adherent were significantly greater with UMEC/VI versus ICS/LABA (odds ratio [95% CI]: 1.71 [1.09, 2.66]; p=0.0185), demonstrating superiority of UMEC/VI. Patients taking UMEC/VI were statistically significantly more adherent than those taking ICS/LABA at 6, 18, and 24 months post-index (p<0.05). Differences in time-to-triple therapy, time-to-moderate COPD exacerbations, HCRU, and direct medical costs were not statistically significant between treatments after IPTW was applied. Conclusion: At 12 months post-treatment initiation, once-daily UMEC/VI was superior to twice-daily ICS/LABA in medication adherence among patients with COPD without exacerbations in the previous year, newly initiating dual maintenance therapy in England. The finding was consistent at 6, 18, and 24 months.

Improving Adolescent Violent Trauma Outcomes With a Hospital-Based Violence Prevention Initiative.

BACKGROUND: Violent trauma results in significant morbidity/mortality in Black/Hispanic males aged 15 to 24 years. Hospital- and community-level interventions may improve patient and community outcomes. OBJECTIVE: To determine if a hospital-based violence prevention intervention using community outreach workers was associated with improved violent trauma patient postdischarge follow-up and reinjury rates. METHODS: This is a retrospective, single-center, cohort study of admitted violent trauma patients to a public hospital in the Bronx, NY. Data were collected from a convenience sample of patients aged 15 to 24 years admitted with International Classification of Diseases, 10th Revision, codes for gunshot wound, stab wound, or physical assault from August 2014 to April 2018. The exposure variable was documentation of intervention team evaluation during admission. The outcome variables included attending >50% scheduled postdischarge follow-up visits, and subsequent violent reinjury (gunshot wound, stab wound, blunt assault) during the study time period. Multivariable regression models were used to determine the association between the exposure and outcome variables. RESULTS: A total of 535 patients were evaluated and were primarily male (92.5%), Black (54%)/Latino (36.4%), with mean age of 19.1 years. Patients in the exposure group had increased odds of attending >50% of scheduled clinic postdischarge follow-up visits (odds ratio, 2.29; 95% confidence interval 1.59-3.29) and decreased odds of subsequent violent reinjury presentation (odds ratio, 0.41; 95% confidence interval 0.22-0.75) 3 months after hospital discharge. CONCLUSION: A hospital-based violence prevention intervention may be associated with decreased odds of violent reinjury and increased odds of postdischarge scheduled appointment adherence in admitted pediatric violent trauma patients.

Associations of IVF singleton birthweight and gestation with clinical treatment and laboratory factors: a multicentre cohort study.

STUDY QUESTION: Do IVF treatment and laboratory factors affect singleton birthweight (BW)? SUMMARY ANSWER: BWs of IVF-conceived singleton babies are increasing with time, but we cannot identify the specific treatment factors responsible. WHAT IS KNOWN ALREADY: IVF-conceived singleton babies from fresh transfers have slightly lower BW than those conceived naturally, whilst those from frozen embryo transfer (FET) cycles are heavier and comparable to naturally conceived offspring. Our recent studies have shown that BW varies significantly between different IVF centres, and in a single centre, is also increasing with time, without a corresponding change in BWs of naturally conceived infants. Although it is likely that factors in the IVF treatment cycle, such as hormonal stimulation or embryo laboratory culture conditions, are associated with BW differences, our previous study designs were not able to confirm this. STUDY DESIGN, SIZE, DURATION: Data relating to BW outcomes, IVF treatment and laboratory parameters were collated from pre-existing electronic records in five participating centres for all singleton babies conceived between August 2007 and December 2014. PARTICIPANTS/MATERIALS, SETTING, METHODS: Seven thousand, five hundred and eighty-eight births, 6207 from fresh and 1381 from FET. Infants with severe congenital abnormalities were excluded. The primary outcome of gestation-adjusted BW and secondary outcomes of unadjusted BW and gestation were analysed using multivariable regression models with robust standard errors to allow for the correlation between infants with the same mother. The models tested treatment factors allowing for confounding by centre, time and patient characteristics. A similar matched analysis of a subgroup of 379 sibling pairs was also performed. MAIN RESULTS AND THE ROLE OF CHANCE: No significant associations of birth outcomes with IVF embryo culture parameters were seen independent of clinic or time, including embryo culture medium, incubator type or oxygen level, although small differences cannot be ruled out. We did not detect any significant differences associated with hormonal stimulation in fresh cycles or hormonal synchronization in FET cycles. Gestation-adjusted BW increased by 13.4 (95% CI 0.6-26.1) g per year over the period of the study, and babies born following FET were 92 (95% CI 57-128) g heavier on average than those from the fresh transfer. LIMITATIONS, REASONS FOR CAUTION: Although no specific relationships have been identified independent of clinic and time, the confidence intervals remain large and do not exclude clinically relevant effect sizes. As this is an observational study, residual confounding may still be present. WIDER IMPLICATIONS OF THE FINDINGS: This study demonstrates the potential for large scale analysis of routine data to address critical questions concerning the long-term implications of IVF treatment, in accordance with the Developmental Origins of Health and Disease hypothesis. However, much larger studies, at a national scale with sufficiently detailed data, are required to identify the treatment parameters associated with differences in BW or other relevant outcomes. STUDY FUNDING/COMPETING INTEREST(S): This work was supported by the EU FP7 project grant, EpiHealthNet (FP7-PEOPLE-2012-ITN-317146). No competing interests were identified. TRIAL REGISTRATION NUMBER: N/A.

The impact of selected embryo culture conditions on ART treatment cycle outcomes: a UK national study.

STUDY QUESTION: Are selected embryo culture conditions namely media, oxygen level, and incubator type, associated with IVF live birth rate (LBR) and the health of singleton offspring at birth? SUMMARY ANSWER: There were statistically significant differences in LBR between the eight culture media systems analysed; however, none of the embryo culture factors showed statistically significant associations with birth weight (BW) in multivariable regression analyses. WHAT IS KNOWN ALREADY: In clinical ART culture media is the initial environment provided for the growth of human embryos. Pre-implantation development is a critical period of developmental plasticity, which could have long-lasting effects on offspring growth and health. Although some studies have shown an impact of culture medium type on BW, the interaction between culture medium type and associated culture conditions on both treatment success rates (LBR) and offspring BW is largely unexplored. This study aimed to examine these factors in a large multicentre national survey capturing the range of clinical practice. STUDY DESIGN SIZE DURATION: In this cross-sectional study, data from a survey circulated to all UK IVF clinics requesting information regarding culture medium type, incubator type, and oxygen level used in ART between January 2011 and December 2013 were merged with routinely recorded treatment and outcome data held in the Human Fertilisation and Embryology Authority Register up to the end of 2014. PARTICIPANTS/MATERIALS SETTING METHODS: Forty-six (62%) UK clinics responded to the survey. A total of 75 287 fresh IVF/ICSI cycles were captured, including 18 693 singleton live births. IVF success (live birth, singleton or multiple; LB), singleton gestation and singleton gestation-adjusted BW were analysed using logistic and linear regression models adjusting for patient/treatment characteristics and clinic-specific effects. MAIN RESULTS AND THE ROLE OF CHANCE: Culture medium type was shown to have some impact on LBR (multivariable logistic regression, (MRL); post-regression Wald test, P < 0.001), but not on BW (MLR; post-regression Wald test, P = 0.215). However, blastocyst culture had the largest observed effect on odds of LBR (odds ratio (OR) = 1.35, CI: 1.29-1.42), increased the risk of pre-term birth even when controlling for oxygen tension (MLR; OR = 1.42, CI: 1.23-1.63), and gestation-adjusted BW (MLR, ß = 38.97 g, CI: 19.42-58.53 g) when compared to cleavage-stage embryo culture. We noted a very strong effect of clinic site on both LBR and BW, thus confounding between treatment practices and clinic site may have masked the effect of culture conditions. LIMITATIONS REASONS FOR CAUTION: Larger datasets with more inter-centre variation are also needed, with key embryo culture variables comprehensively recorded in national treatment registries. WIDER IMPLICATIONS OF THE FINDINGS: This study is the largest investigation of laboratory environmental effects in IVF on both LBR and singleton BW. Our findings largely agree with the literature, which has failed to show a consistent advantage of one culture media type over another. However, we noted some association of LBR with medium type, and the duration of embryo exposure to laboratory conditions (blastocyst culture) was associated with both LBR and singleton health at birth. Because of the strong effect of clinic site noted, further randomized controlled trials are needed in order to reliably determine the effect of embryo culture on IVF success rates and the growth and health of subsequent offspring. STUDY FUNDING/COMPETING INTERESTS: This study was funded by the EU FP7 project grant EpiHealthNet (FP7-PEOPLE-2012-ITN -317 146). The authors have no competing interests to declare.

Polifarmacia en adulto mayor, impacto en su calidad de vida: revision de literatura / Polypharmacy in older adults and impact on their quality of life: literature review / Polifarmácia em idosos, impacto em sua qualidade de vida: revisão da literatura

RESUMEN: Objetivo: Conocer mediante el análisis del estado del conocimiento, el impacto de polifarmacia en calidad de vida de adultos mayores y cuál ha sido el rol de enfermería frente a esta problemática de salud. Métodos: Revisión descriptiva de 62 artículos originales de diversos diseños metodológicos, en bases de datos: EBSCO, PubMed, Web of Science, SciELO, Elsevier, SCOPUS y Dialnet. Resultados: La polifarmacia en adultos mayores se presenta con mayor frecuencia en el sexo femenino, en personas con bajo nivel de escolaridad, sumados a factores socioeconómico. Un gran porcentaje de adultos mayores presenta efecto cascada en consumo de fármacos, por cantidad de medicamentos consumidos y número de médicos consultados, produciendo interacciones farmacológicas, afectando funcionalidad y calidad de vida. Conclusiones: Es necesario mayor control de medicamentos consumidos por adultos mayores, para evitar efectos nocivos. Los profesionales de enfermería deben tener un rol educativo en este grupo etario, para disminuir polifarmacia e impulsar estilos de vida que fomenten el envejecimiento saludable.(AU)

ABSTRACT: Objective: To know, by analyzing the state of knowledge, the impact of the polypharmacy on the quality of life of older adults and the role of nursing when dealing with this health problem. Materials and Methods: Descriptive review of 62 original articles with multiple methodological designs, in the databases EBSCO, PubMed, Web of Science, SciELO, Elsevier, SCOPUS and Dialnet. Results: Polypharmacy in older adults is more frequent in the female sex and people with low level of education, and is associated with socioeconomic factors. A large percentage of older adults present with prescription cascade due to the amount of drugs consumed and the number of doctors consulted, leading to pharmacological interactions that affect functionality and quality of life. Conclusions: More control of drugs consumed by older adults is needed to avoid harmful effects. Nursing professionals should have an educational role in this age group to reduce polypharmacy and promote lifestyles that foster healthy ageing.(AU)

RESUMO: Objetivo: Conhecer, através da análise do estado do conhecimento, o impacto da polifarmácia na qualidade de vida do idoso e qual o papel da enfermagem diante desse problema de saúde. Métodos: Revisão descritiva de 62 artigos originais de vários desenhos metodológicos, nas bases de dados: EBSCO, PubMed, Web of Science, SciELO, Elsevier, SCOPUS e Dialnet. Resultados: A polifarmácia em idosos ocorre mais frequentemente no sexo feminino, em pessoas com baixa escolaridade, somada a fatores socioeconômicos. Uma grande porcentagem de idosos apresenta efeito cascata no consumo de medicamentos, pela quantidade de medicamentos consumidos e número de médicos consultados, produzindo interações farmacológicas, afetando a funcionalidade e a qualidade de vida. Conclusões: É necessário um maior controle dos medicamentos consumidos por idosos para evitar efeitos nocivos. Os profissionais de enfermagem devem ter papel educativo nessa faixa etária, para diminuir a polifarmácia e promover estilos de vida que promovam o envelhecimento saudável.(AU)

The impact of IVF on birthweight from 1991 to 2015: a cross-sectional study.

STUDY QUESTION: Has birthweight (BW) changed over time among IVF-conceived singletons? SUMMARY ANSWER: Singleton BW has increased markedly over the past 25 years. WHAT IS KNOWN ALREADY: IVF conceived singletons have had a higher incidence of low BW compared to spontaneously conceived singletons, and this has raised concerns over long-term increased risks of cardio-metabolic disease. However, few causal links between IVF procedures and BW have been robustly established, and few studies have examined whether BW has changed over time as IVF techniques have developed. STUDY DESIGN, SIZE, DURATION: A total of 2780 live born singletons conceived via IVF or ICSI treated in the reproductive medicine department of a single publicly funded tertiary care centre between 1991 and 2015 were included in this retrospective study. The primary outcome measure was singleton BW adjusted for gestational age, maternal parity and child gender. Multivariable linear regression models were used to estimate the associations between patient prognostic factors and IVF treatment procedures with adjusted BW. PARTICIPANTS/MATERIALS, SETTING, METHODS: All singletons conceived at the centre following IVF/ICSI using the mother's own oocytes, and non-donated fresh or frozen/thawed embryos with complete electronic data records, were investigated. Available electronic records were retrieved from the Human Fertilization and Embryology Authority for dataset collation. Multiple linear regression analysis was used to evaluate associations between IVF treatment parameters and BW, after adjusting for the year of treatment and patient characteristics and pregnancy factors. MAIN RESULTS AND THE ROLE OF CHANCE: In the primary multivariable model, singleton BW increased by 7.4 g per year (95% CI: 3.2-11.6 g, P = 0.001), an increase of close to 180 g throughout the 25-year period after accounting for gestational age, maternal parity, child gender, IVF treatment parameters, patient prognostic characteristics and pregnancy factors. Fresh and frozen embryo transfer-conceived singletons showed a similar increase in BW. Frozen/thawed embryo transfer conceived singletons were on average 53 g heavier than their fresh embryo conceived counterparts (95% CI: 3.7-103.3 g, P = 0.035). LIMITATIONS, REASONS FOR CAUTION: The independent variables included in the study were limited to those that have been consistently recorded and stored electronically over the past two decades. WIDER IMPLICATIONS OF THE FINDINGS: There has been a progressive BW increase in IVF singletons over time in one large centre with consistent treatment eligibility criteria. Such a change is not seen in the general population of live born singletons in the UK or other developed countries, and seems to be specific to this IVF population. This may be a reflection of changes in practice such as undisturbed extended embryo culture to the blastocyst stage, optimized commercial culture media composition, single embryo transfer and ICSI. Moreover, singletons conceived from frozen/thawed embryos had higher birth weights when compared to their fresh embryo transfer counterparts. The causal pathway is unknown; however, it could be due to the impact on embryos of the freeze/thaw process, self-selection of embryos from couples who produce a surplus of embryos, and/or embryo replacement into a more receptive maternal environment. STUDY FUNDING/COMPETING INTEREST(S): This work was supported by the EU FP7 project grant, EpiHealthNet (FP7-PEOPLE-2012-ITN-317146). The authors have no competing interests to declare. TRIAL REGISTRATION NUMBER: N/A.

[Polypharmacy in older adults and impact on their quality of life. Literature review]. / Polifarmacia en adulto mayor, impacto en su calidad de vida. Revision de literatura.

OBJECTIVE: To know, by analyzing the state of knowledge, the impact of the polypharmacy on the quality of life of older adults and the role of nursing when dealing with this health problem. MATERIALS AND METHODS: Descriptive review of 62 original articles with multiple methodological designs, in the databases EBSCO, PubMed, Web of Science, SciELO, Elsevier, SCOPUS and Dialnet. RESULTS: Polypharmacy in older adults is more frequent in the female sex and people with low level of education, and is associated with socioeconomic factors. A large percentage of older adults present with prescription cascade due to the amount of drugs consumed and the number of doctors consulted, leading to pharmacological interactions that affect functionality and quality of life. CONCLUSIONS: More control of drugs consumed by older adults is needed to avoid harmful effects. Nursing professionals should have an educational role in this age group to reduce polypharmacy and promote lifestyles that foster healthy ageing.

OBJETIVO: Conocer mediante el análisis del estado del conocimiento, el impacto de polifarmacia en calidad de vida de adultos mayores y cuál ha sido el rol de enfermería frente a esta problemática de salud. MÉTODOS: Revisión descriptiva de 62 artículos originales de diversos diseños metodológicos, en bases de datos: EBSCO, PubMed, Web of Science, SciELO, Elsevier, SCOPUS y Dialnet. RESULTADOS: La polifarmacia en adultos mayores se presenta con mayor frecuencia en el sexo femenino, en personas con bajo nivel de escolaridad, sumados a factores socioeconómico. Un gran porcentaje de adultos mayores presenta efecto cascada en consumo de fármacos, por cantidad de medicamentos consumidos y número de médicos consultados, produciendo interacciones farmacológicas, afectando funcionalidad y calidad de vida. CONCLUSIONES: Es necesario mayor control de medicamentos consumidos por adultos mayores, para evitar efectos nocivos. Los profesionales de enfermería deben tener un rol educativo en este grupo etario, para disminuir polifarmacia e impulsar estilos de vida que fomenten el envejecimiento saludable.

Predictors of Persistent Tricuspid Regurgitation After Transcatheter Aortic Valve Replacement in Patients With Baseline Tricuspid Regurgitation.

OBJECTIVE: This study sought to analyze outcomes in patients with moderate-severe tricuspid regurgitation (TR) undergoing transcatheter aortic valve replacement (TAVR). The consequences of uncorrected significant TR in patients undergoing TAVR remain undefined. METHODS: Between 2009 and 2014, 369 patients underwent TAVR at our institution, and 58 of these had baseline moderate-severe TR. Preoperative, 30-day, and 1-year transthoracic echocardiograms were analyzed. Predictors of persistent TR at 30 days and survival were assessed. RESULTS: Fifty-eight patients with baseline moderate-severe TR underwent TAVR. Transcatheter aortic valve replacement resulted in significant reductions in pulmonary artery pressures and TR severity (100% vs 64%; P < 0.001) at 30 days. This was sustained at 1 year and was associated with significant improvements in stroke volume index and New York Heart Association functional class. No changes in right ventricular function or size were noted. The only independent predictor of persistent moderate-severe TR at 30 days was preoperative atrial fibrillation [AF; odds ratio (OR), 4.56; 95% confidence interval, 1.1-18.3; P = 0.033]. Independent predictors of overall long-term survival included AF (OR, 0.41; P = 0.001) and chronic lung disease (OR, 0.47; P = 0.011), but not baseline moderate-severe TR. In patients with baseline moderate-severe TR, persistent moderate-severe TR at 30 days was associated with worsened overall survival (log-rank P = 0.02). CONCLUSIONS: Baseline moderate-severe TR is not uncommon in patients undergoing TAVR, and frequently improves. However, the presence of AF suggests that that TR is likely to persist after TAVR and is also indicative of a poor long-term outcome. Whether redirecting such patients to surgery for concomitant tricuspid valve repair will further improve outcomes requires further study.

Quantitative profiling of brain lipid raft proteome in a mouse model of fragile X syndrome.

Fragile X Syndrome, a leading cause of inherited intellectual disability and autism, arises from transcriptional silencing of the FMR1 gene encoding an RNA-binding protein, Fragile X Mental Retardation Protein (FMRP). FMRP can regulate the expression of approximately 4% of brain transcripts through its role in regulation of mRNA transport, stability and translation, thus providing a molecular rationale for its potential pleiotropic effects on neuronal and brain circuitry function. Several intracellular signaling pathways are dysregulated in the absence of FMRP suggesting that cellular deficits may be broad and could result in homeostatic changes. Lipid rafts are specialized regions of the plasma membrane, enriched in cholesterol and glycosphingolipids, involved in regulation of intracellular signaling. Among transcripts targeted by FMRP, a subset encodes proteins involved in lipid biosynthesis and homeostasis, dysregulation of which could affect the integrity and function of lipid rafts. Using a quantitative mass spectrometry-based approach we analyzed the lipid raft proteome of Fmr1 knockout mice, an animal model of Fragile X syndrome, and identified candidate proteins that are differentially represented in Fmr1 knockout mice lipid rafts. Furthermore, network analysis of these candidate proteins reveals connectivity between them and predicts functional connectivity with genes encoding components of myelin sheath, axonal processes and growth cones. Our findings provide insight to aid identification of molecular and cellular dysfunctions arising from Fmr1 silencing and for uncovering shared pathologies between Fragile X syndrome and other autism spectrum disorders.

Barriers to using text message appointment reminders in an HIV clinic.

INTRODUCTION: Failure to attend medical appointments among persons living with human immunodeficiency virus (HIV) has been associated with poor health outcomes. Text message appointment reminders are a novel tool to potentially improve appointment attendance, but the feasibility of this tool among persons living with HIV in the United States is unknown. SUBJECTS AND METHODS: We conducted a randomized, controlled trial of text message reminders in a large HIV clinic. Patients who declined enrollment were asked for reasons for declining. For all patients randomized, demographic and clinical data were collected from medical records. RESULTS: Of 94 patients screened for the study, 42 (45%) did not elect to participate; the most common reason for declining participation was the lack of either a cell phone or text messaging service. Cost, comfort with text messaging, and privacy were other major barriers to study enrollment. Among the 25 subjects randomized to receive text messages, 6 (24%) had their phones disconnected prior to the appointment reminder date. Ultimately, there were no differences in clinic attendance rates between the group that received text reminders versus the group that did not (72% versus 81%, p=0.42) in an intention-to-treat analysis. CONCLUSIONS: Although text message reminders may be successful in certain groups of patients, barriers must be addressed before they are used as a universal approach to improve clinic attendance.

Agonist-dependent signaling by group I metabotropic glutamate receptors is regulated by association with lipid domains.

Group I metabotropic glutamate receptors (mGluRs), mGluR1 and mGluR5, play critical functions in forms of activity-dependent synaptic plasticity and synapse remodeling in physiological and pathological states. Importantly, in animal models of fragile X syndrome, group I mGluR activity is abnormally enhanced, a dysfunction that may partly underlie cognitive deficits in the condition. Lipid rafts are cholesterol- and sphingolipid-enriched membrane domains that are thought to form transient signaling platforms for ligand-activated receptors. Many G protein-coupled receptors, including group I mGluRs, are present in lipid rafts, but the mechanisms underlying recruitment to these membrane domains remain incompletely understood. Here, we show that mGluR1 recruitment to lipid rafts is enhanced by agonist binding and is supported at least in part by an intact cholesterol recognition/interaction amino acid consensus (CRAC) motif in the receptor. Substitutions of critical residues in the motif reduce mGluR1 association with lipid rafts and agonist-induced, mGluR1-dependent activation of extracellular-signal-activated kinase1/2 MAP kinase (ERK-MAPK). We find that alteration of membrane cholesterol content or perturbation of lipid rafts regulates agonist-dependent activation of ERK-MAPK by group I mGluRs, suggesting a potential function for cholesterol as a positive allosteric modulator of receptor function(s). Together, these findings suggest that drugs that alter membrane cholesterol levels or directed to the receptor-cholesterol interface could be employed to modulate abnormal group I mGluR activity in neuropsychiatric conditions, including fragile X syndrome.

Evidence of an equilibrium between selenides and osmium(VIII) reagents and selenoxides and osmium(VI) reagents.

Driving the equilibrium between selenides and osmium(VIII) reagents with selenoxides and osmium(VI) by a subsequent reaction (rearrangement of allyl selenoxides to allyl alcohols or addition of osmium(VIII) species on C=C double bonds) to one side, allows the transformation of methyl geranyl selenides to linalool and of methyl citronellyl selenoxide to 6,7-dihydroxy citronellyl selenide.