Enteral Nutrition in Crohn’s Disease: An Underused Therapy

This paper reviews the literature on the history, efficacy, and putative mechanism of action of enteral nutrition for inflammatory bowel disease in both paediatric and adult patients. It also analyses the reasoning behind the low popularity of exclusive enteral nutrition in clinical practice despite the benefits and safety profile

Budget impact of adding ivabradine to standard of care in patients with chronic systolic heart failure in the United States

BACKGROUND: Heart failure (HF) costs $21 billion annually in direct health care costs, 80 OBJECTIVE: To estimate the budget impact of ivabradine from a U.S. commercial payer perspective. METHODS: A budget impact model estimated the per-member-per month (PMPM) impact of introducing ivabradine to existing formularies by comparing a reference scenario (SoC) and a new drug scenario (ivabradine + SoC) in hypothetical 1 million-member commercial and Medicare Advantage plans. In both scenarios, U.S. claims data were used for the reference cumulative annual rates of hospitalizations (HF, non-HF cardiovascular [CV], and non-CV), and hospitalization rates were adjusted using SHIFT data. The model controlled for mortality risk using SHIFT and U.S. life table data, and hospitalization costs were obtained from U.S. claims data: HF-related =$37,507; non-HF CV = $28,951; and non-CV =$17,904. The annualized wholesale acquisition cost of ivabradine was $4,500, with baseline use for this new drug at 2 RESULTS: Based on the approved U.S. indication, approximately 2,000 commercially insured patients from a 1 million-member commercial plan were eligible to receive ivabradine. Ivabradine resulted in a PMPM cost savings of$0.01 and $0.04 in years 1 and 3 of the core model, respectively. After including the acquisition price for ivabradine, the model showed a decrease in total costs in the commercial ($991,256 and $474,499, respectively) and Medicare populations ($13,849,262 and $4,280,291, respectively) in year 1. This decrease was driven by ivabradine’s reduction in hospitalization rates. For the core model, the estimated pharmacy-only PMPM in year 1 was$0.01 for the commercial population and $0.24 for the Medicare Advantage population. CONCLUSIONS: Adding ivabradine to SoC led to lower average annual treatment costs. The negative PMPM budget impact indicates that ivabradine is an affordable option for U.S. payers

Priming third-party social exclusion does not elicit children's inclusion of out-group members

This study investigates how culture and priming 3- to 7-year-old children (N = 186) with third-party social exclusion affects their subsequent inclusion of out-group members. Children in societies that tend to value social independence (Germany, New Zealand) and interdependence (Northern Cyprus) were randomly assigned to minimal groups. Next, they watched video stimuli depicting third-party social exclusion (exclusion condition) or neutral content (control condition). We assessed children's recognition of the social exclusion expressed in the priming videos and their understanding of the emotional consequences thereof. We furthermore assessed children's inclusion behaviour in a ball-tossing game in which participants could include an out-group agent into an in-group interplay. Children across societies detected third-party social exclusion and ascribed lower mood to excluded than non-excluded protagonists. Children from Germany and New Zealand were more likely to include the out-group agent into the in-group interaction than children from Northern Cyprus. Children's social inclusion remained unaffected by their exposure to third-party social exclusion primes. These results suggest that children from diverse societies recognize social exclusion and correctly forecast its negative emotional consequences, but raise doubt on the notion that social exclusion exposure affects subsequent social inclusion

Challenges and opportunities associated with waste management in India

India faces major environmental challenges associated with waste generation and inadequate waste collection, transport, treatment and disposal. Current systems in India cannot cope with the volumes of waste generated by an increasing urban population, and this impacts on the environment and public health. The challenges and barriers are significant, but so are the opportunities. This paper reports on an international seminar on ‘Sustainable solid waste management for cities: opportunities in South Asian Association for Regional Cooperation (SAARC) countries’ organized by the Council of Scientific and Industrial Research-National Environmental Engineering Research Institute and the Royal Society. A priority is to move from reliance on waste dumps that offer no environmental protection, to waste management systems that retain useful resources within the economy. Waste segregation at source and use of specialized waste processing facilities to separate recyclable materials has a key role. Disposal of residual waste after extraction of material resources needs engineered landfill sites and/or investment in waste-to-energy facilities. The potential for energy generation from landfill via methane extraction or thermal treatment is a major opportunity, but a key barrier is the shortage of qualified engineers and environmental professionals with the experience to deliver improved waste management systems in India

Development of a Molecular Signature to Monitor Pharmacodynamic Responses Mediated by In Vivo Administration of Glucocorticoids

© 2018 American College of Rheumatology. Objective: To develop an objective, readily measurable pharmacodynamic biomarker of glucocorticoid (GC) activity. Methods: Genes modulated by prednisolone were identified from in vitro studies using peripheral blood mononuclear cells from normal healthy volunteers. Using the criteria of a \u3e2-fold change relative to vehicle controls and an adjusted P value cutoff of less than 0.05, 64 up-regulated and 18 down-regulated genes were identified. A composite score of the up-regulated genes was generated using a single-sample gene set enrichment analysis algorithm. Results: GC gene signature expression was significantly elevated in peripheral blood leukocytes from normal healthy volunteers following oral administration of prednisolone. Expression of the signature increased in a dose-dependent manner, peaked at 4 hours postadministration, and returned to baseline levels by 48 hours after dosing. Lower expression was detected in normal healthy volunteers who received a partial GC receptor agonist, which is consistent with the reduced transactivation potential of this compound. In cohorts of patients with systemic lupus erythematosus and patients with rheumatoid arthritis, expression of the GC signature was negatively correlated with the percentages of peripheral blood lymphocytes and positively correlated with peripheral blood neutrophil counts, which is consistent with the known biology of the GC receptor. Expression of the signature largely agreed with reported GC use in these populations, although there was significant interpatient variability within the dose cohorts. Conclusion: The GC gene signature identified in this study represents a pharmacodynamic marker of GC exposure

Unexpected drop of dynamical heterogeneities in colloidal suspensions approaching the jamming transition

As the glass (in molecular fluids\cite{Donth}) or the jamming (in colloids and grains\cite{LiuNature1998}) transitions are approached, the dynamics slow down dramatically with no marked structural changes. Dynamical heterogeneity (DH) plays a crucial role: structural relaxation occurs through correlated rearrangements of particle ``blobs'' of size $\xi$\cite{WeeksScience2000,DauchotPRL2005,Glotzer,Ediger}. On approaching these transitions, $\xi$ grows in glass-formers\cite{Glotzer,Ediger}, colloids\cite{WeeksScience2000,BerthierScience2005}, and driven granular materials\cite{KeysNaturePhys2007} alike, strengthening the analogies between the glass and the jamming transitions. However, little is known yet on the behavior of DH very close to dynamical arrest. Here, we measure in colloids the maximum of a ``dynamical susceptibility'', $\chi^*$, whose growth is usually associated to that of $\xi$\cite{LacevicPRE}. $\chi^*$ initially increases with volume fraction $\phi$, as in\cite{KeysNaturePhys2007}, but strikingly drops dramatically very close to jamming. We show that this unexpected behavior results from the competition between the growth of $\xi$ and the reduced particle displacements associated with rearrangements in very dense suspensions, unveiling a richer-than-expected scenario.Comment: 1st version originally submitted to Nature Physics. See the Nature Physics website fro the final, published versio

Budget impact of adding ivabradine to standard of care in patients with chronic systolic heart failure in the United States

BACKGROUND: Heart failure (HF) costs $21 billion annually in direct health care costs, 80 OBJECTIVE: To estimate the budget impact of ivabradine from a U.S. commercial payer perspective. METHODS: A budget impact model estimated the per-member-per month (PMPM) impact of introducing ivabradine to existing formularies by comparing a reference scenario (SoC) and a new drug scenario (ivabradine + SoC) in hypothetical 1 million-member commercial and Medicare Advantage plans. In both scenarios, U.S. claims data were used for the reference cumulative annual rates of hospitalizations (HF, non-HF cardiovascular [CV], and non-CV), and hospitalization rates were adjusted using SHIFT data. The model controlled for mortality risk using SHIFT and U.S. life table data, and hospitalization costs were obtained from U.S. claims data: HF-related =$37,507; non-HF CV = $28,951; and non-CV =$17,904. The annualized wholesale acquisition cost of ivabradine was $4,500, with baseline use for this new drug at 2 RESULTS: Based on the approved U.S. indication, approximately 2,000 commercially insured patients from a 1 million-member commercial plan were eligible to receive ivabradine. Ivabradine resulted in a PMPM cost savings of$0.01 and $0.04 in years 1 and 3 of the core model, respectively. After including the acquisition price for ivabradine, the model showed a decrease in total costs in the commercial ($991,256 and $474,499, respectively) and Medicare populations ($13,849,262 and $4,280,291, respectively) in year 1. This decrease was driven by ivabradine’s reduction in hospitalization rates. For the core model, the estimated pharmacy-only PMPM in year 1 was$0.01 for the commercial population and $0.24 for the Medicare Advantage population. CONCLUSIONS: Adding ivabradine to SoC led to lower average annual treatment costs. The negative PMPM budget impact indicates that ivabradine is an affordable option for U.S. payers