Changes in Drug Utilization during a Gap in Insurance Coverage: An Examination of the Medicare Part D Coverage Gap

Jennifer Polinski and colleagues estimated the effect of the "coverage gap" during which US Medicare beneficiaries are fully responsible for drug costs and found that the gap was associated with a doubling in discontinuing essential medications

Financial Incentive Increases CPAP Acceptance in Patients from Low Socioeconomic Background

OBJECTIVE: We explored whether financial incentives have a role in patients' decisions to accept (purchase) a continuous positive airway pressure (CPAP) device in a healthcare system that requires cost sharing. DESIGN: Longitudinal interventional study. PATIENTS: The group receiving financial incentive (n = 137, 50.8±10.6 years, apnea/hypopnea index (AHI) 38.7±19.9 events/hr) and the control group (n = 121, 50.9±10.3 years, AHI 39.9±22) underwent attendant titration and a two-week adaptation to CPAP. Patients in the control group had a co-payment of $330-660; the financial incentive group paid a subsidized price of$55. RESULTS: CPAP acceptance was 43% greater (p = 0.02) in the financial incentive group. CPAP acceptance among the low socioeconomic strata (n = 113) (adjusting for age, gender, BMI, tobacco smoking) was enhanced by financial incentive (OR, 95% CI) (3.43, 1.09-10.85), age (1.1, 1.03-1.17), AHI (>30 vs. <30) (4.87, 1.56-15.2), and by family/friends who had positive experience with CPAP (4.29, 1.05-17.51). Among average/high-income patients (n = 145) CPAP acceptance was affected by AHI (>30 vs. <30) (3.16, 1.14-8.75), living with a partner (8.82, 1.03-75.8) but not by the financial incentive. At one-year follow-up CPAP adherence was similar in the financial incentive and control groups, 35% and 39%, respectively (p = 0.82). Adherence rate was sensitive to education (+yr) (1.28, 1.06-1.55) and AHI (>30 vs. <30) (5.25, 1.34-18.5). CONCLUSIONS: Minimizing cost sharing reduces a barrier for CPAP acceptance among low socioeconomic status patients. Thus, financial incentive should be applied as a policy to encourage CPAP treatment, especially among low socioeconomic strata patients

More Stable Productivity of Semi Natural Grasslands than Sown Pastures in a Seasonally Dry Climate

In the Neotropics the predominant pathway to intensify productivity is generally thought to be to convert grasslands to sown pastures, mostly in monoculture. This article examines how above-ground net primary productivity (ANPP) in semi-natural grasslands and sown pastures in Central America respond to rainfall by: (i) assessing the relationships between ANPP and accumulated rainfall and indices of rainfall distribution, (ii) evaluating the variability of ANPP between and within seasons, and (iii) estimating the temporal stability of ANPP. We conducted sequential biomass harvests during 12 periods of 22 days and related those to rainfall. There were significant relationships between ANPP and cumulative rainfall in 22-day periods for both vegetation types and a model including a linear and quadratic term explained 74% of the variation in the data. There was also a significant correlation between ANPP and the number of rainfall events for both vegetation types. Sown pastures had higher ANPP increments per unit rainfall and higher ANPP at the peak of the rainy season than semi-natural grasslands. In contrast, semi-natural grasslands showed higher ANPP early in the dry season. The temporal stability of ANPP was higher in semi-natural grasslands than in the sown pastures in the dry season and over a whole annual cycle. Our results reveal that, contrary to conventional thinking amongst pasture scientists, there appears to be no increase in ANPP arising from replacing semi-natural grasslands with sown pastures under prevailing pasture management practices in seasonally dry climates, while the temporal distribution of ANPP is more even in semi-natural grasslands. Neither sown pastures nor semi-natural grasslands are productive towards the end of the dry season, indicating the potential importance of the widespread practice of retaining tree cover in pastures

Developmental Programming Mediated by Complementary Roles of Imprinted Grb10 in Mother and Pup

Developmental programming links growth in early life with health status in adulthood. Although environmental factors such as maternal diet can influence the growth and adult health status of offspring, the genetic influences on this process are poorly understood. Using the mouse as a model, we identify the imprinted gene Grb10 as a mediator of nutrient supply and demand in the postnatal period. The combined actions of Grb10 expressed in the mother, controlling supply, and Grb10 expressed in the offspring, controlling demand, jointly regulate offspring growth. Furthermore, Grb10 determines the proportions of lean and fat tissue during development, thereby influencing energy homeostasis in the adult. Most strikingly, we show that the development of normal lean/fat proportions depends on the combined effects of Grb10 expressed in the mother, which has the greater effect on offspring adiposity, and Grb10 expressed in the offspring, which influences lean mass. These distinct functions of Grb10 in mother and pup act complementarily, which is consistent with a coadaptation model of imprinting evolution, a model predicted but for which there is limited experimental evidence. In addition, our findings identify Grb10 as a key genetic component of developmental programming, and highlight the need for a better understanding of mother-offspring interactions at the genetic level in predicting adult disease risk

Tailoring pharmacotherapy to specific eating behaviours in obesity: Can recommendations for personalised therapy be made from the current data?

Pharmacotherapy provides an adjunct to behaviour modification in the management of obesity. There are a number of new drug therapies purportedly targeting appetite; liraglutide, and bupropion/naltrexone, which are European Medicines Agency and US Food and Drug Administration (FDA) approved, and lorcaserin and phentermine/topiramate, which have FDA approval only. Each of the six drugs, used singly or in combination, has distinct pharmacological, and presumably distinct behavioural, mechanisms of action, thus the potential to provide defined therapeutic options to personalise the management of obesity. Yet, with regard to pharmacotherapy for obesity, we are far from true personalised medicine. We review the limited mechanistic data with four mono and combination pharmacotherapies, to assess the potential for tailoring their use to target specific obesogenic behaviours. Potential treatment options are considered, but in the absence of adequate research in respect to effects of these drugs on eating behaviour, neural activity and psychological substrates that underlie poorly controlled eating, we are far from definitive therapeutic recommendations. Specific mechanistic studies and broader behavioural phenotyping, possibly in conjunction with pharmacogenetic research, are required to characterise responders for distinct pharmacotherapeutic options

Defoliation and Soil Compaction Jointly Drive Large-Herbivore Grazing Effects on Plants and Soil Arthropods on Clay Soil

In addition to the well-studied impacts of defecation and defoliation, large herbivores also affect plant and arthropod communities through trampling, and the associated soil compaction. Soil compaction can be expected to be particularly important on wet, fine-textured soils. Therefore, we established a full factorial experiment of defoliation (monthly mowing) and soil compaction (using a rammer, annually) on a clay-rich salt marsh at the Dutch coast, aiming to disentangle the importance of these two factors. Additionally, we compared the effects on soil physical properties, plants, and arthropods to those at a nearby cattle-grazed marsh under dry and under waterlogged conditions. Soil physical conditions of the compacted plots were similar to the conditions at cattle-grazed plots, showing decreased soil aeration and increased waterlogging. Soil salinity was doubled by defoliation and quadrupled by combined defoliation and compaction. Cover of the dominant tall grass Elytrigia atherica was decreased by 80% in the defoliated plots, but cover of halophytes only increased under combined defoliation and compaction. Effects on soil micro-arthropods were most severe under waterlogging, showing a fourfold decrease in abundance and a smaller mean body size under compaction. Although the combined treatment of defoliation and trampling indeed proved most similar to the grazed marsh, large discrepancies remained for both plant and soil fauna communities, presumably because of colonization time lags. We conclude that soil compaction and defoliation differently affect plant and arthropod communities in grazed ecosystems, and that the magnitude of their effects depends on herbivore density, productivity, and soil physical properties

Rice actin binding protein RMD controls crown root angle in response to external phosphate

Root angle has a major impact on acquisition of nutrients like phosphate that accumulate in topsoil and in many species; low phosphate induces shallower root growth as an adaptive response. Identifying genes and mechanisms controlling root angle is therefore of paramount importance to plant breeding. Here we show that the actin-binding protein Rice Morphology Determinant (RMD) controls root growth angle by linking actin filaments and gravity-sensing organelles termed statoliths. RMD is upregulated in response to low external phosphate and mutants lacking of RMD have steeper crown root growth angles that are unresponsive to phosphate levels. RMD protein localizes to the surface of statoliths, and rmd mutants exhibit faster gravitropic response owing to more rapid statoliths movement. We conclude that adaptive changes to root angle in response to external phosphate availability are RMD dependent, providing a potential target for breeders

A short history of the 5-HT2C receptor: from the choroid plexus to depression, obesity and addiction treatment

This paper is a personal account on the discovery and characterization of the 5-HT2C receptor (first known as the 5- HT1C receptor) over 30 years ago and how it translated into a number of unsuspected features for a G protein-coupled receptor (GPCR) and a diversity of clinical applications. The 5-HT2C receptor is one of the most intriguing members of the GPCR superfamily. Initially referred to as 5-HT1CR, the 5-HT2CR was discovered while studying the pharmacological features and the distribution of [3H]mesulergine-labelled sites, primarily in the brain using radioligand binding and slice autoradiography. Mesulergine (SDZ CU-085), was, at the time, best defined as a ligand with serotonergic and dopaminergic properties. Autoradiographic studies showed remarkably strong [3H]mesulergine-labelling to the rat choroid plexus. [3H]mesulergine-labelled sites had pharmacological properties different from, at the time, known or purported 5-HT receptors. In spite of similarities with 5-HT2 binding, the new binding site was called 5-HT1C because of its very high affinity for 5-HT itself. Within the following 10 years, the 5-HT1CR (later named 5- HT2C) was extensively characterised pharmacologically, anatomically and functionally: it was one of the first 5-HT receptors to be sequenced and cloned. The 5-HT2CR is a GPCR, with a very complex gene structure. It constitutes a rarity in theGPCR family: many 5-HT2CR variants exist, especially in humans, due to RNA editing, in addition to a few 5-HT2CR splice variants. Intense research led to therapeutically active 5-HT2C receptor ligands, both antagonists (or inverse agonists) and agonists: keeping in mind that a number of antidepressants and antipsychotics are 5- HT2CR antagonists/inverse agonists. Agomelatine, a 5-HT2CR antagonist is registered for the treatment of major depression. The agonist Lorcaserin is registered for the treatment of aspects of obesity and has further potential in addiction, especially nicotine/ smoking. There is good evidence that the 5-HT2CR is involved in spinal cord injury-induced spasms of the lower limbs, which can be treated with 5-HT2CR antagonists/inverse agonists such as cyproheptadine or SB206553. The 5-HT2CR may play a role in schizophrenia and epilepsy. Vabicaserin, a 5-HT2CR agonist has been in development for the treatment of schizophrenia and obesity, but was stopped. As is common, there is potential for further indications for 5-HT2CR ligands, as suggested by a number of preclinical and/or genome-wide association studies (GWAS) on depression, suicide, sexual dysfunction, addictions and obesity. The 5-HT2CR is clearly affected by a number of established antidepressants/antipsychotics and may be one of the culprits in antipsychotic-induced weight gain