Ultra-complex specialty medications: Meeting the challenges of significant medication requirements through an integrated specialty pharmacy model.

Purpose: There is a growing number of specialty medications with accompanying requirements that exceed standard characteristics, which may be referred to as "ultra complex." This article details examples of ultra-complex specialty medications, including the characteristics that make them ultra complex, and strategies implemented by an integrated health-system specialty pharmacy (IHSSP) to maintain an optimal patient journey.

Summary: Before therapy initiation, ultra-complex specialty medications often require additional steps that go beyond what is required of traditional specialty treatments, such as ensuring patients have appointments scheduled and attended and coordinating medical procedures.

Biotic interactions between benthic infauna and aerobic methanotrophs mediate methane fluxes from coastal sediments.

Coastal ecosystems dominate oceanic methane (CH4) emissions. However, there is limited knowledge about how biotic interactions between infauna and aerobic methanotrophs (i.e.

Hyponatraemia and the syndrome of inappropriate antidiuresis (SIAD) in cancer.

Hyponatraemia is a common electrolyte abnormality seen in a wide range of oncological and haematological malignancies and confers poor performance status, prolonged hospital admission and reduced overall survival, in patients with cancer. Syndrome of inappropriate antidiuresis (SIAD) is the commonest cause of hyponatraemia in malignancy and is characterised by clinical euvolaemia, low plasma osmolality and concentrated urine, with normal renal, adrenal and thyroid function. Causes of SIAD include ectopic production of vasopressin (AVP) from an underlying tumour, cancer treatments, nausea and pain.

Exploring rates of PCSK9 inhibitor persistence and reasons for treatment non-persistence in an integrated specialty pharmacy model.

Background: Nearly 40% of patients do not continue proprotein convertase subtilisin/kexin type 9 inhibitor (PCSK9i) therapy after 6 months, despite their ability to lower low-density lipoprotein cholesterol (LDL-C) and risk of cardiovascular events. Limited work has assessed persistence to PCSK9i therapy in an integrated specialty pharmacy model.

Objective: To assess rates of persistence to PCSK9i therapy and report reasons for non-persistence in patients serviced within an integrated specialty pharmacy.

Water quality limitations for tadpoles of the Wood Frog in the northern Great Plains, Canada.

Some wetlands in the northern Great Plains support hundreds to thousands of late-stage tadpoles providing important sources of recruitment to the Wood Frog (Lithobates sylvaticus) population while many other wetlands produce none. Relationships between water quality and late-stage tadpole abundance were determined to identify the water quality parameters associated with tadpole abundance. Water samples were collected, and late-stage tadpole abundances were assessed once each year in late June for 12 years in 26 wetlands.

Concentrations of Herbicides in Wetlands on Organic and Minimum-Tillage Farms.

Wetlands are abundant throughout the agricultural landscape of central Saskatchewan, Canada, and the biota present in these wetlands may be vulnerable to the toxic effects of pesticides used on nearby crops. We hypothesized that herbicide concentrations would be higher in wetlands on minimum-tillage farms than on organic (no herbicide use) farms, and that the principal transport mechanisms of runoff versus atmospheric deposition could be identified based on the concentrations in these two wetland types. To test these hypotheses, 29 herbicides were monitored for 5 yr in 16 wetlands on minimum-tillage farms and in seven wetlands on organic farms.

Relationships for mercury and selenium in muscle and ova of gravid freshwater fish.

At high concentrations, mercury (Hg) is toxic to vertebrates, causing neurological, behavioral, and teratological dysfunction. Selenium (Se) not only is an essential element but also has a high affinity for Hg, binding to organic methyl mercury at a molar ratio of Se/Hg of 1:1. Ratios of <1 increase risk of Hg toxicity.

Persistence of the Sulfonylurea Herbicides Sulfosulfuron, Rimsulfuron, and Nicosulfuron in Farm Dugouts (Ponds).

Sulfonylurea herbicides are applied at relatively low rates (3-40 g ha) to control weeds in a variety of crops grown in the prairie pothole region of south-central Canada. Because of their high phytotoxicity and the likelihood of their transport in surface runoff, there is concern about impacts of sulfonylurea herbicides to wetland ecosystems embedded in agricultural landscapes. In a previous study, dissipation half-lives (DT values) were determined for three sulfonylurea herbicides (thifensulfuron-methyl, ethametsulfuron-methyl, and metsulfuron-methyl), each possessing a hydrolyzable methyl ester linkage.

Species-specific mercury bioaccumulation in a diverse fish community.

Mercury bioaccumulation models developed for fish provide insight into the sources and transfer of Hg within ecosystems. Mercury concentrations were assessed for 16 fish species of the western reach of Lake Diefenbaker, Saskatchewan, Canada. For top predators (northern pike, Esox Lucius; walleye, Sander vitreum), Hg concentrations were positively correlated to δ(15)N, and δ(15)N to fish age, suggesting that throughout life these fish fed on organisms with increasingly higher trophic values and Hg concentrations.

Prevention and treatment of oral mucositis in children with cancer.

Oral mucositis affects more than three-fourths of patients undergoing chemotherapy and represents a significant burden to patients and caregivers. Lesions develop as a result of chemotherapeutic agents attacking the rapidly dividing cells of the gastrointestinal tract. Severity can range from mild, painless tissue changes to bleeding ulcerations that prevent oral intake and require narcotic pain relievers.

Phytoplankton-specific response to enrichment of phosphorus-rich surface waters with ammonium, nitrate, and urea.

Supply of anthropogenic nitrogen (N) to the biosphere has tripled since 1960; however, little is known of how in situ response to N fertilisation differs among phytoplankton, whether species response varies with the chemical form of N, or how interpretation of N effects is influenced by the method of analysis (microscopy, pigment biomarkers). To address these issues, we conducted two 21-day in situ mesocosm (3140 L) experiments to quantify the species- and genus-specific responses of phytoplankton to fertilisation of P-rich lake waters with ammonium (NH(4)(+)), nitrate (NO(3)(-)), and urea ([NH(2)](2)CO). Phytoplankton abundance was estimated using both microscopic enumeration of cell densities and high performance liquid chromatographic (HPLC) analysis of algal pigments.

Discovery and evolution of phenoxypiperidine hydroxyamide dual CCR3/H₁ antagonists. Part I.

The discovery of potent small molecule dual antagonists of the human CCR3 and H(1) receptors is described for the treatment of allergic diseases, for example, asthma and allergic rhinitis. Optimizing in vitro potency and metabolic stability, starting from a CCR1 lead compound, led to compound 20 with potent dual CCR3/H(1) activity and in vitro metabolic stability.

Immunosuppressive properties of a series of novel inhibitors of the monocarboxylate transporter MCT-1.

We have recently described the immunosuppressive properties of AR-C117977 and AR-C122982, representatives of a group of compounds identified as inhibitors of lactate transporters (monocarboxylate transporters; MCTs). These compounds demonstrate the potential therapeutic usefulness of inhibiting MCT-1, but their physical and metabolic properties made them unsuitable for further development. We have therefore tried to find analogues with similar immunosuppressive efficacy and a more suitable profile for oral administration.

Discovery and evolution of phenoxypiperidine hydroxyamide dual CCR3/H₁ antagonists. Part II: optimising in vivo clearance.

The second part of this communication focuses on the resolution of issues surrounding the series of hydroxyamide phenoxypiperidine CCR3/H(1) dual antagonists described in Part I. This involved further structural exploration directed at reducing metabolism and leading to the identification of compound 60 with a greatly improved in vivo pharmacokinetic profile.

The discovery of AZD9164, a novel muscarinic M3 antagonist.

The optimization of a new series of muscarinic M(3) antagonists is described, leading to the identification of AZD9164 which was progressed into the clinic for evaluation of its potential as a treatment for COPD.

Occurrence of glyphosate and acidic herbicides in select urban rivers and streams in Canada, 2007.

Introduction: Public and scientific concern has grown over the last decade in Canada over the cosmetic use of pesticides in urban centers. With this in mind, a national survey was designed to monitor eight commonly used herbicides in urban rivers and streams across Canada.

Materials And Methods: To coordinate sample collections across the country, samples were collected monthly on one of two predetermined dates from April to September, 2007 from 19 sites within 16 watersheds, including 15 sites downstream of urban lands and two reference sites.

The discovery of new spirocyclic muscarinic M3 antagonists.

The optimisation of a new series of high potency muscarinic M3 antagonists, derived from high throughput screening library hit is described.

Mercury and other metals in muscle and ovaries of goldeye (Hiodon alosoides).

Concentrations of 24 trace metals were assessed in gravid ovaries and in muscle of female juvenile and adult female goldeye (Hiodon alosoides), a fish with both low annual growth (16 g/year as adults) and a long life span (maximum longevity of 30 years). It was hypothesized that adult fish with these life-history characteristics would maintain stable concentrations of metals in their tissues with higher levels of essential elements compared with those that are potentially toxic. As hypothesized, the concentration of most metals in muscle of adult female goldeye was similar at all ages, suggesting that uptake and excretion of metals was equal.

Operational tolerance in nonvascularized transplant models induced by AR-C117977, a monocarboxylate transporter inhibitor.

AR-C117977, a monocarboxylate transporter inhibitor, reduces immune responses both in vitro and in vivo, maintains long-term graft survival, and induces operational tolerance. To evaluate the immunosuppressive limitations of AR-C117977, this study was performed in nonvascularized transplant models noted for their refractive response to standard immunosuppressive agents. Rat skin was transplanted from DA(RT1avl) into PVG(RT1c) and the reverse.

Haemonchus contortus: evaluation of two signal sequence trapping systems for detection of secreted molecules.

Given that signal sequences between secreted proteins of different species can be interchanged, it is reasonable to expect that both mammalian and yeast signal sequence trapping (SST) systems would secrete Haemonchus contortus proteins with similar efficiency and quality. To determine if H. contortus cDNAs that contain a signal sequence could re-establish secretion of a reporter protein, mammalian and yeast SST vectors were designed, 10 H.

The specific monocarboxylate transporter (MCT1) inhibitor, AR-C117977, a novel immunosuppressant, prolongs allograft survival in the mouse.

Novel small molecular weight compounds that act by inhibiting the monocarboxylate transporter (MCT1) receptor have been found to cause profound inhibition of T-cell responses to alloantigen in vitro. Here, we have investigated the ability of one compound in this series, AR-C117977, a potent MCT1 inhibitor, to prevent the acute and chronic rejection of vascularized and nonvascularized allografts in the mouse. Treatment with AR-C117977 or cyclosporin A (CsA) administered at a dose of 30 mg/kg subcutaneously for 15 days to adult CBA.