Implementation of a Targeted Inhaled Corticosteroid De-Escalation Process in Patients with Chronic Obstructive Pulmonary Disease in the Primary Care Setting.

Purpose: To evaluate the feasibility and success of a pharmacist-led, targeted inhaled corticosteroid (ICS) de-escalation process in patients with chronic obstructive pulmonary disease (COPD) where the risks of ICS therapy outweigh the potential benefits. Methods: A population health data management tool was leveraged to identify patients who may qualify for ICS de-escalation. Primary care pharmacists clinically reviewed and subsequently contacted patients who were determined to be appropriate candidates. After discussion on the risks and benefits of ICS therapy, a stepwise algorithm was utilized to assist with ICS de-escalation and optimization of bronchodilator therapy. Outcomes analyzed include the proportion of patients for whom ICS was de-escalated, patient acceptability of the intervention, time taken to complete the intervention, barriers to implementation, and the number of additional interventions made by pharmacists. Results: Of the 126 patients originally identified as potential candidates, 58 (46.0%) were deemed appropriate to proceed with ICS de-escalation and successfully contacted by a pharmacist. Of these patients, 49 (84.5%) were agreeable and ultimately 42 were successfully de-escalated with 37 patients maintained off ICS. The average time required for an encounter was 15.8 minutes. Conclusion: There is utility in a pharmacist-driven, targeted ICS de-escalation process to facilitate meeting guideline-directed medication therapy goals in patients with COPD, granted the availability of efficient tools to assist in identifying patients that qualify. Such a targeted approach increases pharmacist involvement in medication management of COPD and can expand the primary care pharmacy practice.

Multiple sclerosis.

Multiple sclerosis is a chronic, unpredictable, and disabling disease. Significant advances have been made in recent years supporting an earlier, more accurate, diagnosis and have led to more than 15 disease-modifying therapies approved by the Food and Drug Administration for relapsing forms of multiple sclerosis. Disease-modifying therapies are now being classified into categories based on level of efficacy. Strategies to use disease-modifying therapies earlier and in a more customizable manner are also emerging. A clinical case study will be used throughout this pearl to review the disease-modifying therapies and use patient-specific factors to develop and provide recommendations on therapeutic strategies for individuals with relapsing forms of multiple sclerosis.

Therapeutic Interferon Interchange in Relapsing Multiple Sclerosis Lowers Health Care and Pharmacy Expenditures with Comparable Safety.

INTRODUCTION: For patients with a less-active (fewer relapses or complete recovery from relapses, less radiologic burden of disease, or no or limited disease-related disability) relapsing form of multiple sclerosis (MS), interferon (IFN) beta-1b subcutaneous is similar in efficacy to IFN beta-1a intramuscular and subcutaneous. The purpose of this study was to assess the impact of patient interchange from an IFN beta-1a to IFN beta-1b. METHODS: This was a retrospective, pre-post study of adult patients with relapsing MS who underwent interchange from an IFN beta-1a to IFN beta-1b between April 15, 2014, and April 30, 2015. Health care financial and utilization outcomes between the 6 months before and after interchange were compared, and safety outcomes after interchange were assessed. RESULTS: A total of 36 primarily white, middle-age, and female patients underwent interchange. Monthly total health care and pharmacy expenditures decreased by approximately 40% and 44%, respectively, from pre-to-post interchange (p < 0.001). Health care utilization was unchanged (p < 0.05). Seven (43.8%) patients underwent interchange back to IFN beta-1a intramuscular. No patients underwent interchange back to IFN beta-1a subcutaneous. The most common adverse effect reported after interchange was injection-site reaction. CONCLUSION: Health care expenditures decreased and adverse effects were limited among patients with MS who underwent an interchange from an IFN beta-1a to IFN beta-1b. These findings suggest that a therapeutic interchange between IFNs for patients with less-active MS disease is well tolerated. Further research is needed to determine the impact of such an interchange on disease progression.

Nutrition Assessment of B-Vitamins in Highly Active and Sedentary Women.

BACKGROUND: Female athletes and active women require adequate nutrition for optimal health and performance. Nutrition assessments are needed to identify potential nutrients of concern. Folate, vitamin B6, and vitamin B12 function in important pathways used during physical activity and female athletes may be at risk for poor status of these micronutrients. This cross-sectional study described a comprehensive nutrition assessment of the B-vitamins (folate, vitamin B6, and vitamin B12) using both dietary (food and dietary supplements) and biochemical assessments among highly active and sedentary women. METHODS: Highly active (n = 29; age 20 ± 2 years; body mass index (BMI) 23.8 ± 3.5 kg/m²) and sedentary (n = 29; age 24 ± 3 years; BMI 22.6 ± 3.0 kg/m²) women were recruited for this study. Participants completed 7-day weighed food records and a fasting blood draw. RESULTS: Although the highly active women reported higher intakes of energy (p < 0.01), folate (p < 0.01), vitamin B6 (p < 0.01), and vitamin B12 (p < 0.01), no significant differences were found between the groups for biomarkers of folate, vitamin B6, and vitamin B12. All of the highly active women had biomarkers within the desired reference ranges, suggesting good status. In general, most participants were able to meet the 1998 Recommended Daily Allowance (RDA) from food alone. For the women that reported using dietary supplements, micronutrient intakes met the 1998 RDA and in some cases, exceeded the Tolerable Upper Intake Level. CONCLUSION: This nutrition assessment documented good status for folate, vitamin B6, and vitamin B12 in the highly active women. Similar assessment approaches (food, dietary supplements, and biomarkers) should to completed with other nutrients of concern for the female athlete.

A conceptual framework for invasion in microbial communities.

There is a growing interest in controlling-promoting or avoiding-the invasion of microbial communities by new community members. Resource availability and community structure have been reported as determinants of invasion success. However, most invasion studies do not adhere to a coherent and consistent terminology nor always include rigorous interpretations of the processes behind invasion. Therefore, we suggest that a consistent set of definitions and a rigorous conceptual framework are needed. We define invasion in a microbial community as the establishment of an alien microbial type in a resident community and argue how simple criteria to define aliens, residents, and alien establishment can be applied for a wide variety of communities. In addition, we suggest an adoption of the community ecology framework advanced by Vellend (2010) to clarify potential determinants of invasion. This framework identifies four fundamental processes that control community dynamics: dispersal, selection, drift and diversification. While selection has received ample attention in microbial community invasion research, the three other processes are often overlooked. Here, we elaborate on the relevance of all four processes and conclude that invasion experiments should be designed to elucidate the role of dispersal, drift and diversification, in order to obtain a complete picture of invasion as a community process.

KLEIP deficiency in mice causes progressive corneal neovascular dystrophy.

PURPOSE: The BTB-kelch protein KLEIP/KLHL20 is an actin binding protein that regulates cell-cell contact formation and cell migration. The aim of our study was to characterize KLEIP's function in ocular health and disease in mice. METHODS: KLEIP(-/-) mice were generated, and corneas were examined histologically and stained for keratin-1, loricrin, keratin-12, keratin-14, CD31, LYVE-1, F4/80, E-cadherin, and Ki67. Corneal abrasions were performed after eyelid opening. RESULTS: Corneas of KLEIP(+/+) and KLEIP(-/-) mice were indistinguishable at birth. After eyelid opening corneal epithelial hyperplasia started to manifest in KLEIP(-/-) mice, showing a progressive epithelial metaplasia leading to total corneal opacity. In KLEIP(-/-) mice the initial stratified squamous corneal epithelium was altered to an epidermal histo-architecture showing several superficial keratinized cells, cell infiltrations into the stroma, and several apoptotic cells. Skin markers keratin 1 and loricrin were positive, and surface disease was accompanied by deep stromal vascularization. Expression analysis for E-cadherin in KLEIP(-/-) corneas showed acellular areas in the squamous epithelium, indicating a progressive fragile corneal integrity. Removal of the virgin epithelium accelerated strongly development of the epithelial and stromal alterations, identifying mechanical injuries as the major trigger for corneal dystrophy formation and scarification in KLEIP(-/-) mice. CONCLUSIONS: The data identify KLEIP as an important molecule regulating corneal epithelial integrity.

Inducible expression of tissue factor in small-cell lung cancer: impact on morphology and matrix metalloproteinase secretion.

PURPOSE: Tissue factor (TF), the transmembrane receptor for factor VIIa (FVIIa), has key regulatory functions in coagulation as well as in tumour progression and metastasis. Small-cell lung cancer (SCLC) metastasises more aggressively than non-small-cell lung cancer (NSCLC). Previously, we described the transition of SCLC cell line H69 to adherent growth and TF expression. Here, we explored the differential expression of TF and its functional impact on morphology and matrix metalloproteinase (MMP) secretion. METHODS: The constitutional TF expression was evaluated in a panel of established NSCLC and SCLC cell lines. Furthermore, in three stress-selected adherent SCLC H69 cells, TF and MMP expressions were determined by mRNA, protein, and activity measurements. RNA interference-mediated TF down-regulation and FVIIa stimulation were used to study the impact of TF on cellular functions. RESULTS: NSCLC cells expressed high TF antigen (median 3.75 ng/mg; range 0.31-65.2 ng/mg protein, n = 8), while SCLC expressed none or low TF (median 0.07 ng/mg; range 0-0.39 ng/mg protein, n = 6). However, selected H69 adherent cells markedly expressed TF (range: 4.8-44.3 ng/mg protein, n = 3) and secreted MMP-2 and MMP-9. FVIIa stimulated MMP-2 and MMP-9 secretion in H69adh cells, whereas TF down-regulation diminished MMP-2 and MMP-9 expression and promoted reversion to suspension growth. CONCLUSIONS: Our data show the significance of TF expression in the reversible growth phenotype of H69. Because TF, MMP expression, and adherence are highly relevant to cancer metastasis, this study suggests a novel mechanism of adaptation, thereby adding to the understanding of SCLC biology and its aggressiveness.

Iron status in highly active and sedentary young women.

This study examined iron status and nutrient intake in highly active (n = 28; 20 +/- 2 yr, >/=12 hr purposeful physical activity per week [PPA/wk]) and sedentary (n = 28; 24 +/- 3 yr,

Comparison of hydraulic and hemolytic properties of different impeller designs of an implantable rotary blood pump by computational fluid dynamics.

A mixed-flow blood pump for long-term applications has been developed at the Helmholtz-Institute in Aachen, Germany. Central features of this implantable pump are a centrally integrated motor, a blood-immersed mechanical bearing, magnetic coupling of the impeller, and a shrouded impeller, which allows a relatively wide clearance. The aim of the study was a numerical analysis of hydraulic and hemolytic properties of different impeller design configurations. In vitro testing and numerical simulation techniques (computational fluid dynamics [CFD]) were applied to achieve a comprehensive overview. Pressure-flow charts were experimentally measured in a mock loop in order to validate the CFD data. In vitro hemolysis tests were performed at the main operating point of each impeller design. General flow patterns, pressure-flow charts, secondary flow rates, torque, and axial forces on the impeller were calculated by means of CFD. Furthermore, based on streak line techniques, shear stress (stress loading), exposure times, and volume percentage with critical stress loading have been determined. Comparison of CFD data with pressure head measurements showed excel-lent agreement. Also, impressive trend conformity was observed between in-vitro hemolysis results and numerical data. Comparison of design variations yielded clear trends and results. Design C revealed the best hydraulic and hemolytic properties and was chosen as the final design for the mixed-flow rotary blood pump.