Intervention to reduce unnecessary dispensing of short-acting {beta}-agonists in patients with asthma.

BACKGROUND: Several clinical studies have suggested that the overuse of short-acting beta-agonists (SABAs) and the underuse of inhaled corticosteroids are prevalent and may compromise patient health and increase the use of scarce health-care resources. OBJECTIVE: To examine the impact of an intervention designed to reduce SABA metered-dose inhaler (MDI) overdispensing on asthma-related drug and healthcare utilization endpoints in a mail order pharmacy benefit population. METHODS: Retrospective pre- and postintervention analysis was conducted on all new SABA prescriptions indicating a quantity more than 1 SABA MDI per month and on asthma patients who were continuously enrolled in the Medco Health Solutions prescription benefit program from July 1, 2006, to June, 30, 2007 (preintervention), and July 1, 2007, to June 30, 2008 (postintervention). The intervention involved a written or verbal request to the prescriber to reduce the quantity of SABA MDIs dispensed to less than 1 SABA MDI per month if determined appropriate by the prescriber. Effectiveness of the intervention on asthma-related drug and health-care utilization outcomes were measured in the overall Medco pharmacy population and in asthma patients receiving more than 1 SABA MDI per month. RESULTS: The percentage of new SABA prescriptions dispensed for more than 1 SABA MDI per month was significantly reduced during year 2 (22.9% vs 9.7%, p < 0.01). Of the 1835 asthma patients who received more than 1 SABA MDI per month in year 1, 1230 (67%) received fewer than 1 SABA MDI per month during year 2. The incidence of asthma-related hospitalizations, emergency department visits, and oral corticosteroid use did not significantly change from year 1 to year 2. CONCLUSIONS: This analysis shows that an intervention can succeed in reducing the overdispensing of quick-relief medication without compromising asthma control. Further investigation is warranted to better understand the interplay between reduction in excessive SABA use and improved clinical outcomes.

Morphology of nascent ziegler-natta polymers.

In the polymerization of alpha-olefins with heterogeneous Ziegler-Natta catalysts, the polymer is formed directly as long fibrillar units with folder chains. It is proposed that the fibrils are formed by the crystallization of polymer chains growing from the active sites on the catalyst surface, a process which is likened to root growth in whiskers.

Water quality modelling of the Mekong River basin: Climate change and socioeconomics drive flow and nutrient flux changes to the Mekong Delta.

The Mekong delta is recognised as one of the world's most vulnerable mega-deltas, being subject to a range of environmental pressures including sea level rise, increasing population, and changes in flows and nutrients from its upland catchment. With changing climate and socioeconomics there is a need to assess how the Mekong catchment will be affected in terms of the delivery of water and nutrients into the delta system. Here we apply the Integrated Catchment model (INCA) to the whole Mekong River Basin to simulate flow and water quality, including nitrate, ammonia, total phosphorus and soluble reactive phosphorus. The impacts of climate change on all these variables have been assessed across 24 river reaches ranging from the Himalayas down to the delta in Vietnam. We used the UK Met Office PRECIS regionally coupled climate model to downscale precipitation and temperature to the Mekong catchment. This was accomplished using the Global Circulation Model GFDL-CM to provide the boundary conditions under two carbon control strategies, namely representative concentration pathways (RCP) 4.5 and a RCP 8.5 scenario. The RCP 4.5 scenario represents the carbon strategy required to meet the Paris Accord, which aims to limit peak global temperatures to below a 2 °C rise whilst seeking to pursue options that limit temperature rise to 1.5 °C. The RCP 8.5 scenario is associated with a larger 3-4 °C rise. In addition, we also constructed a range of socio-economic scenarios to investigate the potential impacts of changing population, atmospheric pollution, economic growth and land use change up to the 2050s. Results of INCA simulations indicate increases in mean flows of up to 24%, with flood flows in the monsoon period increasing by up to 27%, but with increasing periods of drought up to 2050. A shift in the timing of the monsoon is also simulated, with a 4 week advance in the onset of monsoon flows on average. Decreases in nitrogen and phosphorus concentrations occur primarily due to flow dilution, but fluxes of these nutrients also increase by 5%, which reflects the changing flow, land use change and population changes.

Cellulose synthesis by Acetobacter xylinum. I. Low molecular weight compounds present in the region of synthesis.

An analysis has been made of the low molecular weight fraction present in the region of cellulose synthesis in Acetobacter xylinum suspensions. A number of nucleic acid bases, nucleosides and nucleotides, together with alpha-glucose 1-phosphate and UDPG, were detected in various extracts of washed cells supplied with glucose. Since glucose-6-P could be detected in extracts of ultrasonically disrupted cells, but not in extracts of whole cells, it was concluded that separate pools of hexose phosphate exist in A. xylinum. Preferential release of alpha-glucose-1-P, UDPG and nucleotides was observed during ethanol and EDTA treatment of bacteria. Electron microscopic examination of treated and untreated cells revealed that extensive modification of the cell wall region occurred during such treatments. The results support the proposal that alpha-glucose-1-P, UDPG and nucleotide pools are localised in the cell envelope region, possibly in the periplasm, and that A. xylinum possesses a second permeability barrier outside the cytoplasmic membrane. Nucleic acid bases and nucleosides were observed to diffuse freely through the cell wall and accumulate in the medium, probably as the result of nucleic acid breakdown. The results imply that the effects of cell damage caused by the isolation of the bacteria from the surface pellicle of the culture medium, together with nutrient deprivation, should be considered in work using the non-proliferating system. A stydy of the variation in concentration with time of alpha-glucose-1-P and UDPG, during cellulose synthesis, indicated that both components may play an immediate role in cellulose synthesis. Glycosylated lipid compounds were detected in both cell wall extracts and supernatant fluid, but it is not certain whether these compounds are constituents of the supernatant fluid in vivo.

Cellulose synthesis by Acetobacter xylinum. II. Investigation into the relation between cellulose synthesis and cell envelope components.

Cell envelope fractions, capable of cellulose synthesis from uridine diphosphate glucose, alpha-glucose-1-phosphate, glucose-6-phosphate and glucose, have been isolated from Acetobacter xylinum suspensions and various enzymatic properties examined. Essential enzymes were found to be distributed throughout the cell envelope region, with both inner (cytoplasmic) and outer (cell wall) membranes contributing to cellulose synthesis. The central role of UDPG in cellulose synthesis was confirmed and the results indicated that the nucleoside diphosphate sugar functions solely in the cell envelope region of whole cells. A comparison of properties of the cell envelope system with those of different preparations used by other workers, suggested that the method of cell disruption may influence substrate specificity.

Cellulose synthesis by Acetobacter xylinum. III. Matrix, primer and lipid requirements and heat stability of the cellulose-forming enzymes.

The addition of soluble cellodextrins of increasing size to a cell envelope preparation of Acetobacter xylinum stimulated cellulose synthesis from UDPG. This stimulation was attributed to both acceptor and activator effects. Enzymes required for cellulose synthesis were found to be heat-unstable and those required for synthesis of glycosylated lipid components from UDPG, heat-stable. Both heat-inactivated envelope fragments and supernatant fluid from whole cells were necessary for cellulose synthesis from UDPG. Cellulose was not formed from UDPG in the presence of either supernatant fluid alone or heat-inactivated envelopes alone. The combined results of this and previous studies suggest that either the cell envelope is necessary for synthesis of a more immediate precursor to cellulose than UDPG, or that the synthesis from UDPG requires a matrix. The former suggestion and its possible link with lipid intermediate involvement was strengthened by the observation of inefficient glycosylated lipid formation by a celluloseless mutant strain of A. xylinum. The possible locations of various enzyme activities required for the synthesis of the cellulose precursor are indicated and a possible microfibril nucleation process is discussed.

Clonally unrelated BCR-ABL-negative acute myeloblastic leukemia masquerading as blast crisis after busulphan and interferon therapy for BCR-ABL-positive chronic myeloid leukemia.

We report a patient with Philadelphia (Ph)-positive, BCR-ABL rearrangement positive, chronic myeloid leukemia (CML) with a prolonged chronic phase of 24 years who was first prescribed alpha-2 interferon 22 years after initial diagnosis. This therapy was tolerated poorly on account of thrombocytopenia, but an eventual major cytogenetic response was followed soon afterwards by transformation to terminal acute myeloid leukemia (AML). Cytogenetic studies indicated that the transformed myeloblasts were karyotypically normal and Ph negative. Although polymerase chain reaction (PCR) analysis of total leukemic mRNA remained BCR-ABL positive, other molecular studies, including Southern blotting and fluorescent in situ hybridization (FISH) analyses, showed that myeloblasts were BCR-ABL rearrangement negative. PCR-based clonality studies using an X-chromosome-linked restriction fragment polymorphism within the phosphoglycerate kinase gene (PGK1) further showed that the Ph-negative blast cells had a different clonal origin from the Ph-positive clone of chronic phase. We suggest that cases of underlying Ph-negative leukemic transformation in Ph-positive CML warrant further study and should be considered for trial of intensive remission induction therapy as appropriate for acute leukemia.

Polyploidy in myelodysplastic syndrome: a case report.

Structural chromosomal abnormalities are common in myelodysplastic syndromes (MDSs), and complex abnormalities are known to confer a poor prognosis. Polyploidy is rare. We report a patient with MDS in whom 8/15 cells were 77,XYY; 2/15 were 83,XYY, and 5/15 were diploid (46,XY). He experienced rapid evolution of disease, transforming to terminal acute leukemia.

Side-effects and weight gain following a smoking cessation program.

Few prospective studies on possible side-effects of smoking cessation have been reported. In the current study, a variety of side-effects and weight gain were assessed throughout and following a smoking cessation program with 94 subjects. Subjects in a cognitive urge control maintenance condition were found to have gained significantly more weight than other conditions. This group also tended to have the highest abstinence rate and lowest percent baseline smoking at follow-up. Abstainers tended to have gained more weight than relapsers , and had rated themselves as higher on "eating more" and had placed themselves as farthest from "optimal" on a measure of general appetite and overeating. On all other side-effects, however, relapsers appeared to be reporting more negative attributes. These results were discussed within the context of incorporating side-effect control strategies as part of smoking cessation programs.

Turkey poult tolerance to diets containing deoxynivalenol (vomitoxin) and salinomycin.

Feed taken from a commercial turkey farm where poults had refused to eat the feed and high mortality had occurred was analyzed and found to contain .81 mg/kg vomitoxin and 2.2 mg/kg salinomycin. The present four experiments investigated the effects of diets containing salinomycin at 0, 2.2, 5.5, 11, and 22 mg/kg and vomitoxin at 0, 2.2, and 4.4 mg/kg. A factorial design with vomitoxin at 0 and 4.4 mg/kg and salinomycin at 0 and 22 mg/kg was used in Experiment 4. Poults fed the suspect commercial diet had significantly lower feed consumption and higher motality than poults fed a control diet (P less than .05). Poults (0 to 3 wk of age) fed diets containing vomitoxin (4.4 mg/kg), salinomycin (22 mg/kg), or both showed no significant decrease in feed consumption, body weight gain, or viability.

An assessment of the effectiveness of the revised FDA checklist.

In 1978, the Food and Drug Administration (FDA), developed a generic anesthesia equipment preuse checklist. The checklist was first released by the FDA in August 1986 and endorsed by the American Association of Nurse Anesthetists on October 18, 1986. The FDA checklist was revised in 1992 to improve the abilities of anesthesia providers to detect machine faults. In the present study, the investigators attempted to determine the effectiveness of the revised FDA checklist in detection of anesthesia machine faults as compared to providers' usual methods. Whereas no published study of preanesthesia safety inspection had been performed since the revision of the FDA checklist, the authors compared the detection abilities of anesthesia providers before and after inclusion of the revised FDA checklist. Twenty-two anesthesia providers were tested to compare the number of prearranged anesthesia machine faults that could be detected with (1) their usual checkout methods, and (2) with the revised FDA checklist. Data describing the subjects' fault detection abilities were analyzed using the t test for paired observation (P value < 0.05 considered significant). Statistical analysis revealed no significant difference (P = 0.479) when subjects used the FDA checklist and when they used their usual method. Use of the FDA machine checklist was no more effective than the provider's usual method in discovering machine faults. When using their normal method, 54.5% of providers did not discover more than 50% of programmed faults. Approximately 40.9% of providers who used the revised FDA checklist did not discover over 50% of programmed faults.

Combination of chromium and biotin improves coronary risk factors in hypercholesterolemic type 2 diabetes mellitus: a placebo-controlled, double-blind randomized clinical trial.

Dyslipidemia, often found in type 2 diabetes mellitus (T2DM) patients, plays an important role in the progression of cardiometabolic syndrome. Two essential nutrients, chromium and biotin, may maintain optimal glycemic control. The authors report here a randomized, double-blind placebo-controlled trial (N=348; chromium picolinate and biotin combination [CPB]: 226, placebo: 122; T2DM participants with hemoglobin A1c [HbA1c] >or=7%) evaluating the effects of CPB on lipid and lipoprotein levels. Participants were randomly assigned (2:1 ratio) to receive either CPB (600 microg chromium as chromium picolinate and 2 mg biotin) or a matching placebo once daily for 90 days. Statistical analyses were conducted in all eligible participants. Subsequent supplemental analyses were performed in T2DM participants with hypercholesterolemia (HC) and in those using stable doses of statins. In the primary analysis, CPB lowered HbA1c (P<.05) and glucose (P<.02) significantly compared with the placebo group. No significant changes were observed in other lipid levels. In participants with HC and T2DM, significant changes in total cholesterol and low-density lipoprotein cholesterol (LDL-C) levels and atherogenic index were observed in the CPB group (P<.05). Significant decreases in LDL-C, total cholesterol, HbA1c , and very low-density cholesterol levels (P<.05) were observed in the CPB group taking statins. CPB treatment was well tolerated with no adverse effects, dissimilar from those associated with placebo. These data suggest that intervention with CPB improves cardiometabolic risk factors.

Thrombocytopenia-Platelet Support or Growth Factors?

The prevention and treatment of hemorrhage in patients with severe thrombocytopenia following cytotoxic chemotherapy and/or radiotherapy remain important issues in the supportive care of these patients. Platelet transfusions have been available for this purpose for over 30 years, and there have been recent initiatives to refine the way in which they are used and to improve their safety. An alternative to platelet transfusions is the enhancement of platelet recovery through the use of hemopoietic growth factors, and the recent identification of thrombopoietin and its potential for clinical use are exciting developments. Further work is needed to ensure its safety, and to define the appropriate indications for its use. Another alternative to platelet transfusions is the use of platelet substitutes, and a number of products are being developed. The clinical use of hemopoietic growth factors and platelet substitutes raises the prospect of reducing the current high demand for platelet concentrates. However, it remains to be seen whether their potential will be fully realised, and platelet transfusions will continue to be needed for the forseeable future.

A method for the assessment of body image disturbance in patients with eating disorders.

This paper describes a new method for assessing body image disturbances in eating disordered patients. Fifteen bulimic, 25 anorexic, and 24 normal controls served as subjects. All subjects were matched for age and height, and bulimics and controls were matched for weight as well. All subjects completed the Perceived Body Image Scale (PBIS), which required subjects to report on how they see themselves when they look in the mirror, how they think they look, and how they feel themselves to be, reflecting the perceptual, cognitive, and affective aspects of body image, respectively. Subjects also selected their ideal. An objective rating was made. Objective ratings had a high correlation with the subject's weight. Results showed that both eating disorder groups demonstrated more apparent body image disturbance than controls, and that the bulimics showed significantly greater body image dissatisfaction than anorexics or controls. The potential use of the PBIS as a research and clinical instrument is discussed.