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International Journal of Chronic... 2020To determine the clinical and economic consequences of inhaled corticosteroid doses and particle size in patients on triple-inhalation therapy for COPD.
OBJECTIVE
To determine the clinical and economic consequences of inhaled corticosteroid doses and particle size in patients on triple-inhalation therapy for COPD.
METHODS
Patients aged ≥40 years who initiated treatment with multi-inhaler triple-inhaled therapy between 1 January 2015 and 31 March were included and followed for 1 year. Patients were grouped according to inhaled corticosteroid (ICS) dose (low/medium/high) and particle size device (extrafine/non-extrafine particles). Outcome variables were moderate and severe exacerbations, pneumonia and healthcare resource use (HCRU) costs. A multivariate analysis was performed for model correction (p<0.05).
RESULTS
A total of 2185 patients (mean age 72.3 years, 82.9% male) were analysed. Of these, 849 (38.9%) patients received low-dose ICS, 612 medium-dose ICS (28.0%) and 724 (33.1%) high-dose ICS. Exacerbations occurred more frequently with increasing IC dose (low: 26.4%, medium: 28.7% and high: 30.4%; p=0.047), as did the proportion of pneumonia (3.4%, 4.2% and 6.9%, respectively (p=0.041)). The annual mean cost/unit was € 2383 for low dose, € 2401 for medium dose and € 2625 for high dose (p=0.024). Four hundred and sixty-two (31.6%) patients used an extrafine particle device and 999 (68.4%) a non-extrafine particle device: the proportion of exacerbations was 24.0% vs 30.4% (p=0.012), and the annual mean cost/unit was € 2090 vs € 2513, respectively (p<0.001). The number of exacerbations was directly correlated with FEV (β= -0.157), age (β=0.071), Charlson index (β=0.050) and device type (extrafine: β=0.049) (p<0.02).
CONCLUSION
In patients with COPD receiving multi-inhaler triple therapy, higher ICS doses were not associated with a further reduction in exacerbations, whereas we found an increased risk of pneumonia. The use of inhaler devices delivering extrafine ICS particle was associated with a lower rate of exacerbations, resulting in lower overall HCRU costs.
Topics: Administration, Inhalation; Adrenal Cortex Hormones; Adrenergic beta-2 Receptor Agonists; Aged; Female; Humans; Male; Particle Size; Pulmonary Disease, Chronic Obstructive; Respiratory Therapy
PubMed: 33328730
DOI: 10.2147/COPD.S281333 -
The Cochrane Database of Systematic... Jun 2012The outcome of glaucoma surgery can be affected by the rate at which the surgical wound heals. Beta radiation has been proposed as a rapid and simple treatment to slow... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
The outcome of glaucoma surgery can be affected by the rate at which the surgical wound heals. Beta radiation has been proposed as a rapid and simple treatment to slow down the healing response.
OBJECTIVES
To assess the effectiveness of beta radiation during glaucoma surgery (trabeculectomy).
SEARCH METHODS
We searched CENTRAL (which contains the Cochrane Eyes and Vision Group Trials Register) (The Cochrane Library 2012, Issue 3), MEDLINE (January 1950 to March 2012), EMBASE (January 1980 to March 2012), the metaRegister of Controlled Trials (mRCT) (www.controlled-trials.com), ClinicalTrials.gov (www.clinicaltrials.gov) and the WHO International Clinical Trials Registry Platform (ICTRP) (www.who.int/ictrp/search/en). There were no date or language restrictions in the electronic searches for trials. The electronic databases were last searched on 26 March 2012.
SELECTION CRITERIA
We included randomised controlled trials comparing trabeculectomy with beta radiation to trabeculectomy without beta radiation.
DATA COLLECTION AND ANALYSIS
We collected data on surgical failure (intraocular pressure > 21 mmHg), intraocular pressure and adverse effects of glaucoma surgery. We pooled data using a fixed-effect model.
MAIN RESULTS
We found four trials that randomised 551 people to trabeculectomy with beta irradiation versus trabeculectomy alone. Two trials were in Caucasian people (126 people), one trial in black African people (320 people) and one trial in Chinese people (105 people). People who had trabeculectomy with beta irradiation had a lower risk of surgical failure compared to people who had trabeculectomy alone (pooled risk ratio (RR) 0.23 (95% CI 0.14 to 0.40). Beta irradiation was associated with an increased risk of cataract (RR 2.89, 95% CI 1.39 to 6.0).
AUTHORS' CONCLUSIONS
Trabeculectomy with beta irradiation has a lower risk of surgical failure compared to trabeculectomy alone. A trial of beta irradiation versus anti-metabolite is warranted.
Topics: Beta Particles; Cataract; Combined Modality Therapy; Glaucoma; Humans; Randomized Controlled Trials as Topic; Trabeculectomy; Treatment Outcome; Wound Healing
PubMed: 22696336
DOI: 10.1002/14651858.CD003433.pub3 -
Journal of Lipid Research Sep 2001There is general consensus that amphipathic alpha-helices and beta sheets represent the major lipid-associating motifs of apolipoprotein (apo)B-100. In this review, we... (Review)
Review
There is general consensus that amphipathic alpha-helices and beta sheets represent the major lipid-associating motifs of apolipoprotein (apo)B-100. In this review, we examine the existing experimental and computational evidence for the pentapartite domain structure of apoB. In the pentapartite nomenclature presented in this review (NH(2)-betaalpha(1)-beta(1)-alpha(2)-beta(2)-alpha(3)-COOH), the original alpha(1) globular domain (Segrest, J. P. et al. 1994. Arterioscler. Thromb. 14: 1674;-1685) is expanded to include residues 1;-1,000 and renamed the betaalpha(1) domain. This change reflects the likelihood that the betaalpha(1) domain, like lamprey lipovitellin, is a globular composite of alpha-helical and beta-sheet secondary structures that participates in lipid accumulation in the co-translationally assembled prenascent triglyceride-rich lipoprotein particles. Evidence is presented that the hydrophobic faces of the amphipathic beta sheets of the beta(1) and beta(2) domains of apoB-100 are in direct contact with the neutral lipid core of apoB-containing lipoproteins and play a role in core lipid organization. Evidence is also presented that these beta sheets largely determine LDL particle diameter. Analysis of published data shows that with a reduction in particle size, there is an increase in the number of amphipathic helices of the alpha(2) and alpha(3) domains associated with the surface lipids of the LDL particle; these increases modulate the surface pressure decreases caused by a reduction in radius of curvature. The properties of the LDL receptor-binding region within the overall domain structure of apoB-100 are also discussed. Finally, recent three-dimensional models of LDL obtained by cryoelectron microscopy and X-ray crystallography are discussed. These models show three common features: a semidiscoidal shape, a surface knob with the dimensions of the betaC globular domain of lipovitellin, and planar multilayers in the lipid core that are approximately 35 A apart; the multilayers are thought to represent cholesteryl ester in the smectic phase. These models present a conundrum: are LDL particles circulating at 37 degrees C spheroidal in shape, as generally assumed, or are they semidiscoidal in shape, as suggested by the models? The limited evidence available supports a spheroidal shape.
Topics: Animals; Apolipoprotein B-100; Apolipoproteins B; Binding Sites; Computer Simulation; Detergents; Humans; Lipoproteins, LDL; Models, Molecular; Protein Conformation; Protein Structure, Secondary; Receptors, LDL; Solubility; Structure-Activity Relationship
PubMed: 11518754
DOI: No ID Found -
Journal of Biomedical Optics Feb 2013Cerenkov luminescence imaging is an emerging optical preclinical modality based on the detection of Cerenkov radiation induced by beta particles when traveling though...
Cerenkov luminescence imaging is an emerging optical preclinical modality based on the detection of Cerenkov radiation induced by beta particles when traveling though biological tissues with a velocity greater than the speed of light. We present the first human Cerenkography obtained by detecting Cerenkov radiation escaping the thyroid gland of a patient treated for hyperthyroidism. The Cerenkov light was detected using an electron multiplied charge coupled device and a conventional C-mount lens. The system set-up has been tested by using a slab of ex vivo tissue equal to a 1 cm slice of chicken breast in order to simulate optical photons attenuation. We then imaged for 2 min the head and neck region of a patient treated orally 24 h before with 550 MBq of I-131. Co-registration between photographic and Cerenkov images showed a good localization of the Cerenkov light within the thyroid region. In conclusion, we showed that it is possible to obtain a planar image of Cerenkov photons escaping from a human tissue. Cerenkography is a potential novel medical tool to image superficial organs of patients treated with beta minus radiopharmaceuticals and can be extended to the imaging of beta plus emitters.
Topics: Animals; Beta Particles; Chickens; Diagnostic Imaging; Fluorodeoxyglucose F18; Humans; Hyperthyroidism; Luminescence; Optical Devices; Optical Phenomena; Phantoms, Imaging; Radionuclide Imaging; Radiopharmaceuticals; Radiotherapy Dosage; Thyroid Gland
PubMed: 23334715
DOI: 10.1117/1.JBO.18.2.020502 -
Journal of Nuclear Medicine : Official... Jan 2005The use of monoclonal antibodies to deliver radioisotopes directly to tumor cells has become a promising strategy to enhance the antitumor effects of native antibodies.... (Review)
Review
The use of monoclonal antibodies to deliver radioisotopes directly to tumor cells has become a promising strategy to enhance the antitumor effects of native antibodies. Since the alpha- and beta-particles emitted during the decay of radioisotopes differ in significant ways, proper selection of isotope and antibody combinations is crucial to making radioimmunotherapy a standard therapeutic modality. Because of the short pathlength (50-80 microm) and high linear energy transfer ( approximately 100 keV/microm) of alpha-emitting radioisotopes, targeted alpha-particle therapy offers the potential for more specific tumor cell killing with less damage to surrounding normal tissues than beta-emitters. These properties make targeted alpha-particle therapy ideal for the elimination of minimal residual or micrometastatic disease. Radioimmunotherapy using alpha-emitters such as (213)Bi, (211)At, and (225)Ac has shown activity in several in vitro and in vivo experimental models. Clinical trials have demonstrated the safety, feasibility, and activity of targeted alpha-particle therapy in the treatment of small-volume and cytoreduced disease. Further advances will require investigation of more potent isotopes, new sources and methods of isotope production, improved chelation techniques, better methods for pharmacokinetic and dosimetric modeling, and new methods of isotope delivery such as pretargeting. Treatment of patients with less-advanced disease and, ultimately, randomized trials comparing targeted alpha-particle therapy with standard approaches will be required to determine the clinical utility of this approach.
Topics: Alpha Particles; Animals; Antibodies, Monoclonal; Clinical Trials as Topic; Drug Delivery Systems; Humans; Neoplasms; Practice Guidelines as Topic; Practice Patterns, Physicians'; Radioimmunotherapy; Radioisotopes; Radiopharmaceuticals; Treatment Outcome
PubMed: 15653670
DOI: No ID Found -
The Oncologist Feb 2006
Topics: Beta Particles; Humans; Neoplasms; Radioactivity; Radioimmunotherapy; Radioisotopes
PubMed: 16476838
DOI: 10.1634/theoncologist.11-2-181 -
Dalton Transactions (Cambridge, England... Nov 2007Monoclonal antibodies have become a viable strategy for the delivery of therapeutic, particle emitting radionuclides specifically to tumor cells to either augment... (Review)
Review
Monoclonal antibodies have become a viable strategy for the delivery of therapeutic, particle emitting radionuclides specifically to tumor cells to either augment anti-tumor action of the native antibodies or to solely take advantage of their action as targeting vectors. Proper and rational selection of radionuclide and antibody combinations is critical to making radioimmunotherapy (RIT) a standard therapeutic modality due to the fundamental and significant differences in the emission of either alpha- and beta-particles. The alpha-particle has a short path length (50-80 microm) that is characterized by high linear energy transfer (100 keV microm(-1)). Actively targeted alpha-therapy potentially offers a more specific tumor cell killing action with less collateral damage to the surrounding normal tissues than beta-emitters. These properties make targeted alpha-therapy an appropriate therapy to eliminate minimal residual or micrometastatic disease. RIT using alpha-emitters such as (213)Bi, (211)At, (225)Ac, and others has demonstrated significant activity in both in vitro and in vivo model systems. Limited numbers of clinical trials have progressed to demonstrate safety, feasibility, and therapeutic activity of targeted alpha-therapy, despite having to traverse complex obstacles. Further advances may require more potent isotopes, additional sources and more efficient means of isotope production. Refinements in chelation and/or radiolabeling chemistry combined with rational improvements of isotope delivery, targeting vectors, molecular targets, and identification of appropriate clinical applications remain as active areas of research. Ultimately, randomized trials comparing targeted alpha-therapy combined with integration into existing standards of care treatment regimens will determine the clinical utility of this modality.
Topics: Alpha Particles; Antibodies, Monoclonal; Humans; Neoplasms; Radioimmunotherapy
PubMed: 17992276
DOI: 10.1039/b704726f -
Tumour Biology : the Journal of the... Jun 2012The effectiveness of targeted α-therapy (TAT) can be explained by the properties of α-particles. Alpha particles are helium nuclei and are ~8,000 times larger than... (Review)
Review
The effectiveness of targeted α-therapy (TAT) can be explained by the properties of α-particles. Alpha particles are helium nuclei and are ~8,000 times larger than β(-)-particles (electrons). When emitted from radionuclides that decay via an α-decay pathway, they release enormous amounts of energy over a very short distance. Typically, the range of α-particles in tissue is 50-100 μm and they have high linear energy transfer (LET) with a mean energy deposition of 100 keV/μm, providing a more specific tumor cell killing ability without damage to the surrounding normal tissues than β(-)-emitters. Due to these properties, the majority of pre-clinical and clinical trials have demonstrated that α-emitters such as (225)Ac, (211)At, (212)Bi, (213)Bi, (212)Pb, (223)Ra, and (227)Th are ideal for the treatment of smaller tumor burdens, micrometastatic disease, and disseminated disease. Even though these α-emitters have favorable properties, the development of TAT has been limited by high costs, unresolved chemistry, and limited availability of the radionuclides. To overcome these limitations, more potent isotopes, additional sources, and more efficient isotope production methods should be addressed. Furthermore, better chelation and labeling methods with the improvements of isotope delivery, targeting vehicles, molecular targets, and identification of appropriate clinical applications are still required.
Topics: Alpha Particles; Animals; Clinical Trials as Topic; Drug Evaluation, Preclinical; Humans; Neoplasms; Radioimmunotherapy; Radioisotopes
PubMed: 22143940
DOI: 10.1007/s13277-011-0286-y -
Food Science & Nutrition Mar 2021Heat treatment is widely used in food industry. Proteins and polysaccharides as important natural polymers in food, under heat treatment, the interactions between them...
Heat treatment is widely used in food industry. Proteins and polysaccharides as important natural polymers in food, under heat treatment, the interactions between them could mediate the conformation and functional properties of proteins. Thermally induced β-lactoglobulin-gum arabic complexes (β-Lg-GA) were fabricated, and the effect of heat treatment on physicochemical properties of the complexes was systematically investigated. The average particle size of β-Lg-GA complexes decreased with temperature increased, at 85°C, a smaller size of 273 nm was obtained. A saturated adsorption of GA was found when mass ratio of β-Lg/GA was <1:2. At pH = 4.2-7.0, electrostatic attraction between β-Lg and GA was low and a fairly constant turbidity was observed, the formed composite particles had good stability to the pH value. Through UV, fluorescence, and FTIR spectroscopy, it was found that formation of the nanoparticles relied on thermal denaturation and aggregation of protein, the electrostatic, hydrophobic, and hydrogen bonding interactions between β-Lg and GA were also important. Scanning electron microscope further indicated β-Lg and GA had good compatibility, and the complexes had a spherical core-shell structure at molecular level. In addition, these prepared natural nanoparticles by heat treatment show significantly higher encapsulation efficiency for (-)-epigallocatechin-3-gallate (EGCG) than that of unheated, thus could be used as a promising carrier for biologically active substances.
PubMed: 33747454
DOI: 10.1002/fsn3.2103 -
The Yale Journal of Biology and Medicine Dec 2011Radioimmunotherapy (RIT) of lymphoma with Zevalin and Bexxar was approved by FDA in 2002 and 2003, respectively, for the treatment of relapsed or refractory CD20+... (Review)
Review
Radioimmunotherapy (RIT) of lymphoma with Zevalin and Bexxar was approved by FDA in 2002 and 2003, respectively, for the treatment of relapsed or refractory CD20+ follicular B-cell non-Hodgkin´s lymphoma. In 2009, Zevalin was also approved for consolidation therapy in patients with follicular non-Hodgkin's lymphoma that achieve a partial or complete response to first-line chemotherapy. For follicular lymphoma patients, the overall response and progression-free survival rates have significantly improved since the implementation of RIT. The predominant complication of RIT is hematological toxicity that is usually manageable. There are ongoing trials to further define the expanding role of RIT as first line or concomitant therapy in the treatment of lymphoma as well as for certain antibiotic resistant infections and aggressive malignancies. There is also growing interest in the development of newer protocols for increased and more uniform dose delivery resulting in better outcomes and improved patient survival. This review will primarily focus on the role of RIT in treatment of non-Hodgkin's lymphoma, which is of established clinical utility and FDA approved. The mechanism of RIT, available radionuclides and pharmacokinetics, therapy administration, clinical utility and toxicities, and future directions would be discussed.
Topics: Antibodies, Monoclonal; Humans; Lymphoma, Non-Hodgkin; Radioimmunotherapy
PubMed: 22180677
DOI: No ID Found