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Primary Care Respiratory Journal :... Sep 2009Mild persistent asthma should be treated with continuous inhaled corticosteroids (ICS), which reduces exacerbations of disease, controls symptoms and reduces bronchial... (Review)
Review
Mild persistent asthma should be treated with continuous inhaled corticosteroids (ICS), which reduces exacerbations of disease, controls symptoms and reduces bronchial mucosal inflammation. Most patients can be controlled with low dosage ICS (
dosages. There is some evidence of additional benefit of early treatment in terms of better longer term control of symptoms, but not alteration of the natural history of the disease. Withdrawal of ICS therapy results in rapid relapse of symptoms. Although some studies have suggested that intermittent therapy with ICS is not detrimental to asthma control, in the absence of any studies investigating the long term clinical, functional and pathophysiological differences between regular and intermittent therapy, the former continues to be recommended in guidelines. In patients well controlled on low/moderate dosages of ICS there is little benefit of adding any other medication and no rationale for commencing combination therapy routinely as first line controller therapy. There is no evidence that ICS or any other medication prevents the occurrence of asthma, and scanty evidence that the decline in lung function associated with asthma is arrested to any significant degree by ICS therapy. ICS has variable effects on features of airways remodelling but the long term physiological consequences of these effects, if any, are as yet unknown. Topics: Administration, Inhalation; Adrenal Cortex Hormones; Asthma; Drug Administration Schedule; Humans; Primary Health Care
PubMed: 19513496
DOI: 10.4104/pcrj.2009.00035 -
Brazilian Journal of Biology = Revista... 2023Aedes aegypti control is achieved with chemical insecticides that can promote insecticide resistance. In the search for new forms of control, the use of botanical...
Aedes aegypti control is achieved with chemical insecticides that can promote insecticide resistance. In the search for new forms of control, the use of botanical products is currently growing and many tests with oils have already been performed. The plant diversity of Araripe National Forest enables the study of several species against this vector. To evaluate the larvicidal effect of essential oils from plants of this forest, we used field rosemary, copaiba, bay leaf, cashew and pequi. The work was divided into three stages: all oils with the same dosage; the best oil at dosages of 0, 5, 10, 20, 50 and 75 µg/mL; and the best dosage at temperatures of 15, 20, 25, 30 and 35 °C. The oils of field rosemary, copaiba, bay leaf, cashew and pequi were good insecticides when used at dosages above 5 μg/mL. The bay leaf oil showed high larvicidal activity at all dosages tested, showing the highest efficiency at 75 μg/mL. Temperatures of 15 and 35 °C increased the susceptibility of the insect to the effect of the bay leaf oil. The essential oils of field rosemary, copaiba, bay leaf, cashew and pequi, from Araripe National Forest, applied at a dosage of 5μg/mL, showed insecticidal action, although with low efficiency.
Topics: Animals; Oils, Volatile; Aedes; Insecticides; Larva; Mosquito Vectors; Plant Oils
PubMed: 38055504
DOI: 10.1590/1519-6984.275062 -
Indian Journal of Thoracic and... Oct 2019Vitamin K antagonists (VKAs), such as warfarin and acenocoumarol, exert their anti-coagulant effect by inhibiting the subunit 1 of vitamin K epoxide reductase complex...
PURPOSE
Vitamin K antagonists (VKAs), such as warfarin and acenocoumarol, exert their anti-coagulant effect by inhibiting the subunit 1 of vitamin K epoxide reductase complex (VKORC1). CYP2C9 is a hepatic drug-metabolizing enzyme in the CYP450 superfamily and is the primary metabolizing enzyme of warfarin. Three single nucleotide polymorphisms, two in the CYP2C9 gene, namely CYP2C9*2 and CYP2C9*3, and one in the VKORC1 gene (c.- 1639G > A, rs9923231), have been identified to reduce VKA metabolism and enhance their anti-coagulation effect. The purpose of this study is to evaluate the prevalence of CYP2C9 and VKORC1 polymorphism in Indians receiving VKA-based anti-coagulation after valve surgery and to evaluate the usefulness of genetic information in managing VKA-based anti-coagulation.
METHODS
In the current prospective observational study, 150 patients who underwent heart valve surgery and had stable INR were genotyped for VKORC1 (- 1639 G > A), CYP2C9*2, and CYP2C9*3. The VKA dosage was estimated from published algorithms and compared to the clinically stabilized dosage.
RESULTS
Out of 150 patients, 101 (67.33%) were on warfarin and 49 (32.66%) were on acenocoumarol. Majority of the patients, the 83 in warfarin group and the 40 in acenocoumarol group, had a wild CYP2C9 diplotype. The rest had a mutant (CYP2C9*2 or CYP2C9*3) diplotype. Similarly, 67 patients in the warfarin group and 35 patients in the acenocoumarol group had wild type (G/G) of VKORC1 genotype. The rest had a mutant (G/A or A/A) VKORC1 genotype. In the warfarin group, based on the genotype, 51.5% of the patients were extensive or normal metabolizers, and 47.4% of the patients were intermediate metabolizers of VKAs. In the acenocoumarol group, 61.2% of the patients were extensive or normal metabolizers, and 38.8% of the patients were intermediate metabolizers. Individually, alleles of VKORC1 (- 1639 G > A), CYP2C9*2, and CYP2C9*3 had mean dosage reduction effect on VKA dosage, which co-related to the clinically stabilized dosages ( < 0.0001). Among the VKORC1 (- 1639 G > A) cohort, the reduction in warfarin mean weekly dosage was 13.48 mg as compared to the wild-type category ( < 0.0001) and similarly, the reduction in the mean weekly acenocoumarol dose was 6.07 mg ( < 0.03) as compared to the wild type after adjusting for age, gender, and body mass index.
CONCLUSION
Single nucleotide polymorphism in the CYP2C9 gene and in the VKORC1 gene is present in nearly 40% of Indian patients. VKORC1 (- 1639 G > A), CYP2C9*2, and CYP2C9*3 genotypes have significant dosage-lowering effects on VKA-based anti-coagulation therapy. The trend in estimated dosages of VKAs co-related to that of observed the clinically stabilized dosage in the cohort. The pharmacogenomic calculators used in this study tend to overestimate the VKA dosages as compared to clinical dosage due to the limitations in the algorithms and in our study. A new algorithm based on a larger dataset capturing the vast genetic variability across the Indian population and relevant clinical factors could provide better results.
PubMed: 33061049
DOI: 10.1007/s12055-019-00812-3 -
The Journal of Headache and Pain Sep 2014Hemicrania continua ( HC) was described and coined by Sjaastad and Spierings in 1984. Later cases, carrying this appellation should, grossly, conform to this original...
Hemicrania continua ( HC) was described and coined by Sjaastad and Spierings in 1984. Later cases, carrying this appellation should, grossly, conform to this original description. The proposed classification criteria (ICHD, 3rd edition beta version) for HC has major shortcomings, and ordinary HC cases do not fulfill the proposed criteria. Relatively rare symptoms and signs are e.g. made obligatory (point C 1). And the recommended dosage of indomethacin- both test and long-term dosages-is unallowably high. In this way, bogus HC cases are systematically created. This irrational diagnostic system is in urgent need of a major revision.
Topics: Anti-Inflammatory Agents, Non-Steroidal; Female; Headache Disorders; Humans; Indomethacin; Male
PubMed: 25216994
DOI: 10.1186/1129-2377-15-61 -
International Journal of Environmental... Feb 2020The solidification/stabilization (S/S) method is the usual technique for the remediation of soils polluted by heavy metal in recent years. However, freeze-thaw cycles,...
The solidification/stabilization (S/S) method is the usual technique for the remediation of soils polluted by heavy metal in recent years. However, freeze-thaw cycles, an important physical process producing weathering of materials, will affect the long-term stability of engineering characteristics in solidified contaminated soil. In addition, it is still questionable whether using large dosages of binders can enhance the engineering properties of solidified/stabilized contaminated soils. In this study, the three most commonly used binders (i.e., cement, quicklime, and fly ash), alone and mixed in different ratios, were thus added to lead-contaminated soil in various dosages, making a series of cured lead-contaminated soils with different dosages of binders. Afterward, unconfined compression strength tests, direct shear tests, and permeability tests were employed on the resulting samples to find the unconfined compressive strength (UCS), secant modulus ( E 50 ), internal friction angle ( φ ), cohesion ( c ), and permeability coefficient ( k ) of each solidified/stabilized lead-contaminated soil after 0, 3, 7, and 14 days of freeze-thaw cycles. This procedure was aimed at evaluating the influence of freeze-thaw cycle and binder dosage on engineering properties of solidified/stabilized lead-contaminated soils. Results of our experiments showed that cement/quicklime/fly ash could remediate lead-contaminated soils. However, it did not mean that the more the dosage of binder, the better the curing effect. There was a critical dosage. Excessive cementation of contaminated soils caused by too much binder would result in loss of strength and an increase in permeability. Furthermore, it was found that UCS, E 50 , φ , c , and k values generally decreased with the increase in freeze-thaw cycle time-a deterioration effect on the engineering characteristics of solidified lead-contaminated soils. Avoiding excessive cementation, 2.5% cement or quicklime was favorable for the value of E 50 while a 2.5% fly ash additive was beneficial for the k value. It is also suggested that if the freeze-thaw cycle continues beyond the period supported by excessive cementation, such a cycle will rapidly destroy the original structure of the soil and create large cracks, leading to an increase in permeability. The results also showed that the contaminated soils with a larger dosage of binders exhibited more significant deterioration during freeze-thaw cycles.
Topics: Calcium Compounds; Coal Ash; Cold Temperature; Construction Materials; Engineering; Environmental Restoration and Remediation; Lead; Oxides; Soil; Soil Pollutants
PubMed: 32046273
DOI: 10.3390/ijerph17031077 -
Journal of Vector Borne Diseases 2022Bacillus subtilis subsp. subtilis (VCRC B471) and Pseudomonas fluorescens (B426) produce mosquitocidal biosurfactant, surfactin and di-rhamnolipid. The objective of the...
BACKGROUND & OBJECTIVES
Bacillus subtilis subsp. subtilis (VCRC B471) and Pseudomonas fluorescens (B426) produce mosquitocidal biosurfactant, surfactin and di-rhamnolipid. The objective of the study was to carry out a small-scale field evaluation of the two biosurfactants to determine the efficacy, application dosage, residual activity and frequency of application against Anopheles stephensi immatures in selected sites in Goa, India.
METHODS
Surfactin (VCRC B471) and di-rhamnolipid (VCRC B426) were formulated as aqueous suspensions (5% AS), and were applied at the dosages of 34, 51 and 68 mL/m and 27, 41 and 54 mL/m respectively. Two experiments were carried out with the two formulations.
RESULTS
Surfactin (VCRC B471) formulation was effective at all the dosages and there was sustained reduction (>80%) in immature density in the treated sites up to 18 days in experiment 1 and up to 15 days in experiment 2. No pupae were found in the treated sites throughout the study. Di-rhamnolipid (VCRC B426) formulation was also found to reduce the immature density in the treated sites up to 14 days in experiment 1 and up to 15 days in experiment 2.
INTERPRETATION & CONCLUSION
For VCRC B471, the optimum application dosage determined was 51 mL/m and for VCRC B426, 27mL/m. The formulations are to be applied fortnightly for effective control of Anopheles. The application dosage determined in the present study can be used for large scale field evaluation to assess their suitability for use in public health programmes for the control of Anopheles mosquitoes vectoring malaria.
Topics: Animals; Humans; Anopheles; Pseudomonas fluorescens; Malaria; Mosquito Vectors; Bacillus subtilis
PubMed: 36511041
DOI: 10.4103/0972-9062.342401 -
Addiction (Abingdon, England) Jan 2021Ukraine's HIV epidemic remains concentrated among opioid-dependent people who inject drugs (PWID) where opioid agonist therapies (OAT) like methadone (MMT) and... (Observational Study)
Observational Study
BACKGROUND AND AIMS
Ukraine's HIV epidemic remains concentrated among opioid-dependent people who inject drugs (PWID) where opioid agonist therapies (OAT) like methadone (MMT) and buprenorphine (BMT) maintenance treatments are the most cost-effective HIV prevention strategies, but remain under-scaled. This study aimed to measure the association between dose and type of OAT prescribed and treatment retention.
DESIGN
Observational longitudinal cohort study.
PARTICIPANTS AND SETTING
Patients (n = 15 290) prescribed OAT throughout Ukraine from 2004 through 2016.
MEASUREMENTS
Data were analyzed using time-event strategies to estimate cumulative treatment retention, defined as time to OAT discontinuation. Cumulative retention proportions at 1, 12 and 36 months were assessed for outcomes. Cox regression with log-rank likelihood assessed independent predictors of treatment discontinuation.
FINDINGS
The proportion prescribed high (MMT: > 85 mg; BMT: ≥ 16 mg), medium (MMT: > 40-85 mg; BMT: > 6-15 mg) and low (MMT: ≤ 40 mg; BMT: ≤ 6 mg) dosages was 25, 43 and 32%, respectively. Retention was significantly higher for BMT than MMT both at 12 (89 versus 75%) and 36 months (80 versus 56%). Although dosing levels for BMT did not influence retention, increasing dosages for MMT were significantly associated with higher retention rates at 1 (90, 96, 99%), 12 (59, 78, 91%) and 36 (34, 59, 79%) months, respectively. Independent predictors associated with 12-month OAT discontinuation were medium [adjusted hazard ratio (aHR) = 2.23; 95% confidence limit (CL) = 1.95-2.54] and low (aHR = 4.96; 95% CL = 4.37-5.63) OAT dosage relative to high dosage, male sex (aHR = 1.27; 95% CL = 1.14-1.41), MMT relative to BMT prescription (aHR = 1.57; 95% CL = 1.32-1.87) and receiving OAT in general (aHR = 1.22; 95% CL = 1.02-1.46) or tuberculosis (aHR = 1.43; 95% CL = 1.10-1.85) hospitals, relative to specialty addiction treatment and AIDS center settings. Lower dosages contributed more to dropout especially at 1 month (aHR 3.12; 95% CL = 2.21-4.41 and aHR 7.71; 95% CL = 5.51-10.79 for medium and low dosages, respectively). Younger age was significantly associated with OAT discontinuation only at 36 months (aHR = 1.08; 95% CI = 1.02-1.15).
CONCLUSIONS
Higher dosages of opioid agonist therapies, especially for methadone maintenance treatment patients, appear to be associated with higher levels of treatment retention in Ukraine.
Topics: Adult; Analgesics, Opioid; Buprenorphine; Cohort Studies; Female; Humans; Longitudinal Studies; Male; Methadone; Middle Aged; Opiate Substitution Treatment; Opioid-Related Disorders; Patient Dropouts; Time Factors; Ukraine
PubMed: 32428276
DOI: 10.1111/add.15115 -
Antimicrobial Agents and Chemotherapy May 2023Fosfomycin is gaining interest in the treatment of complex osteoarticular infections (OI) due to MDR pathogens. The aims were to conduct population pharmacokinetics of...
Population pharmacokinetics and Monte Carlo simulation for dosage optimization of fosfomycin in the treatment of osteoarticular infections in patients without renal dysfunction.
Fosfomycin is gaining interest in the treatment of complex osteoarticular infections (OI) due to MDR pathogens. The aims were to conduct population pharmacokinetics of fosfomycin in a cohort of OI patients receiving 16g/daily by intermittent (II) or continuous infusion (CI), and to carry out Monte Carlo simulations for dosage optimization in the treatment of these infections. Patients underwent blood sampling on day 5 of therapy (2-3 serial samples). Population pharmacokinetics and Monte Carlo simulations were performed to define the probability of target attainment (PTA) of 70% T>MIC, and the cumulative fraction of response (CFR) against common OI pathogens with dosages of 8, 12, 16, and 20g/day administered by II, extended-infusion (EI) or CI. Forty-eight patients were recruited. A two-compartment open model with infusion input and first-order elimination was developed. Estimated creatinine clearance (CL) was included as covariate in the final model. Monte Carlo simulations showed that optimal PTAs and CFRs (≥90%) may be achieved in three different classes of renal function by administering a daily dosage of: 2g q6h by II against , , ESBL-producing and MRSA; 8g by CI against CoNS, and ESBL-producing ; 12g by CI against , and 16g by CI against KPC-producing Our study provides a strong rationale for considering fosfomycin dosages of 8-16 g daily by CI in several clinical scenarios for OI patients. Feasibility of administration by CI in an elastomeric pump makes fosfomycin a candidate for OPAT programs.
PubMed: 33619055
DOI: 10.1128/AAC.02038-20 -
Anales Del Sistema Sanitario de Navarra 2003Once the efficacy and safety of immunotherapy with allergen extracts has been shown, recently it has become evident the need for perfecting those aspects of the... (Clinical Trial)
Clinical Trial Randomized Controlled Trial
Once the efficacy and safety of immunotherapy with allergen extracts has been shown, recently it has become evident the need for perfecting those aspects of the treatment that can be improved, such as its dosage form. The conventional dosage of subcutaneous immunotherapy in the phase of dose increase is slow in reaching an efficient level. For this reason other alternative dosages to the conventional one have been tried out, such as grouped dosages, which shorten this period of dose increase. On condition that the safety of the treatment is guaranteed, these doses offer the advantages of reducing the economic cost and the time involved, of reducing the discomfort of the treatment and of improving the patient's adherence to the treatment, and possibly of reaching clinical efficacy more rapidly. Nonetheless, it is not easy to determine the suitable dosage of administration (the shortest and with the least number of adverse reactions) and this article reviews the existing problems when it comes to designing these grouped doses. Finally, we present the results of a comparative study between the conventional dose and a grouped dose, with a double blind design, carried out by us, which shows that the grouped dose is quicker in achieving the desired clinical efficacy, shortens the times of reduction of cutaneous sensitivity to the allergen and of modification of the immunological parameters, all with a low frequency of adverse reactions that is similar to that registered with the conventional dosage.
Topics: Adolescent; Adult; Allergens; Dosage Forms; Double-Blind Method; Female; Humans; Immunotherapy; Male; Prospective Studies
PubMed: 13679971
DOI: No ID Found -
NPJ Primary Care Respiratory Medicine Aug 2020There is an ongoing debate about the benefit-risk balance of systemic corticosteroids (SCS) in asthma treatment. We investigated the associations between SCS use and...
There is an ongoing debate about the benefit-risk balance of systemic corticosteroids (SCS) in asthma treatment. We investigated the associations between SCS use and disease burden in a database cohort of asthmatics, categorized into SCS and non-SCS prescription at baseline and quartiles (Q) by cumulative SCS dosage. Of the 10,579 patients, the SCS cohort comprised 3103 patients (29.3%). Mean SCS dosages at baseline were 0.08, 0.29, 0.79, and 4.58 mg/day in Q1, Q2, Q3, and Q4, respectively. Similar SCS dosages were used within each quartile throughout the study period. No remarkable changes in asthma severity or control status were observed. All SCS cohorts had a higher risk of intermittent SCS exposure during the observation period. SCS use was associated with osteoporosis, diabetes, anxiety/neurosis, and depression. SCS-dependent treatment does not necessarily lead to the future improvement of asthma control; rather, it may negatively impact systemic health, even at mean dosages <5 mg/day.
Topics: Adrenal Cortex Hormones; Anti-Asthmatic Agents; Asthma; Cost of Illness; Female; Health Care Costs; Humans; Male; Middle Aged; Risk Assessment; Severity of Illness Index
PubMed: 32753647
DOI: 10.1038/s41533-020-00192-x