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Zeitschriftenartikel zum Thema "Drug-reduced regimens"
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VanScoy, Brian, Jennifer McCauley, Sujata M. Bhavnani, Evelyn J. Ellis-Grosse und Paul G. Ambrose. „Relationship between Fosfomycin Exposure and Amplification of Escherichia coli Subpopulations with Reduced Susceptibility in a Hollow-Fiber Infection Model“. Antimicrobial Agents and Chemotherapy 60, Nr. 9 (06.06.2016): 5141–45. http://dx.doi.org/10.1128/aac.00355-16.
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ABSTRACTUnderstanding the relationship between antibiotic exposure and amplification of bacterial subpopulations with reduced drug susceptibility over time is important for evaluating the adequacy of dosing regimens. We utilized a hollow-fiber infection model to identify the fosfomycin intravenous dosing regimens that prevented the amplification ofEscherichia colibacterial subpopulations with reduced fosfomycin susceptibility. The challenge isolate wasE. coliATCC 25922 (agar MIC with glucose-6-phosphate, 1 mg/liter; agar MIC without glucose-6-phosphate, 32 mg/liter). The fosfomycin dosing regimens studied were 1 to 12 g every 8 h for 10 days to approximate that planned for clinical use. The studies included a no-treatment control regimen. Two bacterial subpopulations were identified, one with reduced susceptibility with agar MIC values ranging from 32 to 128 mg/liter and the other resistant with agar MIC values of 256 to >1,024 mg/liter on plates containing 5× and 256× the baseline MIC value, respectively. An inverted-U-shaped function best described the relationship between the amplification of the two bacterial subpopulations and drug exposure. The lowest fosfomycin dosing regimen that did not amplify a bacterial subpopulation with reduced susceptibility was 4 g administered every 8 h. Nearly immediate amplification of bacterial subpopulations with reduced susceptibility was observed with fosfomycin dosing regimens consisting of 1 to 2 g every 8 h. These data will be useful to support the selection of fosfomycin dosing regimens that minimize the potential for on-therapy amplification of bacterial subpopulations with reduced susceptibility.
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Ang, Zen Yang, Kit Yee Cheah, Nadiah B. Abdullah, Safawati B. Samsuri, Siao Hui Lee, Andrew WH Yem und Malathi AP Sriraman. „Parenteral cytotoxic drug wastage at a tertiary hospital in Kuala Lumpur: How much and why?“ Journal of Oncology Pharmacy Practice 26, Nr. 6 (06.12.2019): 1306–17. http://dx.doi.org/10.1177/1078155219891209.
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Purpose To identify the cost and reasons of returned parenteral chemotherapy regimens at a tertiary hospital in Kuala Lumpur, Malaysia. Methods Data were retrospectively extracted from all the Chemotherapy Return Forms in 2016, which is a compulsory documentation accompanying each return of parenteral chemotherapy regimen. The following data were extracted: patient’s diagnosis, gender, location of treatment (i.e. ward/daycare clinic), start date of chemotherapy regimen, type of cytotoxic drug returned, dose of cytotoxic drug returned, number of cytotoxic drug preparations returned and reason for return as well as whether the returned cytotoxic drug preparations could be re-dispensed. The cost of wastage was calculated based on the cost per mg (or per unit) of the particular returned cytotoxic drug. Results One hundred and fifty-nine cases of returned chemotherapy regimen comprising of 231 parenteral cytotoxic drug preparations were analysed. The total cost of returned chemotherapy regimen for 2016 was €3632, with €756 (20.8%) worth of chemotherapy regimens returned due to preventable reasons and €2876 (79.2%) worth of chemotherapy regimens returned due to non-preventable reasons. Approximately 50% of cases returned chemotherapy regimen were due to deterioration of patient’s clinical condition and another 24.5% of cases of returned chemotherapy regimen were attributed to adverse drug reactions. Conclusion Wastage associated to non-preventable reasons such as adverse drug reactions and preventable causes like refusal of patients can be further reduced by using newer healthcare innovations and establishment of written institutional protocols or standard operating procedures as references for in-charge healthcare personnel when cytotoxic drug-related issues occur. Adoption of cost-saving strategies that have been proven by studies could further improve current cost containment strategies.
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Via, Laura E., Kathleen England, Danielle M. Weiner, Daniel Schimel, Matthew D. Zimmerman, Emmanuel Dayao, Ray Y. Chen et al. „A Sterilizing Tuberculosis Treatment Regimen Is Associated with Faster Clearance of Bacteria in Cavitary Lesions in Marmosets“. Antimicrobial Agents and Chemotherapy 59, Nr. 7 (04.05.2015): 4181–89. http://dx.doi.org/10.1128/aac.00115-15.
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ABSTRACTShortening the lengthy treatment duration for tuberculosis patients is a major goal of current drug development efforts. The common marmoset develops human-like disease pathology and offers an attractive model to better understand the basis for relapse and test regimens for effective shorter duration therapy. We treatedMycobacterium tuberculosis-infected marmosets with two drug regimens known to differ in their relapse rates in human clinical trials: the standard four-drug combination of isoniazid, rifampin, pyrazinamide, and ethambutol (HRZE) that has very low relapse rates and the combination of isoniazid and streptomycin that is associated with higher relapse rates. As early as 2 weeks, the more sterilizing regimen significantly reduced the volume of lung disease by computed tomography (P= 0.035) and also significantly reduced uptake of [18F]-2-fluoro-2-deoxyglucose by positron emission tomography (P= 0.049). After 6 weeks of therapy, both treatments caused similar reductions in granuloma bacterial load, but the more sterilizing, four-drug regimen caused greater reduction in bacterial load in cavitary lesions (P= 0.009). These findings, combined with the association in humans between cavitary disease and relapse, suggest that the basis for improved sterilizing activity of the four-drug combination is both its faster disease volume resolution and its stronger sterilizing effect on cavitary lesions. Definitive data from relapse experiments are needed to support this observation.
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Rhee, Soo-Yon, Philip M. Grant, Philip L. Tzou, Geoffrey Barrow, P. Richard Harrigan, John P. A. Ioannidis und Robert W. Shafer. „A systematic review of the genetic mechanisms of dolutegravir resistance“. Journal of Antimicrobial Chemotherapy 74, Nr. 11 (05.07.2019): 3135–49. http://dx.doi.org/10.1093/jac/dkz256.
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Abstract Background Characterizing the mutations selected by the integrase strand transfer inhibitor (INSTI) dolutegravir and their effects on susceptibility is essential for identifying viruses less likely to respond to dolutegravir therapy and for monitoring persons with virological failure (VF) on dolutegravir therapy. Methods We systematically reviewed dolutegravir resistance studies to identify mutations emerging under dolutegravir selection pressure, the effect of INSTI resistance mutations on in vitro dolutegravir susceptibility, and the virological efficacy of dolutegravir in antiretroviral-experienced persons. Results and conclusions We analysed 14 studies describing 84 in vitro passage experiments, 26 studies describing 63 persons developing VF plus INSTI resistance mutations on a dolutegravir-containing regimen, 41 studies describing dolutegravir susceptibility results, and 22 clinical trials and 16 cohort studies of dolutegravir-containing regimens. The most common INSTI resistance mutations in persons with VF on a dolutegravir-containing regimen were R263K, G118R, N155H and Q148H/R, with R263K and G118R predominating in previously INSTI-naive persons. R263K reduced dolutegravir susceptibility ∼2-fold. G118R generally reduced dolutegravir susceptibility >5-fold. The highest levels of reduced susceptibility occurred in viruses containing Q148 mutations in combination with G140 and/or E138 mutations. Dolutegravir two-drug regimens were highly effective for first-line therapy and for virologically suppressed persons provided dolutegravir’s companion drug was fully active. Dolutegravir three-drug regimens were highly effective for salvage therapy in INSTI-naive persons provided one or more of dolutegravir’s companion drugs was fully active. However, dolutegravir monotherapy in virologically suppressed persons and functional dolutegravir monotherapy in persons with active viral replication were associated with a non-trivial risk of VF plus INSTI resistance mutations.
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Tasneen, Rokeya, Fabrice Betoudji, Sandeep Tyagi, Si-Yang Li, Kathy Williams, Paul J. Converse, Véronique Dartois et al. „Contribution of Oxazolidinones to the Efficacy of Novel Regimens Containing Bedaquiline and Pretomanid in a Mouse Model of Tuberculosis“. Antimicrobial Agents and Chemotherapy 60, Nr. 1 (26.10.2015): 270–77. http://dx.doi.org/10.1128/aac.01691-15.
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ABSTRACTNew regimens based on two or more novel agents are sought to shorten or simplify treatment of tuberculosis (TB). Pretomanid (PMD) is a nitroimidazole in phase 3 trials that has significant bactericidal activity alone and in combination with bedaquiline (BDQ) and/or pyrazinamide (PZA). We previously showed that the novel combination of BDQ+PMD plus the oxazolidinone sutezolid (SZD) had sterilizing activity superior to that of the first-line regimen in a murine model of TB. The present experiments compared the activity of different oxazolidinones in combination with BDQ+PMD with or without PZA in the same model. The 3-drug regimen of BDQ+PMD plus linezolid (LZD) had sterilizing activity approaching that of BDQ+PMD+SZD and superior to that of the first-line regimen. The addition of PZA further enhanced activity. Reducing the duration of LZD to 1 month did not significantly affect the activity of the regimen. Halving the LZD dose or replacing LZD with RWJ-416457 modestly reduced activity over the first month but not after 2 months. AZD5847 and tedizolid also increased the bactericidal activity of BDQ+PMD, but they were less effective than the other oxazolidinones. These results provide optimism for safe, short-course oral regimens for drug-resistant TB that may also be superior to the current first-line regimen for drug-susceptible TB.
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Hawkins, Trevor, Wenoah Veikley, Lucie Durand-Gasselin, Darius Babusis, Y. Sunila Reddy, John F. Flaherty und Adrian S. Ray. „Intracellular Nucleotide Levels during Coadministration of Tenofovir Disoproxil Fumarate and Didanosine in HIV-1-Infected Patients“. Antimicrobial Agents and Chemotherapy 55, Nr. 4 (31.01.2011): 1549–55. http://dx.doi.org/10.1128/aac.00910-10.
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ABSTRACTStudies were conducted to determine if there is a mechanistic basis for reports of suboptimal virologic responses and concerns regarding the safety of regimens containing the combination of tenofovir (TFV) disoproxil fumarate (TDF) and didanosine (ddI) by assessing the pharmacokinetic consequences of coadministration of these drugs on intracellular nucleotides. This was a prospective and longitudinal study in HIV-1-infected patients of adding either TDF or ddI to a stable antiretroviral regimen containing the other drug. Intracellular concentrations of the nucleotide analogs TFV diphosphate (TFV-DP) and ddATP and the endogenous purine nucleotides dATP and 2′-dGTP in peripheral blood mononuclear cells were measured. A total of 16 patients were enrolled into the two study arms and a study extension. Intracellular TFV-DP concentrations (median, 120 fmol/106cells) and ddATP concentrations (range, 1.50 to 7.54 fmol/106cells in two patients) were unaffected following addition of ddI or TDF to a stable regimen containing the other drug. While coadministration of ddI and TDF for 4 weeks did not appear to impact dATP or dGTP concentrations, cross-sectional analysis suggested that extended therapy with ddI-containing regimens, irrespective of TDF coadministration, may decrease dATP and ddATP concentrations. Addition of TDF or ddI to a stable regimen including the other drug, in the context of ddI dose reduction, did not adversely affect the concentration of dATP, dGTP, TFV-DP, or ddATP. The association between longer-term ddI therapy and reduced intracellular nucleotide concentrations and this observation's implication for the efficacy and toxicity of ddI-containing regimens deserve further study.
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Zhdanov, Konstantin V., Oleg V. Maltsev, Kristina V. Kasyanenko, Konstantin V. Kozlov, Vitalii S. Sukachev, Nikolai I. Lvov, Valerian V. Sharabkhanov und Alexander A. Litvinov. „Clinical efficiency and safety of riamilovir under various dosage regimens for treatment of acute respiratory viral infections in adults“. Terapevticheskii arkhiv 95, Nr. 11 (22.12.2023): 930–36. http://dx.doi.org/10.26442/00403660.2023.11.202471.
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Aim. To evaluate the clinical efficacy and safety of antiviral drug riamilovir in patients with acute respiratory viral infections (ARVI) of non-coronavirus (SARS-CoV-2) etiology with different dosing regimens.
Materials and methods. The study included 150 patients with ARVI aged 18–27 years (50 patients received riamilovir in the regimen of 250 mg 3 times a day for 5 days, 50 patients received riamilovir in the off label regimen of 250 mg 5 times a day for 5 days, 50 patients received only pathogenetic treatment).
Results. The use of riamilovir in both treatment regimens led to a reduction in the duration of inpatient treatment. The shortest periods of hospitalization were noted in patients who received the study drug at higher daily dosages. The use of riamilovir reduced the duration and severity of general infectious manifestations of the disease, while the shortest total duration of fever and a number of respiratory tract syndromes was registered among people who received riamilovir in the regimen of 1250 mg per day for 5 days, no adverse events were registered, additionally, 100% elimination of ARVI pathogens was noted in 1250 mg per day group.
Conclusion. Riamilovir has shown clinical efficacy and a good safety profile in in both treatment regimens. The dosage regimen of 1250 mg per day led to more significant clinical effects and to 100% elimination of ARVI pathogens in the study group by the 6th day of hospitalization.
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Dutta, Noton K., Michael L. Pinn und Petros C. Karakousis. „Reduced Emergence of Isoniazid Resistance with Concurrent Use of Thioridazine against Acute Murine Tuberculosis“. Antimicrobial Agents and Chemotherapy 58, Nr. 7 (05.05.2014): 4048–53. http://dx.doi.org/10.1128/aac.02981-14.
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ABSTRACTThe repurposing of existing drugs is being pursued as a means by which to accelerate the development of novel regimens for the treatment of drug-susceptible and drug-resistant tuberculosis (TB). In the current study, we assessed the activity of the antipsychotic drug thioridazine (TRZ) in combination with the standard regimen in a well-validated murine TB model. Single-dose and steady-state pharmacokinetic studies were performed in BALB/c mice to establish human-equivalent doses of TRZ. To determine the bactericidal activity of TRZ against TB in BALB/c mice, three separate studies were performed, including a dose-ranging study of TRZ monotherapy and efficacy studies of human-equivalent doses of TRZ with and without isoniazid (INH) or rifampin (RIF). Therapeutic efficacy was assessed by the change in mycobacterial load in the lung. The human-equivalent dose of thioridazine was determined to be 25 mg/kg of body weight, which was well tolerated in mice. TRZ was found to accumulate at high concentrations in lung tissue relative to serum levels. We observed modest synergy during coadministration of TRZ with INH, and the addition of TRZ reduced the emergence of INH-resistant mutants in mouse lungs. In conclusion, this study further illustrates the opportunity to reevaluate the contribution of TRZ to the sterilizing activity of combination regimens to prevent the emergence of drug-resistantM. tuberculosis.
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Jung, H., R. Medina, N. Castro, T. Corona und J. Sotelo. „Pharmacokinetic study of praziquantel administered alone and in combination with cimetidine in a single-day therapeutic regimen.“ Antimicrobial Agents and Chemotherapy 41, Nr. 6 (Juni 1997): 1256–59. http://dx.doi.org/10.1128/aac.41.6.1256.
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A brief therapeutic regimen of praziquantel, reduced to a single day, has been effective for treatment of neurocysticercosis. To study its pharmacokinetic characteristics, levels of praziquantel in plasma were determined for eight healthy volunteers after the administration of three oral doses of 25 mg/kg of body weight given at 2-h intervals, alone and with the simultaneous administration of cimetidine. Each volunteer received both regimens in a randomized crossover design. Blood samples were taken during a period of 12 h, and praziquantel concentration was measured by high-performance liquid chromatography. Levels of praziquantel in plasma remained above 300 ng/ml during a period of 12 h; they increased 100% when cimetidine was jointly administered. Compared with other regimens, the high levels obtained and the longer duration of action seem to be advantageous in prolonging the exposure of the parasites to the drug and support previous clinical experience showing that the treatment of neurocysticercosis with praziquantel can be reduced from 2 weeks to 1 day with the drug still retaining its cysticidal properties. Moreover, simultaneous administration of praziquantel and cimetidine could improve further the efficacy of the single-day therapy for cysticercosis and other parasitic diseases, such as schistosomiasis.
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Tyczyńska, Agata, Marcela Krzysława Krzempek, Alexander Jorge Cortez, Artur Jurczyszyn, Katarzyna Godlewska, Hanna Ciepłuch, Edyta Subocz et al. „The Real-World Evidence on the Fragility and Its Impact on the Choice of Treatment Regimen in Newly Diagnosed Patients with Multiple Myeloma over 75 Years of Age“. Cancers 15, Nr. 13 (02.07.2023): 3469. http://dx.doi.org/10.3390/cancers15133469.
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Fragility scales are intended to help in therapeutic decisions. Here, we asked if the fragility assessment in MM patients ≥ 75 years old qualified for treatment by the local physician correlates with the choice of treatment: a two- or three-drug regimens. Between 7/2018 and 12/2019, we prospectively enrolled 197 MM patients at the start of treatment from the 13 Polish Myeloma Group centers. The data to assess fragility were prospectively collected, but centrally assessed fragility was not disclosed to the local center. The activity of daily living (ADL) could be assessed in 192 (97.5%) and was independent in 158 (80.2%), moderately impaired in 23 (11.7%), and 11 (5.6%) in completely dependent. Patients with more than three comorbidities made up 26.9% (53 patients). Thus, according to the Palumbo calculator, 43 patients were in the intermediate fitness group (21.8%), and the rest belonged to the frailty group (153, 77.7%). Overall, 79.7% of patients (157) received three-drug regimens and 20.3% (40) received two-drug regimens. In each ECOG group, more than three out of four patients received three-drug regimens. According to the ADL scale, 82.3% of the independent 65.2% of moderately impaired, and 81.8% of the dependent received three-drug regimens. Out of 53 patients with at least four comorbidities, 71.7% received three-drug regimens, and the rest received two-drug regimens. Thirty-four patients from the intermediate fit group (79.0%), and 123 (79.9%) from the frail group received three-drug regimens. Early mortality occurred in 25 patients (12.7%). No one discontinued treatment due to toxicity. To conclude, MM patients over 75 are mainly treated with triple-drug regimens, not only in reduced doses, regardless of their frailty scores. However, the absence of prospective fragility assessment did not negatively affect early mortality and the number of treatment discontinuations, which brings into question the clinical utility of current fragility scales in everyday practice.
Dissertationen zum Thema "Drug-reduced regimens"
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Palich, Romain. „Impact de la résistance virale acquise dans le passé sur les stratégies antirétrovirales actuelles“. Electronic Thesis or Diss., Sorbonne université, 2021. http://www.theses.fr/2021SORUS493.
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Dans le champ de la prise en charge du VIH, aujourd’hui en France, trois situations continuent d’occuper la réflexion : 1) les virémies de bas niveau persistantes, malgré un traitement ARV prolongé et une observance rapportée optimale, 2) la persistance ou la clairance dans le réservoir viral de mutations de résistance sélectionnées dans l’histoire virologique, et 3) l’allègement thérapeutique optimal chez les patients virologiquement contrôlés. Dans un premier travail, nous avons montré que 72% des patients présentant une virémie de bas niveau persistante, déclarant une bonne observance, avaient des concentrations en antirétroviraux optimales dans le sang, et étaient porteurs de virus non résistants au traitement. Deux ans après l’inclusion, 72% gardaient une virémie de bas niveau, sans échec virologique. Dans un deuxième travail, nous avons montré la persistance de la mutation M184V, archivée dans le passé, chez 67% des patients virologiquement contrôlés depuis au moins 5 ans (avec un seuil de détection à 1%), ainsi que la clairance progressive de cette mutation dans le réservoir ADN-VIH. Les deux facteurs associés à la persistance de la M184V étaient la durée et le niveau de réplication sous 3TC/FTC dans le passé. Dans un troisième travail, nous avons montré l’efficacité virologique de bithérapies administrées 5 ou 4 jours par semaines (91% de succès virologique à S96), dans une population longuement exposée aux antirétroviraux. Globalement, ces résultats s’inscrivent dans une volonté d’optimiser les stratégies en réduisant l’exposition aux antirétroviraux, y compris chez les patients ayant une longue histoire virologique et thérapeutiqueIn the field of HIV management, today in France, three situations continue to concern clinicians: 1) persistent low-level viremia, despite prolonged antiretroviral treatment and good self-reported compliance, 2) persistence or clearance in viral reservoir of resistance mutations selected in the past, and 3) optimal drug-reduced antiretroviral treatment in virally suppressed patients. In a first work, we showed that 72% of patients with persistent low-level viremia, with good self-reported compliance, had adequate plasma antiretroviral concentrations, and no past viral resistance explaining the persistent replication. Two years after inclusion, 72% of patients maintained low-level replication without virologic failure. In a second work, we showed the persistence of the M184V mutation, acquired in the past, in 67% of patients with suppressed viremia >5 years (detection threshold: 1%), as well as the progressive clearance of the mutation in the HIV-DNA reservoir. The two factors associated with the persistence of M184V were the duration and the level of replication under 3TC/FTC in the past. In a third work, we showed the virological efficacy of dual therapies given 5 or 4 days a week (virological success: 91% at W96), in a population highly exposed to antiretroviral treatment. Overall, these findings support the optimization of strategies, in order to reduce the exposure to antiretrovirals, including in patients with a long virological and therapeutic history
Bücher zum Thema "Drug-reduced regimens"
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Harper, Lorraine, und David Jayne. The patient with vasculitis. Herausgegeben von Giuseppe Remuzzi. Oxford University Press, 2015. http://dx.doi.org/10.1093/med/9780199592548.003.0160.
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The goals of treatment in renal vasculitis are to stop vasculitic activity and recover renal function. Subsequent strategies are required to prevent vasculitis returning and to address longer-term co-morbidities caused by tissue damage, drug toxicity, and increased cardiovascular and malignancy risk.Cyclophosphamide and high-dose glucocorticoids remain the standard induction therapy with alternative immunosuppressives, such as azathioprine, to prevent relapse. Plasma exchange improves renal recovery in severe presentations. Refractory disease resulting from a failure of induction or remission maintenance therapy requires alternative agents and rituximab has been particularly effective. Replacement of cyclophosphamide by rituximab for remission induction is supported by recent evidence. Methotrexate is effective in non-renal vasculitis but difficult to use in patients with renal impairment. Mycophenolate mofetil seems to be effective but there is less long-term evidence.Drug toxicity contributes to co-morbidity and mortality and has led to newer regimens with reduced cyclophosphamide exposure. Glucocorticoid toxicity remains a major problem with controversy over the rapidity with which glucocorticoids can be reduced or withdrawn.Disease relapse occurs in about 50% of patients. Early detection is less likely to lead to an adverse affect on outcomes. Rates of cardiovascular disease and malignancy are higher than in control populations but strategies to reduce their risk, apart from cyclophosphamide-sparing regimens, have not been developed. Thromboembolic events occur in 10% and may be linked to the recently identified autoantibodies to plasminogen and tissue plasminogen activator.Renal impairment at diagnosis is a strong predictor of patient survival and renal outcome. Other predictors include patient age, antineutrophil cytoplasmic antibody subtype, disease extent and response to therapy. Chronic kidney disease can stabilize for many years but the risks of end-stage renal disease are increased by acute kidney injury at presentation or renal relapse. Renal transplantation is successful with similar outcomes to other causes of end-stage renal disease.
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Jayne, David. Treatment of ANCA-associated vasculitis. Oxford University Press, 2013. http://dx.doi.org/10.1093/med/9780199642489.003.0132.
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The goals of treatment in anti-neutrophil cytoplasm antibody (ANCA) vasculitis are to stop vasculitic activity, to prevent vasculitis returning, and to address longer-term comorbidities caused by tissue damage, drug toxicity, and increased cardiovascular and malignancy risk. Cyclophosphamide and high-dose glucocorticoids remain the standard induction therapy with alternative immunosuppressives, such as methotrexate or azathioprine, to prevent relapse. Refractory disease resulting from a failure of induction or remission maintenance therapy requires alternative agents and rituximab has been particularly effective. Replacement of cyclophosphamide by rituximab for remission induction is supported by recent evidence. Additional therapy with intravenous methylprednisolone and plasma exchange is employed in severe presentations with failing vital organ function. Drug toxicity contributes to comorbidity and mortality and has led to newer regimens with reduced cyclophosphamide exposure. Glucocorticoid toxicity remains a major problem, with controversy over the rapidity with which glucocorticoids can be reduced or withdrawn. Disease relapse occurs in 50% and requires early detection at a stage when it will not adversely affect outcomes. Rates of cardiovascular disease and malignancy are higher than in control populations but strategies to reduce their risk, apart from cyclophosphamide-sparing regimens, have not been developed. Thromboembolic events occur in 10% and may be linked to the recently identified autoantibodies to plasminogen and tissue plasminogen activator. Outcomes of vasculitis depend heavily on the level of tissue damage at diagnosis, especially renal dysfunction, but are also influenced by patient age, ANCA subtype, disease extent, and response to therapy. Eosinophilic granulomatosis with polyangiitis (Churg-Strauss)is treated along similar principles to granulomatosis with polyangiitis (GPA) and microscopic polyangiitis but the persistence of steroid-dependent asthma in over one-third and differences in pathogenesis has suggested alternative treatment approaches. Chronic morbidity results from tissue damage and is especially common in the upper and lower respiratory tract and kidneys. Tracheobronchial disease is a severe late complication of GPA, while deafness, nasal obstruction, and chronic sinusitis are sequelae of nasal and ear vasculitis. Chronic infection of damaged epithelial surfaces acts as a drive for vasculitic activity and adequate infection control is necessary for stable remission. Chronic kidney disease can stabilize for many years but the risks of endstage renal disease (ESRD) are increased by acute kidney injury at presentation or renal relapse. Renal transplantation is successful, with similar outcomes to other causes of ESRD.
Buchteile zum Thema "Drug-reduced regimens"
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Onida, Francesco, und Yves Chalandon. „Myelodysplastic/Myeloproliferative Neoplasms“. In The EBMT Handbook, 685–94. Cham: Springer International Publishing, 2024. http://dx.doi.org/10.1007/978-3-031-44080-9_76.
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AbstractThe myelodysplastic syndrome-myeloproliferative neoplasms (MDS/MPNs) are a heterogeneous group of hematologic malignancies characterized by dysplastic and myeloproliferative clinical, laboratory, and morphological overlapping features, both in marrow and in blood. MDS/MPNs include chronic myelomonocytic leukemia (CMML), MDS/MPN with neutrophilia, MDS/MPN with SF3B1 mutation (in its absence with ringed sideroblasts) and thrombocytosis (MDS/MPN-SF3B1-T), and MDS/MPN not otherwise specified (MDS/MPN-NOS). Prognosis of MDS/MPN is highly variable, being dismal in the majority of patients with CMML, MDS/MPN with neutrophilia and MDS/MPN-NOS. In the absence of disease-modifying treatment options, allo-HCT represents the only curative option for eligible patients. With regard to allo-HCT indication in CMML patient, a number of prognostic systems have been developed over the years. As far as pre-transplant phase, in high-risk patients with MDS/MPN and low blast count (<10%), upfront transplantation is the most frequently preferred strategy. In patients with high blast count, pre-transplant treatment with HMAs, or combination of HMAs with other new agents in clinical trials may be considered. In case of rising leukocytosis and/or organ infiltration, hydroxyurea is the drug of choice. In MDS/MPN patients, the choice of conditioning regimen depends on many different conditions, the major ones being comorbidities, patient age, disease phase at transplant, type of donor, and HSC source. In general, myeloablative regimens may be advisable in young patients without comorbidities aiming to reduce the relapse risk, while reduced-intensity regimens are preferred for patients with older age or comorbidities. As disease recurrence represents the major cause of transplant failure in MDS/MPN, there is a growing interest toward possible post-transplant treatment strategies, both as preemptive and as prophylactic modalities.
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Szturz, Petr, und Jan B. Vermorken. „Systemic Treatment Sequencing and Prediction of First-line Therapy Outcomes in Recurrent or Metastatic Head and Neck Cancer“. In Critical Issues in Head and Neck Oncology, 199–215. Cham: Springer International Publishing, 2023. http://dx.doi.org/10.1007/978-3-031-23175-9_13.
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AbstractIn the palliative management of patients with recurrent and/or metastatic squamous cell carcinoma of the head and neck who are not candidates for a complete resection or full-dose radiotherapy, systemic treatment has seen important advances over the past several decades. In general, there are six major factors impacting on the decision-making process. Four of them belong to a class of continuous functions and include overall health status (from fitness to frailty), disease burden (from high to low), pace of the disease (from fast to slow), and expression of programmed-death ligand 1 (PD-L1, from high to low). In addition, there are two categorical variables including disease site (e.g., locoregional recurrence versus metastatic) and platinum-sensitivity or resistance depending on disease-free interval after previous platinum-based therapy with a usual cut-off of 6 months. Taking into account these six factors and local drug policies, healthcare professionals opt either for 1) chemotherapy with or without cetuximab or 2) immunotherapy with or without chemotherapy. In platinum-sensitive cases, level I evidence based on data from the EXTREME and Keynote-048 randomized trials supports the use of the following three regimens. Biochemotherapy combining platinum, 5-fluorouracil, and cetuximab (the so-called EXTREME regimen) is suitable for fit patients with low PD-L1 expression measured as combined positive score (CPS). Higher CPS is predictive for improved overall survival when replacing cetuximab with the immune checkpoint inhibitor pembrolizumab, an anti-PD-1 antibody (immunochemotherapy regimen). Further, Keynote-048 demonstrated activity of single-agent pembrolizumab in patients with high CPS values. The latter (third) treatment retained its efficacy in the elderly, suggesting possible advantage in less fit patients who otherwise receive best supportive care only or single-agent cytotoxic chemotherapy with dubious impact on survival. In selected patients, the TPEx regimen consisting of cisplatin, docetaxel, and cetuximab represents an alternative to EXTREME. Treatment choice can also be influenced by disease extension (site). Compared with disseminated cancer cases, presence of locoregional recurrence without distant metastases may have a negative predictive value for immune checkpoint inhibitors, while favouring biochemotherapy. If the tumour is deemed platinum-resistant, the only evidence-based systemic approach is monotherapy with either pembrolizumab or nivolumab, another anti-PD-1 antibody. Alternatively, being especially pertinent to resource-limited countries, a taxane with or without cetuximab can be prioritized. Obviously, the list of different treatment schedules is longer, but the level of supporting evidence is proportionally lower. One of modern approaches to multidisciplinary management of SCCHN patients is treatment sequencing. It should be understood as a deliberate process of treatment planning typically starting in the locally advanced setting and reaching beyond several treatment failures. This has been enabled by a growing portfolio of effective anticancer modalities complemented by progress in supportive care. Finally, all therapeutic interventions impact somehow on quality of life, either in a positive or negative way, and the choice of anticancer agents should therefore not be reduced to a simple estimate of survival benefit but should contain an adequate appraisal and understanding of individual patient’s situation comprising emotional and spiritual dimensions, cultural and financial aspects, and environmental, social, and educational contexts.
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Brater, D. Craig. „Antimicrobial dosing regimens in renal patients“. In Infectious complications renal disease, 431–48. Oxford University PressNew York, NY, 2003. http://dx.doi.org/10.1093/oso/9780192632944.003.0021.
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Abstract Renal impairment leads not only to the accumulation of endogenous compounds, but can also result in the retention of exogenously administered antibiotics and their polar metabolites, some of which may be active. For many antibiotics, doses must be reduced to attain concentrations similar to those obtained in patients with normal renal function. Several general characteristics of a drug allow prediction as to whether renal dysfunction is likely to mandate changes in dosing.
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Fabris, Marcieli, Kaio Maciel de Santiago-Silva, Camilo Henrique da Silva Lima, Marcelle de Lima Ferreira Bispo und Priscila Goes Camargo. „Anti-trypanosomatid Drugs/Candidates in Clinical Trials: What's New and What's Missing?“ In Frontiers in Drug Design and Discovery: Volume 12, 1–63. BENTHAM SCIENCE PUBLISHERS, 2023. http://dx.doi.org/10.2174/9789815165258123120002.
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Parasites and infectious agents are responsible for neglected tropical diseases (NTDs) that affect many countries worldwide. At least one NTD is found 149 countries, mostly in low-income countries with poor sanitation, and it impacts over a billion people. According to the World Health Organization, trypanosomiasis is a group of protozoan infections that cause Chagas disease (Trypanosoma cruzi), Human African Trypanosomiasis (sleeping sickness - Trypanosoma brucei rhodesiense or Trypanosoma brucei gambiense), and Leishmaniasis (Leishmania spp. - Trypanosomatidae family), which are all considered NTDs. It is estimated that approximately 500,000 deaths from NTD infections occur annually worldwide. Despite the many cases associated with NTDs, treatments for most of these diseases are available. However, they are associated with significant adverse effects and a growing number of drug-resistant microorganisms and require parenteral administration. Besides that, many trypanosomatid diseases are zoonotic, making eradication extremely difficult. In this way, despite scientific progress over the years, some drug discovery goals remain unmet, such as the development of new therapeutic classes, reduced toxicity, improved administration regimens, or the development of combination therapies. Therefore, this chapter intends to present the six categories of drugs, i.e., the currently used therapeutic agents, nitroaromatic compounds, azole antifungal, benzoxaboroles, nitrogen heterocycles, and miscellaneous agents in clinical trials for NTDs, focusing on infections caused by trypanosomatids. In addition, the review approach presents the development process of the new drugs or treatment regimens in Phase I, II, III, and IV studies of the clinical trials based on the Drugs for Neglected Diseases initiative (DNDi) portfolio published in December 2020.
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Jayne, David. „Treatment of ANCA-associated vasculitis“. In Oxford Textbook of Rheumatology, 1103–12. Oxford University Press, 2013. http://dx.doi.org/10.1093/med/9780199642489.003.0132_update_001.
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The goals of treatment in anti-neutrophil cytoplasm antibody (ANCA) vasculitis are to stop vasculitic activity, to prevent vasculitis returning, and to address longer-term comorbidities caused by tissue damage, drug toxicity, and increased cardiovascular and malignancy risk. Cyclophosphamide and high-dose glucocorticoids remain the standard induction therapy with alternative immunosuppressives, such as methotrexate or azathioprine, to prevent relapse. Refractory disease resulting from a failure of induction or remission maintenance therapy requires alternative agents and rituximab has been particularly effective. Replacement of cyclophosphamide by rituximab for remission induction is supported by recent evidence. Additional therapy with intravenous methylprednisolone and plasma exchange is employed in severe presentations with failing vital organ function. Drug toxicity contributes to comorbidity and mortality and has led to newer regimens with reduced cyclophosphamide exposure. Glucocorticoid toxicity remains a major problem, with controversy over the rapidity with which glucocorticoids can be reduced or withdrawn. Disease relapse occurs in 50% and requires early detection at a stage when it will not adversely affect outcomes. Rates of cardiovascular disease and malignancy are higher than in control populations but strategies to reduce their risk, apart from cyclophosphamide-sparing regimens, have not been developed. Thromboembolic events occur in 10% and may be linked to the recently identified autoantibodies to plasminogen and tissue plasminogen activator. Outcomes of vasculitis depend heavily on the level of tissue damage at diagnosis, especially renal dysfunction, but are also influenced by patient age, ANCA subtype, disease extent, and response to therapy. Eosinophilic granulomatosis with polyangiitis (Churg-Strauss)is treated along similar principles to granulomatosis with polyangiitis (GPA) and microscopic polyangiitis but the persistence of steroid-dependent asthma in over one-third and differences in pathogenesis has suggested alternative treatment approaches. Chronic morbidity results from tissue damage and is especially common in the upper and lower respiratory tract and kidneys. Tracheobronchial disease is a severe late complication of GPA, while deafness, nasal obstruction, and chronic sinusitis are sequelae of nasal and ear vasculitis. Chronic infection of damaged epithelial surfaces acts as a drive for vasculitic activity and adequate infection control is necessary for stable remission. Chronic kidney disease can stabilize for many years but the risks of endstage renal disease (ESRD) are increased by acute kidney injury at presentation or renal relapse. Renal transplantation is successful, with similar outcomes to other causes of ESRD.
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Goldsmith, William W. „Drug-War Politics“. In Saving Our Cities. Cornell University Press, 2016. http://dx.doi.org/10.7591/cornell/9781501704314.003.0008.
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This chapter examines drug-war politics. While many politicians have benefited from supporting the drug war, growing numbers of influential persons express opposition. While private firms may benefit handsomely from provisioning the war, state governments have become more cautious, sensitive to budgetary pressures. Among supporters for drug-law reform, nearly all endorse a policy known as harm reduction; many call for decriminalization, and growing numbers advocate legalization. Indeed, pressures for drug-law and prison-regime reforms have increased and spread since the turn of the twenty-first century. Numerous state referenda, legislative moves, and court rulings have liberalized marijuana restrictions, allowing medical prescriptions and in some cases recreational use. Legislatures have also reduced penalties for use of many drugs and have lessened some of the racial bias. Nevertheless, the drug war remains a major and damaging element of urban policy, with key supporters.
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Raj Daniel Raj Ponniah, Lional. „Alternative Treatment Approaches in Bacterial Keratitis“. In Keratitis - Current Perspectives [Working Title]. IntechOpen, 2023. http://dx.doi.org/10.5772/intechopen.112624.
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Microbial keratitis can cause unilateral blindness, which can occur after ocular trauma and subsequent infection, causing unilateral blindness in 1.5 to 2 million corneal ulceration cases globally per year, particularly in developing and tropical countries. The conventional treatment options are largely topical in a loading dose regimen. This chapter enumerates the recent advances in its management. Parenteral, and intracorneal, intrastromal antimicrobial injections are attempted as adjuvants in refractory cases. Novel drug reservoir contact lenses have higher bioavailability by creating an antimicrobial lake with increased tear film exchange through the fenestration. Sustained release intrastromal antimicrobial implants for the treatment of deep corneal infections and abscesses have increased efficacy. An intensive loading dose with topical agents could be reduced with alternative approaches, thus reducing the treatment burden and improving patient compliance.
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Carpenter, John P., John C. Wood und Dudley J. Pennell. „Myocardial iron overload“. In The EACVI Textbook of Cardiovascular Magnetic Resonance, herausgegeben von Massimo Lombardi, Sven Plein, Steffen Petersen, Chiara Bucciarelli-Ducci, Emanuela R. Valsangiacomo Buechel, Cristina Basso und Victor Ferrari, 364–74. Oxford University Press, 2018. http://dx.doi.org/10.1093/med/9780198779735.003.0033.
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The heart is the target lethal organ in thalassaemia major. Cardiovascular magnetic resonance (CMR) measures iron using the magnetic relaxation time T2*. This allows comparison with the left ventricular function and conventional iron measurements such as liver iron and serum ferritin. The single breath-hold cardiac-gated CMR acquisition takes only 15 seconds, making it cost-efficient and relevant to developing countries. Myocardial T2* of <20 ms (increased iron) correlates with reduced left ventricular ejection fraction, but poor correlation exists with ferritin and liver iron, indicating poor capability to assess future risk. Myocardial T2* of <10 ms is present in >90% of thalassaemia patients developing heart failure, and approximately 50% of patients with T2* of <6 ms will develop heart failure within 1 year without intensified treatment. The technique is validated and calibrated against human heart iron concentration. The treatment for iron overload is iron chelation, and three major trials have been performed for the heart. The first trial showed deferiprone was superior to deferoxamine in removing cardiac iron. The second trial showed a combination therapy of deferiprone with deferoxamine was more effective than deferoxamine monotherapy. The third trial showed that deferasirox was non-inferior to deferoxamine in removing cardiac iron. Each drug in suitable doses can be used to remove cardiac iron, but their use depends on clinical circumstances. Other combination regimes are also being evaluated. Use of T2*, intensification of chelation treatment, and use of deferiprone are associated with reduced mortality (a reduction in deaths by 71% has been shown in the United Kingdom). The use of T2* and iron chelators in the heart has been summarized in recent American Heart Association guidelines.
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K, Dr Vini, Veena V.P und Dr Nissamudeen K. M. „FUTURISTIC TRENDS IN NANOTECHNOLOGY“. In Futuristic Trends in Chemical, Material Sciences & Nano Technology Volume 2 Book 13, 177–89. Iterative International Publishers, Selfypage Developers Pvt Ltd, 2023. http://dx.doi.org/10.58532/v2bs13p3ch3.
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Nanotechnology is one of the propitious technologies of the 21st century. It is the competency to convert the theory of nanoscience to most beneficial applications by measuring, observing, manipulating, controlling and manufacturing particles at the nanometer regime. The potential assistances are breath-taking and brain enhancing. But just like many of the great discoveries on the earth, it is not without risk. Scientists believe that nanotechnology can be used to support human health now and in the future through various applications like improved filters for enhancing water purification, better beneficial methods of drug delivering in the field of medicine and modern ways of furbishing damaged organs and tissues. Nano technology holds great potential for India and a multi pronged arrival will assure that this is fully capitalized. Nanotechnology is applauded as having the capacity to enhance the effectiveness of energy consumption, support clean the environment, and solve major health issues. It is found to be capable to enhance manufacturing production at markedly reduced costs. In the course of time, nano-technology will influence the life of almost every individual on the planet. In the future, nanotechnology might help us make electrical lines, solar cells, and biofuels more efficient, and make nuclear reactors safer. According to the latest report on global nanotechnology market, the industry is estimated to grow at a CAGR of 18.2% between 2016 and 2021
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Post, Robert M. „Lithium and related mood stabilizers“. In New Oxford Textbook of Psychiatry, 1198–208. Oxford University Press, 2012. http://dx.doi.org/10.1093/med/9780199696758.003.0154.
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Lithium is the paradigmatic mood stabilizer. It is effective in the acute and prophylactic treatment of both mania and, to a lesser magnitude, depression. These characteristics are generally paralleled by the widely accepted anticonvulsant mood stabilizers valproate, carbamazepine (Table 6.2.4.1), and potentially by the less well studied putative mood stabilizers oxcarbazepine, zonisamide, and the dihydropyridine L-type calcium channel blocker nimodipine. In contrast, lamotrigine has a profile of better antidepressant effects acutely and prophylactically than antimanic effects. Having grouped lithium, valproate, and carbamazepine together, it is important to note they have subtle differences in their therapeutic profiles and differential clinical predictors of response (Table 6.2.4.1). Response to one of these agents is not predictive of either a positive or negative response to the others. Thus, clinicians are left with only rough estimates and guesses about which drug may be preferentially effective in which patients. Only sequential clinical trials of agents either alone or in combination can verify responsivity in an individual patient. Individual response trumps FDA-approval. Given this clinical conundrum, it is advisable that patients, family members, clinicians, or others carefully rate patients on a longitudinal scale in order to most carefully assess responses and side effects. These are available from the Depression Bipolar Support Alliance (DBSA), the STEP-BD NIMH Network, or www.bipolarnetworknews.org and are highly recommended. The importance of careful longitudinal documentation of symptoms and side effects is highlighted by the increasing use of multiple drugs in combination. This is often required because patients may delay treatment-seeking until after many episodes, and very different patterns and frequencies of depressions, manias, mixed states, as well as multiple comorbidities may be present. Treating patients to the new accepted goal of remission of their mood and other anxillary symptoms usually requires use of several medications. If each component of the regimen is kept below an individual's side-effects threshold, judicious use of multiple agents can reduce rather than increase the overall side-effect burden. There is increasing evidence of reliable abnormalities of biochemistry, function, and anatomy in the brains of patients with bipolar disorder, and some of these are directly related to either duration of illness or number of episodes. Therefore, as treatment resistance to most therapeutic agents is related to number of prior episodes, and brain abnormalities may also increase as well, it behooves the patient to begin and sustain acute and long-term treatment as early as possible. Despite the above academic, personal, and public health recommendations, bipolar disorder often takes ten years or more to diagnose and, hence, treat properly. In fact, a younger age of onset is highly related to presence of a longer delay from illness onset to first treatment, and as well, to a poorer outcome assessed both retrospectively and prospectively. New data indicate that the brain growth factor BDNF (brain-derived neurotrophic factor) which is initially important to synaptogenesis and neural development, and later neuroplasticity and long-term memory in the adult is involved in all phases of bipolar disorder and its treatment. It appears to be: 1) both a genetic (the val-66-val allele of BDNF) and environmental (low BDNF from childhood adversity) risk factor; 2) episode-related (serum BDNF decreasing with each episode of depression or mania in proportion to symptom severity; 3) related to some substance abuse comorbidity (BDNF increases in the VTA with defeat stress and cocaine self-administration); and 4) related to treatment. Lithium, valproate, and carbamazepine increase BDNF and quetiapine and ziprasidone block the decreases in hippocampal BDNF that occur with stress (as do antidepressants). A greater number of prior episodes is related to increased likelihood of: 1) a rapid cycling course; 2) more severe depressive symptoms; 3) more disability; 4) more cognitive dysfunction; and 5) even the incidence of late life dementia. Taken together, the new data suggest a new view not only of bipolar disorder, but its treatment. Adequate effective treatment may not only (a) prevent affective episodes (with their accompanying risk of morbidity, dysfunction, and even death by suicide or the increased medical mortality associated with depression), but may also (b) reverse or prevent some of the biological abnormalities associated with the illness from progressing. Thus, patients should be given timely information pertinent to their stage of illness and recovery that emphasizes not only the risk of treatments, but also their potential, figuratively and literally, life-saving benefits. Long-term treatment and education and targeted psychotherapies are critical to a good outcome. We next highlight several attributes of each mood stabilizer, but recognize that the choice of each agent itself is based on inadequate information from the literature, and sequencing of treatments and their combinations is currently more an art than an evidence-based science. We look forward to these informational and clinical trial deficits being reduced in the near future and the development of single nucleotide polymorphism (SNP) and other neurobiological predictors of individual clinical response to individual drugs. In the meantime, patients and clinicians must struggle with treatment choice based on: 1) the most appropriate targetting of the predominant symptom picture with the most likely effective agent (Table 6.2.4.1 and 6.2.4.2) the best side-effects profile for that patient (Table 6.2.4.2 and 6.2.4.3) using combinations of drugs with different therapeutic targets and mechanisms of action (Table 6.2.4.3 and 6.2.4.4) careful consideration of potential advantageous pharmacodynamic interactions and disadvantageous pharmacokinetic drug-drug interactions that need to be avoided or anticipated.
Konferenzberichte zum Thema "Drug-reduced regimens"
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Versteeg, Henk K., Graham K. Hargrave, Perry A. Genova, Robert C. Williams, Dan Deaton und Prashant Kakade. „Design Optimisation of Novel Pharmaceutical Actuator Using Optical Diagnostics“. In ASME 7th Biennial Conference on Engineering Systems Design and Analysis. ASMEDC, 2004. http://dx.doi.org/10.1115/esda2004-58173.
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Pharmaceutical metered dose inhalers (MDIs) are drug delivery devices that are designed to produce self-propelled aerosols for inhalation therapies. Conventional MDI actuators use configurations based on a “two-orifice-and-sump” design. This promotes partial expansion of the propellant as a pre-atomisation stage. The final aerosol contains large numbers of respirable particles (1–5μm), but the aerosol plume velocity tends to be very high (50–100m/s). The KOS Vortex Nozzle Assembly (VNA) is an innovative actuator concept, which enables a measure of control of plume velocity. The device utilises a combination of a vortex chamber and a Bernoulli horn to reduce the plume velocity whilst increasing the respirable fraction of drug particles. The aerosol generation process in all MDIs, including the KOS VNA, inevitably leads to a certain amount of internal and external drug deposition, which represents an inefficiency of the drug delivery technology that can threaten dose uniformity. This paper reports the findings of an experimental study using optical diagnostics to investigate the primary atomization mechanism and external drug deposition in the VNA. High-speed video imaging is used to document the developing aerosol plume in the near-orifice and mouthpiece regions as well as the flow regime inside the vortex chamber using transparent versions of the VNA manufactured by means of rapid prototyping. We consider how the improved understanding of the flow processes resulting from this study supports measurements of fine-particle fractions and mouthpiece deposition. We also discuss how this type of fundamental investigation using optical diagnostics can be used to drive design improvements to identify VNA geometries with improved aerosol properties and reduced external drug deposition.
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Neri Semeri, G. G., F. Rovelli, G. F. Gensini, S. Pirelli, M. Carnovali und A. Fortini. „FREVENTION OF MYOCARDIAL REINFARCTION BY LOW DOSE HEPARIN“. In XIth International Congress on Thrombosis and Haemostasis. Schattauer GmbH, 1987. http://dx.doi.org/10.1055/s-0038-1643597.
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The effectiveness of low dose heparin in the prevention of myocardial reinfarction was investigated in a multi centric randomized controlled study. After having given their, informed consent to undergo daily subcutaneous heparin adninistratian, 728 patients of both sex aged 50-75 years, who had suffered frcm a transmural myocardial infarction 6-18 months before the enrollment and were in the I or II NYHA class were randomized. 365 patients (control group) were an the therapy usually performed by the 21 experimental canters participating in the study and 363 (heparin group) were treated with subcutaneous calcium heparin (Calciparina®) 12,500 IU daily in addition to the usual therapy of the centers. Curing enrollment the balancement of the two grcups was periodically checked for age, sex, serum cholesterol, cigarette smoking, blood pressure, site of infarction, arrhythmias and drug regimen. The prospect!vely established end-points were: transmural reinfarctioi as primary end-point; general mortality and mortality for cardiovascular events as accessory end-points over a mean follow-up period of 24 nxnths. Statistical analysis was foreseen both on drug efficacy (EE) and intention to treat (IT) basis. Patients of both groups underwent periodical examinations during the study. Acherence to the therapy and bone mineral content (bone density by double isotope technique) were also checked. At the end of the study the balancement for the factors considered was satisfactory and the drop-outs were 7.7% in heparin group and 6.3% in control group (ns). In heparin group the re infarction rate was lcwer by 62.92% than in control group. At life table analysis the difference was statistically significant (p<0.05 DE and p=0.05 IT). Mortality rate was reduced by 47.61% (DE) in heparin group (p<0.05 at life table analysis). Cardiovascular mortality was not significantly reduced (−33.06%), but the mortality attributable to thromboembolism was reduced in heparin group (p<0.05). Sixty patients (16.5%) discontinued heparin treatment, but only in 23 patients (6.3%) suspension was due to side effects.
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Shelyakin, I. D., S. N. Semenov und L. V. Cheskidova. „THE STUDY OF EFFECTS OF АMINOTONE ON HEMATOLOGICAL AND BIOCHEMICAL STATUS OF DOGS IN BABESIOSIS THERAPY“. In THEORY AND PRACTICE OF PARASITIC DISEASE CONTROL. All-Russian Scientific Research Institute for Fundamental and Applied Parasitology of Animals and Plant – a branch of the Federal State Budget Scientific Institution “Federal Scientific Centre VIEV”, 2023. http://dx.doi.org/10.31016/978-5-6048555-6-0.2023.24.532-537.
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When dogs are invaded with Babesia, metabolic and detoxification processes
are disrupted. In this regard, the therapeutic regimen should include drugs that
contribute to the normalization of metabolism, and maintenance of liver and kidney
function. The purpose of our research was to study the effects of Аminotone on the
hematological and biochemical status of dogs during the treatment of babesiosis. For
this purpose, Forticarb was administered as an etiological agent to the animals of the
control group, and Аminotone was additionally administered to the experimental
dogs. Before the experiment and two weeks after the beginning of the treatment, blood
was taken from the dogs for hematological and biochemical studies. It was found that
the control and experimental animals showed a decrease in leukocytes, ESR, ALT and AST activity, urea, and creatinine and bilirubin concentrations after the recovery.
At the same time, an increase in erythrocytes, hematocrit, mean corpuscular volume
and hemoglobin was recorded. Аminotone provided more intensive changes in the
dogs’ biochemical and hematological status: reduced inflammatory reaction, toxic
load on the liver and kidneys, and stimulated hematopoiesis, versus the control.
Thus, the drug can be recommended for the combined therapy of canine babesiosis.
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Isabekov, N. R. „METHOD OF RESPIRATORY SUPPORT FOR ACUTE CHEMICAL LUNG LESIONS OF PROFESSIONAL GENESIS“. In The 4th «OCCUPATION and HEALTH» International Youth Forum (OHIYF-2022). FSBSI «IRIOH», 2022. http://dx.doi.org/10.31089/978-5-6042929-6-9-2022-1-87-90.
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Introduction: Currently, the problem of chemical defeats at work continues to be relevant. According to the Federal Center for Hygiene and Epidemiology of Rospotrebnadzor, diseases (intoxication) caused by chemical factors exposure averaged 5.74–6.39% of occupational diseases per year all registered cases. As result of toxic substances inhalation, direct damage to lungs occurs with the further development of acute respiratory distress syndrome (ARDS). According to the national intensive care guide in the treatment of ARDS, the following main areas are distinguished - respiratory therapy and drug treatment. The latter includes infusion therapy, the use of glucocorticoids, surfactant preparations, narcotic analgesics and diuretics. Respiratory support consists in the use of mechanical ventilation (MV), and if the latter is not effective, extracorporeal membrane oxygenation (ECMO). Methods: literature data analyzes of acute chemical lung lesions treatment, as well as data on types, methods of liquid ventilation lung use. Results: It was found that the use of lungs both partial and total liquid ventilation using perfluorocarbon (PFC) compounds not only improved gas exchange in the lungs, but reduced the severity of the inflammatory response also. It was shown that the method of lung liquid ventilation (LVL) is promising. In turn, the increase in oxygenation we received, the increase in partial blood pressure during the alveolar phase of oedema, shows the advantage of liquid ventilation over existing ventilation regimes MV, thereby reflecting the potential of LAVL as a new method of respiratory support in acute lung lesions.
Berichte der Organisationen zum Thema "Drug-reduced regimens"
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Jorgensen, Frieda, Andre Charlett, Craig Swift, Anais Painset und Nicolae Corcionivoschi. A survey of the levels of Campylobacter spp. contamination and prevalence of selected antimicrobial resistance determinants in fresh whole UK-produced chilled chickens at retail sale (non-major retailers). Food Standards Agency, Juni 2021. http://dx.doi.org/10.46756/sci.fsa.xls618.
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Campylobacter spp. are the most common bacterial cause of foodborne illness in the UK, with chicken considered to be the most important vehicle for this organism. The UK Food Standards Agency (FSA) agreed with industry to reduce Campylobacter spp. contamination in raw chicken and issued a target to reduce the prevalence of the most contaminated chickens (those with more than 1000 cfu per g chicken neck skin) to below 10 % at the end of the slaughter process, initially by 2016. To help monitor progress, a series of UK-wide surveys were undertaken to determine the levels of Campylobacter spp. on whole UK-produced, fresh chicken at retail sale in the UK. The data obtained for the first four years was reported in FSA projects FS241044 (2014/15) and FS102121 (2015 to 2018). The FSA has indicated that the retail proxy target for the percentage of highly contaminated raw whole retail chickens should be less than 7% and while continued monitoring has demonstrated a sustained decline for chickens from major retailer stores, chicken on sale in other stores have yet to meet this target. This report presents results from testing chickens from non-major retailer stores (only) in a fifth survey year from 2018 to 2019. In line with previous practise, samples were collected from stores distributed throughout the UK (in proportion to the population size of each country). Testing was performed by two laboratories - a Public Health England (PHE) laboratory or the Agri-Food & Biosciences Institute (AFBI), Belfast. Enumeration of Campylobacter spp. was performed using the ISO 10272-2 standard enumeration method applied with a detection limit of 10 colony forming units (cfu) per gram (g) of neck skin. Antimicrobial resistance (AMR) to selected antimicrobials in accordance with those advised in the EU harmonised monitoring protocol was predicted from genome sequence data in Campylobacter jejuni and Campylobacter coli isolates The percentage (10.8%) of fresh, whole chicken at retail sale in stores of smaller chains (for example, Iceland, McColl’s, Budgens, Nisa, Costcutter, One Stop), independents and butchers (collectively referred to as non-major retailer stores in this report) in the UK that are highly contaminated (at more than 1000 cfu per g) with Campylobacter spp. has decreased since the previous survey year but is still higher than that found in samples from major retailers. 8 whole fresh raw chickens from non-major retailer stores were collected from August 2018 to July 2019 (n = 1009). Campylobacter spp. were detected in 55.8% of the chicken skin samples obtained from non-major retailer shops, and 10.8% of the samples had counts above 1000 cfu per g chicken skin. Comparison among production plant approval codes showed significant differences of the percentages of chicken samples with more than 1000 cfu per g, ranging from 0% to 28.1%. The percentage of samples with more than 1000 cfu of Campylobacter spp. per g was significantly higher in the period May, June and July than in the period November to April. The percentage of highly contaminated samples was significantly higher for samples taken from larger compared to smaller chickens. There was no statistical difference in the percentage of highly contaminated samples between those obtained from chicken reared with access to range (for example, free-range and organic birds) and those reared under standard regime (for example, no access to range) but the small sample size for organic and to a lesser extent free-range chickens, may have limited the ability to detect important differences should they exist. Campylobacter species was determined for isolates from 93.4% of the positive samples. C. jejuni was isolated from the majority (72.6%) of samples while C. coli was identified in 22.1% of samples. A combination of both species was found in 5.3% of samples. C. coli was more frequently isolated from samples obtained from chicken reared with access to range in comparison to those reared as standard birds. C. jejuni was less prevalent during the summer months of June, July and August compared to the remaining months of the year. Resistance to ciprofloxacin (fluoroquinolone), erythromycin (macrolide), tetracycline, (tetracyclines), gentamicin and streptomycin (aminoglycosides) was predicted from WGS data by the detection of known antimicrobial resistance determinants. Resistance to ciprofloxacin was detected in 185 (51.7%) isolates of C. jejuni and 49 (42.1%) isolates of C. coli; while 220 (61.1%) isolates of C. jejuni and 73 (62.9%) isolates of C. coli isolates were resistant to tetracycline. Three C. coli (2.6%) but none of the C. jejuni isolates harboured 23S mutations predicting reduced susceptibility to erythromycin. Multidrug resistance (MDR), defined as harbouring genetic determinants for resistance to at least three unrelated antimicrobial classes, was found in 10 (8.6%) C. coli isolates but not in any C. jejuni isolates. Co-resistance to ciprofloxacin and erythromycin was predicted in 1.7% of C. coli isolates. 9 Overall, the percentages of isolates with genetic AMR determinants found in this study were similar to those reported in the previous survey year (August 2016 to July 2017) where testing was based on phenotypic break-point testing. Multi-drug resistance was similar to that found in the previous survey years. It is recommended that trends in AMR in Campylobacter spp. isolates from retail chickens continue to be monitored to realise any increasing resistance of concern, particulary to erythromycin (macrolide). Considering that the percentage of fresh, whole chicken from non-major retailer stores in the UK that are highly contaminated (at more than 1000 cfu per g) with Campylobacter spp. continues to be above that in samples from major retailers more action including consideration of interventions such as improved biosecurity and slaughterhouse measures is needed to achieve better control of Campylobacter spp. for this section of the industry. The FSA has indicated that the retail proxy target for the percentage of highly contaminated retail chickens should be less than 7% and while continued monitoring has demonstrated a sustained decline for chickens from major retailer stores, chicken on sale in other stores have yet to meet this target.