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1

Kryvohuz, H. „REGULATORY DOCUMENTS OF MILITARY LOGISTICS: CHANGES AND ADDITIONS“. Collection of scientific works of Odesa Military Academy, Nr. 11 (27.12.2019): 59–70. http://dx.doi.org/10.37129/2313-7509.2019.11.59-70.

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The author identifies deficiencies and suggests amendments and additions to the procedure of operational (combat) orders production (hereinafter referred to as the Procedure) as well as Field Manuals for the mechanized and tank forces of the Land Forces of the Armed Forces of Ukraine in order to improve graphic depiction of the performance of military logistics units at operational and tactical level. The elimination of the identified deficiencies suggests the following changes: use identical typical symbols to depict similar in function units and elements of military logistics within all armed services and branches of the Armed Forces of Ukraine, which requires prior coordination with various military command and control agencies; use only letters of the Ukrainian alphabet in textual modifiers of the conventional symbols, avoid duplication of conventional symbols, which stand for various types of equipment, in textual modifiers; clarify the existing symbols and add some new ones to the Procedure in order to identify the units and technical means of logistics as well as their functional performance while accomplishing their tasks, anticipate the logistics units of the prospective organizational structure as well as local industrial facilities. Taking in consideration the identified deficiencies, the following proposals for making changes and additions to specified regulatory documents are given: use identical symbols to indicate warehouses (artillery, engineering equipment, engineering weapons and ammunition storage, NBC protection equipment, topographic maps, armored vehicles, medical equipment); introduce new conventional symbols to indicate the performance of logistics units and all available means of military logistics (areas and points of transfer of material resources, points of meeting of automobile units with material means of rear services, technical means for cooking and washing clothing, patrols, supply and evacuation routes for the brigade ( regiment), local industrial facilities and economic infrastructure, mobile departments of deployed forces and service support elements); make recommendations regarding the size of letters for the footnotes on topographic maps scales 25,000 and 50,000, as well as codes of the maps used by military personnel with regard to the experience of participation of the Ukrainian Armed Forces in the antiterrorist operation (operation of the combined forces) in the Donetsk and Lugansk regions.
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Jolly, R. T. „Ajax Bay“. Journal of The Royal Naval Medical Service 104, Nr. 1 (2018): 59–62. http://dx.doi.org/10.1136/jrnms-104-59.

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SummaryAs a result of fierce aerial attacks on the fleet supporting the landing force on Friday, 21 May 1982, SS CANBERRA was ordered to sail from San Carlos Water. Elements of her medical organisation were hurriedly put ashore into a deserted refrigeration plant at Ajax Bay. Three weeks later they had treated over 650 battle casualties, performed 210 operations under general anaesthetic, and been bombed by Argentinian aircraft. Despite appalling circumstances, their results were a triumphant success. As Officer Commanding Medical Squadron, Commando Logistics Regiment RM, the author was in charge at Ajax Bay throughout the land phase of hostilities.
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Meredith, Ruby F. „Logistics of therapy with the ibritumomab tiuxetan regimen“. International Journal of Radiation Oncology*Biology*Physics 66, Nr. 2 (Oktober 2006): S35—S38. http://dx.doi.org/10.1016/j.ijrobp.2006.06.009.

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Ahyar, Ibnu, Irwan Taufiqurrachman und Ardhanu Kusumanto. „PERBANDINGAN KUALITAS HIDUP PENDERITA KANKER OVARIUM EPITELIAL YANG DIBERIKAN KEMOTERAPI REGIMEN PACLITAXEL DAN CARBOPLATIN DENGAN REGIMEN CYCLOPHOSPAMIDE, ADRIAMICYN DAN CISPLATIN DI RSUP DR. SARDJITO“. Jurnal Kesehatan Reproduksi 4, Nr. 1 (15.04.2017): 1. http://dx.doi.org/10.22146/jkr.35428.

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Background: Epithelial ovarian cancer is the dominant type of ovarian cancer. Platinum and Taxane regiment has been proved to increase the survival rate of ovarian cancer patientsObjective: To compare the quality of life of ovarian cancer patients who got Paclitaxel and Carboplatin regiments with Cyclophosphamide, Adriamycin and Cisplatin regiments and risk factors which influence themMethod: The design of the study was retrospective cohort. The total subjects were 156 ovarian cancer patients who consisted of 79 patients with paclitaxel and carboplatin regiments and dan 77 patients who got cyclophospamide, adriamicyn dan cisplatin regiments in DR. Sardjito hospital, Yogyakarta. The quality of life was measured with EORTC QLQ-C30. The data distribution were tested with KolmogorovSmirnov and analysed with D Chi-Squaretest for categorical data and Mann-Whitney for continuous data. Multivariable Analysis was done with logistic regression.Result and Discussion: The bivariable analysis of ovarian cancer stage and the quality of life showed that early stage of ovarian cancer patients had quality of life 19,068 times higher than advance stage of ovarian cancer patients (RR 19,068; 95% CI 2,590-140,362). There were signicant differences in quality of life in ovarian cancer patients with low body mass index <18,5 compared to normal body mass index as well as the titer of tumor marker Ca125. Multivariable analysis showed that there was no significant difference in quality of life between ovarian cancer patients who got Paclitaxel plus Carboplatin and ovarian cancer patients who got Cyclophospamide, Adriamicyn plus Cisplatin.Conclusion: there was no significant difference in quality of life between ovarian cancer patients who got Paclitaxel plus Carboplatin and ovarian cancer patients who got Cyclophospamide, Adriamicyn plus Cisplatin in DR. Sardjito Hospital, Yogyakarta.Keywords: Quality of life, ovarian cancer, paclitaxel plus carboplatin regiment, cyclophospamide, adriamicyn plus cisplatin regiment.
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Fein, Joshua A., Avichai Shimoni, Ivetta Danylesko, Noga Shem-Tov, Ronit Yerushalmi, Guy Chowers, Zachary Cohen, Arnon Nagler und Roni Shouval. „Early Organ Toxicity Following Allogeneic Hematopoietic Stem Cell Transplantation Differs By Conditioning Regimen“. Blood 134, Supplement_1 (13.11.2019): 4489. http://dx.doi.org/10.1182/blood-2019-126325.

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Background: In recipients of allogeneic hematopoietic stem cell transplantation (HSCT), organ toxicity is a barrier to administering high-intensity conditioning regimens. We hypothesized that determinants of acute organ toxicity are specific to individual conditioning regimens. We sought to characterize toxicities across common transplantation regimens, evaluate their prognostic implication, and derive predictors of severe toxicity at the regimen level. Methods: This retrospective study included adults undergoing first allogeneic HSCT at a single center between the years of 2001 and 2014 (median: 2010). Patients received grafts from matched sibling or unrelated donors and were conditioned with any of the following regimens: Cyclophosphamide + TBI (Cy/TBI), Busulfan + Cyclophosphamide (Bu/Cy), Fludarabine + 12.8 mg Busulfan (Flu/Bu4), Fludarabine + 6.4 mg Busulfan (Flu/Bu2), Fludarabine + 36-42 gr/m2 Treosulfan (Flu/Treo), and Fludarabine + 100-140 mg/m2 Melphalan (Flu/Mel). Toxicities were defined by the KDIGO scale for acute kidney injury (AKI) and by the CTCAE v. 5.0 for increases in total bilirubin, AST, ALT, and alkaline phosphatase (Alk. Phos.) The incidence of toxicities from the start of conditioning through 30 days post-transplantation was tabulated by regimen. Risk factors for severe organ toxicity were assessed within each regimen cohort using multivariable logistic regressions. Results: In a cohort of 707 patients, the median age was 52 years. The main indications for transplantation were acute leukemia (57%), myelodysplastic syndrome (13%), and aggressive lymphoma (9%). Graft-versus-host-disease prophylaxis included methotrexate in 80% of patients, and 56% received anti-thymocyte globulin (ATG). The most common regimens were Flu/Treo (n = 160) and Bu/Cy (n = 141). As expected, patient characteristics varied between regimens. The incidence of AKI and increased serum bilirubin in each regimen is shown in Figure 1A and 1B, respectively. Sinusoidal-obstructive syndrome (6% overall) accounted for only 17% of gr. ≥ 3 bilirubinemia in the entire cohort. Elevations in AST, ALT, and Alk. Phos of gr. ≥ 3 were not common (<8%). In multivariable logistic regression, AKI gr. ≥ 2, increased bilirubin gr. ≥ 3, AST gr. ≥ 3, and Alk. Phos. gr. ≥ 2 were associated with increased 100-day mortality (p < 0.05). Acute severe organ toxicity (ASOT) was defined as the occurrence of any of these toxicities. ASOT had an odds ratio (OR) of 3.4 (95% CI: 2.2-5.3) for 100-day mortality. Within each regimen, we studied the relationship between ASOT and transplantation/patient characteristics (Figure 1C). Elevations in baseline bilirubin were predictive of ASOT in Cy/TBI (OR: 1.68 [1.19-2.37]), while increasing creatinine was predictive in patients conditioned with Flu/Mel (OR: 1.43 [1.09-1.88]). High-risk disease (DRI) was associated with increased risk in patients receiving Flu/Bu4 (1.26 [1.01-1.58]). In patients treated with Bu/Cy, administration of ATG increased the risk of ASOT (1.31 [1.11-1.55]). Conclusion: Allogeneic stem cell transplantation recipients are at high risk for acute organ damage. We describe patterns of renal and liver toxicity across several regimens. Determinants of acute severe organ toxicity, defined as those associated with short-term mortality, are regimen dependent. Our findings suggest that these factors should be considered when selecting the preparative regimen. While requiring validation, the newly-defined composite endpoint of acute severe organ toxicity (ASOT) may be valuable in studying transplantation strategies. Figure 1 Disclosures No relevant conflicts of interest to declare.
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Fujii, Takeo, Naoki Nishimura, Hisako Kanai, Hiromasa Ishimaru, Junko Kawano, Osamu Takahashi, Hideko Yamauchi und Teruo Yamauchi. „Impact of fosaprepitant use on dermal and vascular adverse events in anthracycline-based regimens administered through peripheral lines.“ Journal of Clinical Oncology 31, Nr. 15_suppl (20.05.2013): 9629. http://dx.doi.org/10.1200/jco.2013.31.15_suppl.9629.

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9629 Background: Fosaprepitant is effective in the prevention of chemotherapy-induced nausea and vomiting. In January 2012, we started using fosaprepitant in anthracycline- and cisplatin-based regimens and observed a tendency for an increase in dermal and vascular adverse events (AEs) at local infusion sites, particularly in the anthracycline group. In this study, we tested the hypothesis that fosaprepitant use is associated with dermal and vascular AEs differentially between anthracycline- and cisplatin-based regimens. Methods: We conducted a retrospective cohort study consisting of all patients who were administered anthracycline- or cisplatin- based regimens in 2011 and 2012 at St. Luke’s International Hospital, Tokyo. Aprepitant was used in 2011 and fosaprepitant was used in 2012. All other factors including pre- and post-hydration, premedication, and injection schedule were the same. Dermal and vascular AEs was defined as any grade pain or skin changes at local infusion sites or infusion veins. Factors we considered include fosaprepitant use, chemotherapy regimen, age, number of prior regimens, and body mass index. Interaction analysis using multivariate logistic regression was used to evaluate the association between treatment regimen, fosaprepitant, and risk of AEs. Results: A total of 268 patients (aged 54.3±12.3) were included, of which 120 (44.8%) used fosaprepitant. Among fosaprepitant users, 50 patients (41.7%) developed dermal and vascular AEs, whereas only 16 patients (10.8%) experienced AEs among non-users (P< .001). When stratified by regimen, fosaprepitant was associated with a statistically significant increased risk of AEs (OR 12.10; 95% CI 5.45-26.93) in the anthracycline group. In contrast, no association was observed in the cisplatin group (OR 1.04; 95% CI 0.29-3.75). Statistically significant evidence of interaction was found (P< .001) between regimen and fosaprepitant in the risk of AEs. Conclusions: Our results support the finding that using fosaprepitant in anthracycline-based regimens increases dermal and vascular AEs. In response, we discourage the use of fosaprepitant in anthracycline-based regimens through peripheral lines.
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Al-Jumayli, Mohammed, Saqib Abbasi, Anup Kasi und Anwaar Saeed. „The association of 5FU-based chemotherapy with pathological response or survival compared to carbo/taxol with locally advanced resectable esophageal cancer.“ Journal of Clinical Oncology 37, Nr. 4_suppl (01.02.2019): 165. http://dx.doi.org/10.1200/jco.2019.37.4_suppl.165.

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165 Background: Neoadjuvant chemoradiation followed by esophagectomy is the standard of care in advanced EC. While 5FU based chemoradiation has been a common regimen in the past, its utilization has declined in recent years as the CROSS trial study regimen of carboplatin/paclitaxel has become widely adopted. A prospective evaluation of the CROSS regimen compared to the 5FU based regimen was never performed. The aim of this study is to report our institutional experience with these two chemotherapy regimens. To the best of our knowledge, this is the largest retrospective study comparing the two types of chemotherapy regimens. Methods: We performed an IRB-approved retrospective review of a prospectively maintained institutional cancer registry. EC patients who completed trimodality therapy with either carboplatin/paclitaxel or 5FU/platinum were identified and divided into groups based on their chemotherapy regimens. Multivariable logistic regression was used to analyze pathologic complete response (pCR) rates, while the Kaplan–Meier and Cox proportional hazards models were utilized to evaluate DFS and OS. Analytical models were adjusted for age, stage, radiation dose, histology sub-type, and time interval from completion of neoadjuvant therapy to surgery. Results: 224 patients treated between January of 2007 and July of 2017 were identified . Of this group, 139(62%) had received Carbo/Taxol, while 85 (37%) had received 5FU/platinum. There was no increase in the odds of pCR with 5FU based chemo compared to CROSS regimen (OR = 2.68, P = 0.671). Furthermore, the OS and DFS of 159 patients(80 5FU/platinum, 77 carbo/taxol) with median follow up of ~ 5 yrs were not statistically different with HR 1.08 (0.6-1.7) and P value 0.71. Conclusions: Neoadjuvant chemoradiation with 5FU/platinum in resectable EC is not associated with higher rates of pCR, DFS and OS compared to the CROSS regimen of carbo/taxol. Those findings will need to be validated in a larger cohort.
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Arlandis, José Luis Catalán, und N. Víctor Jiménez Torres. „Anthropometric and Pharmacotherapeutic Variables on Acute Emesis Induced by Cisplatin-Containing Chemotherapy“. Annals of Pharmacotherapy 34, Nr. 5 (Mai 2000): 573–79. http://dx.doi.org/10.1345/aph.19188.

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OBJECTIVE: To characterize the effects of anthropometric and pharmacotherapeutic variables on acute emesis induced by cisplatin-containing regimens with dosages ·50 mg·m−2. METHODS: A prospective, cross-sectional, noncontrolled study was performed to analyze acute vomiting during the first 24 hours in patients treated in a Spanish hospital. The patients received an intravenous combination of drugs (2 doses of metoclopramide 3 mg/kg, dexamethasone 20 mg) as first-choice antiemetic therapy. Intravenous ondansetron 8 mg and dexamethasone 20 mg served as an alternative regimen in patients <30 years old with a history of extrapyramidal manifestations or emesis in previous cycles. Therapeutic failure was used as a dependent variable, defined as three or more vomiting episodes documented by the patients. Other variables were the chemotherapeutic regimen; antiemetic regimen; patient gender, age, weight, and height; and cycle number. The reference logistic model and two reduced-models derived from the latter were designed. The logistic models were subsequently validated by means of receiving operating characteristic curves. RESULTS: A total of 319 cycles involving 106 patients were studied. The metoclopramide regimen was administered in 66% of the cycles. The therapeutic failure rate was 21% for the metoclopramide regimen and 32% for the ondansetron treatment. The logistic model developed identified the type of chemotherapeutic regimen provided as the most significant prognostic variable (p < 0.0001). Patient weight (odds ratio 1.64) and height (odds ratio 1.28) were identified as prognostic factors related with therapeutic failure. CONCLUSIONS: The type of chemotherapeutic regimen administered and the anthropometric characteristics of the patients exert a clear conditioning effect on risks associated with therapeutic failure against acute emesis following high-dose cisplatin therapy. Such anthropometric parameters have not been previously identified as prognostic factors.
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Noronha, Vanita, Vijay Patil, Amit Joshi, S. Juvekar, Bharatsinha Baburao Bhosale, Bhavesh Poladia, Sushmita Rath et al. „Are three drugs better than two and does docetaxel trump paclitaxel in induction therapy for locally advanced oral cavity cancers?“ Journal of Clinical Oncology 31, Nr. 15_suppl (20.05.2013): 6085. http://dx.doi.org/10.1200/jco.2013.31.15_suppl.6085.

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6085 Background: A variety of regimens have been used for induction chemotherapy in locally advanced head & neck cancers. Cisplatin & 5 FU drug combination is inferior to the combination of taxane & these 2 drugs. However, often in clinical practice at our center giving TPF is difficult in view of logistics & tolerance issues. In such scenarios we prefer to use 2 drug combination of platinum & taxane. However no study has addressed whether when the 2 drug combination includes taxane, is it still inferior to the 3 drug combination and which the taxane of choice is. Methods: This is a retrospective analysis of prospectively collected data of patients undergoing induction chemotherapy in oral cavity cancers from 2010-2012. We chose for analysis those patients who had a baseline scan and a follow-up scan done within 2 weeks of completion of the second cycle of induction chemotherapy. Response was scored in accordance with RECIST 1.1. Data was analyzed using SPSS, version 16. Chi- square analysis was done to compare response rates between regimens. Results: Two hundred & forty five patients were indentified. The median age was 45 years (24-70 years), 208 (84.9%) were male patients & in 154 patients (62.9%) had primary in buccal mucosa. The regimen received were TPF 22 (9%), TP (Docetaxel + cisplatin) 97 (39.6%), PP (paclitaxel+cisplatin) 89 (36.3%), TC (Docetaxel+ carboplatin) 16 (6.5%) & PC (paclitaxel + carboplatin) 21 (8.6%).The overall response rates (RR) were CR, PR,SD & PD in 4 (1.6%), 56 (22.9%), 145 (59.2%) & 40 (16.3%). On comparison, 3 drug regimen (TPF) had 50% RR as against 22% RR with 2 drug regimen (p=0.004). On comparison for taxane, docetaxel containing regimens had 30.3% RR as against 17.2% RR with paclitaxel containing regimens (p=0.018). There was no statistically significant difference in RR between patients receiving carboplatin or cisplatin. Conclusions: TPF had better RR than a 2 drug taxane-containing regimen and docetaxel leads to a better RR than paclitaxel for induction chemotherapy in locally advanced oral cavity cancers.
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Nogaj, Adam. „Evaluation of the correctness of the German military intelligence’s findings concerning armament and equipment of the Polish Army in 1939. Part II. Aviation, Navy, radio communication, means of transport and logistics of the Polish Army“. Scientific Journal of the Military University of Land Forces 197, Nr. 3 (11.09.2020): 600–619. http://dx.doi.org/10.5604/01.3001.0014.3955.

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The presented article constitutes the second part of the publication and is devoted to the current knowledge of the German military intelligence concerning the armament and equipment of land forces, Navy, radio communication, means of transport and logistics of the Polish Army in 1939. The article also attempts to assess the correctness of these findings. The presented article is one of several articles written by the author to present the knowledge of German military intelligence about the Polish Army in 1939, together with the assessment of the correctness of these findings. The article is based on archival materials of the 12th Foreign Armies East Intelligence Section of the General Staff of the High Command of the Land Forces of 1939, which developed synthetic elaborations for the top military commanders of the German army, based on the analysis and collective materials from the individual Abwehstelle. For years, the documents analysed were classified and delivered exclusively to the top commanders of the German army and Hitler’s Chancellery. At present, they are entirely non-confidential and available to researchers at the Bundesarchiv-Militaerarchiv in Freiburg. Copies of parts of these documents, in the form of microfilms, can be found, among others, in the Archive of New Files in Warsaw. According to the author, working out both – the Polish aviation and fleet – was carried out at a high and correct level. Nevertheless, it does not mean that no mistakes were made, even very serious – for example as regards the assessment of the number of submarines. The greatest negligence of the German Military Intelligence’s findings on armament and equipment of the Polish Army concerns the equipment of signal corps. As the German Intelligence overlooked modernisation of communication equipment which took place in the years 1937-1939, there was no knowledge of, among the other things, the “N” type radio stations, which were used in almost every regiment. Scarcity of the Polish Army equipment as regards mechanical means of transport was well known. The shortages in the above scope were enormous. What is interesting, is the fact that logistics of the Polish Army was completely overlooked by the German Intelligence. It should be assumed that the German Military Intelligence’s figuring out of armament and equipment of the Polish Army was carried out on a high and correct level. Nevertheless, it does not mean that all the findings were appropriate and true. The accuracy of the correctness of the German Military Intelligence’s findings concerning figuring out of organisation and composition of the Polish Army, and dislocation of the Polish units in time of peace, should also be highly assessed. Nevertheless, the Intelligence’s findings, as regards signal mobilization process, figuring out the mobilization and operational plans of the Polish Army and organisation and the composition of the Polish Army during war should be evaluated differently. It results from the fact that the German Intelligence was not aware of, among the other things: number of divisions Poland would engage at war, names and composition of the Polish military units, very strong reserve of the High Commander, as well as it was not able to localize the Polish divisions developed over the borders just before the outbreak of war. Knowledge of the Polish economy was also on a very basic level. Therefore, the aforementioned negligence in the German Military Intelligence’s findings on the Polish Army and Poland itself during the period directly preceding the war, should be regarded as major. Taking the above into consideration, the conclusion is that the German agency did not exist among the people holding high positions in the Polish Army; in the Central Staff, General Inspector of Training, Corps District Commands. Nevertheless, the overall view of the Polish Army recorded by the German Military Intelligence was correct. It was noticed that the army is weak, poorly equipped and badly managed and it would not be able to fight the enemy. It was a correct assessment.
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Sisay, Mekonnen, Dumessa Edessa, Yohanes Ayele und Mesay Getachew. „Pattern of and reasons for antiretroviral therapy regimen change among adult HIV/AIDS patients at regional hospital in Eastern Ethiopia: A 10-year retrospective study“. SAGE Open Medicine 7 (Januar 2019): 205031211982709. http://dx.doi.org/10.1177/2050312119827092.

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Objectives: Despite the successes of treatment with antiretroviral therapy in reducing morbidity and mortality among HIV-infected patients, long-term sustainability of the initial regimen has become challenging. Therefore, this study is aimed to address pattern of and reasons for change of antiretroviral therapy regimens among HIV/AIDS patients at Jugel Hospital, Eastern Ethiopia. Methods: A retrospective cross-sectional study was conducted to review medical records of 220 patients who had been on treatment and experienced regimen change at least once from September 2006 to August 2016. Structured data abstraction format was customized from World Health Organization guideline. Data were entered in Epi-data version 3.1, and exported to and analyzed with Statistical Package for Social Sciences version 20. Following descriptive statistics, binary logistic regression was run to determine the association between selected variables and second-time regimen change. Results: The mean age of patients was 37.6 (±8.9) years and 62.3% of them were female. Majority of the patients were presented to the hospital with World Health Organization clinical stage III (59.1%) and CD4 count below 200 cells/mm3 (68.6%). The mean duration of stay on initial regimen was found to be 3.26 (±1.92) years. The average number of initial regimen changes per year was 22 (±11.28). In two-thirds (66.36%) of the patients, their initial regimen was changed to tenofovir disproxil fumarate–based alternatives. The most-frequent reason for initial regimen change was toxicity (32.3%). Among those who experienced the regimen change for the first time, the prevalence of second-time regimen change was found to be 18.18%. Patients who had been taking tuberculosis treatment along with antiretroviral therapy were more likely to get their regimen changed for the second-time compared to those who were not infected with tuberculosis (adjusted odds ratio: 3.40; 95% confidence interval: 1.87–6.47). Besides, patients who were on zidovudine-based (adjusted odds ratio: 0.26; 95% confidence interval: 0.33–0.47) and tenofovir disoproxil fumarate–based regimens (adjusted odds ratio: 0.03; 95% confidence interval: 0.01–0.12) were less likely to get their regimen changed for the second-time compared to those who were on stavudine-based regimens. Conclusion: The majority of the patients had their treatment regimen changed because of drug-related toxicities, treatment failure, and comorbid conditions. Some regimen changes might be attributable to failure of either hospital supply system or patient-related factors which would have been prevented considering limited number of treatment options. There must be consideration of risks and benefits prior to changing a particular regimen.
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Stagg, Helen R., Graham H. Bothamley, Jennifer A. Davidson, Heinke Kunst, Maeve K. Lalor, Marc C. Lipman, Miranda G. Loutet et al. „Fluoroquinolones and isoniazid-resistant tuberculosis: implications for the 2018 WHO guidance“. European Respiratory Journal 54, Nr. 4 (01.08.2019): 1900982. http://dx.doi.org/10.1183/13993003.00982-2019.

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Introduction2018 World Health Organization (WHO) guidelines for the treatment of isoniazid (H)-resistant (Hr) tuberculosis recommend a four-drug regimen: rifampicin (R), ethambutol (E), pyrazinamide (Z) and levofloxacin (Lfx), with or without H ([H]RZE-Lfx). This is used once Hr is known, such that patients complete 6 months of Lfx (≥6[H]RZE-6Lfx). This cohort study assessed the impact of fluoroquinolones (Fq) on treatment effectiveness, accounting for Hr mutations and degree of phenotypic resistance.MethodsThis was a retrospective cohort study of 626 Hr tuberculosis patients notified in London, 2009–2013. Regimens were described and logistic regression undertaken of the association between regimen and negative regimen-specific outcomes (broadly, death due to tuberculosis, treatment failure or disease recurrence).ResultsOf 594 individuals with regimen information, 330 (55.6%) were treated with (H)RfZE (Rf=rifamycins) and 211 (35.5%) with (H)RfZE-Fq. The median overall treatment period was 11.9 months and median Z duration 2.1 months. In a univariable logistic regression model comparing (H)RfZE with and without Fqs, there was no difference in the odds of a negative regimen-specific outcome (baseline (H)RfZE, cluster-specific odds ratio 1.05 (95% CI 0.60–1.82), p=0.87; cluster NHS trust). Results varied minimally in a multivariable model. This odds ratio dropped (0.57, 95% CI 0.14–2.28) when Hr genotype was included, but this analysis lacked power (p=0.42).ConclusionsIn a high-income setting, we found a 12-month (H)RfZE regimen with a short Z duration to be similarly effective for Hr tuberculosis with or without a Fq. This regimen may result in fewer adverse events than the WHO recommendations.
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Rastogi, Sameer, Aditi Aggarwal, Akash Tiwari und Vinod Sharma. „Chemotherapy in Nonmetastatic Osteosarcoma: Recent Advances and Implications for Developing Countries“. Journal of Global Oncology, Nr. 4 (Dezember 2018): 1–5. http://dx.doi.org/10.1200/jgo.2016.007336.

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Purpose Osteosarcoma (OS) is a relatively chemosensitive primary bone tumor, with the peak age of onset occurring in late childhood and early adolescence. The treatment paradigm of nonmetastatic OS has typically been multimodality therapy, including neoadjuvant and adjuvant chemotherapy with definitive surgery. Over the years, various permutations and combinations of chemotherapeutic agents have been used. However, the majority of recent trials have still used high-dose methotrexate as the backbone, with cisplatin and doxorubicin (MAP). In the last decade, various strategies targeted to improving outcomes in OS have included the addition of a fourth drug to the three-drug MAP regimen, changing therapy according to histopathologic response and the addition of immunotherapies. Through this review, we sought to underscore a few pertinent issues related to chemotherapy in nonmetastatic OS, with special reference to challenges confronted in Indian settings. Methods We reviewed the literature, focusing on studies comparing high-dose methotrexate and non–high-dose methotrexate–containing regimens. In addition, this review focuses on non–methotrexate-containing triple-drug therapy. Results Although a high-dose methotrexate regimen has become standard of care in developed countries, there are few data to suggest that it is superior to a non–high-dose methotrexate regimen. Conclusion Developing countries with lack of infrastructure and logistics for high-dose methotrexate might resort to non–high-dose methotrexate–containing regimens with a simultaneous focus on early detection, decreasing abandonment, multidisciplinary clinics, improved surgery, and meticulous pathologic evaluations.
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Tanioka, M., N. Katsumata, T. Hirata, M. Yunokawa, K. Yonemori, T. Kouno, C. Shimizu, K. Tamura, M. Andoh und Y. Fujiwara. „Secondary platinum therapy in patients with uterine cervical cancer previously treated with platinum chemotherapy“. Journal of Clinical Oncology 27, Nr. 15_suppl (20.05.2009): 5588. http://dx.doi.org/10.1200/jco.2009.27.15_suppl.5588.

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5588 Background: Second-line chemotherapy after the front-line platinum based regimens including concurrent chemoradiation (CCRT) has not been established for patients with advanced or recurrent cervical cancer. Platinum based regimens are often selected, but the predictive and prognostic factors of secondary platinum therapy are unclear. We therefore evaluated the relative influence of platinum free interval ( PFI ) between the completion of front-line regimen and the institution of second-line regimen. Methods: This retrospective review was undertaken of 65 patients who received ≥ 2 platinum-based regimens and were assessable for secondary response in National Cancer Center Hospital between 1996 and 2008. We analyzed independent predictive factors associated with secondary response by logistic regression model and prognostic factors associated with subsequent survival by Cox regression model. Results: The median age was 54 years old (range, 28 to 73). The median follow-up of subsequent survival was 11.0 months (1.1 to 66.6). The median PFI was 11.1 months (0.7 to 77.6). Overall secondary response rate was 40%, while response rate for 36 patients after CCRT was 36%. The response increases in frequency with longer PFI ( Table ). Univariate and multivariate analyses using logistic regression model showed PFI for ≥ 9 months (odds ratio [OR] = 0.28; P =.04), PS 0 (OR = 0.19; P =.006) and maximum tumor diameter ≥ 30 mm (OR = 0.23; P =.02) were independent predictive factors of secondary response. Univariate and multivariate analyses using Cox regression model revealed PFI for ≥ 9 months (hazard ratio [HR] = 0.44; P =.005), PS 0 (HR = 0.30; P =.000) and histology of squamous cell carcinoma (HR = 2.20; P =.02) were independent prognostic factors of subsequent survival. Conclusions: Our exploratory study demonstrates that platinum free interval has both predictive and prognostic value for secondary platinum-based treatment for patients with advanced or recurrent cervical cancer. [Table: see text] [Table: see text]
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Griggs, J. J., E. Culakova, M. E. Sorbero, J. Crawford, D. C. Dale, D. A. Wolff, M. S. Poniewierski und G. H. Lyman. „Social and racial disparities in the use of non-standard breast cancer adjuvant chemotherapy regimens“. Journal of Clinical Oncology 24, Nr. 18_suppl (20.06.2006): 6036. http://dx.doi.org/10.1200/jco.2006.24.18_suppl.6036.

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6036 Background: Economically disadvantaged and black women have worse stage-specific breast cancer outcomes than other women, even after controlling for tumor histologic features. Disparities quality of chemotherapy may contribute to differences in outcome. The purpose of this study was to investigate the use of non-standard breast cancer adjuvant chemotherapy regimens in black women and those of lower socioeconomic status (SES). Methods: Detailed information on patient, disease, and treatment factors was collected prospectively on 1,006 patients receiving adjuvant chemotherapy for early-stage breast cancer in 115 oncology practices throughout the US. All patients signed informed consent. Regimens included in the guidelines of the National Comprehensive Cancer Network were considered standard regimens; all others were considered non-standard. Receipt of non-standard regimens was examined according to clinical and non-clinical factors. Differences between groups were assessed using a chi-square test. Multivariate logistic regression was used to identify factors associated with use of non-standard regimens. Results: Non-standard regimens were used in the treatment of 136 (14%) of the participants. Black patients were twice as likely to receive a non-standard regimen as whites (23% vs. 12%, p = .0014). Patients with less than a high school education were twice as likely to receive a non-standard regimen compared with those with a college education (21% vs. 8%, p = 0.0011). Other factors associated with non-standard chemotherapy regimens were past chemotherapy exposure (p < .0001), higher stage disease (p < .0001) and geographic location (p = 0.0059). Age, comorbidity, body mass index, type of insurance, and employment status were not associated with receipt of non-standard chemotherapy. In multivariate analysis, all variables that were significant in the bivariate analysis remained independently associated with receipt of non-standard chemotherapy. Conclusions: The more frequent use of non-guideline concordant adjuvant chemotherapy regimens in black women and women with lower SES may contribute to their less favorable outcomes. These findings offer an opportunity to improve patient care and perhaps cancer outcomes. [Table: see text]
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Cairns, M., B. Cisse, C. Sokhna, C. Cames, K. Simondon, E. H. Ba, J. F. Trape, O. Gaye, B. M. Greenwood und P. J. M. Milligan. „Amodiaquine Dosage and Tolerability for Intermittent Preventive Treatment To Prevent Malaria in Children“. Antimicrobial Agents and Chemotherapy 54, Nr. 3 (11.01.2010): 1265–74. http://dx.doi.org/10.1128/aac.01161-09.

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ABSTRACT Sulfadoxine-pyrimethamine with amodiaquine (SP-AQ) is a highly efficacious regimen for intermittent preventive treatment to prevent malaria in children (IPTc), but the amodiaquine component is not always well tolerated. We determined the association between amodiaquine dosage by body weight and mild adverse events (AEs) and investigated whether alternative age-based regimens could improve dosing accuracy and tolerability, using data from two trials of IPTc in Senegal, one in which AQ dose was determined by age and the other in which it was determined by weight category. Both dosage strategies resulted in some children receiving AQ doses above the recommended therapeutic range. The odds of vomiting increased with increasing amodiaquine dosage. In one study, incidence of fever also increased with increasing dosage. Anthropometric data from 1,956 children were used to predict the dosing accuracy of existing and optimal alternative regimens. Logistic regression models describing the probability of AEs by dosage were used to predict the potential reductions in mild AEs for each regimen. Simple amendments to current AQ dosing schedules based on the child's age could substantially increase dosing accuracy and thus improve the tolerability of IPTc using SP-amodiaquine in situations where weighing the child is impractical.
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Westeel, V., N. Murray, K. Gelmon, A. Shah, F. Sheehan, M. McKenzie, F. Wong et al. „New combination of the old drugs for elderly patients with small-cell lung cancer: a phase II study of the PAVE regimen.“ Journal of Clinical Oncology 16, Nr. 5 (Mai 1998): 1940–47. http://dx.doi.org/10.1200/jco.1998.16.5.1940.

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PURPOSE A regimen of cisplatin, doxorubicin, vincristine, and etoposide (PAVE) was designed for patients with small-cell lung cancer (SCLC) who were older than 65 years, with the following objectives compared with standard chemotherapy regimens: maintain efficacy, diminish toxicity, enhance compliance, and improve chemotherapy administration convenience at an acceptable cost. PATIENTS AND METHODS The PAVE regimen consisted of cisplatin 30 mg/m2 intravenously (i.v.) day 1; doxorubicin 40 mg/m2 i.v. day 1; vincristine 1.0 mg/m2 i.v. day 1; and etoposide 100 mg/m2 i.v. day 1 and orally days 3 and 5. Cycles were repeated every 3 weeks for four cycles. Patients with limited-stage disease and selected patients with extensive-stage disease received thoracic irradiation delivered concurrently with etoposide-cisplatin (EP) at the time of the second chemotherapy cycle. RESULTS Sixty-six eligible patients were treated, which included 25 patients with limited-stage disease and 41 patients with extensive-stage disease. Median survival was 70 weeks and 5-year survival was 25% for limited-stage disease. Median survival was 46 weeks for extensive-stage disease. Only one treatment-related death occurred and severe toxicity was infrequent. The median delivered dose-intensity was according to protocol and the mean delivered total dose was 80% of intended. CONCLUSION The treatment outcome achieved with PAVE in a phase II study of elderly patients compared favorably with published results of standard regimens in patient populations with better prognostic factors. Because the PAVE regimen can be delivered with good compliance, has acceptable toxicity, and is associated with logistic advantages compared with standard regimens, this protocol is suitable for further investigative trials in elderly patients with SCLC.
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Muller, Erildo Vicente, und Suely Godoy Agostinho Gimeno. „Risk factors for cardiovascular disease in HIV/AIDS patients treated with highly active antiretroviral therapy (HAART) in the central-southern region of the state of Paraná – Brazil“. Ciência & Saúde Coletiva 24, Nr. 5 (Mai 2019): 1903–14. http://dx.doi.org/10.1590/1413-81232018245.16682017.

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Abstract The aim of this study was to describe metabolic changes in HIV/AIDS patients according to the treatment regimen. It was a retrospective cohort conducted from 2002 to 2014. Researchers surveyed clinical variables and treatment regimen of 538 individuals. They used measures of central tendency and marginal logistic regression to determine the influence of the treatment regimen on clinical variables over time; survival was estimated using Kaplan-Meier curves. 56.2% of patients were male, 82.2% white, 33.8% had 4 to 7 years of study, 49.2% were married, 98.5% had sexual transmission, and 89.0% were heterosexuals. During the study period, 24.4% had hypertension, 18.2% changed cholesterol, 39.7% low HDL, 51.3% high triglycerides and 33.3% hyperglycemia. Treatment regimens with nucleotide reverse transcriptase inhibitors associated with protease inhibitors, and the association of different classes of antiretrovirals have been associated with greater lipid changes. Higher metabolic changes were observed in patients with longer treatment time. It is concluded that preventive measures, as well as early treatment, can contribute to minimize the risks of developing cardiovascular diseases.
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Raskin, William, Helen Guo, Jaclyn Marie Beca, Wanrudee Isaranuwatchai, Lucy Qiao, Craig Earle, Scott R. Berry et al. „Chemotherapy choice in advanced pancreatic cancer: What patient and disease factors influence prescription patterns?“ Journal of Clinical Oncology 36, Nr. 4_suppl (01.02.2018): 327. http://dx.doi.org/10.1200/jco.2018.36.4_suppl.327.

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327 Background: FOLFIRINOX (FFX), gemcitabine+nab-paclitaxel (GnP) and gemcitabine monotherapy (Gem)) are universally funded as first-line chemotherapy regimens for advanced pancreatic cancer (APC) in Ontario, Canada. However, there is scarce real-world data on factors that may influence choice of chemotherapy regimens in APC. Methods: Patients who received first-line chemotherapy for APC between April 2015-March 2016 in Ontario were identified from CCO’s New Drug Funding Program database and linked to the Ontario Cancer Registry and other provincial databases to ascertain baseline factors. Multinomial logistic regressions were used to examine the associations between the prescribed chemotherapy regimen and baseline factors. Results: 546 patients were identified, with a mean age of 65 and 43.6% female. 9.9% and 9.7% had received adjuvant gemcitabine and radiation treatment respectively. 17.6% had previous pancreatic resection. 68.3% had zero Charlson score and 30.6% had ECOG performance status (PS) of 0. 72.7% had metastatic disease. The majority of the patients received FFX (52.4%) compared to GnP (35.7%) and Gem (11.9%). Age and ECOG PS were strongly associated with choice of chemotherapy regimens. (See Table) Conclusions: In Ontario, increased patient age and worse ECOG PS are strongly associated with choice of Gem compared to GnP and FFX. Previous treatments and stage of disease also impact chemotherapy choice. Understanding how providers choose chemotherapy in APC aids in comprehending our practices. Odds ratio (OR) and p value from multinomial logistic regressions. [Table: see text]
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Yeh, Alicia, Bijal Shah-Manek und Kajua B. Lor. „Medication Regimen Complexity and A1C Goal Attainment in Underserved Adults With Type 2 Diabetes“. Annals of Pharmacotherapy 51, Nr. 2 (17.10.2016): 111–17. http://dx.doi.org/10.1177/1060028016673652.

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Background: From 2009 to 2012, 51.8% of American adults with diabetes had a hemoglobin A1C (A1C) >7.0%. The complexity of antidiabetic medication regimens may have an impact on glycemic control. Objective: The primary objective was to test the hypothesis that higher diabetes-specific medication regimen complexity index (MRCI) was associated with lower attainment of A1C goal <7.0% in an underserved, predominantly Hispanic population of adults with type 2 diabetes. Secondary analyses included less stringent A1C goals of <8.0% and <9.0% and overall patient-level MRCI. Methods: This study was a retrospective, observational, cross-sectional study of individuals with type 2 diabetes from January 2011 to January 2016. Data was obtained from the electronic medical record and MRCI was calculated using the 65-item validated Microsoft Access Version 1.0 medication regimen complexity electronic data capture tool. Logistic regression was used to compute unadjusted and adjusted odds ratios. Results: A total of 368 patients were included in the analysis. High diabetes-specific MRCI was associated with lower attainment of A1C goal <7.0% (adjusted OR = 0.09; 95% CI = 0.04-0.18) controlling for age, gender, ethnicity, insurance, body mass index, smoking status, hypertension, and hyperlipidemia. Similar results were obtained for the less stringent A1C goals. However, results for overall patient-level MRCI were mixed. Conclusions: Higher diabetes-specific medication regimen complexity was associated with poorer glycemic control. Simplifying antidiabetic medication regimens, especially where the treatment guidelines give no preference, could be a step toward achieving treatment goals.
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Thavendiranathan, Paaladinesh, Husam Abdel-Qadir, Hadas D. Fischer, Ying Liu, Ximena Camacho, Eitan Amir, Peter C. Austin und Douglas S. Lee. „Risk-Imaging Mismatch in Cardiac Imaging Practices for Women Receiving Systemic Therapy for Early-Stage Breast Cancer: A Population-Based Cohort Study“. Journal of Clinical Oncology 36, Nr. 30 (20.10.2018): 2980–87. http://dx.doi.org/10.1200/jco.2018.77.9736.

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PurposeTo assess prechemotherapy cardiac imaging practices in relation to patients’ heart failure (HF) risk.MethodsWe performed a population-based retrospective cohort study of women receiving chemotherapy for early-stage breast cancer in Ontario between 2007 and 2012. We surveyed for baseline cardiac imaging 6 months before chemotherapy or within 30 days thereafter. The proportion of patients who underwent imaging and cumulative incidence of major adverse cardiac event (MACE) rates was determined based on chemotherapy regimen and HF risk factors. Logistic regression was used to assess predictors of pretreatment cardiac imaging.ResultsWe studied 18,444 women who had been treated with chemotherapy (median age, 55 years). There was near-universal imaging of women treated with trastuzumab-containing regimens, including those without additional HF risk factors. Women who received anthracyclines without trastuzumab underwent imaging more frequently if they had additional HF risk factors (73.3% v 62.6%; P < .001). The 5-year incidence of MACE was two to six times higher in patients with HF risk factors across all treatment regimens. Patients with HF risk factors who received anthracyclines without trastuzumab had a higher 5-year incidence of MACE (4.5%) than patients without HF risk factors who received trastuzumab without anthracyclines (2.6%). However, cardiac imaging was less frequent in the former group (73.3% v 93.6%; P < .001). Logistic regression indicated that most variation in baseline imaging was related to chemotherapy, followed by physician-level factors. The odds of imaging were doubled with female physicians. Patient-specific factors, including HF risk factors, made minimal contribution to variation in imaging.ConclusionBaseline cardiac imaging was driven by chemotherapy regimen rather than HF risk. This risk-imaging mismatch is an impetus to reconsider current cardiac imaging practices in patients who receive chemotherapy for breast cancer.
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Sam, Matekha, John Peter Masette Masaba, Deborah Alio und Jayne Byakika-Tusiime. „Treatment Failure and Associated Factors among Individuals on Second Line Antiretroviral Therapy in Eastern Uganda: A Retrospective Cohort Study“. Infectious Diseases: Research and Treatment 14 (Januar 2021): 117863372110145. http://dx.doi.org/10.1177/11786337211014518.

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Background: ART failure is a growing public health problem and a major threat to the progress of HIV/AIDS control. In Uganda however, little is documented on treatment outcomes and their associated factors among individuals on second line ART regimen. The rapid scale-up of ART over the past has resulted in substantial reductions in morbidity and mortality. However, as millions of people must be maintained on ART for life, individuals with ART treatment failure are increasingly encountered and the numbers are expected to rise. This could be attributed to factors such as sub-standard regimens, limited access to routine viral load monitoring, treatment interruptions, suboptimal adherence, among others. The purpose of this study was to estimate 5-year cumulative treatment failure and the associated factors among individuals on second line ART regimen Eastern Uganda. Materials and methods: A retrospective analysis of 541 records of HIV positive individuals, switched to second line ART regimen from January 2012 to December 2017. Inferential statistics including the Chi square test and multivariable logistic regression analysis was applied to determine associations of treatment failure against of the selected demographic, laboratory and clinical factors was performed. Associations between treatment failure and the predictors was based on a P-value of less than 5% and confidence intervals level of 95%. Results: We reviewed 541 records of individuals on second line ART regimen, of which 350 (64.7%) were female, 226 (41.8%) were married, and 197 (36.4%) were older than 35 years. The mean age at ART initiation was 30 years (SD = 14.8), while the mean weight at ART initiation was 47 kg (SD = 18.6), (range 4-97 kg). The overall proportion of treatment failure was 23%. The cumulative mortality risk for 5 years was 12.4% and the mortality rate was 2.5 deaths per 100 individuals per year. The odds of developing treatment failure among individuals switched to ATV/r-based regimen were 44% lower as compared to individuals who were switched to LPV/r (ORadj0.56, 95% CI 0.35-0.90, P = .016). while the odds of experiencing treatment failure among individuals that used AZT at ART initiation were 43% lower as compared to individuals that used a TDF based regimen at ART initiation (ORadj0.57, 95% CI 0.33-0.98, P = .041). Conclusion: The 5 year cumulative incidence of treatment failure in a cohort of 541 individuals was 23%. The type of protease inhibitor (PI) used in second line regimen and use of AZT at ART initiation were significantly associated with treatment failure. Our study also shows that the cumulative mortality risk while on second line ART regimen was 12.4% while the mortality rate was 2.5 deaths per 100 individuals per year. Given the high level of treatment failure among individuals on second line ART regimen, yet the current ART protocols limits the use of third line ART regimens to only regional referral hospitals, the Ministry of Health should strengthen the surveillance systems for identifying individuals failing on second line ART regimen even at district hospitals and lower health facilities to facilitate timely switch to optimal regimen. The Ministry of health through the Quality Improvement Division should conduct routine onsite support supervision to sites offering ART to ensure that treatment guides and other standard of care like timely switch to appropriate regimens among others are being adhered to. Knowledge gaps identified can also be addressed through onsite Continuous Medical Educations.
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Sidi Omar, Muhammad Munzir, Nur Amalina Wahida Ab Wahab, Ann Gie Ong, Nurul Izyan Mohamed Azam, Aqilah Muhammad und Siti Nor Asiah Ab Ghani. „Human immunodeficiency virus (HIV)/acquired immunodeficiency syndrome (AIDS): knowledge, perception, and attitude among pharmacists in Kelantan, Malaysia.“ Journal of Pharmacy 1, Nr. 1 (08.01.2021): 8–18. http://dx.doi.org/10.31436/jop.v1i1.44.

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Introduction: Although pharmacists’ role in the care of human immunodeficiency virus (HIV)-infected and acquired immunodeficiency syndrome (AIDS) patients is well established, studies had reported pharmacists’ negative attitudes towards people living with HIV/AIDS (PLWHA), with negative impact on HIV management. This study aimed to explore pharmacists’ knowledge of HIV/AIDS, perception towards the changing of treatment regimens of HIV/AIDS, attitudes towards PLWHA, and to identify factors affecting the pharmacists’ attitudes towards PLWHA in the state of Kelantan, which reportedly have the third highest number of HIV/AIDS patients in Malaysia. Materials and method: A validated online 43-item questionnaire was distributed to 400 pharmacists in Kelantan. Multivariate logistic regression was performed to identify factors associated with pharmacists’ negative attitude towards PLWHA. Results: A total of 170 respondents (response rate 42%) completed the questionnaire. Respondents had knowledge on the potential causes of HIV infection [median(IQR) score=13.00(1); maximum score=14.00], and preventive measures of HIV/AIDS transmission [median(IQR) score=12.00(1); maximum score=12.00]. On decision in changing regimens, the respondents agreed on the need to change treatment regimen for HIV/AIDS when required [median(IQR) score=7.00(2); maximum score=8.00]. Up to 40.6% of respondents thought that the treatment regimen should not be switched based on cost. Two-thirds of the respondents had negative attitudes towards PLWHA (67.1%). Respondents who worked in community pharmacy reported positive attitudes towards PLWHA (Adj OR=0.125; 95%CI=0.025-0.623; p=0.011). Conclusion: Pharmacists in Kelantan had several misconceptions towards the causes of HIV/AIDS, preventive measures of HIV/AIDS transmission, and necessity in changing treatment regimen when required. Despite good disease related knowledge, most pharmacists had negative attitudes towards PLWHA, while pharmacists working in community settings presented more positive attitudes towards PLWHA.
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Ganesan, Anuradha, SeungHyun Won, Evan C. Ewers, William Bradley, Christina Schofield, Gregory Utz, Rhonda Colombo et al. „1014. Factors Associated with Switching from Tenofovir Diproxil Phosphate to a Tenofovir Alafenamide Based Regimen in a Cohort with Unrestricted Access to Care and Medications“. Open Forum Infectious Diseases 7, Supplement_1 (01.10.2020): S536. http://dx.doi.org/10.1093/ofid/ofaa439.1200.

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Abstract Background Background- Tenofovir alafenamide (TAF) is associated with fewer renal and bone toxicities than tenofovir disoproxil phosphate (TDF). Hence, most experts suggest switching to TAF. We examined factors associated with switching to TAF in the US Military HIV Natural History Study (NHS), a cohort of people living with HIV who have unrestricted access to care and medications. Methods Methods- The first formulation of TAF received FDA approval on 1 November 2015; hence, we included all NHS participants with visits between November 2015 and March 2019. Patient factors including race, gender, CD4 count, antiretroviral therapies (ART), viral load, HIV diagnosis era, presence of comorbidities (cancer, heart disease, dyslipidemia, kidney disease and obesity), were assessed for association with a switch to TAF with a logistic regression model. Results Results- Of the 1678 eligible participants, 1324 (63%) had received a TDF-based regimen. Participants who received a TDF-regimen were 94% male 44% African-American [AA], 39% Caucasians and 17% Hispanic. About half the participants who received TDF-based ART switched to a TAF-based regimen (n=682, 52%). Of the 425 (32%) participants receiving TDF/FTC co-formulated with efavirenz, 48% (n=206) switched to TAF. The proportions switching to TAF were higher in those receiving TDF/FTC co-formulated with rilpivirine [59%, n=90] or elvitegravir/cobicistat [68%, n=146]. The common ART regimens after the switch were: TAF co-formulated with elvitegravir/cobicistat (46%), rilpivirine (16%) or bictegravir (12%) and TAF/FTC combined with dolutegravir (15%). In an adjusted analysis, older participants, and participants receiving TDF/FTC in combination with efavirenz, dolutegravir, raltegravir, boosted protease inhibitors or a combination of boosted protease inhibitors and integrase inhibitors (other) were less likely to switch, table 1. Conclusion Conclusions- Despite the unrestricted access to care and ART in the NHS, only half of the participants switched to TAF. Participants on efavirenz-containing regimens were less likely to switch to a TAF-based regimen, possibly due to the lack of a co-formulated single tablet. These trends need to be followed and barriers to switching to TAF (both patient and provider) need examination. Table 1- Factors associated with switching to a Tenofovir Alafenamide Based Regimen Disclosures All Authors: No reported disclosures
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Hamidian, Seyed Mohammad-Taghi, Najmeh-sadat Aletaha, Reza Taslimi und Mohammad Montazeri. „An Additive Effect of Oral N-Acetyl Cysteine on Eradication ofHelicobacter pylori“. Journal of Pathogens 2015 (2015): 1–5. http://dx.doi.org/10.1155/2015/540271.

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Background. Helicobacter pyloriis highly adapted to the gastric environment where it lives within or beneath the gastric mucous layer. The aim of this study was to evaluate whether the addition of N-acetyl cysteine to the treatment regimen ofH. pyloriinfection would affect eradication rates of the disease.Methods.A total of 79H. pyloripositive patients were randomized to two therapeutic groups. Both groups received a 14-day course of three-drug regimen including amoxicillin/clarithromycin/omeprazole. Experimental group (38 subjects) received NAC, and control group (41 subjects) received placebo, besides three-drug regimen.H. pylorieradication was evaluated by urea breath test at least 4 weeks after the cessation of therapy.Results.The rate ofH. pylorieradication was 72.9% and 60.9% in experimental and control groups, respectively (P=0.005). By logistic regression modeling, female gender (OR 3.68, 95% CI: 1.06–5.79;P=0.040) and treatment including NAC (OR 1.88, 95% CI: 0.68–3.15;P=0.021) were independent factors associated withH. pylorieradication.Conclusion.The results of the present study show that NAC has an additive effect on the eradication rates ofH. pyloriobtained with three-drug regimen and appears to be a promising means of eradicatingH. pyloriinfection.
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Keating, M. J., H. Kantarjian, T. L. Smith, E. Estey, R. Walters, B. Andersson, M. Beran, K. B. McCredie und E. J. Freireich. „Response to salvage therapy and survival after relapse in acute myelogenous leukemia.“ Journal of Clinical Oncology 7, Nr. 8 (August 1989): 1071–80. http://dx.doi.org/10.1200/jco.1989.7.8.1071.

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The response to and survival following first salvage therapy regimens for 243 patients with acute myelogenous leukemia (AML) treated between 1974 and 1985 were evaluated. Eighty (33%) patients obtained a complete remission (CR), 24% died prior to achieving a response, and 43% were resistant on their first salvage regimen. The median survival was 18 weeks. Five percent overall and 16% of the CR patients are predicted to survive for more than 5 years. The factor most strongly associated with response and survival was the duration of the initial remission with 49 of 82 (60%) patients whose initial CR duration was at least 1 year in duration obtaining a second CR v 31 of 161 (19%) for patients with a shorter remission (P less than .01). Age, liver function, serum lactic dehydrogenase (LDH), karyotype, and the proportion of blasts plus promyelocytes present at the time of starting salvage therapy were strongly associated with probability of response and survival. Multivariate analysis was used to develop logistic regression and proportional hazard models to predict probability of response and survival, respectively. The major regimens used were conventional-dose cytarabine (ara-C) (combined with anthracyclines or amsacrine), high-dose ara-C, rubidazone, amsacrine (AMSA), other anthracyclines, and autologous or allogeneic transplant programs. After allowing for the prognostic factors in the models, specific treatment regimens were not strongly associated with prognosis.
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Ramos, Jorge, Sarah Holt, George Schade, Matt D. Galsky, Jonathan L. Wright, John L. Gore und Evan Y. Yu. „Association of chemotherapy regimen with venous thromboembolic risk in patients with urothelial tract cancer.“ Journal of Clinical Oncology 35, Nr. 6_suppl (20.02.2017): 314. http://dx.doi.org/10.1200/jco.2017.35.6_suppl.314.

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314 Background: Cisplatin chemotherapy (CTX) is associated with increased risk of venous thromboembolism (VTE); however, other agents have also been hypothesized to increase risk. We assessed the association of VTE with different CTX regimens in urothelial tract cancer patients. Methods: We identified > 66 year-old patients diagnosed with urothelial tract cancers (excluding renal pelvis) from the Surveillance, Epidemiology, and End Results (SEER) Medicare-linked database from 1998 to 2011. CTX regimens included gemcitabine/cisplatin (GC), methotrexate/vinblastine/doxorubicin/cisplatin (MVAC), or gemcitabine/carboplatin (GCarbo). We calculated VTE rates within 120 days of CTX initiation and compared VTE by CTX regimen with multivariable logistic regression models adjusted for patient and cancer characteristics. Results: Of 5050 identified patients, VTE occurred in 13.1% (660/5050). VTE rates were 15.3% (265/1737) and highest for GC; 8.8% (23/262) and 12.2% (372/3051) of MVAC and GCarbo patients experienced VTE, respectively. Adjusted for patient demographic and cancer-specific variables, MVAC and GCarbo were associated with lower odds of VTE compared with GC (see Table). Conclusions: Compared with GC, MVAC and GCarbo are associated with a decreased rate of VTE. This finding suggests that gemcitabine may add to the increased thrombosis risk from cisplatin. Patients treated with GC should be counseled about this association. Sensitivity analyses to assess VTE risk of different CTX regimens in the perioperative setting will be presented. [Table: see text]
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Grant, Robert C., Rahim Moineddin, Zhan Yao, Melanie Lynn Powis, Ruth Croxford, Eva Grunfeld, Vishal Kukreti und Monika K. Krzyzanowska. „Predicting acute care use following the initiation of systemic therapy for solid tumors.“ Journal of Clinical Oncology 36, Nr. 30_suppl (20.10.2018): 6. http://dx.doi.org/10.1200/jco.2018.36.30_suppl.6.

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6 Background: Emergency department (ED) visits and hospitalizations are undesirable and costly. We developed and validated the PROACCT (PRediction Of Acute Care use during Cancer Treatment) score to predict at least one acute care visit during the first 30 days (AC30) after initiating systemic therapy for cancer. Methods: Using administrative data, we identified patients in Ontario with the 18 most common solid tumors who started systemic treatment from July 1, 2014 to June 30, 2015. Southwestern and Northeastern Ontario formed the development and validation cohorts, respectively. We created a score to predict AC30 using multivariate logistic regression in the development cohort. Combinations of tumor sites and regimens were grouped into quintiles based on AC30. The score was assessed in the validation cohort. Results: AC30 occurred in 23% (4438/19359) of patients. Eleven factors predicted AC30 and formed the score: tumor site and regimen (2nd quintile: 2; 3rd-4th: 3; 5th: 4), recent ED visit (2), recent palliative radiation (1), rural residence (1) and Edmonton Symptom Assessment Scale anxiety (4+: 1), lack of appetite (4+: 1), pain (4+: 1), and wellbeing (4+: 1). Among the 204 tumor-regimen combinations, tumors with poor prognoses, such as pancreatic and lung, and platinum- and taxane-containing regimens, carried the highest risk for AC30. The score had moderate discrimination (c-statistic 0.65; P< 0.001) and strong calibration (Table) in the validation cohort. Conclusions: PROACCT identifies factors that predict AC30 in patients starting systemic treatment for solid tumors and could be incorporated into electronic health records to select patients for preventative interventions. [Table: see text]
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Francescutti, V., F. Farrokhyar, R. Tozer, B. Heller, P. Lovrics, G. Jansz und K. Kahnamoui. „Primary tumor and patient characteristics in breast cancer as predictors of adjuvant chemotherapy regimen: A regression model“. Journal of Clinical Oncology 27, Nr. 15_suppl (20.05.2009): e11632-e11632. http://dx.doi.org/10.1200/jco.2009.27.15_suppl.e11632.

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e11632 Background: Adjuvant chemotherapy is used to reduce the risk of recurrence of breast cancer. This study was undertaken to determine which patient and tumor characteristics are important in guiding the choice of adjuvant chemotherapy. Methods: A retrospective review was undertaken of patients diagnosed with breast cancer (stages I-III) at a regional cancer center from 2004–7. Patient and tumor characteristics were identified and chemotherapy regimens compared. Binary logistic regression analysis was performed to the choice of FEC/D, CEF, AC/T, or ddAC/T against AC or CMF, or the choice of chemotherapy to hormonal therapy only. Univariate analysis was used to select factors (p<0.1) for entry into a multivariate stepwise logistic regression model using the forward method. Odds ratios with 95% CI were calculated. A p-value of < 0.05 was significant and comparisons were two tailed. Results: Model 1 (n=871) included regimen (AC or CMF vs. aggressive regimen) as the dependant variable. Indicators of choice of aggressive regimen were higher stage [OR 4.7 (CI 3.3, 6.8)], positive nodes [2.5 (1.6, 3.8)], negative PR [2.1 (1.4, 3.1)], higher grade [1.4 (1.0, 1.8)], and age [0.91 (0.88, 0.92)]. Model 2 (n=640) involved choice of any regimen (chemotherapy vs. hormonal therapy only) as the dependant variable. Indicators of choice of chemotherapy were higher stage [7.19 (2.8, 18.4)], higher grade [7.02 (3.3, 14.8)], positive nodes [3.25 (0.98, 10.77)], age [0.85 (0.81, 0.90)], and ER negativity [0.04 (0.004, 0.37)]. Factors not significant in both models were: family history, comorbidities (renal/hepatic dysfunction, diabetes, cardiac history, or neuropathy), treating medical oncologist, histology, Her2/neu, > 3 positive nodes, ratio of positive to total nodes, multicentricity, multifocality, and positive margin status. Conclusions: This study verifies known important factors for choice of chemotherapy regimen as found in current guidelines, quantifies their effects at our center, and excludes others thought to be important. Further studies are required to confirm these results both nationally and internationally, where risk stratification may be different, and if variables predicting adjuvant radiation therapy are similar. No significant financial relationships to disclose.
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Costa, Juliana de Oliveira, Maria das Graças Braga Ceccato, Micheline Rosa Silveira, Palmira de Fátima Bonolo, Edna Afonso Reis und Francisco de Assis Acurcio. „Effectiveness of antiretroviral therapy in the single-tablet regimen era“. Revista de Saúde Pública 52 (12.11.2018): 87. http://dx.doi.org/10.11606/s1518-8787.2018052000399.

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OBJECTIVE: To evaluate the effectiveness of antiretroviral therapy and the associated factors according to the type of regimen used: Single Tablet Regimen or Multiple Tablet Regimen. METHODS: Prospective cohort of 440 patients (male, 74.3%, median age, 36 years old) who initiated antiretroviral therapy between Jan/14 and Dec/15 at a referral service in Belo Horizonte. Efficacy was defined as viral suppression (viral load, VL < 50 copies/ml) and evaluated after six and twelve months of treatment. Sociodemographic, clinical and behavioral data were collected from clinical charts and from Information Systems. Multivariate analysis of overall effectiveness was performed by logistic regression. RESULTS: Most patients initiated Multiple Tablet Regimen antiretroviral therapy (n = 255, 58%). At six months, overall viral suppression was 74.6%, being higher among patients who used Single Tablet Regimen (80.6%, p = 0.04). At twelve months, 83.2% of patients reached viral suppression, with no difference between groups (p = 0.93). Factors independently associated with viral suppression at six and twelve months varied, being negatively associated with effectiveness: VL ≥ 100,000 copies/ml, symptoms of AIDS, longer interval time between diagnosis and initiation of antiretroviral therapy, antiretroviral switching, smoking or current illicit drugs usage (p < 0.05). Factors positively associated with viral suppression included adherence to antiretroviral therapy and category of risk/exposure of men who have sex with men (p < 0.05). Reaching viral suppression at six months was the main predictor of effectiveness at one year (OR = 8.96 and p < 0.01). CONCLUSIONS: Viral suppression was high and better results were achieved for patients who used Single Tablet Regimen regimens at six months. Clinical, behavioral, and antiretroviral therapy -related factors influence viral suppression and highlight the need for interventions to increase early diagnosis and initiation of antiretroviral therapy, patient’s adherence, and to reduce illicit drugs and cigarette smoking in this population.
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Pariente, Alexandre, Jean-Pierre Arpurt, André-Jean Rémy, Isabelle Rosa-Hézode, Xavier Causse, Frédéric Heluwaert, Gilles Macaigne et al. „Effects of Age on Treatment of Chronic Hepatitis C with Direct Acting Antivirals“. Annals of Hepatology 17, Nr. 5 (18.09.2018): 0–10. http://dx.doi.org/10.5604/01.3001.0012.4893.

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Introduction and aim: Data on the efficacy and tolerance of interferon-free treatment in chronic hepatitis C (CHC) in elderly patients are limited in phase II-III trials. Methods: A prospective cohort of adult patients with CHC treated in French general hospitals. Results: Data from 1,123 patients, distributed into four age groups, were analyzed. Of these, 278 were ≥ 64 years old (fourth quartile) and 133 were ≥73 years old (tenth decile). Elderly patients weighed less, were more frequently treatment-experienced women infected with genotype 1b or 2, while they less frequently had genotype 3 or HIV coinfection, but had more frequent comorbidities and drug consumption. Half of the patients had cirrhosis, whatever their ages. The main treatment regimens were sofosbuvir/ledipasvir (37.8%), sofosbuvir/daclatasvir (31.8%), sofosbuvir/simeprevir (16.9%), sofosbuvir/ribavirin (7.8%); ribavirin was given to 24% of patients. The overall sustained virological response (SVR) rate was 91.0 % (95% CI: 89.2-92.5 %) with no difference according to age. Logistic regression of the independent predictors of SVR were albumin, hepatocellular carcinoma and treatment regimen, but not age. The rate of severe adverse events (66 in 59/1062 [5.6%] patients) tended to be greater in patients older than 64 years of age (21/261, 8.1%), but the only independent predictors of SAE by logistic regression were cirrhosis and baseline hemoglobin. Patient-reported overall tolerance was excellent in all age groups, and patient-reported fatigue decreased during and after treatment, independent of age. Conclusions: The high efficacy and tolerance of interferon-free regimens is confirmed in elderly patients in real-life conditions.
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Subbiah, Ishwaria Mohan, Shanda H. Blackmon, Arlene M. Correa, Bryan K. Kee, Ara A. Vaporciyan, Stephen Swisher und Cathy Eng. „Preoperative chemotherapy prior to pulmonary metastatecomy in patients with prior surgically resected primary colorectal carcinoma.“ Journal of Clinical Oncology 31, Nr. 4_suppl (01.02.2013): 490. http://dx.doi.org/10.1200/jco.2013.31.4_suppl.490.

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490 Background: The exact benefit of preoperative chemotherapy prior to pulmonary metastasectomy for patients with metastatic colorectal carcinoma (CRC) is unknown. Here, we identify outcomes of preop chemo in pts w previously resected primary CRC who then had resectable pulmonary CRC metastases. Methods: We queried a prospectively collected database to identify pts who underwent pulmonary CRC metastasectomy and the specific chemo regimen given prior to but w/i 3 months of surgery. Two multivariate logistic analyses were performed to identify preop regimen as predictors of overall survival (OS) and progression free survival (PFS). Results: From Feb 2000 onwards, 229 pts underwent lung met resection (median age 61, range 24-82). Of those pts, 114 received preop chemo for a median duration of 4months (range 0.1-25.3mos). 41pts receiving 0-3 mos of preop chemo, 37 3-6mos, and 36 >6mos. 38pts received an oxaliplatin-based regimen (23 FOLFOX+bevacizumab [bev], 5 XELOX, 5 FOLFOX alone, 3 FOLFOX+cetuximab, 1 FOLFOX + novel TR-2/DR5 antibody, 1 oxali+irinotecan). 53 pts received an irinotecan-regimen. 29 received a capecitabine therapy. Pts on an oxali-based therapy had an improved OS vs alternate chemo regimen (mean OS 77.6 mos vs 54.2 mos, median OS not reached in oxali-group, p .001). However pts on an irinotecan-based regimen had a lower OS vs alternate chemo (median OS of 49.1mos vs 57.9mos, p .024). 5FU, capecitabine, or bev-based therapies did not significantly impact OS. The type of preop chemo regimen did not significantly affect PFS after lung met resection. Oxali-based regimen moved towards a favorable OS when compared to OS without any preop chemo but not of statistical significance (HR 0.69; 95% CI 0.287 to 1.663, p 0.409) while receiving a non-oxali-based preop regimen was associated with a shorter OS when compared to no preop chemo (HR 2.64; 95% CI 1.634 to 4.275, p <0.001). Conclusions: Preop chemo with an oxaliplatin regimen prior to pulm met resection may improve OS, providing long-term benefit, whereas a preop irinotecan-based therapy appears to result in a shorter OS. Prospective trials on specific preop regimens and criteria for patient selection are planned.
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TAYLOR, MARK J., ACHIM HOERAUF, SIMON TOWNSON, BARTON E. SLATKO und STEPHEN A. WARD. „Anti-Wolbachia drug discovery and development: safe macrofilaricides for onchocerciasis and lymphatic filariasis“. Parasitology 141, Nr. 1 (18.07.2013): 119–27. http://dx.doi.org/10.1017/s0031182013001108.

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SUMMARYAnti-Wolbachia therapy delivers safe macrofilaricidal activity with superior therapeutic outcomes compared to all standard anti-filarial treatments, with the added benefit of substantial improvements in clinical pathology. These outcomes can be achieved, in principle, with existing registered drugs, e.g. doxycycline, that are affordable, available to endemic communities and have well known, albeit population-limiting, safety profiles. The key barriers to using doxycycline as an mass drug administration (MDA) strategy for widespread community-based control are the logistics of a relatively lengthy course of treatment (4–6 weeks) and contraindications in children under eight years and pregnancy. Therefore, the primary goal of the anti-Wolbachia (A·WOL) consortium is to find drugs and regimens that reduce the period of treatment from weeks to days (7 days or less), and to find drugs which would be safe in excluded target populations (pregnancy and children). A secondary goal is to refine regimens of existing antibiotics suitable for a more restricted use, prior to the availability of a regimen that is compatible with MDA usage. For example, for use in the event of the emergence of drug-resistance, in individuals with high loiasis co-infection and at risk of severe adverse events (SAE) to ivermectin, or in post-MDA ‘endgame scenarios’, where test and treat strategies become more cost effective and deliverable.
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Russo, Alessandro, Giancarlo Ceccarelli, Valeria Bellelli, Luigi Bianchi, Federica Marincola Cattaneo, Fabrizio Gregori, Valeria Palmarini et al. „Efficacy of Daptomycin-Containing Regimen for Treatment of Staphylococcal or Enterococcal Vertebral Osteomyelitis: A Prospective Clinical Experience“. Antibiotics 9, Nr. 12 (10.12.2020): 889. http://dx.doi.org/10.3390/antibiotics9120889.

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Vertebral osteomyelitis (VO) is a compelling clinical entity for clinicians, because of its insidious and indolent course that makes diagnosis difficult. A concern is reported about the choice of antibiotic regimens, duration of therapy, and criteria to switch to oral therapy. We conducted a prospective observational study. All consecutive hospitalized patients with a confirmed diagnosis of VO caused by staphylococcal or enterococcal strains were analyzed. The primary endpoint was the analysis of clinical cure at the end of therapy. A propensity score for receiving therapy with daptomycin was added to the model. During the study period, 60 episodes of confirmed VO were observed. The main etiology of infection was methicillin-resistant Staphylococcus aureus (29%). Overall, clinical failure at end of therapy was reported in 11 (18.3%) patients. Logistic regression analysis, after propensity score, showed that >2 vertebrae involved (OR 2.4, CI95% 1.12–5.24, p = 0.002) and inadequate drainage of infection (OR 4.8, CI95% 2.45–8.51, p < 0.001) were independently associated with failure of therapy, while the use of a daptomycin-containing-regimen (OR 0.15, CI 95% 0.04–0.46, p < 0.001) with clinical cure. VO caused by staphylococcal or enterococcal strains is associated with an important rate of clinical failure. Daptomycin-containing regimen was strongly associated with clinical cure. Considering that over 70% of VO etiology is caused by Gram-positive strains but the etiology of infection is obtained in about 75% of cases, these data may help physicians to choose the appropriate antibiotic regimen.
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Cabral, Stephanie, Timileyin Adediran, Anthony Harris, Pranita Tamma, Sara Cosgrove, Daniel Morgan, Kathryn Dzintars et al. „Factors Associated With Inappropriate Antibiotic Use in Hospitalized Patients“. Infection Control & Hospital Epidemiology 41, S1 (Oktober 2020): s233—s234. http://dx.doi.org/10.1017/ice.2020.785.

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Background: Inappropriate antibiotic prescription leads to increased Clostridiodes difficile infections, adverse effects including organ toxicity, and generation of antibiotic-resistant bacteria. Despite efforts to improve antibiotic use in acute-care settings, unnecessary and inappropriate prescription still occur in 30%–50% of patients. Objectives: We assessed factors associated with inappropriate antibiotic prescription at 2 time points: (1) initial, empiric therapy and (2) 3–5 days after therapy initiation. Methods: As part of a multicenter study investigating strategies to reduce antibiotic therapy after 3–5 days of use, antibiotic prescription data were collected from 11 adult and pediatric intensive care and general medical units at 6 hospitals in Maryland in 2014 and 2015. We performed a retrospective cohort study of all hospitalized patients who received any of 23 common antibiotics for at least 3 days. Each medical record was reviewed for demographics, admission and discharge dates, patient comorbidities, and antibiotic regimen by at least 1 infectious disease physician or pharmacist. Classification of antibiotic inappropriateness was based on each institution’s guidelines and standards. Bivariate analyses were performed using logistic regression for both initial therapy and therapy at days 3–5. Multivariable logistic regression was performed using covariates meeting the significance level of P < .05. Results: In total, 3,436 antibiotic courses were assessed at time of initial therapy, and 1541 regimens were continued and reviewed again at days 3–5 of therapy. For the initial therapy, 1,255 regimens (37%) were inappropriate; 45% of these were considered unnecessary and 41% were too broad in spectrum. In the multivariable regression, older age and antibiotic prescription during the summer were associated with the receipt of inappropriate antibiotics (Table 1). Having end-stage renal disease as a comorbid condition was protective against inappropriate use. At days 3–5 of therapy, 688 (45%) of the antibiotic courses were inappropriate. Reasons regimens were considered inappropriate included unnecessary antibiotic prescriptions (49%) and antibiotics being too broad (38%). Older age and receiving cefepime or piperacillin-tazobactam on day 3 of therapy were factors associated with inappropriate use (Table 2). Having undergone a transplant or a surgical procedure was protective of inappropriate antimicrobial use at days 3–5 of therapy. Conclusions: Older patients are more likely to receive inappropriate antibiotics at both initial regimen and 3–5 days later. Patients receiving cefepime or piperacillin-tazobactam are at greater risk of receiving inappropriate antibiotics at days 3–5 due to failure to de-escalate. Antibiotic stewardship strategies targeting these patient populations may limit inappropriate use.Funding: NoneDisclosures: None
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Saria, Marlon G., Courtney Corle, Toni Rush und Santosh Kesari. „Improved survival of patients with glioblastoma at NCI-designated clinical cancer centers.“ Journal of Clinical Oncology 31, Nr. 31_suppl (01.11.2013): 122. http://dx.doi.org/10.1200/jco.2013.31.31_suppl.122.

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122 Background: Glioblastomas are considered the most life-threatening central nervous system (CNS) tumors. With such a rapidly progressing disease resulting in low survival rates, it is no surprise that many of the factors related to first-course treatment regimens are also related to patient survival. There is a need to investigate treatment patterns and survival trends so that optimal care standards can be developed for patients diagnosed with this devastating disease. Methods: Patients diagnosed with glioblastoma between 1999-2008 were identified in the California Cancer Registry. Survival estimates were calculated using Kaplan-Meier method and hazard ratios were calculated using Cox proportional hazards model. Multiple logistic regressions were used to determine the relationships between location of treatment and a patient’s first-course treatment regimen after adjusting for gender, age, race, socioeconomic status, type of insurance, and year of diagnosis. Results: 8,527 patients diagnosed with glioblastoma were included in the analysis. Patients receiving surgery, radiation, and chemotherapy as a first-course treatment regimen had a 1-year survival of 62.5% (95% CI: 61.6-63.4) compared to patients receiving any other treatment combination with a 1-year survival rate of 24.3% (95% CI: 23.7-24.9) (p<0.0001). After adjusting for covariates, patients treated at National Cancer Institute-designated Clinical Cancer Centers (NCI-CCCs) were 1.31 (95% CI: 1.14-1.5) more likely to receive all three treatment options as a first-course regimen. Patients receiving care at NCI-CCCs had 11% increase in survival compared to patients receiving care elsewhere. Conclusions: Surgery, radiation, and chemotherapy given as a first-course treatment regimen for glioblastoma patients provide significant survival benefits and were more likely to be provided together at NCI-CCCs.
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Ichikawa, Wataru, Keisuke Uehara, Keisuke Minamimura, Chihiro Tanaka, Yasumasa Takii, Sotaro Sadahiro, Hideaki Miyauchi et al. „Prospective analysis of UGT1A1 genotyping for predicting toxicities in advanced colorectal cancer (aCRC) treated with irinotecan (IRI)-based regimens: Interim safety analysis of a Japanese observational study.“ Journal of Clinical Oncology 31, Nr. 15_suppl (20.05.2013): 3535. http://dx.doi.org/10.1200/jco.2013.31.15_suppl.3535.

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3535 Background: UGT1A1*6 and UGT1A1*28 are risk factors for severe IRI-related toxicities in Asians, but recommended IRI doses based on UGT1A1 genotypes and other risk factors are unclear. We conducted a prospective analysis to examine the correlation between UGT1A1 genotypes and the efficacy and safety of IRI-based regimens in Japanese aCRC patients (pts), (NCT 01039506). Methods: Pts who had histologically confirmed aCRC, PS of 0–2, received IRI-based regimens (FOLFIRI, IRI+S-1, IRI monotherapy), were UGT1A1 genotyped, and provided written informed consent were included. UGT1A1 polymorphisms were analyzed and categorized into 3 groups: wild (*1/*1), hetero (*1/*6, *1/*28), and homo (*6/*6, *6/*28, *28/*28). Detailed toxicities in the first 3 months of treatment were prospectively recorded. For interim safety analysis, incidences of grade 3–4 (severe) toxicities were compared among UGT1A1 genotypes and a logistic regression model was used to predict the risk of severe toxicities. Severe toxicities and associated risk factors were predicted using a nomogram and bootstrap validation was performed. Results: We enrolled 1376 pts between October 2009 and March 2012. At the time of abstract submission, toxicity data of 504 pts were available; 46% pts had wild, 44% hetero, and 11% homo polymorphisms. FOLFIRI was administered to 63% pts. Severe neutropenia developed during the first 3 months of treatment in 33% pts: 36% in hetero [OR, 1.5; 95% CI, 1.0–2.3], 47% in homo (OR, 2.3; 95% CI, 1.2–4.4), and 28% in wild. Severe diarrhea incidence was 5%, which did not correlate with UGT1A1 genotypes. Multiple logistic regression model included regimen, initial IRI dose, gender, age, UGT1A1 genotype, and PS as predictors of severe neutropenia in the first treatment cycle. The resulting nomogram demonstrated good accuracy in predicting severe neutropenia, with a bootstrap-corrected concordance index of 0.74. Conclusions: Considering UGT1A1 genotype along with other clinical factors is important for managing pts undergoing IRI-based regimens. Our presentation will provide analysis of data from more than 1000 pts. Clinical trial information: NCT01039506.
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Ashdown, Martin L., Andrew P. Robinson, Steven L. Yatomi-Clarke, M. Luisa Ashdown, Andrew Allison, Derek Abbott, Svetomir N. Markovic und Brendon J. Coventry. „Chemotherapy for Late-Stage Cancer Patients: Meta-Analysis of Complete Response Rates“. F1000Research 4 (13.07.2015): 232. http://dx.doi.org/10.12688/f1000research.6760.1.

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Complete response (CR) rates reported for cytotoxic chemotherapy for late-stage cancer patients are generally low, with few exceptions, regardless of the solid cancer type or drug regimen. We investigated CR rates reported in the literature for clinical trials using chemotherapy alone, across a wide range of tumour types and chemotherapeutic regimens, to determine an overall CR rate for late-stage cancers. A total of 141 reports were located using the PubMed database. A meta-analysis was performed of reported CR from 68 chemotherapy trials (total 2732 patients) using standard agents across late-stage solid cancers—a binomial model with random effects was adopted. Mean CR rates were compared for different cancer types, and for chemotherapeutic agents with different mechanisms of action, using a logistic regression. Our results showed that the CR rates for chemotherapy treatment of late-stage cancer were generally low at 7.4%, regardless of the cancer type or drug regimen used. We found no evidence that CR rates differed between different chemotherapy drug types, but amongst different cancer types small CR differences were evident, although none exceeded a mean CR rate of 11%. This remarkable concordance of CR rates regardless of cancer or therapy type remains currently unexplained, and motivates further investigation.
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Seephetdee, Chotiwat, Nattawut Buasri, Kanit Bhukhai, Kitima Srisanga, Suwimon Manopwisedjaroen, Sarat Lertjintanakit, Nut Phueakphud et al. „Mice Immunized with the Vaccine Candidate HexaPro Spike Produce Neutralizing Antibodies against SARS-CoV-2“. Vaccines 9, Nr. 5 (12.05.2021): 498. http://dx.doi.org/10.3390/vaccines9050498.

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Updated and revised versions of COVID-19 vaccines are vital due to genetic variations of the SARS-CoV-2 spike antigen. Furthermore, vaccines that are safe, cost-effective, and logistic-friendly are critically needed for global equity, especially for middle- to low-income countries. Recombinant protein-based subunit vaccines against SARS-CoV-2 have been reported using the receptor-binding domain (RBD) and the prefusion spike trimers (S-2P). Recently, a new version of prefusion spike trimers, named HexaPro, has been shown to possess two RBD in the “up” conformation, due to its physical property, as opposed to just one exposed RBD found in S-2P. Importantly, this HexaPro spike antigen is more stable than S-2P, raising its feasibility for global logistics and supply chain. Here, we report that the spike protein HexaPro offers a promising candidate for the SARS-CoV-2 vaccine. Mice immunized by the recombinant HexaPro adjuvanted with aluminum hydroxide using a prime-boost regimen produced high-titer neutralizing antibodies for up to 56 days after initial immunization against live SARS-CoV-2 infection. Also, the level of neutralization activity is comparable to that of convalescence sera. Our results indicate that the HexaPro subunit vaccine confers neutralization activity in sera collected from mice receiving the prime-boost regimen.
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Xia, Tingsong, Juan Chen, Jian Rui, Jinxu Li und Yuli Guo. „What affected Chinese parents’ decisions about tuberculosis (TB) treatment: Implications based on a cross-sectional survey“. PLOS ONE 16, Nr. 1 (25.01.2021): e0245691. http://dx.doi.org/10.1371/journal.pone.0245691.

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Objective Although progress has been made in tuberculosis (TB) treatment, China still remains one of the high-burden TB countries. One important reason that has not received sufficient scholarly attention is that Chinese individuals tend to underestimate the threat of TB. This contributed to the high rate of delay in seeking TB treatment and noncompliance with doctors’ regimen. Hence, this research examined how TB knowledge affected Chinese parents’ risk perceptions and their efficacy appraisal in TB treatment, and how their risk perception and efficacy appraisal affected their intentions to seek timely TB treatment for their children and adhere to doctors’ regimen. Methods We conducted an online cross-sectional survey with 1129 parents of children attending kindergarten, primary school, and middle school in Shajing, a region with high TB incidence in China. Perceived severity of TB threat to self and to others, perceived susceptibility, response efficacy, and self-efficacy were measured, in addition to TB knowledge and intentions to seek timely TB treatment and adhere to doctors’ regimens. Results Ordinal least squares regression demonstrated that TB knowledge was positively associated with perceived severity of TB threat to self, perceived severity of TB threat to others, perceived susceptibility, response efficacy, and self-efficacy, but it did not affect their medical decisions. In addition, binary logistic regression revealed that response efficacy and self-efficacy predicted both intentions positively, and perceived severity of TB threat to self only enhanced Chinese individuals’ intention to follow doctors’ regimens. Conclusion Health education aimed at knowledge improvement may be effective in changing one’s perceptions of the given health threat but may not be effective to change their behavior. Thus, practitioners need to focus on changing Chinese parents’ perceptions of TB rather than simply improving their knowledge. Specifically, it is necessary to lower their efficacy in self-management and enhance their perceived infectiousness of TB.
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Cazzaniga, Marina Elena, Virginia Casadei, Katia Cagossi, Luigi Cavanna, Maria Concetta Cursano, Enrico Maria Romano De Conciliis, Vittorio Gebbia et al. „Metronomic chemotherapy (mCHT) in HER2-ve advanced breast cancer (ABC) patients (pts): What has changed over the time? Preliminary results of the VICTOR-6 study.“ Journal of Clinical Oncology 35, Nr. 15_suppl (20.05.2017): e12552-e12552. http://dx.doi.org/10.1200/jco.2017.35.15_suppl.e12552.

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e12552 Background: mCHT is the minimum biologically effective dose of a chemotherapeutic agent, given at regular dosing regimen with no prolonged drug free interval, that leads to anti-tumor activity. Old regimens included Cyclophosphamide-Methotrexate (CM), whereas in the last years new regimens, such as Vinorelbine (VRL) and Capecitabine (CAPE)-based have been developed. Aim of this observational retrospective ongoing study is to describe the use of mCHT in ABC pts across 5 years and the clinical characteristics of the pts together with efficacy of old (CM-like) vs new (VRL/CAPE-based) metronomic regimens in terms of response and disease control. Methods: We retrospectively identified from clinical records those HER2-ve ABC pts who have received any kind of mCHT in the years 2011-2015, alone, or in combination with a non-metronomic drug. Standard statistical approaches were used for describing the sample characteristics. Logistic and non proportional hazard analysis were used to identify factors associated with response, and time to treatment failure and survival, respectively. This preliminary analysis focuses on Response Rate (RR) and Disease Control Rate (DCR). Results: From June 2011 to December 2015, 267 pts have been identified till now and 233 are fully evaluable. Median age at mCHT start was 67 years. 81% was HR+ and 33% had non-visceral metastatic disease. 22% of the pts received CM, 55% VRL-based and 23% mCAPE-based regimens. mCHT use increased over the time from 15.0% (2011) to 30% (2015). As 1st-line treatment, CM was administered in 27% of compared with more than 48% of patients receiving CAPE/VRL-based regimens. Overall Response Rate (ORR) was 28% and Disease Control Rate (DCR) was 79%. Median duration of mCHT was 6.2 months. New generation metronomic regimens produced higher ORR in comparison to old ones (32% vs 13.5%), with similar duration of treatment (6.4 vs 5.4 months, respectively). Conclusions: The use of mCHT in the treatment of HER2-ve ABC pts has deeply changed across the last 5 years, being new generation regimens used in earlier lines of treatment, producing interesting results in terms of objective response and disease control.
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Schofield, Christina, Xun Wang, Patrick Monahan, Xiuping Chu, Margaret Glancey, Anuradha Ganesan, Jason F. Okulicz und Brian K. Agan. „Regimen Switching After Initial Haart By Race in a Military Cohort“. Open Public Health Journal 10, Nr. 1 (28.10.2017): 195–207. http://dx.doi.org/10.2174/1874944501710010195.

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Background: Prior studies have suggested that HAART switching may vary by ethnicity, but these associations may be confounded by socioeconomic differences between ethnic groups. Utilizing the U.S. military healthcare system, which minimizes many socioeconomic confounders, we analyzed whether HAART switching varies by race/ethnicity. Methods: HAART-naïve participants in the U.S. Military HIV Natural History Study who initiated HAART between 1996-2012 and had at least 12-months of follow-up were assessed for factors associated with HAART regimen change (e.g. NNRTI to PI) within one year of initiation. Multiple logistic regression was used to compare those who switched versus those who did not switch regimens. Results: 2457 participants were evaluated; 91.4% male, 42.3% Caucasian, 42.8% African-American, and 9% Hispanic. In a multivariate analysis, African-Americans had lower odds (OR 0.76, 95% CI 0.65, 0.98) while Hispanics had no significant difference with respect to HAART switching compared to Caucasians; however, Other race was noted to have higher odds (OR 1.77, 95% CI 1.11, 2.83). Additional significantly associated factors included CD4 <200 cells/uL at HAART initiation, higher viral load, prior ARV use, and history of depression. Conclusion: In this cohort with open access to healthcare, African-American and Hispanic races were not associated with increased odds of switching HAART regimen at 12 months, but Other race was. The lack of association between race/ethnicity and regimen change suggest that associations previously demonstrated in the literature may be due to socioeconomic or other confounders which are minimized in the military setting.
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Gerberich, Amanda J., Mark R. Attilio und Alison Svoboda. „Revisiting same day administration of pegfilgrastim in the age of biosimilars: A review of literature“. Journal of Oncology Pharmacy Practice 26, Nr. 8 (09.09.2020): 1970–76. http://dx.doi.org/10.1177/1078155220956305.

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Purpose Since 2018, several pegfilgrastim biosimilars were approved, which may affect insurance reimbursement. Guidelines recommend pegfilgrastim be administered the days following chemotherapy to prevent hematopoietic toxicity. To date, only the reference pegfilgrastim product has an available autoinjector-device. This has contributed to logistical issues in administering biosimilar agents per guideline recommendations. Administration on the same day as chemotherapy may be a potential alternative when logistical issues are present. This review will assess current evidence on this practice to inform clinical decisions. Data sources: A comprehensive literature search was performed in PubMed/Medline for studies examining the administration of pegfilgrastim on the same day as chemotherapy. Data summary: Several studies were identified, including a systematic review, retrospective reviews, and insurance claim data. Studies had significant limitations, and chemotherapy regimens and cancer types varied among studies. Studies showed inconsistent results in terms of incidence, duration, and severity of febrile neutropenia. In studies with patients with head and neck, urothelial, gynecologic, gastrointestinal, and prostate cancer, no difference in outcomes was detected or outcomes supported the feasibility of same-day administration. In patients with breast cancer, outcomes were worse with same-day administration. Outcomes were mixed in studies with non-Hodgkin’s lymphoma, non-small cell lung cancer, and various solid tumors. Conclusion Administration of pegfilgrastim on the same day as chemotherapy may be safe and an acceptable alternative, if logistics prohibit a patient from receiving administration the days after chemotherapy. Clinicians should consider patient risk factors and prescribed chemotherapy regimens, along with available evidence when contemplating administration of same-day pegfilgrastim.
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Chan, Ebby Waqqash Mohamad, Mohamad Shariff A. Hamid, Faridzal Harrymen Mohd Din, Rozali Ahmad, Ali Md Nadzalan und Eliza Hafiz. „Prevalence and factors associated with low back pain among Malaysian army personnel stationed in Klang Valley“. Biomedical Human Kinetics 11, Nr. 1 (01.01.2019): 9–18. http://dx.doi.org/10.2478/bhk-2019-0002.

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Abstract Study aim: The aims of this study were to examine the prevalence of low back pain (LBP) and explore possible factors associ­ated with LBP among Malaysian army personnel deployed in Klang Valley in the year 2018. Material and methods: A self-administered questionnaire on sociodemographic data, occupational background, occupational exposure and LBP evaluation was used in this study. A total of 330 respondents participated in this study and 321 (97%) of them completed and returned the questionnaires. Results: One hundred and fifty-seven respondents complained of LBP, giving a prevalence of 48.9%. LBP was found to be associated with smoking status, history of LBP, history of accident, military rank, category of regiment, lifting weights, push­ing weights, pulling weights and job-related physical activity. Logistic regression analysis identified four associated risk fac­tors of LBP: history of accident (OR = 4.42, 95% 2.29-8.55), history of LBP (OR=1.92, 95% 1.11-3.31), combat regiment (OR = 1.97, 95% 1.14-3.42) and high job-related physical activity (OR = 2.35, 95% 1.31-4.20). Conclusion: Almost half of Malaysian army personnel stationed in Klang Valley reported LBP symptoms. Smoking status, history of LBP, history of accident, junior non-commissioned officers (NCOs), combat regiments, manual handling of objects and moderate/high job-related physical activity are associated with LBP, but there is no evidence of a temporal relationship in the current study. Further exploration with a longitudinal study is needed to identify a cause and effect relationship between occupational exposure and LBP among Malaysian army personnel.
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Oh, Yuna, Alexander Bang, Nicholas Kurtansky, Niloufer Khan, Melissa Pulitzer und Sarah Noor. „Dermatologic adverse events of brentuximab vedotin: Characteristics, management, and their relationship with dose regimen.“ Journal of Clinical Oncology 39, Nr. 15_suppl (20.05.2021): 3049. http://dx.doi.org/10.1200/jco.2021.39.15_suppl.3049.

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3049 Background: Owing to its high efficacy and tolerability, brentuximab vedotin (BV) is increasingly being favored over other aggressive systemic therapies for the treatment of various CD30+ Hodgkin and non-Hodgkin lymphomas, including peripheral T-cell lymphoma and cutaneous T-cell lymphomas. Dermatologic adverse events (dAE) are one of the most common toxicities associated with BV but data regarding their characteristics including correlation to dose, time to occurrence, and management is scarce. We aim to describe the clinical and pathologic characteristics of dAEs associated with BV, their relationship with administered dose regimen, and available management strategies. Methods: An IRB-approved retrospective analysis was conducted for all patients who had received at least one cycle of BV from Memorial Sloan Kettering Cancer Center in 2009-2020. Logistic regression, χ2, student’s t-test were performed for univariate analyses. Kaplan-Meier survival and multivariate Cox proportional hazard model evaluated dAE occurrence stratified by 5 major dose regimens (single cycle, 1.2mg q1w, 1.2mg q2w, 1.2mg q3w, 1.8mg q3w). Results: Of 611 patients, 201 experienced dAE with median time-to-event of 24 days and 29% experiencing > 1 dAEs. Rash was the most common (62%; 142/230), followed by alopecia (20%) and xerosis (13%). For rash, 50% reported involvement of only the extremities and/or acral sites compared to 25% who had generalized rash. Of those reported (111), 68 patients had grade 1 dAE (61%), 38 grade 2 (34%), and 5 grade 3 (5%)-all grade 3 were rash (maculopapular/morbilliform). 14 cases (7%) resulted in treatment interruptions and 6 in discontinuations due to dAEs (3%). Pathology were often nonspecific consistent with a hypersensitivity reaction: spongiotic/psoriasiform dermatitis with perivascular lymphocytic infiltrates . Patients undergoing weekly regimen were at a statistically and clinically significantly higher risk of dAE during the first 100 days of BV treatment (p = 0.001). Between the two most frequently administered dose regimens (1.8mg vs. 1.2mg, q3w), the higher dose carried 105% higher risk for dAE (HR: 2.047, p = 0.053). Those who had received a single cycle of BV had the lowest risk compared to all other regimen (1/42, p = 0.001). Topical and/or systemic steroids were most frequently prescribed (43%) with 12% of patients requiring systemic steroids. Other treatments varied ranging from antihistamines to moisturizers. Conclusions: Understanding of the detailed characteristics, management strategies, dose-dependent effects associated with BV is critical to provide clinical guidance for primary providers and minimize treatment interruptions or discontinuations. The results overall suggest that the risk for dAEs is dose-dependent with those undergoing frequent dosing regimens having a greater risk, although most dAEs remain mild or low-grade.
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Li, Edward, Bridgette Kanz Schroader, David Campbell, Kim Campbell und Weijia Wang. „The Impact of Baseline Risk Factors on the Incidence of Febrile Neutropenia in Breast Cancer Patients Receiving Chemotherapy with Pegfilgrastim Prophylaxis: A Real-World Data Analysis“. Journal of Health Economics and Outcomes Research 8, Nr. 1 (22.06.2021): 106–15. http://dx.doi.org/10.36469/jheor.2021.24564.

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Background: There are sparse data addressing whether standard risk factors for febrile neutropenia (FN) are relevant in patients receiving myelosuppressive chemotherapy and primary prophylaxis for FN, which would have implications for variables to consider during real-world comparative analyses of FN incidence. Objective: To assess the impact of baseline patient-specific risk factors and regimen risk on the incidence of FN in patients receiving pegfilgrastim primary prophylaxis. Methods: This was a retrospective observational study in patients with breast cancer (BC) who received myelosuppressive chemotherapy and prophylactic pegfilgrastim identified January 1, 2017-May 31, 2018 from MarketScan® research databases. The outcomes were defined as incidence of FN in the first cycle and among all cycles of chemotherapy using three different definitions for FN. Logistic regression and generalized estimating equations models were used to compare outcomes among patients with and without patient-specific risk factors and among those receiving regimens categorized as high-, intermediate-, or other-risk for FN (low-risk or undefinable by clinical practice guidelines). Results: A total of 4460 patients were identified. In the first cycle of therapy, patients receiving intermediate-risk regimens were at up to 2 times higher risk for FN across all definitions than those receiving high-risk regimens (P<0.01). The odds ratio for main FN among patients with ≥4 versus 0 risk factors was 15.8 (95% confidence interval [CI]: 1.5, 169.4; P<0.01). Patients with ≥3 FN risk factors had significantly greater risks for FN across all cycles of treatment than those with no risk factors; this was true for all FN definitions. Discussion: The choice of FN definition significantly changed the impact of risk factors on the FN outcomes in our study, demonstrating the importance of evaluating all proxies for true FN events in a database study. This is particularly important during real-world study planning where potential missteps may lead to bias or confounding effects that render a study meaningless. Conclusions: In patients with BC receiving chemotherapy with pegfilgrastim prophylaxis, patient-specific risk factors and regimen risk levels are determinants of FN risk. In real-world studies evaluating FN incidence, it is imperative to consider and control for these risk factors when conducting comparative analyses.
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McBride, Ali, Kelly Yiu, Emad Elquza, Daniel Oscar Persky und Abhijeet Kumar. „Transition of dose-adjusted EPOCH therapy into the outpatient healthcare setting: Quality and cost considerations for outpatient treatment.“ Journal of Clinical Oncology 36, Nr. 30_suppl (20.10.2018): 110. http://dx.doi.org/10.1200/jco.2018.36.30_suppl.110.

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110 Background: Dose-adjusted etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin (EPOCH)-containing regimens are frequently utilized in lymphoma, however, outpatient EPOCH or modified inpatient/outpatient EPOCH has not been described extensively. We transitioned inpatient EPOCH to the outpatient setting and modified EPCOH to be given in the inpatient setting with rituximab outpatient to improve quality of care and access to patient assistance programs. We describe our institutional experiences with inpatient and modified EPOCH to the outpatient setting. Methods: A single-center, institutional review board-approved retrospective study was conducted for adults receiving EPOCH-based regimens. Clinical and financial data were collected by chart review for each patient. Descriptive statistics were utilized for analysis. Results: A total of 31 patients received 116 cycles of an EPOCH-containing regimen (11 [9.5%] inpatient), 54 [46.5%] outpatient, and 51 [44.0%] hybrid inpatient and outpatient). Nine outpatient cycles, 9 (17.6%) hybrid cycles and no inpatient cycles resulted in admissions for FN. Two inpatient cycles were delayed (18.2%) due to disease-related procedures and one (9.1%) was delayed due to low blood counts. Five (9.2%) outpatient cycles were delayed due to logistics (i.e. insurance delays, scheduling errors) and two (3.7%) outpatient cycles were delayed due to disease-related adverse events (bowel obstruction, chest pain). Transitioning EPOCH to the outpatient setting decreased overall costs for hospital stays on average by $19,792 per cycle with an overall approximate cost savings to the health-system of 1,114,992 dollars with 432 bed days saved. Costs savings to patients with medications assistance programs is pending final analysis. Conclusions: EPOCH-containing regimens can be safely transitioned into the outpatient setting, side effects can be monitored and outcomes optimized, to better adapt treatment strategies for individualized patient therapies. As new healthcare payment models are developed, outpatient treatments allow for adaptive financial options both for the health-system and the patient.
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Hopkins, Maeve, Sarah Dotters-Katz, Kim Boggess, R. Heine und Marcela Smid. „Perioperative Antibiotic Choice in Labored versus Unlabored Cesareans and Risk of Postcesarean Infectious Morbidity“. American Journal of Perinatology 35, Nr. 02 (24.08.2017): 127–33. http://dx.doi.org/10.1055/s-0037-1606187.

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Objective This study aims to estimate postcesarean infectious morbidity in women receiving perioperative β-lactam versus non-β-lactam antibiotics. Methods We conducted a retrospective cohort analysis of the Maternal-Fetal Medicine Unit Cesarean Registry. The exposure was β-lactam perioperative antibiotics versus non-β-lactam regimens at cesarean delivery (CD). We stratified by labored versus unlabored CD. The primary composite outcome included wound infection, seroma, hematoma, endometritis, readmission due to wound complication, or debridement. Multivariable logistic regression estimated odds of wound complication by antibiotic regimen after adjusting for relevant confounders. Results Our analysis included 43,735 women who delivered via CD, 48% following labor. In both groups, 95% of women received β-lactam antibiotics. In the labored CD group (n = 20,860), there was no significant difference in primary outcome by β-lactam versus non-β-lactam antibiotics (10.5 vs. 9.9%, p = 0.53). In the unlabored CD group (n = 22,875), women receiving non-β-lactam antibiotics were more likely to experience a wound complication compared with those in the β-lactam group (6.2 vs. 4.7%, p = 0.02, adjusted odds ratio: 1.39, 95% confidence interval: 1.08–1.80) after adjustment for clinical confounders. Conclusion In unlabored CD, non-β-lactam antibiotics have a higher risk of wound complications compared with β-lactam regimens. Further study to optimize antibiotic prophylaxis for β-lactam allergic women undergoing unlabored CD is warranted.
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Ariano, Robert E., Christine Franczuk, Adrian Fine, Godfrey K. M. Harding und Sheryl A. Zelenitsky. „Challenging the Current Treatment Paradigm for Methicillin-Resistant Staphylococcus Epidermidis Peritonitis in Peritoneal Dialysis Patients“. Peritoneal Dialysis International: Journal of the International Society for Peritoneal Dialysis 22, Nr. 3 (Mai 2002): 335–38. http://dx.doi.org/10.1177/089686080202200306.

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Objectives To analyze clinical outcomes of Staphylococcus epidermidis peritoneal dialysis peritonitis before and after an interventional switch from a vancomycin/tobramycin to a cefazolin/tobramycin regimen for empiric treatment. To examine risk factors associated with clinical failure. Design A retrospective study. Setting A peritoneal dialysis program within a university-affiliated tertiary-care hospital. Patients 93 episodes of S. epidermidis peritonitis over a 6-year period. Interventions Clinical responses were compared between treatments using chi-square or Fisher's exact test. Univariate and multivariate analyses were used to identify significant risk factors for clinical failure. Measurements and Main Results There was no difference in the overall response rates observed with vancomycin (40/49; 81.6%) and cefazolin (23/29; 79.3%) regimens for episodes of S. epidermidis peritonitis. Furthermore, the presence of methicillin resistance in 63 of 93 cases (67.7%) had no influence on clinical outcome, with response rates of 83.9% (26/31) and 82.4% (14/17) for empiric vancomycin and cefazolin regimens, respectively. Tobramycin therapy of less than 2 days was an independent risk factor for clinical failure in multivariate logistic regression analysis (odds ratio 4.44, 95% confidence interval 1.28 – 15.48; p = 0.02). Conclusions Empiric treatment with intraperitoneal cefazolin was as effective as vancomycin for S. epidermidis peritonitis despite a high prevalence of methicillin resistance. Tobramycin therapy of less than 2 days was strongly associated with treatment failure.
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Neesgaard, Bastian, Amanda Mocroft, Robert Zangerle, Ferdinand Wit, Fiona Lampe, Huldrych F. Günthard, Coca Necsoi et al. „Virologic and immunologic outcomes of treatment with integrase inhibitors in a real-world setting: The RESPOND cohort consortium“. PLOS ONE 15, Nr. 12 (31.12.2020): e0243625. http://dx.doi.org/10.1371/journal.pone.0243625.

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Objectives To compare virologic and immunologic outcomes of integrase inhibitor (INSTI)-containing, contemporary boosted protease inhibitor (PI/b)-containing and non-nucleotide reverse transcriptase inhibitor (NNRTI)-containing regimens in a real-life setting. Methods Using logistic regression, virologic and immunologic outcomes of INSTI use were compared to outcomes of PI/b or NNRTI treatment 12 months after treatment start or switch, for participants in the RESPOND cohort consortium. A composite treatment outcome (cTO) was used, defining success as viral load (VL) <200 copies/mL and failure as at least one of: VL ≥200 copies/mL, unknown VL in the time window, any changes of antiretroviral therapy (ART) regimen, AIDS, or death. In addition, on-treatment analysis including only individuals with known VL and no regimen changes was performed. Favorable immunologic response was defined as a 25% increase in CD4 count or as reaching ≥750 CD4 cells/μL. Results Between January 2012 and January 2019, 13,703 (33.0% ART-naïve) individuals were included, of whom 7,147 started/switched to a regimen with an INSTI, 3,102 to a PI/b and 3,454 to an NNRTI-containing regimen. The main reason for cTO failure in all treatment groups were changes in ART regimen. Compared to INSTIs, the adjusted odds ratio (aOR) of cTO success was significantly lower for PI/b (0.74 [95% confidence interval, CI 0.67–0.82], p <0.001), but similar for NNRTIs (1.07 [CI 0.97–1.17], p = 0.11). On-treatment analysis and sensitivity analyses using a VL cut-off of 50 copies/mL were consistent. Compared to INSTIs, the aORs of a 25% increase in CD4 count were lower for NNRTIs (0.80 [CI 0.71–0.91], p<0.001) and PI/b (0.87 [CI 0.76–0.99], p = 0.04). Conclusion In this large analysis of a real-world population, cTO and on-treatment success were similar between INSTIs and NNRTIs, but lower for PI/b, though residual confounding cannot be fully excluded. Obtaining favorable immunologic outcomes were more likely for INSTIs than the other drug classes.
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