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최영근. "Individualized Treatment Regime for Personalized Medicine: A Review." Quantitative Bio-Science 36, no. 1 (May 2017): 7–13. http://dx.doi.org/10.22283/qbs.2017.36.1.7.
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Huang, Xinyang, Yair Goldberg, and Jin Xu. "Multicategory individualized treatment regime using outcome weighted learning." Biometrics 75, no. 4 (August 28, 2019): 1216–27. http://dx.doi.org/10.1111/biom.13084.
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Feshchenko, Yu I., N. A. Litvinenko, N. V. Grankina, M. V. Pogrebna, Yu O. Senko, L. M. Protsyk, and R. L. Liubevych. "Treatment of patients with multidrugresistant and extensively drug resistant tuberculosis depending on the composition of individualized regimens: immediate and longterm results." Tuberculosis, Lung Diseases, HIV Infection, no. 4 (December 15, 2021): 7–15. http://dx.doi.org/10.30978/tb2021-4-7.
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Objective — to study the effectiveness of treatment of MDR-TB (multidrug-resistant tuberculosis) and preXDR-TB/XDR-TB (pre-extensively and extensively drug resistant tuberculosis), depending on the composition of ITRs (individualized treatment regimens).
Materials and methods. Тhe prospective observational study included 566 patients with MDR/preXDR-TB and XDR-TB during 2016—2020 on the scientific clinical bases of the SI «National Institute of Phthisiology and Pulmonology named after F.G. Yanovsky NAMS of Ukraine» and ME «Kryvyi Rih Anti-tuberculosis Dispensary» Dnipropetrovsk Regional Council Department. Patients were prescribed individualized treatment regimens in cases where short (standard or modified) regimens could not be prescribed. Patients were divided into comparison groups: 469 of them were treated with antimycobacterial therapy including bedaquiline and other effective antimycobacterial drugs groups A—C (without delamanid) — group 1. And 97 patients who were treated with the inclusion of both new antimycobacterial drugs (bedaquiline and delamanid) — group 2.
Results and discussion. Regardless of whether the delamanid, in addition to bedaquiline and other drugs selected for the scheme according to WHO recommendations, «effective treatment» was found in 91.3 against 88.6 % of patients. In the remote period (6-month — 4-year follow-up period) there was no recurrence of the disease, regardless of the composition of the regime. The loss of treatment effectiveness was due to deaths from non-tuberculosis reasons and those lost for follow-up.
Conclusions. For highly effective treatment, individualized regimens should include bedaquidine and linezolid from group A, and for previously ineffectively treated patients, clofazimine and carbapenems must be included (possibility to include 4 or more effective AMDs in ITR). For patients with fluoroquinolone resistance, treatment should include delamanid.
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Rich, Benjamin, Erica E. M. Moodie, and David A. Stephens. "Influence Re-weighted G-Estimation." International Journal of Biostatistics 12, no. 1 (May 1, 2016): 157–77. http://dx.doi.org/10.1515/ijb-2015-0015.
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Abstract Individualized medicine is an area that is growing, both in clinical and statistical settings, where in the latter, personalized treatment strategies are often referred to as dynamic treatment regimens. Estimation of the optimal dynamic treatment regime has focused primarily on semi-parametric approaches, some of which are said to be doubly robust in that they give rise to consistent estimators provided at least one of two models is correctly specified. In particular, the locally efficient doubly robust g-estimation is robust to misspecification of the treatment-free outcome model so long as the propensity model is specified correctly, at the cost of an increase in variability. In this paper, we propose data-adaptive weighting schemes that serve to decrease the impact of influential points and thus stabilize the estimator. In doing so, we provide a doubly robust g-estimator that is also robust in the sense of Hampel (15).
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Olivieri, Martin, Christoph Königs, Christine Heller, Silvia Horneff, Johannes Oldenburg, Susan Halimeh, Karim Kentouche, et al. "Prevalence of Obesity in Young Patients with Severe Haemophilia and Its Potential Impact on Factor VIII Consumption in Germany." Hämostaseologie 39, no. 04 (February 5, 2019): 355–59. http://dx.doi.org/10.1055/s-0039-1677874.
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AbstractSimilar to the general population, overweight and obesity have increasingly become a medical and economic burden also in patients with haemophilia in industrialized nations. In this study in seven German haemophilia centres, we identified a prevalence of overweight and obesity of 25.2% among 254 young patients <30 years (median: 13 years; range: 0–30 years) with severe haemophilia A and without a history of inhibitors. The median FVIII dosage based on bodyweight was significantly higher in normal weight compared with overweight or obese patients (96.9 vs. 72.9 IU/kg/week, respectively; p < 0.0001). This suggests that an individualized dosing regime which might be based on FVIII pharmacokinetics, physical activity and pre-existing haemophilic arthropathy is applied rather than dosing by bodyweight only. The bleeding rates observed in obese (median: 1; range: 0–17) versus normal weight patients (median: 2; range: 0–28) did not differ significantly (p = 0.057). Lower bleeding rates might be due to reduced activity or expected higher FVIII plasma levels in overweight patients. Due to the increasing prevalence of overweight/obesity in patients with haemophilia an interdisciplinary approach for individualized haemophilia treatment and weight loss programmes might be helpful for optimal and economical treatment for this group of patients.
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Bidu, Nadielle S., Bruno J. D. Fernandes, Eduardo J. C. Dias, Jucelino N. C. Filho, Regina E. A. Bastos, Ana L. P. C. Godoy, Francine J. Azeredo, Joice N. R. Pedreira, and Ricardo D. Couto. "Vancomycin Therapeutic Regime Adjustment in Newborns and Infants with Bacterial Infection: Case Series." Current Pharmaceutical Biotechnology 20, no. 4 (May 28, 2019): 346–51. http://dx.doi.org/10.2174/1389201020666190319161511.
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Background: Vancomycin is used mostly to overcome infections caused by methicillinresistant microorganisms. There are no well-established administration protocols for neonates and infants, so the leak of a specific administration regime in that population may lead to serum concentrations beyond the specified range. Objective: This case series evaluated the pharmacokinetics adjustment from a vancomycin therapeutic regimen prescribed to neonates and infants with bacterial infection at a neonatal public hospital intensive- care-unit, with the primary purpose to verify cases of nephrotoxicity. Methods: Three neonates and four infants taking vancomycin therapy, hospitalized in a public hospital from November 2014 to March 2015, were included in the study. Vancomycin serum concentrations were determined by particle-enhanced-turbidimetric inhibition-immunoassay. The vancomycin concentrations were used for dose adjustment by USC*Pack-PC-Collection®, a non-parametric maximization program. The trough serum concentration range of 10 to 20mg.L-1 was considered therapeutic. Results: Three patients had serum concentration outside the reference-range, one with subtherapeutic, and two with supratherapeutic concentrations. All patients had concomitant use of drugs which interfered with vancomycin distribution and excretion pharmacokinetics parameters, including drugs that may enhance nephrotoxicity. One patient showed signs of acute renal damage, by low vancomycin and creatinine estimated clearances. Conclusion: The pharmacokinetic adjustment has been proven to be a useful and necessary tool to increase therapeutic efficacy and treatment benefits. The standard dose of vancomycin can be used to initiate therapy in neonates and infants admitted to the ICU, but after reaching the drug steady state, the dosing regimen should be individualized and guided by pharmacokinetic parameters.
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Hoffmann, Christian, Toke Ringbaek, Anja Eckstein, Wolfgang Deya, Alina Santiago, Martin Heintz, Wolfgang Lübcke, et al. "Long-Term Follow-Up of Patients with Conjunctival Lymphoma after Individualized Lens-Sparing Electron Radiotherapy: Results from a Longitudinal Study." Cancers 15, no. 22 (November 15, 2023): 5433. http://dx.doi.org/10.3390/cancers15225433.
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Irradiation with electrons is the primary treatment regime for localized conjunctival low-grade lymphomas. However, radiation-induced cataracts are a major cause of treatment-related morbidity. This study investigates whether lens-sparing electron irradiation produces sufficient disease control rates while preventing cataract formation. All consecutive patients with strictly conjunctival, low-grade Ann Arbor stage IE lymphoma treated with superficial electron irradiation between 1999 and 2021 at our department were reviewed. A total of 56 patients with 65 treated eyes were enrolled with a median follow-up of 65 months. The median dose was 30.96 Gy. A lens-spearing technique featuring a hanging rod blocking the central beam axis was used in 89.2% of all cases. Cumulative incidences of 5- and 10-year infield recurrences were 4.3% and 14.6%, incidences of 5- and 10-year outfield progression were 10.4% and 13.4%. We used patients with involvement of retroorbital structures treated with whole-orbit photon irradiation without lens protection—of which we reported in a previous study—as a control group. The cumulative cataract incidence for patients treated with electrons and lens protection was significantly lower (p = 0.005) when compared to patients irradiated without lens protection. Thus, electrons are an effective treatment option for conjunctival low-grade lymphomas. The presented lens-sparing technique effectively prevents cataract formation.
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Zhang, Jianzhong, ChaoZhao Liang, Xuejun Shang, and Hongjun Li. "Chronic Prostatitis/Chronic Pelvic Pain Syndrome: A Disease or Symptom? Current Perspectives on Diagnosis, Treatment, and Prognosis." American Journal of Men's Health 14, no. 1 (January 2020): 155798832090320. http://dx.doi.org/10.1177/1557988320903200.
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Definitive diagnosis and selection of effective treatment for chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) are frustrations encountered frequently by urology care providers in their practice. Knowledge of etiology and pathophysiology is not sufficient and therapeutic guidelines have not yielded acceptable outcomes and prognoses for both patients and care providers. The authors present updated perspectives on CP/CPPS, including definition, diagnosis, treatment, and prognosis, based on literature review and clinical experience. A key point is to shift the diagnostic and therapeutic focus from a single entity of disease toward associated symptoms of CP/CPPS. An individualized multimodal treatment approach to cope with the course of the disorder is proposed. Communications and personal/family/community supports are emphasized as an important component in the therapeutic regime and rehabilitation of patients with CP/CPPS. The purpose is to improve comprehension on CP/CPPS and to help care providers and patients to achieve the goal of medical intervention—relieving associated symptoms of CP/CPPS and improving the quality of life.
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Frelick, Bill. "What’s Wrong with Temporary Protected Status and How to Fix It: Exploring a Complementary Protection Regime." Journal on Migration and Human Security 8, no. 1 (February 26, 2020): 42–53. http://dx.doi.org/10.1177/2331502419901266.
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Executive Summary Temporary Protected Status (TPS) became part of the US protection regime in 1990 to expand protection beyond what had been available under the US Refugee Act of 1980, which had limited asylum to those who met the refugee definition from the United Nations’ 1951 Refugee Convention. The TPS statute authorized the attorney general to designate foreign countries for TPS based on armed conflict, environmental disasters, and other extraordinary and temporary conditions that prevent designated nationals from returning in safety. While providing blanket protection that very likely has saved lives, TPS has nonetheless proven to be a blunt instrument that has frustrated advocates on both sides of the larger immigration debate. This article evaluates the purpose and effectiveness of the TPS statute and identifies inadequacies in the TPS regime and related protection gaps in the US asylum system. It argues that TPS has not proven to be an effective mechanism for the United States to protect foreigners from generalized conditions of danger in their home countries. It calls for changing the US protection regime to make it more responsive to the risks many asylum seekers actually face by creating a broader “complementary protection” standard and a more effective procedure for assessing individual protection claims, while reserving “temporary protection” for rare situations of mass influx that overwhelm the government’s capacity to process individual asylum claims. The article looks at alternative models for complementary protection from other jurisdictions, and shows how the US asylum and TPS system (in contrast to most other jurisdictions) fails to provide a mechanism for protecting arriving asylum seekers who do not qualify as refugees but who nevertheless would be at real risk of serious harm based on cruel, inhuman, or degrading treatment or punishment or because of situations of violence or other exceptional circumstances, including natural or human-made disasters or other serious events that disturb public order, that would threaten their lives or personal security. The article proposes that the United States adopt an individualized complementary protection standard for arriving asylum seekers who are not able to meet the 1951 Refugee Convention standard but who would face a serious threat to life or physical integrity if returned because of a real risk of (1) cruel, inhuman, or degrading treatment or punishment; (2) violence; or (3) exceptional situations, for which there is no adequate domestic remedy.
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Ranade, Manjiri Anil. "Ayurgenomics – A narrative review." BLDE University Journal of Health Sciences 9, no. 1 (January 2024): 91–94. http://dx.doi.org/10.4103/bjhs.bjhs_169_23.
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Abstract: Ayurgenomics is the integration of Ayurvedic principles with genomics to provide personalized approaches for the predictive, preventive, and curative aspects of medicine. It focuses on the interindividual variability due to genetic variability in humans, using the concept of Prakriti, which is a fusion of the comparative proportion of three main things, i.e., Tridoshas, namely, Vata, Pitta, and Kapha. Prakriti is used to define physical, physiological, and psychological traits of an individual and is the template for individualized diet, lifestyle counseling, and treatment. Ayurgenomics is an emerging field of interest where the therapeutic and lifestyle regime selection is made on the basis of clinical assessment of an individual maintaining one’s Prakriti. It is a novel concept of genomics suitable for one’s genetic makeup with the help of Ayurveda. It is possible that as Ayurveda gains more recognition and acceptance in mainstream health care, practitioners may incorporate more Ayurvedic principles and techniques in their practices, including categorizing patients based on Ayurvedic theories such as Prakriti. However, it is important to note that Ayurveda and allopathic medicine are based on different principles and may not always be compatible, so it is important for practitioners to have proper training and understanding of both systems before combining them in treatment. It is also important to note that while some studies have found correlation between Prakriti and genetics, more research is needed to establish the validity of Ayurgenomics as a field. Therefore, practitioners should be cautious in using Ayurvedic principles to make treatment decisions without thorough understanding of the patient’s condition and the potential risks and benefits of the treatment.
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Scheetz, J. S., G. S. Morris, K. E. Brueilly, E. A. Brannan, and E. Del Fabbro. "Effects of glucocorticoid treatment on the functional capacity of stem cell transplant recipients entering a rehabilitation program." Journal of Clinical Oncology 27, no. 15_suppl (May 20, 2009): 7104. http://dx.doi.org/10.1200/jco.2009.27.15_suppl.7104.
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7104 Background: Emerging data strongly supports the concept that stem cell transplant (SCT) recipients derive psychological and physiological benefit from participation in exercise training programs. Many SCT recipients receive glucocorticoids (GC) for prolonged periods, increasing their risk for proximal muscle damage and raising the possibility that SCT recipients on GC may differ from those SCT recipients not receiving GC in terms of their exercise/functional capacity. This becomes an important reconditioning issue because exercise prescription and progression is predicated on initial exercise capacity. Therefore the purpose of this study was to compare the initial functional capacity of outpatient STC recipients receiving GC to STC recipients not receiving GC. Methods: The medical records of 163 successive SCT recipients referred to Rehabilitation Services for reconditioning were retrospectively reviewed for demographic information and measures of exercise/functional capacity (6-min walk test, 50-ft fast walk, and repeated sit-to-stand times) collected at the initial physical therapy visit. Data from SCT recipients on GC (ON) were compared with that of SCT recipients not on GC (OFF) by means of an unpaired t-test (α=0.05). Data are presented as mean + standard deviation. Results: Demographic and functional measures are presented in the following tables. Significant differences between group means are denoted by an asterisk. Conclusions: STC recipients on steroids have comparable endurance capacity to those STC recipients not on steroids, but are less capable of performing lower extremity activities requiring rapid movement and receive rehabilitation services later in the post transplant recovery course. These results suggest rehabilitation strategies are 1) needed for STC patients, 2) should be individualized according to the patient's drug regime, and 3) should be initiated soon after the stem cell transplant. [Table: see text] No significant financial relationships to disclose.
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Nguyen, Crystal T., Daniel J. Luckett, Anna R. Kahkoska, Grace E. Shearrer, Donna Spruijt‐Metz, Jaimie N. Davis, and Michael R. Kosorok. "Estimating individualized treatment regimes from crossover designs." Biometrics 76, no. 3 (December 19, 2019): 778–88. http://dx.doi.org/10.1111/biom.13186.
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Laber, E. B., and Y. Q. Zhao. "Tree-based methods for individualized treatment regimes." Biometrika 102, no. 3 (July 15, 2015): 501–14. http://dx.doi.org/10.1093/biomet/asv028.
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Laber, Eric B., and Ana-Maria Staicu. "Functional Feature Construction for Individualized Treatment Regimes." Journal of the American Statistical Association 113, no. 523 (July 3, 2018): 1219–27. http://dx.doi.org/10.1080/01621459.2017.1321545.
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Yang, Huiyu, Jiangang Zhang, Ying Shan, Yanan Wang, Yaning Cao, Yuning Sun, Ying Jin, et al. "Patient-derived 3D bioprinting pan-cancer drug screening platform for personalized medicine." Journal of Clinical Oncology 42, no. 16_suppl (June 1, 2024): e15088-e15088. http://dx.doi.org/10.1200/jco.2024.42.16_suppl.e15088.
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e15088 Background: Patient-derived tumor model offers an individualized approach to overcome interpatient heterogeneity in cancer therapy. 3D bioprinting (3DB) enables construction of in vitro model with high-throughput, high-fidelity, and high efficacy. We hereby report a pipeline of establishing pan-cancer patient-derived 3DB (PT-3DB) models with personalized drug sensitivity results in 148 patients from multiple medical centers. Methods: Tumor tissues of 148 patients were collected with informed consent at 4 medical centers in Beijing, Hangzhou and Ningbo from 2022-12 to 2023-12. Tumors were digested into cell suspension and mixed with GelMA, and PT-3DB was fabricated by extrusion-based bioprinter. A panel of chemotherapies and targeted therapies was selected based on first-line treatment of corresponding cancer type. PT-3DB was treated with drugs in dose gradient at DIV 5. Cell viability was measured by ATP quantification at DIV 8 and dose-response curve and IC50 of each drug was calculated. Results: We have established PT-3DB in 148 patients with success rate of > 95% and turnaround time of only 8 days. 137 were surgically resected samples and 11 were biopsy samples. Cancer types included ovarian cancer (OC, n = 52), colorectal cancer (CRC, n = 51), hepatobiliary cancer (HBC, n = 17), breast cancer (BC, n = 10), high-grade glioma (HGG, n = 10), cervical cancer (CC, n = 4), pancreatic cancer (PC, n = 2), and gastric cancer (GC, n = 2). A total of 27 drugs were screened, of which 15 were chemotherapies and 12 were targeted therapies. The median number of drugs tested for each patient was 5 (4-6) (Q25-Q75). Significant interpatient heterogeneous drug response was observed within each cancer type and between tumors with the same treatment regime. Representative data were presented in the attached table. Conclusions: We have successfully constructed pan-cancer PT-3DB platform for personalized drug screening in 148 cases, with outstanding stability across multiple centers. The timeline of 8 days preceded pathological diagnosis, which is the earliest start of systematic treatment, underscoring its high translational potential. PT-3DB has demonstrated interpatient heterogeneous response to systematic treatment, providing a strong foundation for precision medicine. Our ongoing research aims to correlate PT-3DB drug responses with clinical outcomes. [Table: see text]
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Fan, Caiyun, Wenbin Lu, Rui Song, and Yong Zhou. "Concordance-assisted learning for estimating optimal individualized treatment regimes." Journal of the Royal Statistical Society: Series B (Statistical Methodology) 79, no. 5 (October 31, 2016): 1565–82. http://dx.doi.org/10.1111/rssb.12216.
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Huang, Xuelin, Jing Ning, and Abdus S. Wahed. "Optimization of individualized dynamic treatment regimes for recurrent diseases." Statistics in Medicine 33, no. 14 (February 9, 2014): 2363–78. http://dx.doi.org/10.1002/sim.6104.
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Wu, Chi-Shin, Albert C. Yang, Shu-Sen Chang, Chia-Ming Chang, Yi-Hung Liu, Shih-Cheng Liao, and Hui-Ju Tsai. "Validation of Machine Learning-Based Individualized Treatment for Depressive Disorder Using Target Trial Emulation." Journal of Personalized Medicine 11, no. 12 (December 7, 2021): 1316. http://dx.doi.org/10.3390/jpm11121316.
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This study aims to develop and validate the use of machine learning-based prediction models to select individualized pharmacological treatment for patients with depressive disorder. This study used data from Taiwan’s National Health Insurance Research Database. Patients with incident depressive disorders were included in this study. The study outcome was treatment failure, which was defined as psychiatric hospitalization, self-harm hospitalization, emergency visits, or treatment change. Prediction models based on the Super Learner ensemble were trained separately for the initial and the next-step treatments if the previous treatments failed. An individualized treatment strategy was developed for selecting the drug with the lowest probability of treatment failure for each patient as the model-selected regimen. We emulated clinical trials to estimate the effectiveness of individualized treatments. The area under the curve of the prediction model using Super Learner was 0.627 and 0.751 for the initial treatment and the next-step treatment, respectively. Model-selected regimens were associated with reduced treatment failure rates, with a 0.84-fold (95% confidence interval (CI) 0.82–0.86) decrease for the initial treatment and a 0.82-fold (95% CI 0.80–0.83) decrease for the next-step. In emulation of clinical trials, the model-selected regimen was associated with a reduced treatment failure rate.
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Pazos, Montserrat, Stephan Schönecker, Daniel Reitz, Paul Rogowski, Maximilian Niyazi, Filippo Alongi, Christiane Matuschek, et al. "Recent Developments in Radiation Oncology: An Overview of Individualised Treatment Strategies in Breast Cancer." Breast Care 13, no. 4 (2018): 285–91. http://dx.doi.org/10.1159/000488189.
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Radiation therapy (RT) for breast cancer has dramatically changed over the past years, leading to individualized risk-adapted treatment strategies. Historically, the choice of RT regimen was limited to conventional fractionation protocols using standard tangential fields. Nowadays, technological and technical improvements in modern RT have added a variety of other RT modalities, different fractionation schedules, and individualised treatment volumes to the portfolio of breast RT. This review aims to give a short overview on the main topics which have recently found their way into clinical practice: hypofractionated treatment protocols, accelerated partial breast irradiation (APBI) for low-risk patients, deep inspiration breath hold (DIBH) for maximal heart protection, extent of regional nodal irradiation for high-risk patients, and the implementation of new radiation techniques such as intensity modulated RT (IMRT) and volumetric modulated RT (VMAT).
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Shvartsur, Anna, Hermes Garban, and Benjamin Bonavida. "Overexpression of Raf Kinase Inhibitor Protein (RKIP) in Multiple Myeloma and Its Molecular Signature." Blood 128, no. 22 (December 2, 2016): 5673. http://dx.doi.org/10.1182/blood.v128.22.5673.5673.
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Abstract Multiple myeloma (MM) is a clonal plasma-cell neoplastic disorder arising from an indolent premalignant disease known as monoclonal gammopathy of undetermined significance (MGUS) that can evolve to asymptomatic pre-MM and later to symptomatic MM. MM is a biologically complex heterogeneous disease reflected by its variable clinical responses of patients receiving the same treatment. Therefore, a molecular identification of stage-specific biomarkers will support a more individualized precise diagnostic/prognostic approach, an effective therapeutic regime, and will assist in the identification of novel therapeutic molecular targets. The metastatic suppressor/anti-resistance factor Raf-1 kinase inhibitor protein (RKIP) inhibits the Raf/MEK/ERK1/2 and NF-κB pathways and sensitizes resistant tumors to drug-induced apoptosis. Whereby all tumors examined exhibited low levels of RKIP, in contrast, our prior findings demonstrated that RKIP is overexpressed (primarily in its inactive phosphorylated form) in MM cell lines and patients-derived tumor tissues (Baritaki et. al, FIDT 2:1-13, 2011). We examined transcriptomic datasets on Oncomine platform (Life Technologies) for the expression of RKIP and several-associated gene products in both pre-MM and MM. Several gene products were found to be overexpressed such as RKIP, Bcl-2, and DR5 and underexpressed such as Bcl-6 and TNFR2 in both pre-MM and MM. A differentially expressed pro-apoptotic genes were observed in pre-MM versus expression of anti-apoptotic genes in MM. Based on these analyses on mRNA levels and on protein levels in published studies of the above differentially expressed genes, we have found a molecular signature each for pre-MM and MM. Once the molecular signatures are validated experimentally, they will be useful for a more precise diagnosis/prognosis of the disease stages and will also identify novel molecular therapeutic targets. Disclosures No relevant conflicts of interest to declare.
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García-Layana, Alfredo, Marta S. Figueroa, Luis Arias, Javier Araiz, José María Ruiz-Moreno, José García-Arumí, Francisco Gómez-Ulla, et al. "Individualized Therapy with Ranibizumab in Wet Age-Related Macular Degeneration." Journal of Ophthalmology 2015 (2015): 1–8. http://dx.doi.org/10.1155/2015/412903.
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Individualized treatment regimens may reduce patient burden with satisfactory patient outcomes in neovascular age-related macular degeneration. Intravitreal anti-VEGF drugs are the current gold standard. Fixed monthly injections offer the best visual outcome but this regimen is not commonly followed outside clinical trials. A PRN regimen requires monthly visits where the patient is treated in the presence of signs of lesion activity. Therefore, an early detection of reactivation of the disease with immediate retreatment is crucial to prevent visual acuity loss. Several trials suggest that “treat and extend” and other proactive regimens provide a reasonable approach. The rationale of the proactive regimens is to perform treatment anticipating relapses or recurrences and therefore avoid drops in vision while individualizing patient followup. Treat and extend study results in significant direct medical cost savings from fewer treatments and office visits compared to monthly treatment. Current data suggest that, for one year, PRN is less expensive, but treat and extend regimen would likely be less expensive for subsequent years. Once a patient is not a candidate to continue with treatment, he/she should be sent to an outpatient unit with adequate resources to follow nAMD patients in order to reduce the burden of specialized ophthalmologist services.
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Volokhina, E., K. Wijnsma, R. van der Molen, N. Roeleveld, T. van der Velden, J. Goertz, F. Sweep, et al. "Eculizumab Dosing Regimen in Atypical HUS: Possibilities for Individualized Treatment." Clinical Pharmacology & Therapeutics 102, no. 4 (May 26, 2017): 671–78. http://dx.doi.org/10.1002/cpt.686.
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Denic, Kristina Zoran, Sibylle Neuhoff, Joel Reid, and Rachel Kudget. "Abstract A140: A physiologically based pharmacokinetic modeling approach for predicting the exposure of irinotecan and its active metabolite (SN-38) in cancer patients." Molecular Cancer Therapeutics 22, no. 12_Supplement (December 1, 2023): A140. http://dx.doi.org/10.1158/1535-7163.targ-23-a140.
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Abstract Introduction: Irinotecan is an inhibitor of the topoisomerase I enzyme that is essential in DNA transcription, replication, and repair. It is considered a “backbone” regime in colorectal cancer in adults and in pediatric gliomas to which other antineoplastic agents are added to improve the outcome. It is used as well in the treatment of many other types of adult and pediatric cancers. Irinotecan acts as a prodrug of SN-38 which has approximately 100-1000-fold greater cytotoxic activity. The metabolic and pharmacokinetic behavior of irinotecan is very complex and currently not completely elucidated. Clinical data have shown high variability in treated patients in the efficacy, toxicity, and pharmacokinetic profile of the drug. To increase safety and efficacy, a physiologically based pharmacokinetic modeling (PBPK) approach was used to predict the optimal dose for treatment initiation. Methods: Clinical data were used in combination with measured physicochemical and blood-binding data to inform the model. Hence a middle-out approach was used to build the parent model for a population of adult cancer patients. While the default Sim-Cancer population available within the Simcyp Simulator (v21) was used, the unbound fraction in plasma for the healthy population was incorporated into the PBPK model. By using the reverse translational tool and a retrograde approach, the irinotecan metabolism was described by incorporating CYP3A (Km 14.4±1.6 μM, Vmax 14.7± 0.6 pmol/min/mg protein) and an additional clearance. This additional clearance was then explained by scaled esterases (CES1 and CES2) enzyme kinetic from in vitro data. Besides the clinical study that was used to build the model, other independent intravenously administered irinotecan studies were used for verification. Results: The model predicted the plasma concentration of the parent drug and its metabolite (SN-38) in good agreement with observed data from the clinical study that was used to build the model, as well as from several clinical studies that were not used to build the initial model, covering a dose range of 50-750 mg/m2. Conclusion: We developed a PBPK model that accurately predicts the pharmacokinetic behavior of irinotecan and its metabolite (SN-38) in an adult cancer population. Future directions involve the adaption of the model to the pediatric cancer population to predict the optimal dose for initiation of first-in-human Phase I studies and to identify potential drug interactions and unanticipated toxicities when this “backbone” regimen is combined with other investigated anticancer agents. This will then lead to an increase in individualized treatment. Citation Format: Kristina Zoran Denic, Sibylle Neuhoff, Joel Reid, Rachel Kudget. A physiologically based pharmacokinetic modeling approach for predicting the exposure of irinotecan and its active metabolite (SN-38) in cancer patients [abstract]. In: Proceedings of the AACR-NCI-EORTC Virtual International Conference on Molecular Targets and Cancer Therapeutics; 2023 Oct 11-15; Boston, MA. Philadelphia (PA): AACR; Mol Cancer Ther 2023;22(12 Suppl):Abstract nr A140.
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Procházka, Vít K., Štěpánka Matuštíková, Tomáš Fürst, David Belada, Andrea Janíková, Kateřina Benešová, Heidi Mociková, et al. "Bayesian Network Modelling As a New Tool in Predicting of the Early Progression of Disease in Follicular Lymphoma Patients." Blood 136, Supplement 1 (November 5, 2020): 20–21. http://dx.doi.org/10.1182/blood-2020-139830.
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Background: Twenty percent of patients (pts) with high-tumor burden follicular lymphoma (FL) develop progression/relapse of disease within 24 months of frontline immune-chemotherapy (POD24). Those ultra-high-risk cases are at 50% risk of dying within 5-years since the POD event. Unmet need is to identify such pts at the time of initial treatment. The traditional approach used for building predictive scores (such as FLIPI, PRIMA-PI) is multivariable logistic regression (LR). LR is the tool of choice in case of many predictors (continuous or categorical) and a single binary (yes/no) outcome. Bayesian network (BN) offer an alternative strategy which may overcome several drawbacks of LR (risk of overfitting, missing data handling, problems of odds ratio interpretation), brings more insight into the complex relations among the variables, and offer an individualized prediction. Aim: The goal was to build a model to predict the risk of POD24 from the parameters known at diagnosis and compare LR to BN approach. Methods: The study (ClinicalTrials.gov No NCT03199066) comprised 1394 FL (grade I-IIIA) patients from the Czech Lymphoma Study Group registry treated with frontline rituximab-containing regimen and diagnosed between 10. 4. 2000 and 28. 12. 2016. The following parameters were analyzed: gender, age at diagnosis, clinical stage, lymphoma grade, no. of LNs regions, bone marrow involvement, no. of extranodal localizations, longest tumor diameter, systemic symptoms, performance status, LDH, beta-2-microglobulin, hemoglobin, and leucocyte, lymphocyte, and thrombocyte counts, induction regime, radiotherapy, ASCT, maintenance application, response to treatment, and OS, PFS and POD24 as outcome parameters. POD24 was defined as relapse, progression, change of therapy for 24 months since the induction started. Only parameters known at diagnosis were used for the prediction of POD24. Results: The median age was 59 yrs (range 26-89 yrs) with female predominance (59.2%), advanced disease stage (III/IV) was seen in 85.9% of the cases and FLIPI risk groups distribution was as follows: low (18.8%), intermediate (30.9%) and high (50.3%). The most frequent regime used was R-CHOP (76.8%), followed by R-CVP (12.4%), R-bendamustine (4.7%), intensive protocols (3.3), and fludarabine-based (2.8%). Consolidative IF-radiotherapy was applied in 5.1% and up-front ASCT in 2.9% of the pts. Maintenance immunotherapy was given in 67.1% of the pts. Response to therapy was known in all but 28 pts (98%) with CR/CRu 67.9%, PR 26.6%, SD 1.8%, and PD in 3.2% of the cases. After a median follow-up of 7.64 yrs, 484 (34.7%) of the pts progressed or relapsed and 316 (22.6%) have died. POD24 was recorded in 266 (19.0%) of the pts. The 5-year OS reached 86.4% and 5-year PFS 64.2%. LR model (PFS) building strategy included testing for significance as this model performed better than the model with all parameters. Overfitting was prevented by splitting the data into training (75%) and testing (25%) set. The performance of the model was assessed using the AUC criterion computed on the ROC curve. The LR model reached AUC of 0.69, and at 80% specificity, it reached about 51% sensitivity. Next, the BN (Augmented Naïve Bayes Classifier) was trained. Links of all predictors to POD24 were forced and all links to age and gender were forbidden, otherwise the network structure was inferred from the data. The performance of the BN was similar to the LR - AUC of 0.67 and about 50% sensitivity at the specificity of 80%. Both these models were compared to the standard PRIMA-PI risk classifier and were found to better stratify the population into risk groups (Table 1). An example of a patient is presented who was low-risk according to PRIMA-PI but actually experienced the POD24 event. The BN estimated the probability of the event to 91% (Figure 1). Conclusion: Lymphoma-related death following POD24 remains the most frequent cause of mortality in FL patients. BN modelling is a non-inferior prognostic tool compared to LR in term of POD24 prediction. Unlike LR, it also allows visualisation of complex relations among the predictors and individualized prediction of the patient's POD24 risk, even if some of the predictors are unknown. Both "ad hoc" trained LR and BN were found to better stratify the population into risk groups with respect to POD24 event than the traditional PRIMA-PI score. Acknowledgement: MZ Czech Republic DRO grant (FNOL, 00098892). Disclosures Procházka: F. Hoffmann-La Roche AG: Consultancy, Honoraria; Takeda Pharmaceuticals, Inc: Consultancy, Research Funding. Belada:Roche: Consultancy, Membership on an entity's Board of Directors or advisory committees, Other: Travel expenses, Research Funding; Janssen: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Gilead: Consultancy, Membership on an entity's Board of Directors or advisory committees, Other: Travel expenses, Research Funding; Celgene: Research Funding; Takeda: Consultancy, Membership on an entity's Board of Directors or advisory committees, Other: Travel expenses, Research Funding. Trněný:Janssen: Consultancy, Honoraria, Other: Travel Expenses; Gilead: Consultancy, Honoraria, Other: Travel Expenses; Takeda: Consultancy, Honoraria, Other: Travel Expenses; Bristol-Myers Squibb Company: Consultancy, Honoraria, Other: Travel Expenses; Amgen: Honoraria; Abbvie: Consultancy, Honoraria, Other: Travel Expenses; Roche: Consultancy, Honoraria, Other: Travel Expenses; MorphoSys: Consultancy, Honoraria; Incyte: Consultancy, Honoraria; Celgene: Consultancy.
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Zhang, Haixiang, Jian Huang, and Liuquan Sun. "A rank-based approach to estimating monotone individualized two treatment regimes." Computational Statistics & Data Analysis 151 (November 2020): 107015. http://dx.doi.org/10.1016/j.csda.2020.107015.
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Gorodnova, T. V., A. P. Sokolenko, Kh B. Kotiv, A. O. Ivantsov, E. A. Nekrasova, Z. N. Ibragimov, I. V. Berlev, and E. N. Imyanitov. "Acquired Platinum Resistance of BRCA1-associated Ovarian Cancer after Neoadjuvant Chemotherapy." Doctor.Ru 21, no. 5 (2022): 87–91. http://dx.doi.org/10.31550/1727-2378-2022-21-5-87-91.
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Objective of the Paper: To individualise the treatment programme for patients with advanced BRCA-associated ovarian cancer. Key points. Ovarian cancer is a highly aggressive disease characterized by low overall survival rates. The search for molecular markers, predictors of the effectiveness of drug therapy, is an urgent area of research. The article describes a clinical case of a fundamentally new approach to the combined treatment of a patient with BRCA1-associated advanced ovarian cancer. Conclusion. Molecular testing proved tumor resistance, which evolved during neoadjuvant therapy, so adjustment of the drug regimen was required. A comprehensive approach in the assessment of molecular genetic status and tumor prevalence allows to individualize the treatment program for patients with advanced BRCA-associated ovarian cancer. Keywords: ovarian cancer, chemoresistance, mutations in BRCA genes.
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Rich, M. L., U. Khan, C. Zeng, A. LaHood, M. F. Franke, S. Atwood, M. Bastard, et al. "Outcomes of WHO-conforming, longer, all-oral multidrug-resistant TB regimens and analysis implications." International Journal of Tuberculosis and Lung Disease 27, no. 6 (June 1, 2023): 451–57. http://dx.doi.org/10.5588/ijtld.22.0613.
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BACKGROUND: Evidence of the effectiveness of the WHO-recommended design of longer individualized regimens for multidrug- or rifampicin-resistant TB (MDR/RR-TB) is limited.OBJECTIVES: To report end-of-treatment outcomes for MDR/RR-TB patients from a 2015–2018 multi-country cohort that received a regimen consistent with current 2022 WHO updated recommendations and describe the complexities of comparing regimens.METHODS: We analyzed a subset of participants from the endTB Observational Study who initiated a longer MDR/RR-TB regimen that was consistent with subsequent 2022 WHO guidance on regimen design for longer treatments. We excluded individuals who received an injectable agent or who received fewer than four likely effective drugs.RESULTS: Of the 759 participants analyzed, 607 (80.0%, 95% CI 77.0–82.7) experienced successful end-of-treatment outcomes. The frequency of success was high across groups, whether stratified on number of Group A drugs or fluoroquinolone resistance, and ranged from 72.1% to 90.0%. Regimens were highly variable regarding composition and the duration of individual drugs.CONCLUSIONS: Longer, all-oral, individualized regimens that were consistent with 2022 WHO guidance on regimen design had high frequencies of treatment success. Heterogeneous regimen compositions and drug durations precluded meaningful comparisons. Future research should examine which combinations of drugs maximize safety/tolerability and effectiveness.
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Verboven, Lennert, Steven Callens, John Black, Gary Maartens, Kelly E. Dooley, Samantha Potgieter, Ruben Cartuyvels, Kris Laukens, Robin M. Warren, and Annelies Van Rie. "A machine-learning based model for automated recommendation of individualized treatment of rifampicin-resistant tuberculosis." PLOS ONE 19, no. 9 (September 6, 2024): e0306101. http://dx.doi.org/10.1371/journal.pone.0306101.
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Background Rifampicin resistant tuberculosis remains a global health problem with almost half a million new cases annually. In high-income countries patients empirically start a standardized treatment regimen, followed by an individualized regimen guided by drug susceptibility test (DST) results. In most settings, DST information is not available or is limited to isoniazid and fluoroquinolones. Whole genome sequencing could more accurately guide individualized treatment as the full drug resistance profile is obtained with a single test. Whole genome sequencing has not reached its full potential for patient care, in part due to the complexity of translating a resistance profile into the most effective individualized regimen. Methods We developed a treatment recommender clinical decision support system (CDSS) and an accompanying web application for user-friendly recommendation of the optimal individualized treatment regimen to a clinician. Results Following expert stakeholder meetings and literature review, nine drug features and 14 treatment regimen features were identified and quantified. Using machine learning, a model was developed to predict the optimal treatment regimen based on a training set of 3895 treatment regimen-expert feedback pairs. The acceptability of the treatment recommender CDSS was assessed as part of a clinical trial and in a routine care setting. Within the clinical trial setting, all patients received the CDSS recommended treatment. In 8 of 20 cases, the initial recommendation was recomputed because of stock out, clinical contra-indication or toxicity. In routine care setting, physicians rejected the treatment recommendation in 7 out of 15 cases because it deviated from the national TB treatment guidelines. A survey indicated that the treatment recommender CDSS is easy to use and useful in clinical practice but requires digital infrastructure support and training. Conclusions Our findings suggest that global implementation of the novel treatment recommender CDSS holds the potential to improve treatment outcomes of patients with RR-TB, especially those with ‘difficult-to-treat’ forms of RR-TB.
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Niesley, Michelle, Kathryn Doran, Nhu Huynh, and Marie Winters. "A model for coordinated delivery of individualized complementary and integrative medicine care for cancer survivors." Journal of Clinical Oncology 34, no. 3_suppl (January 20, 2016): e286-e286. http://dx.doi.org/10.1200/jco.2016.34.3_suppl.e286.
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e286 Background: Cancer survivors may experience both physical and psychosocial sequelae as a result of cancer treatment. Many patients consult either their oncologist or primary care physician for lifestyle interventions to address survivorship issues. While studies demonstrate complementary and integrative medicine (CIM) therapies may reduce the risk of both all-cause mortality and cancer-specific mortality by 50% (Frenkel M et al. Curr Oncol Rep. 2015 May;17(5):445), the most effective method to ensure compliance with individualized dietary counseling, exercise, or nutritional supplement information to the patient is unknown. Here we present a multidisciplinary survivorship care model to increase compliance with CIM practices that positively impact survivorship outcomes. Methods: Each Patient Empowered Care (PEC) team at our hospital consists of a medical oncologist, naturopathic doctor, nurse care manager, and a nutritionist, who discuss the assessment and plan for each patient they will see that day. Additional integrative services include chiropractic care, acupuncture, and Oncology Rehab (physical, occupational, speech, and massage therapy). Naturopathic doctors recommend nutritional supplements specific to both the patient’s oncology regimen and other comorbidities, and also ensure these supplements do not interfere with metabolism of other active medications. Oncology Rehab encourages exercise via our Motion for Life program, where physical fitness programs are tailored to the patient’s individual needs. The Nutrition program provides individualized coaching and nutritional management. Patients continue CIM therapies long after oncology care has concluded. Results: Patients satisfaction and outcomes are improved by facilitating compliance with individualized lifestyle recommendations. Conclusions: This model increases compliance with CIM recommendations by facilitating transparent communication among PEC team members, while providing the patient with a single facility that individualizes their wellness regimen.
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Virág, Marcell, Tamas Leiner, Mate Rottler, Klementina Ocskay, and Zsolt Molnar. "Individualized Hemodynamic Management in Sepsis." Journal of Personalized Medicine 11, no. 2 (February 23, 2021): 157. http://dx.doi.org/10.3390/jpm11020157.
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Hemodynamic optimization remains the cornerstone of resuscitation in the treatment of sepsis and septic shock. Delay or inadequate management will inevitably lead to hypoperfusion, tissue hypoxia or edema, and fluid overload, leading eventually to multiple organ failure, seriously affecting outcomes. According to a large international survey (FENICE study), physicians frequently use inadequate indices to guide fluid management in intensive care units. Goal-directed and “restrictive” infusion strategies have been recommended by guidelines over “liberal” approaches for several years. Unfortunately, these “fixed regimen” treatment protocols neglect the patient’s individual needs, and what is shown to be beneficial for a given population may not be so for the individual patient. However, applying multimodal, contextualized, and personalized management could potentially overcome this problem. The aim of this review was to give an insight into the pathophysiological rationale and clinical application of this relatively new approach in the hemodynamic management of septic patients.
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Chihara, Kazuo, Ekaterina Koledova, Akira Shimatsu, Yuzuru Kato, Hitoshi Kohno, Toshiaki Tanaka, Akira Teramoto, Peter C. Bates, and Andrea F. Attanasio. "An individualized GH dose regimen for long-term GH treatment in Japanese patients with adult GH deficiency." European Journal of Endocrinology 153, no. 1 (July 2005): 57–65. http://dx.doi.org/10.1530/eje.1.01936.
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Objectives: To investigate the effects of growth hormone (GH) treatment, using a dose-adjustment regimen based on serum insulin-like growth factor (IGF)-I concentrations, in adult Japanese hypopituitary patients with GH deficiency. Study design: Japanese patients who had initially been administered GH (n = 31) or placebo (n = 28) in a 24-week double-blind study received individualized GH treatment in an open-label study for 48 weeks. Body composition from dual-energy X-ray absorptiometry (DXA) and serum IGF-I, IGF-binding protein 3 (IGFBP-3) and lipid levels were determined centrally. Results: Significant increases in lean body mass (4.5%) and decreases in fat mass (−10.5%) were observed in the group that received individualized GH doses in the present open-label study following placebo in the double-blind study. This was comparable with the changes observed in these parameters (4.7 and −9.2%, respectively) with fixed-dose GH treatment in the double-blind study; this latter group maintained these improvements throughout the open-label study. Individualized dose adjustment allowed for more moderate dose increases than the fixed-dose titration method. Individualized dosing also resulted in a lower mean dose for adult-onset compared with childhood-onset GH-deficient patients (0.032±0.019 versus 0.061±0.023 mg/kg per week for patients treated with GH for 48 weeks in the open-label study following placebo in the double-blind study). Dosing patterns in the two groups were paralleled by the changes in IGF-I and IGFBP-3. The incidence of oedema and cases with high IGF-I level were less frequent under the IGF-I controlled regimen compared with those during the fixed-dose titration method. Conclusion: Individualized GH administration based on IGF-I levels was safe and effective. This regimen demonstrated differences in dose requirements between adult- and childhood-onset patients. An individualized dose regimen is recommended in adult Japanese GH-deficient patients.
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Yang, Chin-Yi, Ja-Hon Lin, and Chien-Ming Chen. "Optical Coherence Tomography as a Diagnosis-Assisted Tool for Guiding the Treatment of Melasma: A Case Series Study." Diagnostics 14, no. 18 (September 20, 2024): 2083. http://dx.doi.org/10.3390/diagnostics14182083.
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Background/Objectives: Multiple underlying pathomechanisms may lead to melasma, but there has been no report on the use of optical coherence tomography (OCT) to reveal specific pathomechanisms in individual patients and provide individualized treatments accordingly. Using real-time OCT images, we studied the pathomechanisms of melasma in 12 female patients and the effects of individualized treatments. Methods: Patients were divided into good and bad improved groups according to the improvement in hyperpigmentation at month 4. Results: In the bad improved group, all melanin or confetti melanin had significantly decreased at month 2 or month 4 while granular melanin ratio at month or month 4 significantly increased, the most parameters of dendritic-sharped cells (DCs) before and after treatment were not significantly different, the collagen area or collagen density at month 4 significantly decreased. In the good improved group, there was slightly low all melanin/confetti melanin at month 4 and high granular melanin at month 4 in comparison to the bad improved group. Moreover, most of the parameters in the DCs at month 4 significantly increased while most parameters in collagen at month 4 significantly decreased. Conclusions: OCT is useful in revealing the involved pathomechanisms of melasma in individualized patients. Positive treatment results can be achieved through individualized therapy regimen targeting the pathomechanisms.
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Paul, Christer, Henrik Green, Ingrid Jakobsen Falk, Kourosh Lotfi, Esbjorn Paul, Monika Hermansson, Richard Rosenquist, Kerstin Jonsson-Videsater, and Hareth Nahi. "Implications On Drug Resistance and Survival of ABCB1 Single Nucleotide Polymorphisms in Normal Karyotype De Novo AML." Blood 114, no. 22 (November 20, 2009): 2648. http://dx.doi.org/10.1182/blood.v114.22.2648.2648.
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Abstract Abstract 2648 Poster Board II-624 Background: Multidrug resistance and expression of the ATP-dependent drug transporting protein ABCB1 is a clinically relevant problem in the treatment of acute myeloid leukaemia. Several single nucleotide polymorphisms (SNPs) in the ABCB1 have been associated with altered P-glycoprotein expression and phenotype. These SNPs might influence the clinical outcome in AML and predict individual differences in response to therapy with ABCB1 substrates. Aims: To investigate the impact of the ABCB1 SNPs in exon 11, 12, 21 and 26 on treatment response, survival and in vitro drug sensitivity in AML patients. Methods: PCR and Pyrosequencing were used to determine the genotype of the SNPs G1199T/A, C1236T, A1308G, G2677T/A and C3435T in 100 de novo AML patients with normal karyotype treated at Linköping University Hospital or Karolinska University Hospital. Almost all patients were treated with one anthracycline and Ara-C during the induction regime. The affect of the genetic variants in ABCB1 on survival were analysed by Kaplan-Meier Log-rank tests and multivariant analysis by Cox regression. Patients receiving transplantation were censored at that point in the analysis. A Nordic reference material of 400 healthy volunteers of equal age and sex distribution was also included. NPM1 and FLT3-ITD mutations were determined by PCR. Leukemic cells were isolated and drug sensitivity was measured after 4 days culturing by a bioluminescence ATP-assay. Results: The survival of the AML patients was significantly correlated to the ABCB1 genotypes C1236T (P=0.02) and G2677T (P=0.02), with a borderline significance for G1199A (p=0.06). For the C1236T SNP the mean survival was 0.7, 1.3 and 1.8 years for the wild type, heterozygous and homozygous variants, respectively. The mean survival for patients with G/G, G/T and T/T genotype of SNP G2677T/A was 0.7, 1.2 and 1.7 years, respectively. Only the wild type of A1308T was found in the material and C3435T did not correlate to survival. Multivariate analysis showed that 1236T/T and 2677T/T were independent factors for survival (hazard ratio 0.24 and 0.22). Comparison of allele frequencies between AML patients and healthy volunteers showed no significant difference. In vitro testing showed that leukemic cells from patients carrying 1236T/T or 2677T/T were significantly more susceptible for mitoxantrone and borderline susceptible to daunorubicine and etoposide, substrates for Pgp but not to Ara-C. Conclusions: Our findings suggest that ABCB1 SNPs do not affect the development of the disease but the survival after chemotherapy possibly by impact on drug sensitivity. The correlation between ABCB1 genotype and the overall survival of AML patients might provide useful information for treatment strategies and individualized chemotherapy. Disclosures: Paul: Aprea AB: Consultancy, Research Funding.
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Lytvynenko, N. A., M. V. Pogrebna, Yu O. Senko, L. M. Protsyk, S. P. Korotchenko, and R. L. Liubevych. "Treatment of MDR-TB/HIV/CMV patients under individualized regimes of antimycobacterial therapy." Infusion & Chemotherapy, no. 4 (December 28, 2022): 52–58. http://dx.doi.org/10.32902/2663-0338-2022-4-52-58.
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BACKGROUND. Often in practice there are combinations of several diseases, or tuberculosis of the respiratory organs develops against the background of various comorbidities, including HIV.
OBJECTIVE. To demonstrate best clinical practices for selecting the optimal individualized treatment regimen (ITR) in a patient with multidrug-resistant tuberculosis (MDR-TB) associated with HIV in the setting of severe immunosuppression and complicated by poor tolerability.
MATERIALS AND METHODS. Presented clinical analysis of newly diagnosed generalized MDR-TB associated with HIV, treated for ITR for 9 months, which was assigned according to the World Health Organization step-by-step algorithm based on phenotypic drug susceptibility testing data. At the time of assessment, the patient was taking 273 doses of ITR. ITR required extended monitoring and selection during its first months of treatment, as it was accompanied by severe intolerance to antimycobacterial drugs.
RESULTS AND DISCUSSION. The expressed adverse events of 3-4 degrees were managed at the expense of carrying out the strengthened clinical and laboratory monitoring and consultations of narrow experts that allowed to select optimum ITR and in addition to carry out symptomatic treatment. Such tactics led to the normalization of hematological parameters with the disappearance of clinical manifestations of other adverse events and provided high intermediate results of treatment at the 9th month of ITR. Steady negativity of smear and culture (from1st month of treatment), positive radiological dynamics and significant improvement of well-being were obtained.
CONCLUSIONS. Management of patients with MDR-TB/HIV co-infection with severe immunosuppression in patients who are treated by ITR requires enhanced monitoring of adverse reactions and rapid changes in the composition of ITR and early symptomatic treatment to ensure better adherence to treatment and positive outcomes.
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Bucheeri, Mohamed Abdulla Ghuloom Abdulla, Marion Elligsen, Philip W. Lam, Nick Daneman, and Derek MacFadden. "A sepsis treatment algorithm to improve early antibiotic de-escalation while maintaining adequacy of coverage (Early-IDEAS): A prospective observational study." PLOS ONE 18, no. 12 (December 20, 2023): e0295908. http://dx.doi.org/10.1371/journal.pone.0295908.
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Background Empiric antibiotic treatment selection should provide adequate coverage for potential pathogens while minimizing unnecessary broad-spectrum antibiotic use. We sought to pilot a sepsis treatment algorithm to individualize antibiotic recommendations, and thereby improve early antibiotic de-escalation while maintaining adequacy of coverage (Early-IDEAS). Methods In this observational study, the Early-IDEAS decision support algorithm was derived from previous Gram- negative and Gram-positive prediction rules and models along with local guidelines, and then applied to prospectively identified consecutive adults within 24 hours of suspected sepsis. The primary outcome was the proportion of patients for whom de-escalation of the primary antibiotic regimen was recommended by the algorithm. Secondary outcomes included: (1) proportion of patients for whom escalation was recommended; (2) number of recommended de-escalation steps along a pre-specified antibiotic cascade; and (3) adequacy of therapy in patients with culture-confirmed infection. Results We screened 578 patients, of whom 107 eligible patients were included. The Early-IDEAS treatment recommendation was informed by Gram-negative models in 76 (71%) patients, Gram-positive rules in 64 (59.8%), and local guidelines in 27 (25.2%). Antibiotic de-escalation was recommended in almost half of all patients (n = 52, 48.6%), with a median of 2 steps down the a priori antibiotic treatment cascade. No treatment change was recommended in 45 patients (42.1%), and escalation was recommended in 10 (9.3%). Among the 17 patients with positive blood cultures, both the clinician prescribed regimen and the algorithm recommendation provided adequate coverage for the isolated pathogen in 12 patients (70.6%), (p = 1). Among the 25 patients with positive relevant, non-blood cultures, both the clinician prescribed regimen and the algorithm recommendation provided adequate coverage in 20 (80%), (p = 1). Conclusion An individualized decision support algorithm in early sepsis could lead to substantial antibiotic de-escalation without compromising adequate antibiotic coverage.
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Zhdanova, Elena, Olga Goncharova, Hayk Davtyan, Sevak Alaverdyan, Aelita Sargsyan, Anthony D. Harries, and Bolot Maykanaev. "9-12 months short treatment for patients with MDR-TB increases treatment success in Kyrgyzstan." Journal of Infection in Developing Countries 15, no. 09.1 (September 29, 2021): 66S—74S. http://dx.doi.org/10.3855/jidc.13757.
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Introduction: MDR/RR-TB is a growing problem in Kyrgyzstan. In 2005, the country introduced standard or individualized treatment for 20-24 months. Because of poor treatment outcomes, in 2017 a short treatment with strict eligibility criteria was introduced. The aim of this study was to compare characteristics and treatment outcomes of MDR/RR-TB patients receiving short (9-12 months) treatment in 2017 with those receiving standard or individualized (20-24 months) treatment in 2016/2017.
Methodology: A comparative cohort study using routine programmatic data. Characteristics, sputum culture conversion and treatment outcomes were compared between those on short treatment with those on standard/individualized treatment using the chi-square test, crude and adjusted risk ratios (RR and aRR).
Results: The study included 274, 82 and 132 patients on standard, individualized and short treatment, respectively. There were more females, fewer migrants/homeless and unemployed and more new TB patients on short treatment compared with the other two groups. A favorable outcome (cure and treatment completed) was significantly higher in short treatment patients (83%) compared with those on standard (50%) or individualized (59%) treatment (p < 0.001). There was higher 1-month sputum culture conversion with short treatment (35%) compared with the other two groups (19% and 24%, p < 0.05). Short treatment (aRR 1.6, 1.4-1.8), female gender (aRR 1.2, 1.1-1.4), not being homeless (aRR 12.9, 4.5-17.3) and having new TB (aRR 1.3, 1.0-1.5) were independently associated with a favorable outcome.
Conclusions: The treatment success was higher in selected MDR-TB patients given short treatment in Kyrgyzstan: this regimen should be scaled-up to all MDR-TB patients.
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Logan, Brent R., Rodney Sparapani, Robert E. McCulloch, and Purushottam W. Laud. "Decision making and uncertainty quantification for individualized treatments using Bayesian Additive Regression Trees." Statistical Methods in Medical Research 28, no. 4 (December 18, 2017): 1079–93. http://dx.doi.org/10.1177/0962280217746191.
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Individualized treatment rules can improve health outcomes by recognizing that patients may respond differently to treatment and assigning therapy with the most desirable predicted outcome for each individual. Flexible and efficient prediction models are desired as a basis for such individualized treatment rules to handle potentially complex interactions between patient factors and treatment. Modern Bayesian semiparametric and nonparametric regression models provide an attractive avenue in this regard as these allow natural posterior uncertainty quantification of patient specific treatment decisions as well as the population wide value of the prediction-based individualized treatment rule. In addition, via the use of such models, inference is also available for the value of the optimal individualized treatment rules. We propose such an approach and implement it using Bayesian Additive Regression Trees as this model has been shown to perform well in fitting nonparametric regression functions to continuous and binary responses, even with many covariates. It is also computationally efficient for use in practice. With Bayesian Additive Regression Trees, we investigate a treatment strategy which utilizes individualized predictions of patient outcomes from Bayesian Additive Regression Trees models. Posterior distributions of patient outcomes under each treatment are used to assign the treatment that maximizes the expected posterior utility. We also describe how to approximate such a treatment policy with a clinically interpretable individualized treatment rule, and quantify its expected outcome. The proposed method performs very well in extensive simulation studies in comparison with several existing methods. We illustrate the usage of the proposed method to identify an individualized choice of conditioning regimen for patients undergoing hematopoietic cell transplantation and quantify the value of this method of choice in relation to the optimal individualized treatment rule as well as non-individualized treatment strategies.
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Symonds, Lynn K., and Stacey A. Cohen. "Use of perioperative chemotherapy in colorectal cancer metastatic to the liver." Gastroenterology Report 7, no. 5 (August 21, 2019): 301–11. http://dx.doi.org/10.1093/gastro/goz035.
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Abstract A curative-intent approach may improve survival in carefully selected patients with oligometastatic colorectal cancer. Aggressive treatments are most frequently administered to patients with isolated liver metastasis, though they may be judiciously considered for other sites of metastasis. To be considered for curative intent with surgery, patients must have disease that can be definitively treated while leaving a sufficient functional liver remnant. Neoadjuvant chemotherapy may be used for upfront resectable disease as a test of tumor biology and/or for upfront unresectable disease to increase the likelihood of resectability (so-called ‘conversion’ chemotherapy). While conversion chemotherapy in this setting aims to improve survival, the choice of a regimen remains a complex and highly individualized decision. In this review, we discuss the role of RAS status, primary site, sidedness, and other clinical features that affect chemotherapy treatment selection as well as key factors of patients that guide individualized patient-treatment recommendations for colorectal-cancer patients being considered for definitive treatment with metastasectomy.
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Abidi, Syed, Jay Achar, Mourtala Mohamed Assao Neino, Didi Bang, Andrea Benedetti, Sarah Brode, Jonathon R. Campbell, et al. "Standardised shorter regimens versus individualised longer regimens for rifampin- or multidrug-resistant tuberculosis." European Respiratory Journal 55, no. 3 (December 20, 2019): 1901467. http://dx.doi.org/10.1183/13993003.01467-2019.
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We sought to compare the effectiveness of two World Health Organization (WHO)-recommended regimens for the treatment of rifampin- or multidrug-resistant (RR/MDR) tuberculosis (TB): a standardised regimen of 9–12 months (the “shorter regimen”) and individualised regimens of ≥20 months (“longer regimens”).We collected individual patient data from observational studies identified through systematic reviews and a public call for data. We included patients meeting WHO eligibility criteria for the shorter regimen: not previously treated with second-line drugs, and with fluoroquinolone- and second-line injectable agent-susceptible RR/MDR-TB. We used propensity score matched, mixed effects meta-regression to calculate adjusted odds ratios and adjusted risk differences (aRDs) for failure or relapse, death within 12 months of treatment initiation and loss to follow-up.We included 2625 out of 3378 (77.7%) individuals from nine studies of shorter regimens and 2717 out of 13 104 (20.7%) individuals from 53 studies of longer regimens. Treatment success was higher with the shorter regimen than with longer regimens (pooled proportions 80.0% versus 75.3%), due to less loss to follow-up with the former (aRD −0.15, 95% CI −0.17– −0.12). The risk difference for failure or relapse was slightly higher with the shorter regimen overall (aRD 0.02, 95% CI 0–0.05) and greater in magnitude with baseline resistance to pyrazinamide (aRD 0.12, 95% CI 0.07–0.16), prothionamide/ethionamide (aRD 0.07, 95% CI −0.01–0.16) or ethambutol (aRD 0.09, 95% CI 0.04–0.13).In patients meeting WHO criteria for its use, the standardised shorter regimen was associated with substantially less loss to follow-up during treatment compared with individualised longer regimens and with more failure or relapse in the presence of resistance to component medications. Our findings support the need to improve access to reliable drug susceptibility testing.
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Wajnrajch, M. P., J. Hey-Hadavi, and N. Rajicic. "P26 An individualized, target-driven treatment regimen for children with idiopathic short stature (ISS)." Growth Hormone & IGF Research 20 (January 2010): S49. http://dx.doi.org/10.1016/s1096-6374(10)70126-x.
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Skaarud, Kristin J., Marianne J. Hjermstad, Asta Bye, Marit B. Veierød, Anne M. Gudmundstuen, Knut E. A. Lundin, Sonia Distante, Lorentz Brinch, Geir E. Tjønnfjord, and Per O. Iversen. "No Effect of Individualized Nutrition on Quality of Life, Acute Graft-Versus-Host Disease or Oral Mucositis after Allogeneic Stem Cell Transplantation: A Randomized Controlled Trial." Blood 128, no. 22 (December 2, 2016): 2211. http://dx.doi.org/10.1182/blood.v128.22.2211.2211.
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Abstract Introduction: Patients with hematological cancers treated with allogeneic stem cell transplantation (allo-SCT) after myeloablative conditioning are at risk of malnutrition due to inadequate energy intake. This may cause or contribute to adverse outcomes. The best way to prevent and treat malnutrition and optimize nutritional status in these patients, remains unknown. We therefore conducted a randomized controlled trial to examine the effect of an individualized nutritional intervention to optimize energy intake, on quality of life (QoL), severe acute graft-versus-host disease (aGVHD) and severe oral mucositis 3 months after allo-SCT. Methods: One-hundred and seventy-one patients were eligible for the trial, of whom 117 (68%) agreed to participate and were randomized to either the intervention- (n=57) or control (n=60) group. As the primary outcome we determined QoL using the 2 item-global QoL/health of the European Organisation for Research and Treatment of Cancer Quality of Life Core Questionnaire-30. Secondary outcomes were (i) the prevalence of aGVHD grades 3 and 4 diagnosed according to the modified Glucksberg criteria; and (ii) the prevalence and (iii) the number of days with oral mucositis. The goal of the intervention was to supply a daily minimum of 30 kcal/kg body weight from the day the patients commenced the conditioning regime and until discharge. Oral intake was monitored daily during the entire hospital stay. In addition to regular food, the intervention group also received energy-dense and low-lactose oral supplements while in hospital. A nasojejunal tube was inserted within day 5 after allo-SCT. If the energy needs were not met orally or tube feeding was not tolerated, these patients received additional parenteral nutrition. Prior to discharge the intervention group received dietary advices to optimize their nutrient- and energy intake. In the control group oral intake was not monitored while hospitalized, tube feeding was not given and a standard amount of parenteral nutrition was administered only if necessary. Three months after allo-SCT energy intake per body weight was calculated for both study groups using one-day unweighted dietary records. The study was registered in Clinical Trials (NCT01181076). Results: Median age (n=117) at inclusion was 44 (range 18 - 65) years and 61% were males. The compliance with the intervention during hospital stay (median length 36 days, range 19-93 days) was high: The median energy intake in the intervention group was of 31.2 (14.4 - 42.9) kcal/kg corresponding to about 100% of the target of 30 kcal/kg. Three months after allo-SCT energy intake was available from 72 patients. The intervention group (n=36) had a median daily energy intake of 30.0 (7.7 - 65.0) kcal/kg, whereas the corresponding value was 26.7 (9.3-75.9) kcal/kg in the control group (n=36; p=0.84). A total of 88/117 (75%) patients were eligible for analysis of global QoL scores (40 in the intervention- and 48 in the control group) 3 months after allo-HSCT. The remaining 29 patients had either died (intervention group n= 9, control group n=5), relapsed (intervention group n=4, control group n=3), or had not returned the QoL questionnaire (intervention group n=4, control group n=4). The mean difference in global QoL between the intervention- and control group was not significant: 2.7 (95% CI -7.7 to 13.2; p=0.60; intervention group mean -11.7, SD 24.1; control group mean -14.4, SD 24.8). A total of 117 patients were included in the analyses of aGVHD and oral mucositis. Twenty patients were diagnosed with aGVHD grades 3 and 4 (intervention group n=8, control group n=12), yielding an odds ratio of 0.65 (95% CI 0.25 to1.74; p=0.39). Eighty-nine patients (intervention group n=43, control group n=46) were diagnosed with oral mucositis grades 3 and 4, yielding an odds ratio of 0.93 (95% CI 0.40 to 2.19; p=0.88). The mean difference in number of days with oral mucositis grades 3 and 4 between the intervention- and control group was not significant: -0.55 (95% CI -1.92 to 0.81; p=0.42). Conclusion: In this first randomized controlled trial testing an individually tailored nutritional intervention in patients undergoing allo-SCT, we found no significant difference in global quality of life, prevalence of acute graft-versus-host disease, or prevalence or duration of oral mucositis 3 months after allo-SCT with myeloablative conditioning. Disclosures No relevant conflicts of interest to declare.
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Delage, Gilles, Lucie Desautels, Sylvie Legault, Roger Lasalle, Jean-Guy Lapierre, André Lamarre, Pierre Masson, and Sheldon Spier. "Individualized Aminoglycoside Dosage Regimens in Patients with Cystic Fibrosis." Drug Intelligence & Clinical Pharmacy 22, no. 5 (May 1988): 386–89. http://dx.doi.org/10.1177/106002808802200504.
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Individualized dosage regimens have recently been recommended for patients treated with aminoglycoside antibiotics. We have developed a calculator-based program for our patients with cystic fibrosis and have studied 93 courses of intravenous aminoglycoside treatment, comparing predicted and measured values in 45 courses. Pharmacokinetic parameters differed notably among subjects: This was reflected by widely variable total daily aminglycoside dosage requirements. The mean daily dosage requirements (± SD) for tobramycin (62 treatment courses) was 13.0 ± 3.74 mg/kg, and for gentamicin (26 treatment courses) was 11.5 ± 2.6 mg/kg. The accuracy of the program was evaluated by its ability to predict peak and trough values in individuals: 84 percent of measured peaks were within 2 μg/ml of predicted peaks and 93 percent of trough levels were within 1 μg/ml of the predicted level. Nephrotoxicity was observed in one patient, ototoxicity in three. This program provides a simple, safe, and effective method of tailoring an aminoglycoside regimen to the patient's needs.
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Chen, Jiaying, David A. Solomon, Nancy Ann Oberheim Bush, Jennifer A. Grabowsky, Cassie Kline, Deanna L. Kroetz, Jennie W. Taylor, et al. "CTNI-49. PRECISION MEDICINE CLINICAL TRIAL FOR ADULT PATIENTS WITH RECURRENT GLIOBLASTOMA." Neuro-Oncology 26, Supplement_8 (November 1, 2024): viii107. http://dx.doi.org/10.1093/neuonc/noae165.0416.
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Abstract Salvage therapies for recurrent glioblastoma (rGBM) have limited efficacy, with median overall survival of 9 months (OS-9) and 6-month progression-free survival (PFS-6) of 10-25%. Given GBM’s molecular heterogeneity, targeting a single molecular abnormality in isolation has consistently failed as a strategy, and precision combination approaches are needed. An initial 15-patient cohort evaluated the feasibility and safety of treating patients with rGBM with an individualized treatment regimen; we added a second 15-patient expansion cohort to improve the power of preliminary efficacy assessment. Patients underwent clinically indicated surgery with genomic profiling using the UCSF500 targeted DNA sequencing panel. Each personalized treatment regimen combined up to 4 FDA-approved drugs, including one cytotoxic agent, as determined by consensus discussion at an individualized molecular tumor board for each patient. Bevacizumab was not utilized in these combinations. The primary objective of the combined 30-patient cohort was efficacy of individualized treatment regimens by OS-9; secondary objectives included safety and additional efficacy measures including PFS-6. Median age was 53 years (range 32-71). Of 30 patients, 18 were male, 23 were enrolled at first recurrence, 29 had IDH-wildtype glioblastoma, 1 had IDH-mutant astrocytoma, and 10 had MGMT promoter methylation. A total of 12 FDA-approved drugs were used in 18 combinations; the most common regimen prescribed was lomustine, afatinib, and abemaciclib (7; 23%,); second-most common was temozolomide, olaparib, and afatinib (4; 13%). OS-9 of the combined cohort was 70% (95% CI 0.55 – 0.89) and PFS-6 was 27% (95% CI 0.15 – 0.48), with median OS of 11.6 months (95% CI 9.7 – 16.7) and median PFS of 3.7 months (95% CI 2.0 – 5.5).While overall efficacy was modest, implementation of individualized treatment regimens in a timely fashion was safe and feasible for patients with surgically resectable rGBM. Analysis is ongoing to assess whether specific genomic profiles or treatment regimens were particularly efficacious.
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Yang, Yang, Jia Wei, Juan Du, Lixia Yu, Hanqing Qian, Yan Yang, Xiaoping Qian, and Baorui Liu. "Phase III study of individualized intraperitoneal/intravenous/oral chemotherapy compared with standard intravenous/oral chemotherapy in patients with advanced gastric cancer." Journal of Clinical Oncology 35, no. 15_suppl (May 20, 2017): 4021. http://dx.doi.org/10.1200/jco.2017.35.15_suppl.4021.
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4021 Background: Tumor mRNA expression levels may have a promising role as potential predictive biomarkers for chemotherapy. Intraperitoneal (IP) chemotherapy provides sustained high local concentrations, and its efficacy has been shown in ovarian cancer and gastric cancer patients with peritoneal metastasis. We developed a regimen combining IP/intravenous(IV)/oral chemotherapy for the treatment of advanced gastric cancer patients with individualized chemotherapeutics according to mRNA expression. This multicenter phase III study evaluated the efficacy of individualized multi-route chemotherapy compared to standard systemic chemotherapy. Methods: Eligibility criteria included pathologically confirmed advanced gastric adenocarcinoma, and no prior chemotherapy. Patients were randomized 3:1 to an individualized arm (IN) and standard arm (ST). Randomization was stratified by center. Patients in individualized arm first underwent mRNA expression (BRCA1/TOPO1/TS) to choose sensltive chemotherapeutics from oxaliplatin/cisplatin/docetaxel/irinotecan/S-1 and then received individualized IP/IV/oral chemotherapy. The primary endpoint was overall survival (OS). Secondary endpoints were response rate, progression-free survival (PFS), and safety. Results: Between April 2013 and December 2015, 231 patients were enrolled, and 218 patients were included in the efficacy analysis. Baseline patient characteristics were balanced between the two arms. The median OS for IN and ST were 16.3 and 14.1 months, respectively (adjusted hazard ratio [aHR] 0.77, 95% confidence interval [CI] 0.61-0.98, p < 0.05). The overall response rate was 44.0% in the IN arm, and 33.9% in the ST arm (p < 0.05). Both regimens were tolerable. Conclusions: The primary analysis showed the statistical superiority of the individualized multi-route regimen. It suggested clinical efficacy of this regimen in patients with advanced gastric cancer. Clinical trial information: ChiCTR-IPR-15006201.
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Weber, Simon A., Malte Pietzsch, Oriol Bestard, Josep M. Grinyo, Ondrej Viklicky, and Petra Reinke. "Investigating the health-economic profiles of biomarker-driven immunosuppresion (BIO-DrIM) following solid organ transplantation." Advances in Precision Medicine 1, no. 1 (March 17, 2016): 48. http://dx.doi.org/10.18063/apm.2016.01.004.
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Immunosuppression (IS) following solid organ transplantation is indicated to avoid rejection but puts a sig-nificant burden on patients and healthcare systems due to life-long medication dependency and associated costs. Or-gan-tolerance with low or no IS medication has been observed, and might be forecasted with the help of appropriate biomarkers. Individualized treatments raise the question whether benefits of individualization outweigh the costs of stratification. This article outlines the importance of early economic evaluation in the context of biomarker-guided IS and discusses challenges that an economic evaluation should address, using the BIO-DrIM project as a reference exam-ple. We report on design aspects and health-economic study integration into several newly designed biomarker trials. In these studies, health-economic endpoints were defined to measure benefits of individualization and to compare them to the costs associated with stratification. Key economic outcomes to be collected are resource consumption and patient quality of life. Test accuracy of the biomarker-stratification is critical for the clinical success and the health-economic viability of an individualized reduced IS regime. However, IS regimes are not well standardized, rendering comparator choice difficult. The multi-national character of the trials adds further complexity that needs to be addressed. Develop-ers of biomarker tests should stress the importance of integrating health-economic evaluations early into prod-uct-development.
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Barnabas, A., D. Joshi, J. O'Grady, N. Heaton, M. Heneghan, I. Carey, A. Suddle, and K. Agarwal. "175 LOW ACCELERATING DOSE INDIVIDUALISED DURATION TREATMENT REGIMEN FOR RECURENT HCV POST LIVER TRANSPLANTATION." Journal of Hepatology 56 (April 2012): S76. http://dx.doi.org/10.1016/s0168-8278(12)60188-3.
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Mitic, Gorana, Ljubica Povazan, and Aleksandar Lucic. "Treatment of pregnancy related venous thromboembolism." Medical review 62, no. 7-8 (2009): 346–51. http://dx.doi.org/10.2298/mpns0908346m.
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Introduction. Prevention and treatment of venous thromboembolism during pregnancy are complicated since the use of antithrombotic drugs carries a certain risk to the mother, the fetus or both. Coumarins cross the placental barrier and may be responsible for bleeding, teratogenicity and central nervous system abnormalities. The risk of embriopathy is particularly high between 6 and 12 weeks of gestation. Treatement. Heparin is the treatment of choice for thrombosis during pregnancy because it is entirely safe for the fetus, unlike oral anticoagulants. The frequency of heparin-induced thrombocytopenia and osteoporosis is significantly lower if LMWH is applied, so this heparin type is preferable to UFH during pregnancy. Treatment of women with VTE during pregnancy, especially those with thrombophilia, requires individualized dosing and duration of antithrombotic thrapy. Peripartal management. In order to avoid the peripartum anticoagulant heparin effect and possible bleeding, heparin should be discontinued prior to the delivery and reintroduced after the parturition. PROPHYLACTIC REGIMEn. Prophylactic antithrombotic regimen during subsequent pregnancies should also be individualized. The use of low molecular weight heparins is becoming more widespread. They have reliable pharmacokinetics, require less frequent injections than unfractionated heparin and carry a lower risk of treatment complications. LMW heparins are safe and effective and they are replacing UFH as the anticoagulant of choice during pregnancy. Both UFH and LMWH are not secreted into breast milk and can be safely given to nursing mothers. Warfarin does not induce an anticoagulant effect in the breast-fed infant, so it can be safely used in women who require postpartum anticoagulant therapy.
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Zaman, Forhad. "Journey of Tuberculosis Control in India: From then till now." Journal of Comprehensive Health 9, no. 1 (June 30, 2021): 5–10. http://dx.doi.org/10.53553/jch.v09i01.003.
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The history of Tuberculosis control in India dates back to 1951 with mass vaccination with BCG and it started as a National Programme in 1962. Radical changes in the form of DOTS were incorporated with the start of Revised National Tuberculosis Control Programme (RNTCP) in 1997. Since then, TB control efforts have witnessed many changes in the form of daily DOTS, Injection free regimen for both drug sensitive & drug resistant TB, moving from fixed Categories of treatment regimen to Individualized treatment regimen based on prior Universal Drug susceptibility testing. Flexibility has been incorporated in the programme to accommodate Private practitioners in the form of various incentives. Introduction of Active case finding strategy has helped in early diagnosis leading to prompt treatments. Engagement of Community and leaders from all sectors and various organizations has helped to reach all communities in this fight against TB. India hopes to End TB by 2025 with rechristening the programme to National TB Elimination Programme (NTEP) and bringing in the much needed changes & flexibilities in the programme.
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Clarke, Jennifer Leigh, David Solomon, Nancy Ann Oberheim Bush, Jennifer A. Grabowsky, Cassie Kline, Deanna L. Kroetz, Jennie Webster Taylor, et al. "Pilot trial treating recurrent GBM patients with precision medicine regimens." Journal of Clinical Oncology 39, no. 15_suppl (May 20, 2021): 2045. http://dx.doi.org/10.1200/jco.2021.39.15_suppl.2045.
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2045 Background: Recurrence of GBM after initial treatment with surgery, radiation, and chemotherapy is nearly universal. Salvage therapies have limited efficacy with median overall survival (OS) of approximately 9 months and 6-month-progression-free survival (PFS-6) of 10-25% for both targeted and traditional therapies. Given GBM’s molecular heterogeneity, targeting a single molecular abnormality in isolation has consistently failed as a strategy, and precision combination approaches are needed. Methods: The primary objective was to demonstrate the feasibility of implementing a personalized drug regimen for patients (pts) with surgically resectable recurrent GBM within 35 days of surgery. Secondary objectives included safety and efficacy. Eligible pts signed consent before surgery, and tumor tissue was analyzed using the CLIA-approved “UCSF500” next-generation sequencing panel with paired tumor/germline sequencing. A specialized genomic tumor board made individualized treatment recommendations incorporating sequencing results of the recurrent tumor and clinical history for each pt, using up to 4 FDA-approved drugs in combination (all drugs provided by study). Correlative studies will be reported separately. Results: 19 pts signed consent and 16 pts had surgery on trial, 1 with pathology showing treatment effect only. The remaining 15 pts were all genetically profiled and successfully started their individualized treatment within 35 days of surgery, meeting the primary feasibility endpoint. Conclusions: Implementation of an individualized treatment regimen was feasible in a timely fashion in surgically resectable recurrent GBM pts, with encouraging preliminary efficacy results. Further investigation is warranted, both to validate efficacy and to streamline this approach in larger pt populations. Clinical trial information: NCT03681028. [Table: see text]
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Teoh, Chia Wei, Kathleen Mary Gorman, Bryan Lynch, Timothy H. J. Goodship, Niamh Marie Dolan, Mary Waldron, Michael Riordan, and Atif Awan. "Clinical Relapses of Atypical HUS on Eculizumab: Clinical Gap for Monitoring and Individualised Therapy." Case Reports in Nephrology 2018 (2018): 1–4. http://dx.doi.org/10.1155/2018/2781789.
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Atypical hemolytic uremic syndrome (aHUS) is caused by dysregulation of the complement system. A humanised anti-C5 monoclonal antibody (eculizumab) is available for the treatment of aHUS. We present the first description of atypical HUS in a child with a coexistent diagnosis of a POL-III leukodystrophy. On standard eculizumab dosing regime, there was evidence of ongoing C5 cleavage and clinical relapses when immunologically challenged. Eculizumab is an effective therapy for aHUS, but the recommended doses may not be adequate for all patients, highlighting the need for ongoing efforts to develop a strategy for monitoring of treatment efficacy and potential individualisation of therapy.