Dose Modification Research Articles

Linezolid as a Treatment for Multidrug-resistant Tuberculosis: A Literature Review

Multidrug-resistant tuberculosis (MDR-TB) emerges when Mycobacterium tuberculosis develops resistance to both rifampicin and isoniazid, representing a significant threat that undermines global efforts to combat tuberculosis. The unfavorable prognosis of MDR-TB can be attributed to prolonged treatment duration, the utilization of multiple medications, and the adverse effects associated with drug therapy. This drug moved from Group C (third line) in 2016 and Group 5 (unclear efficacy) in 2011. This is a synthetic oxazolidinone antimicrobial drug and a non-selective mono oxidase inhibitor. Antimicrobials that are both vulnerable to and resistant to gram-positive bacteria can be effectively combatted by linezolid. This study investigates and appraises the utilization of linezolid as a therapeutic intervention in individuals afflicted with MDR-TB, while also scrutinizing the pharmacological attributes of the drug. We also discuss Linezolid’s safety, efficacy, and tolerability for treating MDR-TB. Linezolid medication should be utilized for most patients and is a part of more recent short-course regimens since it has been known to increase the success rate of treatment of DR-TB by increasing the conversion sputum rate. However, primarily hematologic and neurologic, linezolid toxicity is typically treatment-limiting yet should be monitored. Recent studies suggest that dose modification and intermittency can reduce linezolid toxicity. Also, using linezolid in the regimen potentially reduces the treatment duration, but it needs further research. Keywords: efficacy, linezolid, safety, MDR-TB, tolerability

Best Patient Care Practices for Administering PSMA-Targeted Radiopharmaceutical Therapy.

Optimal patient management protocols for metastatic castration-resistant prostate cancer (mCRPC) are poorly defined and even further complexified with new therapy approvals, such as radiopharmaceuticals. The prostate-specific membrane antigen (PSMA)-targeted agent 177Lu vipivotide tetraxetan ([177Lu]Lu-PSMA-617), approved after the phase III VISION study, presents physicians with additional aspects of patient management, including specific adverse event (AE) monitoring and management, as well as radiation safety. Drawing on our experience as VISION study investigators, here we provide guidance on best practices for delivering PSMA-targeted radiopharmaceutical therapy (RPT) to patients with mCRPC. After a comprehensive review of published evidence and guidelines on RPT management in prostate cancer, we identified educational gaps in managing the radiation safety and AEs associated with [177Lu]Lu-PSMA-617. Our results showed that providing sufficient education on AEs (e.g., fatigue and dry mouth) and radiation safety principles is key to effective delivery and management of patient expectations. Patient counseling by health care professionals, across disciplines, is a cornerstone of optimal patient management during PSMA-targeted RPT. Multidisciplinary collaboration is crucial, and physicians must adhere to radiation safety protocols and counsel patients on radiation safety considerations. Treatment with [177Lu]Lu-PSMA-617 is generally well tolerated; however, additional interventions may be required, such as dosing modification, medications, or transfusions. Urinary incontinence can be challenging in the context of radiation safety. Multidisciplinary collaboration between medical oncologists and nuclear medicine teams ensures that patients are monitored and managed safely and efficiently. In clinical practice, the benefit-to-risk ratio should always be evaluated on a case-by-case basis.

B-297 Tacrolimus Concentrations in Envarsus vs Prograf Patients: An Evaluation of the Clinical Impact of LC-MS/MS and Immunoassay Methods on Tacrolimus measurement

Abstract Background Tacrolimus is a calcineurin inhibitor used as part of an immunosuppressive regimen in kidney and liver transplant patients to prevent graft-versus-host disease (GvHD) and requires therapeutic drug monitoring due to its narrow therapeutic index. Tacrolimus levels are commonly measured using two different methodologies - immunoassay and liquid chromatography tandem mass spectrometry (LC-MS/MS). A global proficiency study to assess and compare the measurement of trough levels by these two methodologies noted a positive bias with the ARCHITECT immunoassay which is likely due to the presence of tacrolimus metabolites. The aim of our study is to assess the impact of two different formulations of tacrolimus on the accuracy of its analytical measurement. While differences between immunoassay and LC-MS/MS results have been evaluated for immediate-release tacrolimus (Prograf), it has yet to be characterized for extended-release formulations such as Envarsus. The discrepancy between immunoassay and LC-MS/MS has clinical implications, as dosage modifications are based on measured concentrations, analytical variation may cause intervals of subtherapeutic or supratherapeutic exposure, increasing the risk of graft rejection or toxicity. Methods Development of an LC-MS/MS method for the simultaneous quantification of tacrolimus and its major metabolite, desmethyl tacrolimus, was performed in whole blood. Traceable calibrators and quality control material for tacrolimus and specimens supplemented with desmethyl tacrolimus were used to determine accuracy and precision. Tacrolimus concentrations were measured by LC-MS/MS and ARCHITECT immunoassay methods in excess whole blood specimens from patients treated with either Prograf or Envarsus. Measurement biases between LC-MS/MS and immunoassay methodologies were determined for both formulations of tacrolimus. Results External calibration curves for both tacrolimus and desmethyl tacrolimus were linear (R2>0.995), and the analytical measurement range (AMR) for tacrolimus spanned from 1.1 - 31.6 ng/ml. Calibrator and Quality control (QC) biases were within 15% of their target values throughout the AMR and within-run imprecision was less than 10% (n=25) for all calibrators and QCs. Between-run imprecision for Low, Mid, and High QC levels over a period of 2 weeks (n=5 days) was less than 10%. Comparative bias of tacrolimus concentrations between immunoassay and LC-MS/MS was significantly lower (P value=0.0074) for Envarsus (n=20 specimens) relative to Prograf (n=32 specimens). Conclusions The differential bias between immunoassay and LC-MS/MS in the measurement of tacrolimus in patients dosed with immediate-release versus extended-release formulations suggests that their distinct pharmacokinetic profile may impact the accuracy of the measurement. Therefore, applying observed measurement biases from different assays derived from Prograf patients to Envarsus patients and vice versa may result in erroneous estimation of tacrolimus concentrations.

Synthesis of Activated Carbon from Banana Peel Biomass Using NaCl and Gamma Co-60 Irradiation

Abstract Indonesian Institute of Sciences (LIPI) stated that the potential for biomass resources in Indonesia is estimated at 49,810 MW originating from plants and waste in 2013 and of course it continues to grow, considering that the source of biomass is from nature. An example of biomass is banana peel. This banana peel can be used as activated carbon. Known from several journals that activated carbon can be applied in various ways such as being a hydrogen storage material, water purification, etc. There are three steps to synthesis activated carbon that divided into initial steps, the first is synthesis of activated carbon, which begins with drying banana peels and then cutting them, then drying them below the sun. Then it is carbonized at 400°C and immersed chemically activated with a salt activator, NaCl. The second step is combining or modifying activated carbon via gamma irradiation and the last step is characterization using BET to know surface area and FTIR to analyze the functional group. The result shows that as an effect of the modification of gamma irradiation doses by 10 kGy, 30 kGy and 50 kGy on activated carbon banana peel, the FTIR spectra increased markedly by the widening of the last stretch. Modification the banana peel with gamma irradiaton Co-60 is the surface area is increase than those without irradiation, but not significantly. It occurred due to the process of carbon degrade due to gamma irradiation of Co-60 can degrade cellulose structures.

A phase 2/3 study of romiplostim N01 in chemotherapy-induced thrombocytopenia (CIT).

217 Background: CIT causes dose reduction or delay of chemotherapy (chemo), bleeding, and platelet (PLT) transfusion. This phase 2/3 study aimed to assess the efficacy and safety of romiplostim N01 in CIT. Methods: This trial comprising Part A (open-label) and B (randomized double-blinded) recruited patients (pts) with solid tumors or lymphoma and with CIT. In Part A, pts with a PLT count ≤200×10 9 /L before the day of chemo were included. Romiplostim N01 was injected subcutaneously per week (QW) for a 3-week chemo cycle at 1 μg/kg (group 1) or 2 μg/kg (group 2) for pts with a PLT count 100~200×10 9 /L, and at 2 μg/kg (group 3) for pts with a PLT count <100×10 9 /L. Primary endpoint was proportion of responders on the last day of chemo cycle, defined as pts who had an increase in PLT count of ≥30×10 9 /L from baseline for pts with a PLT count 100~200×10 9 /L, and an increase in PLT count of ≥30×10 9 /L or a PLT count ≥100×10 9 /L for pts with a PLT count <100×10 9 /L. In Part B, pts with a PLT count 75~150×10 9 /L were included and randomized 2:1 to receive romiplostim N01 or placebo QW at 2 μg/kg on day 1, and at 1 μg/kg on day 8 and 15 for two chemo cycles. Primary endpoint was proportion of responders, defined as pts resuming two consecutive chemo cycles without thrombocytopenia-induced dose modification (dose reduction by ≥15% or delay by ≥4 days or discontinuation) and without a rescue therapy. Results: In Part A, 50 pts were included between Mar 12, 2021 and Jul 29, 2021. The proportions of responders were 66.7% (10/15) in group 1, 53.3% (8/15) in group 2, and 90.0% (18/20) in group 3. Between Nov 8, 2022 and Jan 15, 2024, 63 pts were randomized in Part B. The proportion of responders in the romiplostim N01 group was significantly higher than that in placebo group (68.3% vs 40.9%). The adjusted rate difference was 27.6% (95% confidence interval [CI]: 2.1%, 50.2%). Treatment-related adverse events (TRAEs) occurred in 17 (41.5%) and 12 (54.5%) pts in the romiplostim N01 and placebo groups, of whom 1 (2.4%) and 0 were ≥grade 3. The most frequent TRAEs were nausea (12.2% vs 0), vomiting (12.2% vs 0), and increased aspartate aminotransferase (9.8% vs 4.5%). No treatment-related hemorrhage or death occurred. In pool analysis, the proportion of responders was 73.3% and 40.9% in pts treated with romiplostim N01 and placebo, respectively. The rate difference was 32.4% (95% CI: 9.2%, 52.9%). Conclusions: Romiplostim N01 showed promising efficacy and manageable safety in patients with CIT. Clinical trial information: PartA:NCT05851027 ; PartB:NCT05554913 . Pool analysis of Part A (pts with PLT count ≥75×10 9 /L) and Part B (all pts). Romiplostim N01 Placebo Rate Difference Part A+B (n=75) Part B (n=22) Romiplostim N01 (Part A+B) vs Placebo Lowest PLT count in Cycle 1, ×10 9 /L 85±41 59±32 / Highest PLT count in Cycle 1, ×10 9 /L 226±101 132±45 / Proportion of responders who completed the first chemo cycle without rescue therapy and without thrombocytopenia-induced dose modification of the second chemo cycle 55 (73.3%) 9 (40.9%) 32.4% 95% CI 61.9~82.9% 20.7~63.6% 9.2~52.9%

Optimation of Adsorpsi and Desorpsi of Mn2+ Ions on Gel-GPTMS Silica (Glycidoxypropyltrimethoxysilane) Modified with Sulfonates

Silica gel is an adsorbent often used in chromatography columns as a resin or stationary phase. Silica gel has active groups on its surface in the form of silanol (-SiOH) and siloxane (-Si-O-Si-). The effectiveness of silica gel in absorbing heavy metal ions is very low, so modification is needed to increase the absorption capacity of silica gel to metal ions. The addition of sulfonate with the GPTMS linkage compound dose modification. Adsorption and desorption are two methods that can be used to separate manganese metal. This research aims to obtain the optimum desorption agent (NaCl and CaCl2) and the concentration of the AAS-characterised desorption agent. This study used the column method for the adsorption and desorption process. This study used the column method for the adsorption and desorption process. The column method is a technique used to separate certain substances from a mixture by utilizing the interaction between adsorbent and adsorbate. The results obtained optimum desorption agent CaCl2 where the weight desorbed 0.1168002 mg with a percent desorption of 92.3%, the optimum concentration of CaCl2 0.05 M where the weight desorbed 0.132264 mg with a percent desorption of 95% Adsorbent characterization was conducted with FTIR and XRF.

Understanding the Drivers of Inhaler Non-Adherence in Asthma and its Influence on Asthma Control

Background Asthma remains a significant global health concern, with adherence to inhaler therapy playing a crucial role in its management. Understanding demographic characteristics and adherence behaviours among asthma patients is essential for optimizing treatment outcomes. This study delves into the multifaceted factors associated with non-adherence to inhaler therapy among asthma patients in India, to enhance adherence and improve asthma management outcomes. MethodsA cross-sectional study was conducted among 195 asthma patients at Shaikh-UI-Hind Maulana Mahmood Hasan Medical College in Saharanpur, India. Asthma control was assessed using standardized criteria, and adherence to inhaler therapy was evaluated through self-reported questionnaires. Demographic variables including smoking habit, possession of health insurance, comorbidities, duration of asthma, and duration of inhaler use were also recorded.ResultsAnalysis of demographic characteristics revealed a higher prevalence of asthma among females, aged 18-45, and individuals from low-income rural families. Additionally, a substantial proportion of patients had comorbidities and had been diagnosed with asthma for more than five years. Asthma control levels indicated a concerning proportion of patients with poorly controlled asthma, highlighting challenges in achieving optimal management outcomes. Furthermore, significant challenges in adherence to inhaler medication regimens were observed, including medication dosage modification without medical guidance and barriers to proper device use.Conclusions This study reveals significant challenges in asthma control and inhaler adherence, particularly among females and low-income rural patients in India. The patient’s education are essential to address these issues and improve asthma management outcomes.

A Role of Artificial Intelligences in Drug Discovery and Drug Development – A Critical Review.

Artificial intelligence (AI) is lowering the period and cost of the medication research and discovery process Artificial Intelligence is a revolution of medical research in pharmaceutical companies. In a review article, we give a summary of the many artificial intelligence tools of machine learning (ML) and deep learning (DL) techniques that will be used in drug research and discovery in the future. AI techniques and tools are more specifically designed or better programmed to mimic the operations of the human brain. AI is frequently used in drug discovery for de novo drug creation, virtual screening, reaction prediction, and de novo protein design. In addition, the application of AI and techniques of AI. ML is a disease diagnosis, de novo drug design, drug prediction for diseases, and big data prediction using ANN, CNN, and SNN, as well as deep learning. Furthermore, the function, applications, and methods of AI. Technological hurdles also face the contemporary XAI, and “low level” molecular representations (such as SMILES strings) that are useful for machine learning and AI tools are ‘deep chem’ in drug development several cutting-edge methods referred to as Knowledge Base Systems (KBS). The AI-based nanorobots are drug discovery on creating implantable nanorobots for the targeted delivery of medications and genes, factors including sustained release, dose modification, and control release need to be taken into consideration. Finally recent development of ML and DL techniques and AI models are more useful in the drug development and drug discovery process.

Abstract C013: Racial disparities in Interpersonal Processes of Care (IPC) during early stage breast cancer chemotherapy: Associations with symptoms and the ability to receive dose-intensive chemotherapy

Abstract Purpose: Documented racial disparities exist in the dose intensity of early-stage breast cancer (ESBC) chemotherapy, partly due to chemotherapy symptom toxicity and subsequent dose modifications. Effective communication is crucial for early symptom mitigation. We explored the associations between racial differences in patient-clinician communication, symptom experience, and the ability to receive the full dose of ESBC chemotherapy. Methods - A descriptive, correlational design compared clinician communication, symptoms, and the ability to obtain dose-intensive ESBC chemotherapy by race. Multi-site - large, urban breast cancer outpatient clinics. Patients completed the 18-item Interpersonal Processes of Care (IPC) and 13-item Symptom Distress Scale (SDS) at baseline and each chemotherapy visit. The IPC assesses clarity of communication, elicitation of concerns, explaining results, shared decision-making, compassion, discrimination due to race/ethnicity, and disrespectful office staff. Mean scores for IPC and SDS were calculated for each visit, and average scores across all visits were created for each participant; chemotherapy dose intensity - Receiving 85% or more of the prescribed chemotherapy within the projected timeline, dichotomized to yes or no—Analysis - IBM® SPSS®, version 27. Descriptive statistics were generated for raw data. Pearson’s correlations were used to examine bivariate associations and univariate and multivariate logistic or linear regression models to explore associations further. Results – N = 216 women, 37% - Black and 63% - White. The mean age was 52.99 ± 12.31 years. IPC - Black patients reported significantly higher (worse) IPC scores for "lack of clarity," "discrimination," and "disrespectful office staff" compared to White patients (all ps ≤ 0.01). Associations of SDS and IPC - Patients with higher IPC subscale scores for "lack of clarity," "discrimination," and "disrespectful office staff," and lower scores for "compassion and respect" experienced significantly higher levels of symptom distress (all ps < 0.05). Associations between IPC and Dose Intensity - Patients reporting higher (worse) discrimination scores were less likely to receive 85% of the prescribed chemotherapy. The IPC "discrimination" subdomain score was significantly associated with chemotherapy dose intensity (χ2(1)=6.910, p=0.009). Each one-unit increase in perceived "discrimination" subdomain score increased the likelihood of not receiving prescribed chemotherapy (B=0.985, OR=2.602, p=0.014) by approximately 160.2%. Conclusions - Black patients perceive poorer quality IPC than White patients during ESBC chemotherapy. Specific subdomains of IPC are associated with worse symptom distress and the inability to receive the full dose of ESBC chemotherapy, primarily driven by perceived discrimination. We must understand the relationship between race, communication, symptoms, and the ability to receive appropriate chemotherapy dose intensity. Citation Format: Margaret Q. Rosenzweig, Hiba Q. Abujaradeh. Racial disparities in Interpersonal Processes of Care (IPC) during early stage breast cancer chemotherapy: Associations with symptoms and the ability to receive dose-intensive chemotherapy [abstract]. In: Proceedings of the 17th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2024 Sep 21-24; Los Angeles, CA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2024;33(9 Suppl):Abstract nr C013.

Protocol-Stipulated Dose Modification to Manage Chemotherapy-Induced Peripheral Neuropathy in Children, Adolescents, and Young Adults With High-Risk Hodgkin Lymphoma.

Brentuximab vedotin (BV) incorporation into frontline chemotherapy regimens improved outcomes for classic Hodgkin lymphoma (cHL). The shared mechanism of action of BV and vinca alkaloids as microtubulin inhibitors increased the potential risk of chemotherapy-induced peripheral neuropathy (CIPN). Rates of CIPN and use of protocol-stipulated dose modifications of a microtubulin inhibitor were examined on the Children's Oncology Group AHOD1331 study, which compared BV, doxorubicin, vincristine (VCR), etoposide, prednisone, cyclophosphamide (BV-AVE-PC; BV arm) with bleomycin containing doxorubicin, bleomycin, vincristine, etoposide, prednisone, cyclophosphamide (ABVE-PC; standard arm) in patients with high-risk cHL ages 2-21 years. AHOD1331 required clinician grading and reporting of ≥grade 2 CIPN. Protocol-stipulated dose modifications of VCR preceded modification of BV for ≥grade 2 CIPN in the BV arm, but only required modification of VCR for ≥grade 3 in the standard arm. Outcomes included CIPN rates, dose modification of microtubulin inhibitors by study arm, clinical factors associated with dose modifications, and event-free survival (EFS) by the presence of dose modification. Among the 582 patients who began protocol therapy, 112 developed ≥grade 2 CIPN. Cumulative incidence of CIPN did not differ by study arm (19.2 v 19.8%, P = .91). CIPN dose modifications occurred more frequently in the BV arm (9.5% v 2.8%, P = .001); however, most patients with CIPN on the BV arm received full-dose BV. EFS did not differ by the presence of dose modifications after accounting for study arm, age, sex, and stage, although older age was significantly associated with the risk of VCR dose modifications for CIPN. A staged dose modification plan for vinca alkaloids and BV as administered in AHOD1331 minimized the effect of incorporating a second microtubulin inhibitor on CIPN without compromising treatment efficacy in the BV arm.

Evaluation of voriconazole therapeutic drug monitoring in malignant hematology patients.

Malignant hematology (MH) patients are susceptible to invasive fungal infections due to prolonged neutropenia and immunosuppressive therapies, which may require voriconazole therapy. Although voriconazole therapeutic drug monitoring (TDM) is common, evidence describing this practice is limited. The primary objective of this study was to describe the current practice of voriconazole TDM in MH patients at the Princess Margaret Cancer Centre (PM). A retrospective chart review was conducted for MH inpatients initiated on voriconazole at PM between November 1st, 2019 and November 13th, 2020. Data regarding voriconazole doses, levels, dose changes, and adverse effects were collected. The primary endpoint was the proportion of patients with initial voriconazole levels within therapeutic range (1-5 mg/L). Fifty-six patients were included in the study. The most common reason for starting voriconazole was possible invasive fungal infection (44 patients, 78.6%). Fifty-one patients (91.1%) received a loading dose of voriconazole, averaging 386.5 ± 78.5 mg. The average maintenance dose was 242.1 ± 45.7 mg. An average of 2.6 ± 2.9 levels were drawn per patient with an average level of 3.2 ± 2.4 mg/L. Forty-one patients (73.2%) had an initial voriconazole level within therapeutic range and 90 out of 145 total levels (62.1%) were within therapeutic range. There were 52 dose modifications made; 31 (60.8%) doses adjusted, 12 (23.5%) doses held, and 9 (17.6%) doses discontinued. For the 31 dose adjustments, 26 (83.9%) had a level redrawn and 17 (65.4%) of those levels were within therapeutic range. Twenty-three (41.1%) patients developed adverse effects, 8 (34.8%) of which were associated with supratherapeutic levels. Of these 23 patients, 19 (33.9%) experienced transaminitis, 3 (5.4%) experienced both transaminitis and neurotoxicity, and 1 (1.8%) experienced photopsia. Overall, 41 (73.2%) patients achieved an initial voriconazole level within therapeutic range. Of these 41 patients, 30 (73.2%) remained within therapeutic range for the duration of their inpatient voriconazole therapy. These findings suggest that the current practice of voriconazole TDM at our institution is yielding largely positive results, but still has room for improvement.

Evaluation of the Potential for Cytochrome P450 and Transporter-Mediated Drug-Drug Interactions for Firsocostat, a Liver-Targeted Inhibitor of Acetyl-CoA Carboxylase.

Firsocostat is an oral, liver-targeted inhibitor of acetyl-CoA carboxylase in clinical development for the treatment of metabolic dysfunction-associated steatohepatitis. This work evaluated the potential drug-drug interactions (DDIs) of firsocostat as a victim and as a perpetrator, to inform concomitant medication use. In this phase I study, healthy participants (n=13-30 in each of four cohorts) received firsocostat alone or in combination with either victims or perpetrators of cytochrome P450 (CYP) enzymes and drug transporters to evaluate firsocostat as both a victim and perpetrator of DDIs, respectively. Overall, 80 participants completed the study. As a victim of DDI, firsocostat plasma exposure (area under the plasma concentration-time curve [AUC] from 0 to infinity [AUC∝]) was 19-fold, 22-fold, 63%, and 38% higher when administered with single-dose rifampin 600 mg (organic anion transporting polypeptide [OATP] 1B1/B3 inhibitor), single-dose cyclosporine A 600 mg (OATP/P-glycoprotein/CYP3A inhibitor), multiple-dose probenecid 500 mg twice daily (evaluated as a uridine diphosphate glucuronosyltransferase [UGT] inhibitor), and multiple-dose voriconazole 200 mg twice daily (CYP3A inhibitor), respectively, compared with the administration of firsocostat alone. As a perpetrator of DDI, multiple-dose administration of firsocostat did not affect the exposure of midazolam 2 mg (CYP3A substrate) or drospirenone/ethinylestradiol 3 mg/0.02 mg (combined oral contraceptive). Study treatments were well-tolerated and all adverse events were mild. Firsocostat can be administered with CYP3A and UGT inhibitors without dose adjustment. However, firsocostat should not be coadministered with strong OATP1B/3 inhibitors, such as rifampin and cyclosporine A. Firsocostat can be administered with CYP3A substrates or combined oral contraceptives without dose modification.

To study the efficacy of romiplostim in chemotherapy-induced thrombocytopenia in head and neck cancer patients

Objectives Scheduled delivery of adequate dose of chemotherapy is important to replicate the results expected from original trials. In head and neck malignancies, undue delay of chemotherapy is likely to be associated with poor control or progression. Chemotherapy-induced thrombocytopenia (CIT) is one of the reasons to delay chemotherapy. Thrombopoietin agonists (TPO-A) have been found to increase platelet counts by increasing production and mobilization of platelets. Romiplostim is a TPO agonist, studied widely and found to have good impact on prevention and treatment of CIT. The purpose of this study was to analyze the use and effect of romiplostim in CIT in locally advanced head and neck cancer patients. Material and Methods It is a retrospective study regarding practices of romiplostim use in controlling CIT, among patients of locally advanced head and neck carcinoma undergoing induction chemotherapy at a tertiary care cancer center. Data regarding delays in chemotherapy, response assessment, and modification of chemotherapy doses were also noted. Results Out of a total of 110 patients of head and neck malignancy enrolled during the study period, 18 patients received romiplostim support at least once in chemotherapy cycles and were analyzed. All patients were locally advanced and planned for induction chemotherapy. Median platelet counts before starting romiplostim was 76,000 per cumm. A median delay of ten days was noted among these cases where romiplostim was introduced after the first cycle of chemotherapy. Patient receiving romiplostim after the second cycle (n = 6) showed a median delay of 11.5 days (6–18 days) in the initiation of subsequent chemotherapy. None of them was shifted out of chemotherapy plan due to low platelet count. No dose reduction was noted in any of the cases. Conclusion This study provides a good insight about feasibility of using romiplostim in this subset of patients without delay, dose reduction, or discontinuation of chemotherapy.

Tuberculosis in kidney transplant candidates and recipients.

Tuberculosis (TB) is the leading cause of infectious mortality and morbidity in the world, second only to coronavirus disease 2019. Patients with chronic kidney disease and kidney transplant recipients are at a higher risk of developing TB than the general population. Active TB is difficult to diagnose in this population due to close mimics. All transplant candidates should be screened for latent TB infection and given TB prophylaxis. Patients who develop active TB pre- or post-transplantation should receive multidrug combination therapy of antitubercular therapy for the recommended duration with optimal dose modification as per glomerular filtration rate.

New findings on the incidence and management of CNS adverse reactions in ALK-positive NSCLC with lorlatinib treatment

To explore the presentation and control of CNS adverse reactions in patients with ALK-positive NSCLC treated with lorlatinib. This study includes a retrospective case report from Sir Run Run Shaw Hospital on a lorlatinib-treated patient with CNS adverse reactions and a systematic literature review of similar cases until January 2023. The report detailed a case of a 74-year-old male with Grade III CNS adverse reactions 25 days after starting lorlatinib, which were reversible with dose modification and pharmacotherapy. The review indicated a 19.39% occurrence rate of such reactions, with a 17% improvement rate post-dose adjustment. CNS adverse reactions frequently occur in ALK-positive NSCLC patients on lorlatinib, yet they are reversible with appropriate management. Research should continue to optimize treatment protocols to decrease these reactions' frequency.

Resistance Training and Nutritional Supplementation in Older Adults with Sarcopenia after Acute Disease: A Feasibility Study.

Resistance exercise and protein supplementation are recognized as effective treatment strategies for age-related sarcopenia; however, there are limited data on their feasibility, tolerability, and safety. The primary outcome of this study was feasibility, evaluated through the 15-item TELOS (Technological, Economics, Legal, Operational, and Scheduling) feasibility components and by recruitment, retention, and consent rates. Tolerability was measured by examining permanent treatment discontinuation, treatment interruption, exercise dose modification, early termination, rescheduling of missed sessions, losses to follow-up, attendance, and nutritional compliance. Safety was evaluated using the parameters provided by the European Medicines Agency, adapted for exercise interventions. Thirty-two subjects were recruited (average age 81.6 [SD 9.3] years). The TELOS components were assessed before the intervention; out of 15 questions relevant for successful implementation, 4 operational needs answers required specific actions to prevent potential barriers. The recruitment rate was 74%. Eleven patients (34.4%) had permanent treatment interruption (retention rate = 65.6%). Patients attended a mean of 23 (SD 12.0) exercise sessions, with a mean of 56 (SD 32.6) nutritional compliances. A total of 21 patients (65.6%) experienced adverse events unrelated to the intervention, while 7 patients (21.9%) presented adverse reactions to strength exercise. The main barriers to feasibility were operational components and recruitment challenges. Although the intervention was generally safe, the high rate of probable adverse effects, unrelated to the intervention but associated with the individual's baseline health condition, may affect adherence to treatment programs of this kind.

Cancer Trial Eligibility and Therapy Modifications for Individuals With Duffy Null–Associated Neutrophil Count

Absolute neutrophil counts (ANCs) are used to determine cancer clinical trial (CCT) eligibility and systemic anticancer therapy (SACT) dose modifications. Duffy null-associated ANC (DANC) is a nonpathologic phenotype associated with lower ANC and most frequently seen in individuals with African and Middle Eastern ancestry. It is unclear whether CCTs exclude or SACT regimens modify doses for individuals with ANC within the DANC reference range. To investigate CCT exclusions and SACT dose modifications for ANC within the DANC reference range. This cross-sectional study of contemporary CCTs and SACT regimens included adult, interventional, phase 3 CCTs for the 5 most prevalent cancers in the US and United Kingdom (prostate, breast, melanoma, colorectal, and lung cancers) testing SACTs with start dates between November 1, 2021, and November 1, 2023, and that were registered on ClinicalTrials.gov. Preferred curative-intent SACT regimens were listed in National Comprehensive Cancer Network guidelines. Cancer clinical trial exclusions and SACT regimen modifications. Proportions of CCTs that exclude and SACT regimens that modify doses for individuals with an ANC within the DANC reference range. For CCTs, 289 of 382 trials (75.7%) were eligible, of which 221 (76.5% [95% CI, 71.1%-81.2%]) excluded patients with ANC values within the DANC reference range. Colorectal CCTs had the highest (38 of 44 [86.4% (95% CI, 72.6%-94.8%)]) and prostate CCTs had the lowest (11 of 23 [47.8% (95% CI, 26.8%-69.4%)]) proportions of exclusions. Of CCTs testing cytotoxic chemotherapy, 116 of 142 (81.7% [95% CI, 74.3%-87.7%]) had exclusions; 93 of 123 (75.6% [95% CI, 67.0%-82.9%]) CCTs testing targeted therapies alone and 12 of 24 (50.0% [95% CI, 29.1%-70.9%]) testing hormonal therapies alone had exclusions. Among the 113 US- and UK-based trials, exclusions were present in 89 (78.8% [95% CI, 70.1%-85.9%]). Of 71 SACT regimens, 38 (53.5% [95% CI, 41.3%-65.5%]) included dose modifications for ANC values within the DANC reference range. Lung cancer regimens had the highest (23 of 31 [74.2% (95% CI, 55.4%-88.1%)]) and prostate cancer had the lowest (0 of 12 [0 (95% CI, 0%-26.4%)]) proportions of modifications. Regimens including chemotherapy had modifications in 32 of 44 (72.7% [95% CI, 57.2%-85.0%]); 11 of 20 (55.0% [95% CI, 31.5%-76.9%]) of targeted therapy regimens and 0 of 16 (0% [95% CI, 0%-20.6%]) of hormonal therapy regimens had modifications. Among regimens including chemotherapy and/or targeted therapy, modifications were present in 38 of 55 (69.1% [95% CI, 49.7%-73.2%]). In this cross-sectional study, substantial proportions of CCTs excluded and SACT regimens modified doses for patients with ANCs in the DANC reference range. These practices structurally discriminate against patients of African and Middle Eastern ancestry. While determining optimal SACT dose modifications requires further study, CCT exclusion criteria should be revised.

Effects of Clinical Pharmacist Intervention in a Saudi ICU: A Prospective, Cross-Sectional Study

Given their contributions to better patient outcomes, medication safety, and lower drug cost, critical care pharmacists are especially prepared to play a major role within the critical care interdisciplinary team in managing the therapeutic element. Consequently, this research set out to evaluate the ICU clinical pharmacist interventions' frequency, kind, and effect, as well as the acceptability of these interventions by the doctors who provide them. The research was prospective and cross-sectional in nature. Over the course of six months, from April 1, 2023, to October 1, 2023, data was collected daily from a minimum of 380 interventions. This research covered all patients hospitalized to the intensive care unit at Saudi Arabia throughout the specified time frame. Over the duration of the 6-month trial, 120 patients had a total of 500 interventions. Of these, 490 (98%) had physician approval for clinical pharmacist treatments. The majority of the recommendations (34.8%, or 174 out of 500) were related to safety concerns; among these, 48.27%, or 48 out of 174, were for medication cessation owing to extended duration, while 30.46%, or 53 out of 174, were for renal dosage modification. Coming up as a close second, another therapeutic intervention involving indication made up 22.8% (114/500). A total of 124 interventions, or 24.8 percent of the total, had some kind of cost-related component, according to the study's findings on cost-saving treatments. The results of this research showed that clinical pharmacists have the potential to improve quality treatment for critically ill patients and lower healthcare expenditures. Furthermore, it provides helpful information on the incorporation of clinical pharmacists in intensive care units, particularly in areas with limited resources.

Real world data of cabozantinib in patients with hepatocellular carcinoma: Focusing on dose setting and modification.

To investigate the outcomes of cabozantinib in patients with unresectable hepatocellular carcinoma (uHCC), focusing on dose setting and modification. We retrospectively analyzed 34 Japanese patients who received cabozantinib for uHCC. Trough concentrations (Ctrough) of cabozantinib were also measured weekly for 6 weeks in the 18 patients. Sixteen patients received ≥40 mg (high-dose group), and 18 patients received 20 mg (low-dose group). Dose escalations were performed in 27.8% of the patients in the low-dose group. Although median duration of the first dose reduction or interruption in the low-dose group was twice that in the high-dose group (28 vs. 14 days, p < 0.001), there were no significant differences in the relative dose intensity (RDI) during 6 weeks, progression free survival (PFS), and overall survival (p = 0.162, p = 0.950, p = 0.817, respectively) between the two groups. Patients who received RDI during 6 weeks ≥33.4% showed a trend toward longer median PFS (p = 0.054). Each serum aldolase value during the 6 weeks was significantly correlated with the Ctrough at any point (r = 0.500, p < 0.001). In multivariate analyses, aldolase ≥8.7 U/L within 2 weeks was significantly associated with the very early dose reduction or interruption (odds ratio 20.0, p = 0.002). An initial dose of 20 mg cabozantinib could be a safe option in Japanese patients. The serum aldolase value could be useful for making appropriate dose modifications of cabozantinib.

Prevalence of Potential Drug Interactions With Direct-Acting Antivirals for COVID-19 Among Hospitalized Patients

PurposeClinicians consider polypharmacy, comorbidities, and other factors including the potential for drug-drug interactions (DDIs) when evaluating therapeutic options for specific clinical diagnoses. Contemporary treatment for coronavirus disease 2019 (COVID-19) includes direct-acting antivirals (DAAs). We sought to characterize patients’ characteristics, comorbidities, and medications received during their hospitalization for COVID-19 and quantify potential DDIs that clinicians consider in selecting appropriate DAAs. MethodsPatients hospitalized with a primary diagnosis of COVID-19 between May 2020 and December 2022 from the PINC AI Healthcare Database were identified. Medications administered during the hospitalization with the potential to cause DDIs with nirmatrelvir/ritonavir, remdesivir, or molnupiravir (per the Emergency Use Authorization factsheet or package insert) were assessed. For DDIs with nirmatrelvir/ritonavir, medications are categorized as “Contraindicated,” “Avoid Concomitant Use,” or “Other DDIs” (includes recommendation for dose modification or clinical and laboratory monitoring). For remdesivir, coadministration with chloroquine phosphate and hydroxychloroquine sulfate was not recommended. For molnupiravir, no drugs are listed as having potential DDIs. In a subset of patients, a multivariable logistic regression model was used to examine the association between documented patient/hospital characteristics and the likelihood of being “Contraindicated” to receive nirmatrelvir/ritonavir. FindingsOf the 788,238 patients hospitalized for COVID-19 in 920 hospitals, 53% were ≥ 65 years old, and 31% had Charlson Comorbidity Index (CCI) ≥ 3. During the study period, about half of the patients received medications categorized as “Contraindicated” (11%) and/or “Avoid Concomitant Use” (41%) with nirmatrelvir/ritonavir. The frequency of administered drugs was higher in those aged ≥ 65 years (68%), CCI ≥ 3 (78%), with high-risk underlying conditions (55%). About 1% of patients received medications that were not recommended to be coadmistered with remdesivir. Among a subset of patients hospitalized for COVID-19 in 2022, those who were older, had higher CCI, high-risk underlying conditions, severe hepatic impairment, Medicare insurance, and hospitalized in larger hospitals were significantly more likely to be categorized as “Contraindicated” when considering nirmatrelvir/ritonavir as a therapeutic option to manage COVID-19. ImplicationsA significant proportion of patients hospitalized for COVID-19 receive medications for other conditions that have the potential to result in DDIs with DAAs; most predominantly with nirmatrelvir/ritonavir, a strong CYP3A enzyme inhibitor, fewer with remdesivir, and none with molnupiravir. Higher age and comorbidity burden were significantly associated with a higher likelihood of receiving medications that are “Contraindicated” with nirmatrelvir/ritonavir. In the evolving COVID-19 era, these findings provide insights into patients hospitalized for COVID-19, and the polypharmacy evaluations that clinicians may encounter when selecting among DAAs to manage COVID-19.