Treatment Schedule Research Articles

The Effectiveness of Budesonide Once Daily as Maintenance Treatment of Eosinophilic Esophagitis.

Swallowed topical corticosteroids (STC) are an effective first-line therapy for patients with eosinophilic esophagitis (EoE), both for induction and maintenance of remission. All interventional trials with STC used twice-daily dosing regimens. However, in other inflammatory gastrointestinal disorders, corticosteroids are given once daily (OD) with equal outcomes and improved compliance. To evaluate the effectiveness of topical budesonide maintenance treatment in a once-daily dosing schedule. Retrospective analysis of confirmed patients with EoE, treated with topical budesonide as maintenance therapy OD, with adequate follow-up available. Patients currently treated with budesonide were contacted to fill out online questionnaires regarding symptoms and health-related quality of life (HRQOL). The primary end point was histologic remission, defined as peak eosinophil count (PEC) <15 eosinophils per high power field (HPF) after >12 weeks of budesonide OD. We included 29 patients on STC OD (1mg, N=28; 0.5mg, N=1), either budesonide orodispersible tablet (BOT, Jorveza, Dr. Falk Pharma; N=12) or budesonide viscous solution (BVS; N=17). After a median follow-up of 767 days on OD dosing (range: 103 to 2396), 86% of patients were in histologic remission. Four patients had histologic disease activity, of which one was treated with BOT. Two patients experienced a slight increase in PEC after dose reduction of BVS to OD (to PEC of 25 and 35/HPF, respectively). However, after switching the formulation to BOT OD they achieved histologic remission. In this retrospective study, we demonstrated favorable results in the majority of patients treated with budesonide 1mg OD as maintenance treatment for eosinophilic esophagitis.

Lipid-Lowering Efficiency and Safety of Alirocumab 300 mg Using a 2-mL Autoinjector Device in Real-World Practice: The MARS Study.

Alirocumab is a fully human monoclonal antibody to proprotein convertase subtilisin kexin type 9 used for the reduction of low-density lipoprotein cholesterol (LDL-C) in high-risk patients not reaching their LDL-C target. Recently, a 2-mL prefilled autoinjector has been developed to support the monthly 300-mg dosing regimen with a single-injection administration. Monthly application of 300 mg AlirRocumab (Praluent®) using the 2-mL SYDNEY Device (MARS) is a non-interventional, open, prospective, multi-center cohort study conducted in Germany between 2021 and 2023 with an observational period of 12 weeks. Patients included had primary hypercholesterolemia (heterozygous familial or non-familial) or mixed dyslipidemia and confirmed vascular disease and other risk factors or confirmed familial heterozygous hypercholesterolemia. Primary objectives were to assess the effectiveness of the 2-mL SYDNEY autoinjector measured by the lipid-lowering effect of alirocumab and to document therapy satisfaction, patient adherence, and persistence. Secondary objectives were to assess safety (adverse events) and tolerability. A total of 146 patients were analyzed: 110 (75.3%) patients were proprotein convertase subtilisin kexin type 9 inhibitor naïve and 36 (24.7%) were pre-treated with a proprotein convertase subtilisin kexin type 9 inhibitor. Patient mean age was 65.6 years with a preponderance of male gender (59.6%). At 12 weeks, the LDL-C value had decreased by a median of 59.5 mg/dL (1.5 mmol/L) in naïve patients (median relative decrease: -52.0%). In the pre-treated group, the LDL-C value remained mainly unchanged (median slight numerical relative increase: 1.6%). Treatment satisfaction was rated similarly in both groups with most patients being satisfied/very satisfied and rating the injection as effective, safe, and easy to handle. Twenty-three adverse events in 13 patients (8.0%) were documented. Three patients experienced one serious adverse event each; for five patients, an adverse drug reaction was observed, although none was serious. The occurrence of adverse events was similar in both groups. Alirocumab 300 mg administered with the 2-mL SYDNEY autoinjector was safe and effective in lowering LDL-C after 12 weeks in a routine clinical setting in Germany. The treatment schedule was perceived to be beneficial with excellent device acceptance and satisfaction, potentially increasing patient adherence. Clinicaltrials.gov: NCT05129241.

Computed tomography-based nomogram for estimating progression-free survival probability in bladder cancer patients undergoing partial cystectomy.

To establish a prognostic model to estimate progression-free survival (PFS) probability in bladder cancer (BCa) patients undergoing partial cystectomy. Consecutive patients who underwent partial cystectomy between August 2012 and April 2021 were enrolled. The primary endpoint was PFS during the follow-up. The following features were assessed: tumor location, amount, size, tortuous blood vessels around or within the lesions, perivesical fat stranding, stalk, computed tomography (CT) enhancement, calcification, cystic degeneration, CT reported lymph nodes status, and presence of hydronephrosis. Univariate Cox regression and LASSO regression, followed by backward stepwise multivariable Cox, were used to construct the nomogram. A total of 106 patients were enrolled. Gender, histology, tortuous blood vessels, and perivesical fat stranding were used to fit the nomogram. The overall Harrell's concordance index (C-index) was 0.752. The area under the receiver operator characteristic curves (AUC) at 1-year, 2-year and 3-year were 0.733, 0.789 and 0.833, respectively. The calibration curves showed remarkable consistency. A nomogram model constructed based on the CT features and clinical risk factors is potentially feasible for predicting the PFS within 3years after PC for BCa, which can assist in the choice of treatment and follow-up scheduling.

The Determinants of Toxicity in the Treatment of Prostate Cancer with a Focal, Intraprostatic "Microboost".

A single phase III trial has demonstrated that prostate radiotherapy with a focal, intra-prostatic "microboost" can improve disease control without an overall increase in toxicity. It is unclear how these results generalize to other treatment schedules and protocols. A systematic search of PubMed and the Cochrane Review was performed for studies published on or before September 1, 2023. A random-effects meta-analysis was used to pool the cumulative incidence of grade ≥2 (≥G2) acute and late genitourinary (GU) and gastrointestinal (GI) toxicity. Heterogeneity was assessed, and the association of trial-level covariates with toxicity were examined via subgroup analyses and meta-regression. Odds ratios (ORs) for dose metrics were reported per Gy EQD2. Thirty-eight patient cohorts were included. The pooled estimate of the cumulative incidence of ≥G2 acute and late GU toxicity was 25.3% (95% confidence interval [CI]: 19.1%-32.8%) and 21.1% (95% CI: 16.7%-26.3%), respectively. Late ≥G2 GI toxicity was less frequent, estimated at 5.6% (95% CI: 3.5%-8.7%) and 6.9% (95% CI: 4.6%-10.1%), respectively. Subgroup factors associated with at least one ≥G2 toxicity category were treatment technique, imaging used for boost volume definition, intrafraction motion management, trial phase, and toxicity grading. Rectal DMax was associated with acute ≥G2 GI toxicity (OR: 1.05 [95% CI: 1.02-1.08], p < 0.001). Additionally, urethral DMax was associated with late ≥G2 GU toxicity (OR: 1.02 [95% CI: 1.01-1.03], p < 0.001), and a stronger relationship was observed with the average plan urethral DMax (OR: 1.05 [95% CI: 1.03-1.07], p < 0.001). No association of toxicity with any bladder dose metric examined was observed. The utilization of a microboost appears tolerable across treatment protocols; however, subgroup factors, including the use of intrafraction motion management and the type of imaging modality utilized, may influence the probability of toxicity. Attention to rectal DMax constraints and urethral DMax dose constraints may help to mitigate GI and GU toxicity, respectively. No association between toxicity and bladder dose constraints was observed.

Ketamine and Ketamine-Assisted Psychotherapy for Psychiatric and Existential Distress in Patients with Serious Medical Illness: A Narrative Review.

Context: Psychiatric and existential distress are common and difficult-to-treat symptoms that are frequently encountered in the palliative care setting; current treatment options are limited in efficacy and tolerability. Psychedelic-assisted therapies (PAT) have gained public and scientific interest in their potential to induce rapid and effective reductions in psychiatric and existential distress in patients with serious medical illness, but remain available only in the research setting. Ketamine as a pharmacologic agent has a large body of evidence in the treatment of refractory depression. Objectives: To review the evidence that exists for use of ketamine or ketamine-assisted psychotherapy (KAP) for psychiatric and existential distress in patients with serious medical illness, aiming to identify therapeutic signals and gaps in research. Methods: A literature search identified publications of (1) ketamine or KAP, (2) psychiatric or existential distress, and (3) palliative care or patients with serious medical illness. Identified reports were carefully reviewed with attention to population and treatment-related factors, which were described in a narrative and aggregate format. Results: Nine studies and 12 case reports were identified that reported positive results and a good safety profile. There was significant variation in patient population, setting, route of administration, dosing schedule, and concurrent treatments. Most reports were of ketamine as a pharmacologic agent for symptoms of psychiatric distress. Conclusion: Evidence suggests that ketamine may induce rapid and transient improvements in psychiatric symptoms in patients with serious medical illness. A large gap in research exists for KAP and symptoms of existential distress. There is a signal that suggests ketamine could be used in a psychedelic therapy model with potential benefits over classical psychedelics.

P0783 High risk of adrenal insufficiency in patients with Inflammatory Bowel Disease treated with a conventional course of systemic corticosteroids: Results from a prospective study

Abstract Background Corticosteroids (CS) remain the first-line treatment for inflammatory bowel disease (IBD) although they can cause adrenal insufficiency (AI) due to the alteration of the hypothalamic-pituitary-adrenal (HPA) axis. Assessing this risk is essential, as these patients are often in stressful situations, and AI can mimic IBD symptoms, leading to misdiagnosis. However, there is a lack of studies adequately assessing adrenal function in these patients. The objectives of this study were to determine the proportion of IBD patients who present HPA axis suppression following CS treatment, assess the time required for axis recovery, and identify risk factors for AI. Methods A prospective observational study was conducted including adult patients with active IBD who started systemic CS treatment and with no exposure to CS within the last 6 months. They all followed a pre-defined regimen of 1 mg/kg/day of prednisone (maximum 60mg) for 2 weeks, tapering by 10 mg weekly until reaching 20 mg, then tapering by 5 mg weekly. The HPA axis was assessed 24 hours after CS discontinuation by the measurement of baseline cortisol and ACTH, and cortisol 30 and 60 minutes after stimulation with 250 mcg of ACTH. HPA axis recovery was evaluated 3 and 6 months after CS discontinuation. The association between clinical and demographic variables and the occurrence of AI was analysed. Results Ninety-two patients were included (58% Crohn's disease, 39% ulcerative colitis, mean age 39.8±16 years, 50% women), who received a total CS dose of 2000.7±543.1 mg for 63.5±14.1 days. Forty patients (43.5%) were diagnosed with AI (32 partial, 8 complete). The recovery test was not performed in 10/40 patients (5 due to loss of follow-up, 5 due to need of a new course of CS). 23/30 patients recovered the adrenal function 3 months after stopping CS, and 27/30 patients after 6 months. In the univariate analysis, only fecal calprotectin at the end of CS treatment was associated with AI (P=0.026). Conclusion A high proportion of IBD patients treated with a conventional CS treatment schedule develop HPA axis suppression, although most of them recover adrenal function within six months. The development of AI was not associated with any of the studied variables, except for faecal calprotectin levels. Our results highlight the potential risks associated with prolonged CS use and underscore the importance of considering AI in this context, particularly when the patient faces physical stress.

Optimization of dose-dense methotrexate, vinblastine, doxorubicin, and cisplatin therapy for Japanese patients with urothelial carcinoma.

Dose-dense methotrexate, vinblastine, doxorubicin, and cisplatin (dd-MVAC) regimen has been established as a systemic chemotherapy for patients with urothelial carcinoma. However, it is rarely used in Japan owing to the challenges associated with managing the related adverse events. This study aimed to optimize the dd-MVAC protocol for Japanese patients. Criteria were developed to adjust the doses of anticancer drugs used in dd-MVAC. In this regimen, the initial cycle of methotrexate and cisplatin was administered at 75% of the full dose. Patients who did not experience significant toxicities during the first cycle subsequently received the full dose starting from the second cycle. Additionally, the doses of methotrexate and cisplatin were adjusted according to the Cockcroft-Gault creatinine clearance. Based on these criteria, patients with urothelial carcinoma underwent dd-MVAC between August 2018 and May 2023, and all patients were scheduled to undergo six cycles. A total of 86 patients received dd-MVAC, with 36, 15, and 35 patients receiving it as neoadjuvant, adjuvant, and salvage chemotherapy, respectively. Fifty-nine patients (68.6%) completed the six scheduled cycles. Grade≥3 toxicities of Common Terminology Criteria for Adverse Events were observed in 76 (88.4%) patients; however, most were manageable. In the neoadjuvant cohort, the pathological complete response rate was 52.2% among patients with clinical N0 lower tract urothelial carcinoma. High levels of alkaline phosphatase at the initiation of treatment were correlated with failure to complete six cycles of dd-MVAC. Adjusting the dd-MVAC regimen based on renal function and significant adverse events may result in a high completion rate of scheduled treatments in Japanese patients with urothelial carcinoma.

The Missing Link in Antiamyloid Therapy.

Alzheimer's disease (AD) impacts millions of elderly adults worldwide causing cognitive decline and severe deterioration of activities of daily life. The popular causal hypotheses for several decades include beta-amyloid (Aβ) deposition and tau hyperphosphorylation. AD research and more than 34% of clinical trials in AD are based on these two hypotheses. A phase-III clinical trial of lecanemab in early AD and mild cognitive impaired (MCI) patients reported a delay in cognitive decline of 27% over an 18-month treatment schedule. This multicenter trial found high specificity of lecanemab toward toxic protofibrils and subsequent clearance of beta-amyloid. There were, however, adverse events, which included cerebral edema and intracerebral hemorrhages in 23.1% of patients compared to 9.3% for those who received a placebo. Suboptimal clinical outcomes, brain volume loss, and adverse events in lecanemab treatment prompted a search for an alternative etiopathogenic explanation. Our research and others have focused on the oxidative stress (OS) hypothesis in AD. Autopsy studies have found significant depletion of the master antioxidant glutathione (GSH) in the hippocampal region, and is believed to be an early event in AD progression. Hippocampal GSH depletion is positively correlated with memory impairment. We have confirmed non-invasively with magnetic resonance spectroscopy (MRS) the depletion of GSH in patients with MCI and AD. We therefore propose a combinational therapy involving oral supplementation of gamma-glutamylcysteine (GGC), an early precursor of glutathione, to replenish brain GSH in addition to lecanemab, potentially to maximize desirable outcomes from combined therapeutic approach.

MANAGEMENT OF CERVICAL SPONDYLOSIS THROUGH AYURVEDA: A RE-SEARCH STUDY

Cervical spondylosis is a common spinal problem that is seen nowadays. Though degeneration of cervical vertebrae is mostly seen in older adults, its prevalence also increases in early or middle age. In the present case study, a diagnosed case of cervical spondylosis has been included for its Ayurvedic management. Chief complaints were pain in the neck region radiating towards both shoulders, stiffness over the neck for 5 to 6 months, and on &amp; off episodes of dizziness. The effect of oral medication of Tab Trayodashanga guggulu, Tab Ekangaveera rasa, Ashwagandharishta, Dashmoola arista and external application of Kottamchukkadi oil on cervical spondylosis had been evaluated. Different parameters have been assessed during and after the treatment schedule. There is complete relief in the parameters like neck pain, stiffness &amp; vertigo, and it has also shown significant improvement.

Strategies to enhance management of HER2-positive breast cancer in the elderly: an expert consensus perspective.

Therapeutic decision-making for older patients with human epidermal growth factor receptor 2 (HER2)-positive breast cancer highlights the importance of a comprehensive geriatric assessment (CGA). This assessment considers the functional status, comorbidities, and relevant conditions of the patient, and allows for an estimation of life expectancy, but it does not facilitate individualized treatment plans. There are also other challenges to consider related to the cardiac toxicity of the treatments and the under-representation of older patients in clinical trials. The Oncogeriatrics Section of the Spanish Society of Medical Oncology (Sociedad Española de Oncología Médica, SEOM), the Spanish Group for Breast Cancer Research (Grupo Español de Investigación en Cáncer de Mama, GEICAM) and the Spanish Group of Study, Treatment and other Experimental Strategies in Solid Tumours (Grupo Español de Estudio, Tratamiento y otras Estrategias Experimentales en Tumores Sólidos, SOLTI) have gathered an expert committee to evaluate the scientific evidence on the management of older patients with HER2-positive breast cancer and to establish recommendations based on a comprehensive review of the existing literature. These recommendations underscore the importance of individualizing treatment plans based on the patient's physical status and tolerability to maximize efficacy while minimizing toxicity. Emphasis is placed on adapting neoadjuvant and adjuvant therapies according to geriatric assessment and specific patient needs. A careful selection of treatment schedules for advanced stages is needed to improve survival and quality of life, assuming that scientific evidence in this age group is limited.

Mathematic Modeling of Tumor Growth During [177Lu]Lu-PSMA Therapy: Insights into Treatment Optimization.

The treatment regimen for [177Lu]Lu-prostate-specific membrane antigen (PSMA) 617 therapy follows that of chemotherapy: 6 administrations of a fixed activity, each separated by 6 wk. Mathematic modeling can be used to test the hypothesis that the current treatment regimen for a radiopharmaceutical modality is suboptimal. Methods: A mathematic model was developed to describe tumor growth during [177Lu]Lu-PSMA therapy. The model examined alternative treatment schedules to maximize tumor mass reduction while still maintaining an acceptable biologically effective dose to kidneys. Median patients' pharmacokinetics from literature reports were used to obtain the dose rate over time. The model incorporates the Gompertz tumor growth and linear quadratic models to describe the effect of radiation-induced cell kill on tumor growth. For a fixed total activity of 44.4 GBq of [177Lu]Lu-PSMA-617 and a 6-wk interval between cycles, the efficacy of the standard fractionation (6-cycle) treatment schedule was compared with different treatment regimens for a distribution of published tumor masses. A treatment schedule whereby 7.4 GBq are administered in the first cycle, and the remaining activity (37 GBq) in the second cycle (1-2-cycle treatment), was examined. Results: When tumor mass nadir was used as the optimization metric, a lower tumor burden (e.g., <4 g) was insensitive to the number of cycles; the 6-cycle treatment was equivalent to the 1-2-cycle treatment. For larger masses, fewer cycles yielded better results. For a 7-g tumor, the 5-cycle, 4-cycle, 3-cycle and 1-2-cycle schedules were 24%, 50%, 76%, and 84% more efficacious, respectively, than the 6-cycle schedule. The absorbed doses to kidneys, parotid glands, lacrimal glands, and red marrow were 23, 16, 70, and 1 Gy, respectively. In all fractionated schedules, the biologically effective dose to kidneys was within tolerance (<40 Gy). Conclusion: On the basis of model-derived simulations, treatment delivered in a 1-2-cycle schedule is recommended to achieve better outcomes for patients undergoing [177Lu]Lu-PSMA therapy.

Urban and Rural Differences in Cancer Treatment Disruption Among Patients With COVID-19: An Analysis of the US ASCO COVID-19 in Oncology Registry.

Cancer patients in rural areas experience greater barriers to treatment access compared with patients in urban areas. There is limited research on how the COVID-19 pandemic affected cancer treatment delivery for rural patients who were also diagnosed with COVID-19. This study has two objectives: to assess (1) the urban-rural differences in cancer care and (2) the predictors of cancer treatment delay or discontinuation (TDD) among patients diagnosed with COVID-19. We used data from the American Society of Clinical Oncology Survey on COVID-19 in Oncology Registry (March 2020-September 2022), which included cancer patients with test-confirmed SARS-CoV-2 infection (N = 3797). Data included patient sociodemographic characteristics, COVID-19 diagnosis information, cancer clinical characteristics, and changes to cancer treatment. Cancer TDD was defined as any scheduled treatment by more than 2 weeks. Rurality was examined through both patient residence and oncology practice. We computed adjusted prevalence ratios (aPRs) using multivariable Poisson regressions to assess predictors of cancer TDD in urban and rural areas. During the study period, 44.1% of patients with COVID-19 experienced either cancer treatment delay or discontinuation and 5.7% experienced cancer treatment discontinuation. Controlling for other factors, receiving care in a rural oncology practice was associated with cancer TDD (aPR: 1.25, 95% CI: 1.01-1.55). Differences in cancer TDD were not found across rurality of patient residence. Among rural patients (N = 582), Hispanic/Latinx cancer patients had greater prevalence of cancer TDD (aPR: 1.55, 95% CI: 1.04-2.33) compared with non-Hispanic White cancer patients. Our findings can be used to inform programs and policies to minimize the impact of future public health emergencies on cancer care delivery in rural areas. Additional research is needed to explore potential differences in cancer care delivery across urban and rural oncology practices and patients.

On the effect of heat treatment schedules on the structure-property behaviour of heat-affected zones of ASTM A335 steel: Gleeble thermal-mechanical simulation

On the effect of heat treatment schedules on the structure-property behaviour of heat-affected zones of ASTM A335 steel: Gleeble thermal-mechanical simulation

Intravitreal anti‐vegf agents and combination treatment in proliferative diabetic retinopathy

Proliferative diabetic retinopathy (PDR) poses as a significant threat to patient's vision if untreated or treated insufficiently. Panretinal photocoagulation (PRP) has long been a mainstay treatment for this condition. The advent of anti‐VEGF therapy provided an additional option for the management of this condition. The aim of the presentation is to present the effects of anti VEGF treatment in PDR with special emphasis on the combination: PRP with anti‐VEGF therapy. Results of treatment with these modalities, especially regression of neovascularization, together with the incidence of potential complications will be discussed. Additional aspects of such therapy, such as BCVA improvement and central retinal thickness reduction will also be presented. Potential indications for such treatment will be outlined as well as possible treatment schedules for such management.

Comparative Efficacy of Basal-Bolus Versus Premixed Insulin Regimens in Achieving Glycemic Control Among Patients with Type 2 Diabetes Mellitus: A Systemic Review

Background: T2DM is one of the most prevalent chronic illnesses, requiring effective management to prevent complications. Oral antidiabetic agents are typically needed only in the initial stage to control blood glucose level, while insulin therapy becomes essential as the disease progresses. This includes both basal-bolus and premixed insulin regiments. Therefore, defining an optimal treatment schedule is crucial to improve outcomes in T2DM management and minimize associated attack. Objective: This systematic review assesses the efficacy and safety of the basal-bolus regimen compared to premixed insulin in treating glycemia in T2DM. Methods: The study search involved PubMed, EMBASE, Cochrane Library, and Scopus; the search done strictly applied the PRISMA guidelines. A Review of RCTs, cohort studies, and systematic reviews for comparing basal-bolus regimens to the premixed insulin regimens in A-T2DM was done. These were HbA1c, FPG, and PPG. Secondary endpoints were the incidence of hypoglycemia, adherence to therapy, and disease-specific quality of life. Results: From the above search, we identified 45 studies that meet the inclusion criteria. Daily basal-bolus regimens demonstrated a slightly better reduction in HbA1c, FPG, and PPG than premixed regimens with the trade-offs related to hypoglycemia and regimen complexity. However, basal-bolus regimens are disadvantaged by having more hypoglycemia episodes than the a priori premixed regimens for patients requiring fewer injections. Conclusion: While basal-bolus regimens give better glycaemic control than premixed ones, the latter are safer and easier to use in some patients. Sources call into question of patient’s characteristics in particular, features of T2DM, the patient’s behavior, and his/her genetic background in order to come up with the most effective and individualized treatment plan more consequently than in any other case.

Strategies to Overcome Intrinsic and Acquired Resistance to Chemoradiotherapy in Head and Neck Cancer

Definitive chemoradiotherapy (CRT) is a cornerstone of treatment for locoregionally advanced head and neck cancer (HNC). Research is ongoing on how to improve the tumor response to treatment and limit normal tissue toxicity. A major limitation in that regard is the growing occurrence of intrinsic or acquired treatment resistance in advanced cases. In this review, we will discuss how overexpression of efflux pumps, perturbation of apoptosis-related factors, increased expression of antioxidants, glucose metabolism, metallotheionein expression, increased DNA repair, cancer stem cells, epithelial-mesenchymal transition, non-coding RNA and the tumour microenvironment contribute towards resistance of HNC to chemotherapy and/or radiotherapy. These mechanisms have been investigated for years and been exploited for therapeutic gain in resistant patients, paving the way to the development of new promising drugs. Since in vitro studies on resistance requires a suitable model, we will also summarize published techniques and treatment schedules that have been shown to generate acquired resistance to chemo- and/or radiotherapy that most closely mimics the clinical scenario.

Beyond Longer Intervals: Advocating for Regular Treatment of Neovascular AMD.

Personalizing the management of neovascular age-related macular degeneration (nAMD) poses significant challenges for practicing retina specialists and their patients. This commentary addresses some of these complexities, particularly those that arise in the context of an expanding array of intravitreal agents targeting vascular endothelial growth factor (VEGF) and related retinal disease targets. Many of these newer agents approved by the Food and Drug Administration (FDA) for the treatment of nAMD have labeling that indicates that they can provide non-inferior visual outcomes when compared head-to-head with previously available treatments and can be used at significantly extended dosing intervals in some patients. It can be difficult to know if patients should be transitioned to these agents, especially those who are doing well on existing therapies. Although offering extended intervals may be appropriate for some patients with excellent disease control, retina specialists know that undertreatment risks the loss of visual acuity (VA). It can also be challenging for clinicians to interpret the results delivered by clinical trial treatment protocols compared with what is likely to occur in real-world office settings. Many retina specialists use less liberal treatment paradigms than employed in clinical study protocols and consequently many patients experience shorter injection intervals. Since VA is most closely linked to quality of life, it should be prioritized compared with other endpoints. The authors advocate for maintaining consistent treatment schedules dictated by disease control instead of switching therapies even in the presence of small amounts of macular fluid that may occur with longer injection intervals.

Obinutuzumab in Combination with Alternative Chlorambucil Schedules in Front-Line Treatment of Chronic Lymphocytic Leukemia: A Study by KroHem, the Croatian Cooperative Group for Hematologic Diseases.

Background/Objectives: Obinutuzumab was approved for front-line treatment of chronic lymphocytic leukemia in combination with chlorambucil pulses administered every 2 wks. Alternative schedules of chlorambucil enable the administration of higher total chlorambucil doses, and have better antileukemia activity. So far, evidence on the feasibility of combining obinutuzumab with alternative chlorambucil schedules is lacking. We performed this retrospective analysis to analyze real life outcomes in chronic lymphocytic leukemia patients receiving a combination of obinutuzumab with different chlorambucil schedules. Methods: This was a retrospective survey performed in order to analyze the feasibility and efficacy of different obinutuzumab and chlorambucil combinations in a real-life setting. Patients receiving this combination as a front-line therapy for chronic lymphocytic leukemia in participating centers, outside of clinical trials, in 2017 and 2018 were included. Results: Seventy-three patients fulfilling entry criteria were identified. Their median age was 76 years, and ranged from 58 to 90 years. The median follow up time was 59 months. The response rate was 89%, with a median progression-free survival time of 27 months, and an overall survival time of 49 months. Chlorambucil was administered as planned in 15 of the 22 (79%) patients treated with chlorambucil pulses every 2 weeks; in 15 of the 42 (34%) patients treated with 7-day courses of chlorambucil administered every 4 weeks; and in 0 of the 10 patients treated with a continuous high dose of chlorambucil (p = 0.002). Changes in treatment schedules were made due to side effects. The progression-free and overall survival rates were similar between the three groups. Conclusions: The combinations of obinutuzumab with more intensive chlorambucil schedules are less feasible, preventing the administration of the intended higher total dose of chlorambucil, and do not improve outcomes in comparison to chlorambucil pulses administered every 2 weeks.

Balanced scheduling for medical waste treatment in public health emergencies via Simulation-Driven Mixed Integer Linear Programming

This study introduces a Simulation-Driven Mixed Integer Linear Programming (SD-MILP) model developed to optimize the scheduling of medical waste treatment during emergencies. Our approach integrates simulation to reflect the complexities of the real world, providing solutions that are adaptable to dynamic conditions. Initially, we formulate the problem using an MILP model to optimize waste allocation and alleviate operational pressures. We then incorporate a simulation mechanism within the MILP framework, which simulates waste generation to address uncertainties in epidemic transmission and the rehabilitation process. Through computational experiments conducted on benchmark instances, we evaluate the model’s performance. The results confirm its efficacy in reducing waste treatment costs, including transportation, fixed expansion costs and temporary overload operating costs at treatment stations, while ensuring equitable load distribution among treatment stations.

The increasing role of the allergist in the management of infusion reactions at the Oncology Infusion Center.

Hypersensitivity reactions to chemotherapy disrupt treatment schedules and compromise patient outcomes. Rapid Drug Desensitization (RDD) enables patients to tolerate future treatments after an allergy workup. However, Same-Day Desensitization (SDD) is a novel approach that capitalizes on RDD to allow the continuation of chemotherapy on the same day as the index reaction, preventing treatment delays. To evaluate the safety and efficacy of SDD in managing hypersensitivity reactions during chemotherapy and emphasize the essential role of allergists in the Oncology Infusion Center (OIC) for accurate drugs hypersensitivity reactions (DHRs) phenotyping and management. This retrospective cohort included patients experiencing DHRs during chemotherapy. Under allergist supervision, SDD was performed once the index reaction was controlled. At a later date, clinical phenotypes and endotypes of DHRs were assessed through clinical history, skin tests, serum biomarkers (including tryptase and IL-6 levels), and drug provocation testing (DPT) to reach an accurate diagnosis. SDD was successful in 35 cases, even for patients with severe initial reactions. Only 14% experienced breakthrough reactions, all mild. Same-day assessment by allergists ensured a 92% correlation between initial and final diagnoses, optimizing DHR management. Early engagement with Allergy allowed 86% of reactive patients to continue treatment through RDD or after ruling out an allergy. SDD is a safe and effective procedure that ensures that patients don't miss their oncology treatment on the day of a reaction. The presence of an allergist in the OIC is crucial for rapid access to accurate DHR phenotyping and optimal management, supporting personalized precision medicine in oncology.