Cost Of Therapy Research Articles

Transfersomes: Recent Advances, Mechanisms, Exhaustive Applications, Clinical Trials, and Patents

A feasible nano transdermal delivery system generally intends to have specific ideal and distinct characteristics primarily for safety, clinical efficacy, and boosted therapeutic index. The delivery of drugs, particularly macromolecules, across the skin is one of the most strenuous obstacles in front of pharmaceutical scientists. Technology advancement has provided some opportunities to overcome this difficulty by utilising microneedle arrays, ablation, laser methods etc. However, associated uneasiness, painful sensation, and higher cost of therapies limit their day-to-day use. Therefore, researchers have focused on developing alternate carriers like ultra-deformable liposomes, also termed transfersomes. Transfersomes are composed of a lipid bilayer containing phospholipids and an edge activator to facilitate drug delivery via transdermal route to deeper layers of skin and for higher systemic bioavailability. The bilayer structure of transfersomes allows ease of encapsulation of both hydrophilic and lipophilic drugs with higher permeability than typical liposomes. Therefore, among various vesicular systems, transfersomes have developed much interest in targeted and sustained drug delivery. The current review primarily emphasizes critical aspects of transfersomes, including their applications, clinical trial studies, and patents found in various literature sources.

Comparison of Six versus Three Doses of Intrapleural Fibrinolytic Therapy in Children with Empyema: A Randomized Controlled Trial.

To compare six doses of intrapleural streptokinase (SK) vs. the conventional three doses in children with empyema. In this randomized controlled trial, children with empyema received intrapleural streptokinase, either twice daily for 3 d (total 6 doses); or once daily for 3 d (total 3 doses). The outcomes assessed were treatment failure, volume of fluid drained, duration of fever, duration of respiratory distress, length of hospitalization, need for surgical decortication, adverse events and cost. Thirty-six children were enrolled. Cumulative pleural pus drainage was significantly higher with six doses [median (IQR) 367 (266, 850) vs. 195 (142, 422) ml, p 0.02]. The mean (SD) durations of fever and respiratory distress, after completing intrapleural therapy were also shorter; 2.3 (0.8) vs. 5.7 (1.6) d, p 0.04; and 2.2 (0.9) vs. 6.3 (1.9) d, p 0.03 respectively. However, there were no statistically significant differences in the length of hospitalization after completing therapy [median (IQR) 9 (6, 17) vs. 12 (4, 16) d], total duration of intercostal drainage [median (IQR) 13 (11, 21) vs. 12 (7, 19) d], treatment failure rate [4/16 (25%) vs. 7/16 (43.7%)], or need for surgical decortication [2/16 (16.2%) vs. 1/16 (6.2%)]. There were no significant adverse effects necessitating cessation or modification of therapy in either group. The cost of therapy was identical in both groups. Six doses of intrapleural streptokinase appear superior to the conventional three doses in children with empyema, with comparable safety and cost.

Impact of Advanced Therapy Medicinal Products status in European regulations on their production cost: The case of hematopoietic stem cells.

The therapeutic promises of somatic cell and gene therapy (Advanced Therapy Medicinal Products - ATMP) and the significant current or future costs of such therapies raise questions about the impact of European health policy on these expenses. Regulation 1394/2007 currently imposes the medicinal product status on many treatments derived from cell therapy. This study aims to determine the impact of new regulations on manufacturing costs of cell therapy treatments, used as ATMP. In our study, using counterfactual reasoning, we analyze the consequences that a change of status would have on the hematopoietic stem cells (HSC) used for treatment of leukemia. Under the existing status of cell transplantation (CT, Directive 2004/23/EC), the annual production cost of these cell therapy products (CTP) in France is estimated at euro 5.6 million. If the HSC used in leukemia indication were under the medicinal product status of ATMP, the cost would rise to approximately euro 9.9 million, without accounting for expenses related to facilities, which are much higher for ATMP than for CT. This additional burden for manufacturers must be weighed against the theoretical benefits for patients, such as reduced contamination risk. Given the very low contamination levels reported by facilities using transplant standards, the extra cost seems excessive and could hinder the development of new advanced therapies. Furthermore, it raises the need to adapt existing Good Manufacturing Practice guidelines for autologous products or those made from a single donor for a single patient, ensuring safety and cost reduction, which should encourage further development of cell therapy.

P-1636. Real World Outpatient Utilization of Novel Anti-MRSA Antimicrobials: Patterns in Prescribing and Cost of Oral and Long-Acting Injectable Anti-MRSA Therapies in United States Medicaid Beneficiaries

Abstract Background Methicillin Resistant Staph Aureus (MRSA) isolates with resistance to traditional oral anti-MRSA antimicrobials represent a major public health concern. Since 2014, the United States (US) Food and Drug Administration (FDA) approved three oral (tedizolid [2014], delafloxacin [2017], omadacycline [2018]) and two long-acting injectable (LAI) antimicrobials (dalbavancin [2014], oritavancin [2014]) with potent activity against MRSA. Little has been reported about the real-world outpatient utilization and cost of these important therapies. Methods We conducted a retrospective analysis of utilization and cost of these 5 antimicrobials between January 1st, 2014 and December 31st, 2022 in the Medicaid State Drug Utilization Database (SDUD). The SDUD contains all covered outpatient medications excluding those reimbursed under bundled services and suppresses medication data for years with fewer than 11 prescriptions. Annual cost was calculated as the sum of Medicaid and non-Medicaid reimbursement. We approximated the annual per prescription cost (APPC) as the quotient of total cost and prescription count. Results Trends in utilization, total cost and APPC are depicted in Figures 1, 2 and 3 respectively. There was a 1–2-year lag between FDA approval and utilization. Dalbavancin utilization and cost rose from 13 prescriptions and $26,224 in 2014 to 4970 prescriptions and $16,403,304 in 2022, while oritavancin increased from 27 to 566 prescriptions and from $62,309 in $944,657costs. The dalbavancin APPC increased over the study period ending in 2022 at $3,300 while the oritavancin APPC declined to $1669 in 2022. Of the oral antimicrobials, tedizolid utilization and total cost peaked in 2019 at 755 prescriptions and $3,193,571, after which total cost and utilization fell to 283 prescriptions and $1,773,238 by 2022. Delafloxacin utilization and total cost remained low while omadacycline had an increasing trend in utilization, total cost and APPC in the three years it was included. Conclusion Utilization and total cost of dalbavancin rose substantially over the study dwarfing that of oritavancin and the novel oral antimicrobials by the latter half of the study period. Omadacycline, the newest approved antimicrobial included, demonstrated a prompt rise in utilization and total cost. Disclosures All Authors: No reported disclosures

P-172. Assessment of the HIV Case Epidemiological Surveillance System in Sughd Region, Tajikistan, 2024 year

Abstract Background In recent times, the HIV epidemic has emerged as a major challenge in contemporary healthcare, leading to the demise of 40.4 million individuals globally. Across the timeline of the ailment, fatalities have been recorded, and the spread of the virus persists worldwide, Tajikistan included, where over 10.5 thousand cases have been documented. This study aimed to evaluate the efficiency of the HIV surveillance system, which stands as a pivotal strategy in combating HIV/AIDS. Methods Between February and March 2024, we conducted a descriptive evaluation study of the existing surveillance system using the CDC's methodology. The analysis covered data from the AIDS Centre and three health centers in Khujand, including a survey of 33 health workers to assess aspects of surveillance such as flexibility, timeliness, sensitivity, predictive positive value, cost, and overall effectiveness. Results According to the decision of the Government of the Republic of Tajikistan, from 2012 to 2022, 12 AIDS centers were organized in the cities and districts of the region. However, to date, the infrastructure of these centres has not yet been fully developed. Also, 30% of commission blood samples are collected with a delay. The sensitivity of the system has reached 91%, which means that 91% of the estimated number of people living with HIV are detected by surveillance. The positive predictive value is 78%, indicating the probability that the reported case is indeed consistent with a real case of HIV. The cost of confirming an HIV diagnosis per person was $19.94. Also, the cost of antiretroviral therapy per month ranges from US$3.78 to US$23.94, which remains cost-effective, while HIV prevention costs US$3.06. In the region, HIV testing coverage increased by 1.2 times and reached 13.9% in 2023 compared to previous years, which led to a decrease in the mortality rate by 1% and indicates the effectiveness of the system. Conclusion The system shows potential for further improvement and adaptation. Improved strategies need to be implemented to increase timeliness and flexibility in responses to epidemiological changes. Particular attention should be paid to optimizing logistics processes and expanding infrastructure to achieve higher standards in HIV diagnosis and treatment. Disclosures All Authors: No reported disclosures

418. Comparing the Effects of Commercial to Manual Initial Specimen Diversion Techniques (ISDT) on Clinical Outcomes and Institutional Costs

Abstract Background Blood cultures are widely used to diagnose systemic infections. Blood culture contamination (BCC) can lead to unnecessary treatment and prolonged hospitalization. There are three primary ISDT: two commercial options (Steripath and Kurin Lock) and one manual approach (open ISDT). This study aimed to compare the effects of switching from the Steripath ISDT to open ISDT on BCC rates, length of stay (LOS), antibiotic days of therapy (DOT), and laboratory costs.Figure 1.Difference-in-difference (DID) plots for Study OutcomesThis figure shows difference-in-difference plots for blood culture contamination (BCC) (A), length of stay (LOS) (B), days of therapy (DOT) (C), and laboratory costs in USD (D). The green line represents the treatment group (center 1), while the red line represents the control group (centers 2 and 3). The blue dashed line represents the intervention of switching from Steripath ISDT to open ISDT. Methods This was a non-randomized prospective controlled study conducted at three medical centers in Texas from January 2022 through December 2023. Two centers comprised the control arm, utilizing the open ISDT throughout the study period. One center served as the treatment arm where it had Steripath ISDT (pre-intervention) and then was switched to open ISDT (post-intervention). The outcomes were evaluated using multiple regression models (logistic for BCC, linear for log LOS and laboratory costs, and zero-inflated negative binomial for DOT). The difference-in-difference (DID) method compared outcome changes over time between the control and treatment groups (Figure 1).Table 1.Multiple Variable Regressions for Study OutcomesThis table shows the effects of switching from Steripath ISDT to open ISDT on the study outcomes: blood culture contamination (logistic regression), length of stay (logarithmic values, linear regression), days of therapy (negative binomial count and negative binomial zero-inflated models) and laboratory costs (linear regression). The Treated x Time variable represents the treatment effect. (OR = odds ratio; IRR = incidence rate ratio; DOT = days of therapy). Results A total of 12,616 patients were included in the study, with 7,339 in the pre-intervention period and 5,277 in the post-intervention period. The intervention did not significantly impact BCC rates (OR 1.51, p=0.115, Table 1), log LOS (0.02, p=0.534), or DOT (count-model IRR 1.03, p=0.98, and zero-inflated model IRR 0.98, p=0.851). However, a significant difference in laboratory costs was observed following the switch to the open ISDT (reduction of $26.58, p< 0.001). For 1,882 patients in the treatment arm of the post-intervention period, the adjusted cost difference of $26.58 per patient implied an estimated yearly savings of $75,035.40 USD. Conclusion Switching from Steripath to open ISDT had no significant effect on BCC rates, LOS, or antibiotic DOT. However, it did lead to a substantial reduction in laboratory costs. Considering the financial constraints faced by hospitals, this presents an opportunity for improved resource allocation. Future studies should include prospective, randomized control trials to thoroughly examine the effects of various ISDT outcomes and associated costs. Disclosures All Authors: No reported disclosures

P-2359. CLEAR Hepatitis C – Development and impact of a regional collaborative to facilitate identification and treatment of patients with Hepatitis C

Abstract Background Despite advancements in therapy, hepatitis C continues to significantly impact public health and individual patients. Untreated hepatitis C can lead to liver failure and death. The introduction of oral therapies provides an opportunity to cure patients’ hepatitis C and limit the spread. However, challenges persist in the identification of patients, access to specialists trained in the treatment of hepatitis C and the medication therapy costs. FirstHealth of the Carolinas (FHC) developed partnerships and care pathways within our regional medication community including employed and non-employed physician practices. The principles of the care pathway were, CLEAR Hepatitis C (Figure 1). The purpose of our study was to evaluate the outcomes associated with a comprehensive regional approach to identification and treatment of patients with hepatitis C. CLEAR Hepatitis C acronym Outlines care pathway developed for the treatment of hepatitis C Methods A retrospective study was conducted at FHC reviewing outcomes associated with the CLEAR Hepatitis C initiative undertaken from September 2023 through April 2024. Data evaluated included: hepatitis C antibody screens conducted by primary care providers, Infectious Disease clinic referrals for hepatitis C treatment, oral therapies prescribed by Infectious Disease providers, patients assisted with medication therapy by specialty pharmacists and pharmacy technicians and patients receiving a curative diagnosis. CLEAR Hepatitis Results Results associated with each step of the care pathway. Results Primary care provider education and promotion of CLEAR Hepatitis C initiative commenced in November 2023. Comparing the fourth month periods of September-December of 2023 to January-April 2024: the total hepatitis C antibody screens conducted increased from 1169 to 1514 (p < 0.05); Infectious Disease clinic visits with a primary diagnosis of hepatitis C increased from 7 to 18; Prescriptions from Infectious Disease providers increased from 9 to 19; Patients assisted with medication access increased from 6 to 15. During the study period, 4 patients received a curative diagnosis. An additional 8 patients have completed treatment and are awaiting confirmatory lab testing (Figure 2). Conclusion Development of a collaborative, integrated hepatitis C care pathway within our regional medical community successfully increased the number of patients identified and treated for hepatitis C in our region. Disclosures All Authors: No reported disclosures

The Budget Impact of Adopting Oral Pre-Exposure Prophylaxis for HIV Prevention: A Rapid Review

The World Health Organization (WHO) recommended the use of oral pre-exposure prophylaxis (PrEP) for HIV prevention in 2015. Although the number of countries with national PrEP recommendations increased from 2 in 2015 to 121 in 2019, there has been slow progress in Africa. The reason for this slow progress is that developing countries have budgetary constraints. Budget impact analysis (BIA) is an economic analysis that can help explore the affordability of oral PrEP. A rapid review was conducted to summarise the existing literature on the budget impact of adopting oral PrEP for HIV prevention. PubMed and Google Scholar databases were searched for relevant studies. Studies included in the review utilised primary data. Eleven studies met the inclusion criteria. This review reveals that most studies took a healthcare service provider perspective, targeted men who have sex with men (MSM), had time horizons of more than 10 years, used macro-costing, and performed univariate sensitivity analysis and discounting. If countries wish to perform a budget impact analysis of adopting oral PrEP for HIV prevention, we recommend that they select a target population that is most at risk of acquiring HIV. In addition, a time horizon of ten years or more should be used, and accurate values of the cost of oral PrEP and antiretroviral therapy (ART) and adherence to oral PrEP should be researched. Furthermore, deterministic sensitivity analysis should be carried out instead of probabilistic sensitivity analysis (PSA), as the degree of variability and the extent of the correlation among the parameters may not be known.

P0856 Reasons for switching subcutaneous and oral advanced therapies for IBD: a single-centre experience

Abstract Background The evolution of biologic and small molecule treatments has revolutionised the management of patients with IBD. Yet, a proportion of patients require switching therapy. Switching therapy places high demand on healthcare resource, limits future treatment options and can induce anxiety for patients. The purpose of this study was to explore and quantify the reasons for switching therapy and determine which drugs (and drug classes) were associated with more frequent switches. Methods Observational data was obtained from a database of prescriptions for people with IBD who had their therapy switched within Swansea Bay University Health Board. Study period: 30/1/2022 to 20/9/2024 (964 days). Total no. patients 339. Total no. prescriptions 1104 (adalimumab 487; ustekinumab 333; upadacitinib 106; vedolizumab 78; tofacitinib 47; infliximab 44; filgotinib 8; risankinumab 1). Number drug switches 73 (25 male, 48 female; 32 with Ulcerative Colitis, 41 with Crohn’s Disease; average age 39.5 years). Results In terms of absolute numbers, the 5 most common reasons for switching were: secondary loss of response, biosimilar switching, primary loss of response, adverse drug reactions and development of antibodies. The 5 most common drug class switches were: Anti-TNF → Anti-TNF (biosimilar switches), Anti-TNF → IL-12/23i, IL-12/23i → JAKi, Anti-TNF → JAKi, JAKi → JAKi. The average no. days on drug was greatest for adalimumab, vedolizumab and ustekinumab respectively. Conclusion Secondary loss of response was greatest for adalimumab (9 switches, 1.8% of total ADA prescriptions) and ustekinumab (10 switches, 3.0% of total UST prescriptions). Primary loss of response was greatest for ustekinumab (4 switches, 1.2% of total UST prescriptions) and adalimumab (3 switches, 0.6% of total ADA prescriptions). These data are expected because these drugs are prescribed more frequently, and typically before other therapies are used. We do not routinely check anti-drug antibodies for vedolizumab nor ustekinumab hence only adalimumab was associated with development of antibodies. After biosimilar switches, switching between drug classes was more common than intra-class switches. Of all prescriptions (n=1104), adalimumab was prescribed for the greatest average no. days (1024 days) followed by vedolizumab (693 days) and ustekinumab (599 days). This supports the continued prescription of anti-TNF drugs which constitute a major part of our therapeutic arsenal despite the emergence of novel therapies. Prescribing data can provide insights into the reasons for switching advanced therapies in the treatment of IBD. The longevity of advanced treatments needs to be considered alongside therapy costs when developing drug formularies and treatment pathways.

Development of Lentiviral Packaging Cells and Scale Up of Production to Meet the Growing Demand in Cell and Gene Therapy.

Gamma-Retroviral (RVVs) and lentiviral vectors (LVVs) represent indispensable tools in somatic gene therapy, mediating the efficient, stable transfer of therapeutic genes into a variety of human target cells. LVVs, in contrast to RVVs, are capable of stably genetically modifying non-proliferating target cells, making them the superior instrument in cell and gene therapy. To date, the LVV manufacturing process employs human embryonic kidney cells (HEK293) and derivatives thereof transiently transfected with multiple plasmids encoding the required viral vector components. Alternatively, stable packaging cell lines were developed and engineered to express all vector components in trans. Currently, these cells are mostly cultured in cell stacks, where they grow adherently in 2D layers, limiting the scale-up of vector production. The production of viral vectors using stable suspension cell lines enables larger-scale production and higher yields under controlled conditions. Here, we review the improvements made to enhance vector safety and production yield. Current advancements in the establishment of stable packaging cell lines enabling inducible and constitutive LVV production are summarized and discussed. Manufacturing processes for lentiviral vectors using bioreactors with perfusion systems are required to meet the growing demand in cell and gene therapy and to reduce production and therapy costs.

Association Between Positive Airway Pressure Therapy and Healthcare Costs Among Older Adults with Comorbid Obstructive Sleep Apnea and Common Chronic Conditions: An Actuarial Analysis.

To determine the association between adherence to positive airway pressure and healthcare costs among a national sample of older adults with comorbid OSA and common chronic conditions. Our data source was a random sample of Medicare administrative claims for years 2016-2019. Inclusion criteria included age >65 years and new diagnosis of OSA. Exclusion criteria included evidence of prior OSA treatment during the 12 months prior to the index date, active cancer, or end-stage renal disease. OSA was defined using physician-assigned diagnostic codes. Common chronic conditions included chronic obstructive pulmonary disease, congestive heart failure, depression, hypertension, type 2 diabetes mellitus, obesity, and stroke. Based on Medicare policy, individuals were classified as adherers, non-adherers, or non-initiators. Risk adjustment was based on the CMS-HCC approach developed by the Centers for Medicaid and Medicare Service specifically to estimate anticipated costs. To examine the impact of PAP adherence on costs, we employed a weighted DID regression framework to account for baseline variations in health status and other confounding factors. Participants included 28,220 Medicare beneficiaries with comorbid OSA. Of these, 45% were adherent to PAP, 10% were non-adherent, and 44% did not initiate PAP. Relative to non-initiators, beneficiaries who initiated PAP displayed $195 reduced per-member per-month costs over 24 months. This finding remained consistent across all seven medical and psychiatric subgroups, as well as among individuals with multimorbidity. In this national analysis of Medicare beneficiaries with common chronic conditions, PAP adherence was associated with reduced costs over 24 months.

Antisense oligonucleotide as novel therapies for neurogenetic disorders

Antisense oligonucleotide (ASO) was discovered several decades ago and initially used only as a research tool in the laboratory. In recent years, several ASO therapeutics have been developed for neurological disorders. Some of these therapeutics, including eteplirsen, golodirsen, viltolarsen, nusinersen and inotersen, have been approved by the Food and Drug Administration (FDA) and begun to draw the public's attention as an effective therapeutic approach. These novel therapeutics have shown great performance, while many similar therapeutics are under investigation and in clinical trials. This n-of-1 precision medicine may start a new chapter in the paradigm of therapeutics. Clinicians, clinical geneticists, and genetic counselors may know about this novel therapy, but very few may understand the background in details. During genetic counseling, they have the responsibility to convey the effectiveness, side effects and cost of such therapies to patients and their families. As these target therapies will require precise genetic diagnosis before treatment, healthcare professionals and genetic counselors play a vital role in relating the patients to the corresponding ASO drugs. This review has elaborated the mechanism of ASO therapies, including basic rationales, modifications, side effects and delivery routes. It also systemically summarized the FDA-approved ASO therapeutics and their applications for various neurological disorders, and discussed the limitations and challenges the real-world market may face and issues genetic counselor should take into consideration in the near future.

The applications and mechanisms of Rosmarinus officinalis L. in the management of different wounds and UV-irradiated skin.

Chronic wounds, especially non-healing wounds, significantly affect patients' quality of life and raise the costs of therapy. Wound healing is a complicated process involving interdependent stages, which may be impaired and delayed by infections with multi-drug resistant pathogens. Current medical strategies for wound healing, especially the treatment of non-healing wounds, exert limited therapeutic effects, thus become a dramatic challenge for modern medicine. There has been growing interest in exploring complementary approaches to enhance the wound healing process, and complementary therapy using herbs and their related products has gained increasing attention. Apart from skin wounds, dermal pathological changes caused by UV irradiation, may also benefit from such complementary therapy. The antimicrobial, anti-inflammatory, antioxidant, analgesic and collagen-promoting properties of extract from Rosmarinus officinalis L. (rosemary) have all been considered to contribute to the beneficial effects on different stages and multiple aspects of skin recovery after various wounds or UV irradiation. This review aims to summarize the applications and their underlying mechanisms of rosemary as part of the complementary therapy for injured and UV-irradiated skin based on the currently available evidence. The medicinal properties of rosemary and its application in wound dressing are first discussed, followed by summarization of its application in different types of wounds. A conclusion is reached and future directions are discussed. As research in this area continue to evolve, rosemary-derived products may become an integral part of holistic wound care strategies, offering a complementary approach to conventional treatments.

Employer-Sponsored Medicare Advantage Plans and the 2018 Therapy Cap Repeal: Reduced Overall Spending Does Not Constrain Out-of-Pocket Costs.

Policy impacting traditional Medicare beneficiaries may have unintended effects for privately insured patients. After the repeal of a longstanding $1500 outpatient therapy cap in 2018, we aimed to evaluate if this policy change was associated with differences in use of cost of postoperative therapy after common hand surgeries, including carpal tunnel release, trigger finger release, ganglion cyst excision, De Quervain tenosynovitis release, carpometacarpal arthroplasty, and distal radius fracture open reduction/internal fixation or percutaneous pinning. The Medicare Supplement and Coordination of Benefits files from Marketscan were used. Frequency of therapy appointments, overall costs, and out-of-pocket costs were obtained. A segmented interrupted time series with Poisson and log-transformed linear regression was performed. No significant monthly change in odds of therapy use was found in the postpolicy period for patients who underwent trigger finger release, carpal tunnel release, Ganglion cyst excision, De Quervain tenosynovitis release, carpometacarpal arthroplasty, or distal radius fracture, pinning, or open reduction/internal fixation. Overall cost decreased in the postpolicy period by 2% for comprehensive plans (95% confidence interval [CI]: -0.03 to -0.01, P < 0.001), by 7% for those with exclusive provider organizations (95% CI: -0.10 to -0.04, P < 0.001), by 1% for HMOs (95% CI: -0.01 to 0.002, P = 0.01), and by 3% for preferred provider organizations (95% CI: -0.03 to -0.02, P < 0.001). In the postpolicy period, no monthly change in out-of-pocket cost was observed for patients with comprehensive, exclusive provider organization, health maintenance organization, preferred provider organization, or point of service with capitation insurance plans. Patients with employer-sponsored Medicare Advantage plans experienced increased out-of-pocket costs for therapy despite lower net costs. These data highlight an urgent need for policy ensuring that patients benefit when overall costs of care decrease.

Direct medical cost of adjuvant systemic treatment for HER2-positive breast cancer in Vietnam

Context: HER2-positive breast cancer, one of the most aggressive subtypes of breast cancer, is associated with the high cost of HER2-targeted therapies. However, its financial burden in Vietnam has not been fully investigated. Aims: To determine the direct medical costs associated with HER2-positive breast cancer treatment in Vietnam from the perspective of healthcare payers, including social health insurance providers and patients. Methods: A multicenter study was conducted in two tertiary hospitals from January to December 2022. Retrospective patient-level data of 303 HER2-positive breast cancer patients who underwent adjuvant systemic treatment for initial treatment was analyzed. A micro-costing bottom-up approach was used to estimate the direct medical cost per inpatient admission in 2022. All cost calculations are presented as USD values using an exchange rate in 2022. Results: The average cost per inpatient admission was $680.0 ± $431.7. Of these, out-of-pocket costs accounted for approximately 42%. Drug costs were the main driver of total spending (92.9%), followed by hospital beds (2.2%), laboratory tests, and diagnostic imaging (2%). The cost of HER2-targeted therapy was responsible for 82.9% of the total direct medical cost. The average cost per inpatient admission of patients receiving chemotherapy with anti-HER2 agents was seven times higher than that of patients receiving chemotherapy alone ($864.0 vs. $120.6). Factors affecting the cost per inpatient admission were age, residence (urban or rural), occupation, and health insurance reimbursement rate. Conclusions: HER-positive breast cancer treatment imposes a significant financial burden in Vietnam, particularly with regimens containing HER2-targeted therapies. The findings of our study add to the increasing literature on the cost of breast cancer treatment and can contribute to the pharmacoeconomic analysis of HER2-positive breast cancer treatment in Vietnam.

The hidden economic and environmental costs of antimicrobial therapies: a call to action

Abstract The overuse and inappropriate use of antimicrobials have led to environmental waste and drug shortages. This challenges the ecological and economical sustainability of our healthcare system and worsens antimicrobial resistance. Antimicrobial stewardship programs (ASP) commonly consider the cost of drug acquisition but may be failing to recognize the hidden costs of multi-dose intravenous regimens including additional nursing administration time, tubing and fluids, and potentially increased hospital length of stay. They also rarely consider the environmental impact of medical waste creation and disposal, which contributes to the global antimicrobial resistance crisis. These costs are harder to calculate but crucial to a comprehensive assessment of a medication’s total impact. In this invited commentary, we provide an example of a stewardship evaluation at our institution focused on changing from meropenem (MER) to ertapenem (ETP) for infections caused by extended-spectrum beta-lactamase producing organisms. We found that despite an increase in acquisition costs, changing from MER to ETP is associated with overall savings and decreased waste production. A secondary analysis suggests that stay length may also be improved with this substitution. We present a holistic approach to antimicrobial stewardship that considers the total cost of an antimicrobial. By broadening their view to include hidden costs and secondary effects, ASPs can further demonstrate their value to the healthcare system, reduce resistance, and improve their environmental impact.

BCOR abnormalities in endometrial stromal sarcoma.

Endometrial stromal tumors (ESTs) are uncommon mesenchymal tumors of the reproductive system associated with heterogeneous histomolecular features. According to the World Health Organization (WHO), ESTs are classified into benign endometrial stromal nodules (BESN) and endometrial stromal sarcomas (ESSs), which are further divided into low-grade and high-grade subtypes. High-grade ESS is frequently associated with YWHAE-NUTM2 gene fusions, while a newly recognized subtype with BCOR rearrangements, including fusions, alterations, and internal tandem duplications (ITDs), has recently been incorporated into the molecular classification of ESS. BCOR, a transcriptional corepressor of BCL-6, contributes to tumor progression through its role in polycomb repressive complex 1 (PRC1), underscoring its importance in oncogenesis and potential as a therapeutic target. Advances in molecular diagnostics, such as next-generation sequencing (NGS) and fluorescence in situ hybridization (FISH), have improved the precision of diagnosing BCOR-altered ESS, enabling better prognostic stratification. These findings also support the development of targeted therapies, including CDK4/6 inhibitors and immunotherapies targeting PD-1 and CTLA-4 pathways. Despite these advancements, barriers such as limited access to molecular diagnostics and the high cost of novel therapies remain significant challenges. This review bridges molecular and clinical insights into ESS, emphasizing the diagnostic, prognostic, and therapeutic implications of BCOR rearrangements. By integrating these advances into clinical practice, it aims to improve outcomes for patients with this rare and aggressive malignancy.

Association Between the Need to Change Initial Antifungal Therapy and Treatment Costs in Patients With Invasive Aspergillosis.

Early antifungal initiation in invasive aspergillosis (IA) is recommended. Changing antifungals occurs for a myriad of reasons but associated costs are unclear. US claims data for adults admitted for IA were identified from 10/1/2015 to 11/30/2022. Patients were stratified by those who did and did not change antifungal therapy. Adjusted all-cause healthcare utilization and costs/patient during index hospitalization and at 1, 6, and 12-months after the index date between the cohorts that did and did not change antifungal therapy were compared. Among 1,192 IA patients, 707 (59.3%) changed their initial antifungal therapy over follow-up. The index hospital length of stay was longer (Δ = 6 days, P < .001) and costs were higher (Δ = $65,149, P < .001) in the change vs. no change cohort. Median 1, 6, and 12-months all-cause costs were higher in patients changing antifungal therapy vs. not (Δ = $90,938-$192,953). Changing antifungals was associated with longer hospital stays and costs and higher all-cause costs over 12-months.

A CRISPR/Cas approach to β-haemoglobinopathies

Beta-haemoglobinopathies are severe genetic anemias caused by mutations that affect adult haemoglobin production. Many therapeutic approaches aim to reactivate the expression of the fetal hemoglobin genes. To this end, the CRISPR/Cas9 system has recently been used to genetically modify patients' hematopoietic stem/progenitor cells ex vivo and reactivate fetal hemoglobin expression in their erythroid progeny. More than 70 patients with severe β-thalassemia and sickle cell disease have been treated with the Casgevy® therapy. Most have achieved a significant improvement of clinical phenotype, with high editing efficiency in hematopoietic cells associated with normal or near normal hemoglobin levels. While the long-term safety and efficacy of this powerful approach still need to be evaluated, new strategies are being developed to further improve therapeutic outcomes, reduce potential genotoxicity and lower the costs of therapy.

Safety of 1 mcg/mL as the starting dose in cluster protocol for hymenoptera immunotherapy.

Hymenoptera venom allergy is a potentially severe allergic reaction in the general population. The only preventative approach in these cases is venom immunotherapy (VIT), which follows different protocols. The recommended initial dose is 0.001-0.1 mcg of venom extract. However, few reports have declared the safety of 1 mcg venom as the starting dose. The study was conducted on Iranian patients with a history of anaphylaxis to venom. Skin tests confirmed hypersensitivity to honeybee, yellow jacket, and/or paper wasp from subfamily Polistes using Apis melifera, Vespula spp, and Polistes spp venom extracts, respectively. Subsequently, the patients were treated with the cluster protocol. Twenty-two patients (17 males and 5 females, aged 28.3±11.8 years) were enrolled in the study. Skin prick tests and intradermal tests showed positive results for yellow jacket in 17 (77.3%) and 21 (95.4%) patients, honeybee in 14 (63.6%) and 17 (77.3%) patients, and wasp in 14 (63.6%) and 17 (77.3%) patients, respectively. Upon administering the initial dose of 1 mcg/mL, 40.9% (9 cases) of patients presented mild local reactions, including 7 with yellow jacket allergy, 5 with honeybee allergy, and 3 with wasp allergy. One patient with yellow jacket allergy had a mild systemic reaction. Patients with a positive skin test for wasp had significantly lower rate of reactions after the first dose of venom (p=0.026). Throughout the entire build-up phase, more than 90% (20 of 22) of patients experienced mild local reactions, followed by large local reactions (3 cases, 13.6%), mild systemic reactions (1 case at 1 mcg/mL dose), and moderate-to-severe systemic reactions (3 cases, 13.6%). Large local and moderate-to-severe systemic reactions were detected after injecting 50 mcg (each one case) and 100 mcg (each 2 cases) of venom extracts. This study recommends 1 mcg/mL of the venom extract as a safe starting dose for VIT. This accelerated protocol could successfully reduce the time and costs of therapy for patients undergoing out-patient cluster VIT.