Compromise Treatment Outcomes Research Articles

Development and validation of a machine learning model for predicting drug-drug interactions with oral diabetes medications

Diabetes management is often complicated by comorbidities, requiring complex medication regimens that increase the risk of drug-drug interactions (DDIs), potentially compromising treatment outcomes or causing toxicity. Although machine learning (ML) models have made strides in DDI prediction, existing approaches lack specificity for oral diabetes medications and face challenges in interpretability. To address these limitations, we propose a novel ML-based framework utilizing the Simplified Molecular Input Line Entry System (SMILES) to encode structural information of oral diabetes drugs. Using this representation, we developed an XGBoost model, selecting molecular features through LASSO. Our dataset, sourced from DrugBank, included 42 oral diabetes drugs and 1,884 interacting drugs, divided into training, validation, and testing sets. The model identified 606 optimal features, achieving an F1-score of 0.8182. SHAP analysis was employed for feature interpretation, enhancing model transparency and clinical relevance. By predicting adverse DDIs, our model offers a valuable tool for clinical decision-making, aiding safer prescription practices. The 606 critical features provide insights into atomic-level interactions, linking computational predictions with biological experiments. We present a classification model specifically designed for predicting DDIs associated with oral diabetes medications, with an openly accessible web application to support diabetes management in multi-drug regimens and comorbidity settings.

Cancer Therapy-Induced Encephalitis

Encephalitis associated with cancer therapies is a rare but serious complication that can significantly impact patients’ quality of life and it requires prompt identification and management. Over the past two decades, immunotherapy—particularly immune checkpoint inhibitors—has become a cornerstone of cancer treatment, with up to half of metastatic cancer patients in economically developed countries now receiving these therapies. The widespread adoption of immunotherapy has led to improved survival rates and long-term remissions, even in patients with advanced metastatic disease. However, as immune modulators, these therapies can trigger a range of immune-related adverse events, including a variety of novel neurological toxicities. Among these, encephalitis is of particular concern due to its potential severity, which can compromise treatment outcomes. This review aims to provide a comprehensive overview of the literature on this condition, highlighting optimal diagnostic strategies and management approaches to mitigate the risk of significant morbidity, while also comparing encephalitis induced by immunotherapy with that caused by traditional chemotherapies and targeted oncologic treatments.

A randomized clinical trial of emotional freedom techniques for chronic pain: Live versus self-paced delivery with 6-month follow-up.

Chronic pain represents a major global healthcare crisis, and current treatments are limited in effectiveness and safety. Emotional freedom techniques (EFTs) show promise as a potential psychological treatment. The current study investigated the effect of a randomized clinical trial of EFT for chronic pain in a sample of 147 adult chronic pain sufferers (89.9% female; mean 54.63 years). Participants engaged in a 6-week EFT programme (either online self-paced or in-person). The per-protocol analysis indicated pain severity and interference scores were significantly lower at the end of treatment for the EFT group compared to waitlist, and these were sustained at follow-up. There were no differences between the in-person or self-paced programmes at follow-up for pain severity and interference. Somatic symptoms were significantly lower after EFT, although no further differences at follow-up. Quality of life scores were significantly higher after EFT, which were sustained at follow-up, and no differences between two styles of programme. No significant effects were found for anxiety, depression, happiness or satisfaction with life across the 6-week programmes for either style of delivery or at follow-up. These are discussed in terms of clinical score meanings. Intent-to-treat analysis was consistent with the per-protocol analyses. Limitations of the study are identified and future directions are discussed. Findings offer early promise for EFT as a potentially effective pain management strategy, as well as support for online intervention without compromising treatment outcomes. An emerging body-based intervention for chronic pain may be a possible solution for remote clients who cannot attend in-person sessions. In this clinical trial Emotional Freedom Techniques (EFT) significantly reduced chronic pain severity and interference, and there were no differences between and online self-paced program toan online in-person EFT intervention. Both were equally effective, also enhancing quality of life without compromising outcomes. The results were significant at 6-month follow-up/. These findings highlight a body-based approach as a promising, accessible pain management strategy, and highlights that online programs may be part of the solution for chronic pain patients.

Bending the rules: A novel approach to laryngeal surgery in a body donor study.

Transoral laser microsurgery, the standard surgical approach for early-stage laryngeal cancer, necessitates an unobstructed line of sight to the operating field. However, achieving adequate laryngeal exposure can be challenging, potentially compromising treatment outcomes. We developed a 3D-printed curved laryngoscope (sMAC), designed to match the upper airway anatomy. In a user study (n = 15) with a human body donor we compared the sMAC system to conventional microlaryngoscopy regarding laryngeal exposure and accessibility in a difficult exposure scenario. All 15 participants achieved complete glottic exposure and successfully manipulated laryngeal landmarks using the sMAC system. Only four participants achieved partial exposure using microlaryngoscopy. Positioning of the sMAC system was significantly faster (p = 0.023). A vocal cord resection was conducted successfully (n = 2) using the sMAC system. The sMAC system effectively addresses challenges associated with transoral laryngeal surgery. Ongoing development aims to overcome current limitations of the system and prepare first clinical trials.

O-174 Marginal gains: can small actions in the ART lab improve the environmental impact of medically assisted reproduction?

Abstract Marginal gains can small actions in the ART laboratory improve the environmental impact of medically assisted reproduction? (Invitation) Study question Is it possible to reduce the environmental impact of assisted reproductive technology (ART) laboratories while maintaining quality and safety? Summary answer While individual interventions may yield modest results, their cumulative effect on a wider scale can lead to substantial reductions in resource consumption and emissions over time without compromising treatment outcomes or patient/staff safety. What is known already According to the World Health Organisation (WHO) the change in global climate is one of the gravest threats facing humanity, with pregnant women, new-born and child health considered highly vulnerable. In recent years growing evidence has linked climate change, air pollution, pollutant exposure and microplastics to compromised male and female reproductive health and even spontaneous and in vitro fertilisation (IVF) outcomes. Ironically, the healthcare industry is a major contributor of greenhouse gas emissions, and the rapidly increasing utilisation of ART has raised concerns regarding its environmental footprint. A field primarily driven by highly specialised, energy-intensive laboratory processes, continuous monitoring of hormone testing, single-use consumables and large amounts of waste; the quest for bringing awareness to sustainable practices within ART laboratories is critical, not just for the planet, but for our patients and future generations. Study design, size, duration Alongside a comprehensive review of existing literature, a panel of international professionals and enthusiasts within reproductive medicine, law and environmental science convened in a green conferencing format to discuss key environmental challenges associated with ART and explored potential avenues for enhancing sustainability in the laboratory. A survey and interviews with stakeholders also took place to understand current attitudes and provide real-time social, economic and environmental examples of sustainability in ART laboratories. Main Results I will present a roadmap for sustainability in the IVF laboratory so far. A selection of actions which result in marginal gains within the ART laboratory include but are not limited to: Participate in a ‘green certification’ programme specifically tailored to the IVF laboratory and consider forming a ‘green team’ Aim for energy efficiency, renewable energy, preventive maintenance and consider plug load of non-essential equipment for cost savings. Consider widening operating ranges for temperature and humidity, air circulation changes and HVAC design where possible for energy savings of 15–30% Correct waste management can result in > 30% reduction in clinical waste alongside €11,600 annual savings, with focus on prevention of unnecessary consumables (dishes, media), reducing use of plastics and other single-use items to the extent that is possible and safe, and reusing where appropriate (e.g., training vitrification straws). Adopt electronic platforms for consents/laboratory paperwork; avoiding the use of > 40 pages per cycle in the UK. Reuse packaging materials (cold gel packs, bubble wrap) or form partnerships with local businesses who can reuse. Manage inventory carefully, asking for products with longer expiry dates, and consolidate purchase order to minimise frequency. Minimise liquid nitrogen loss during routine activities and consider batching samples for cryo-transport to minimise frequency of shipments. Limitations Every country, region and laboratory is different and will have their own myriad of regulatory constraints and industry standards to adhere to. This may present barriers to the adoption of certain sustainability measures in ART laboratories and is therefore imperative to seek local guidance first. Wider implications of the findings The carbon footprint of ART extends beyond the laboratory and into the supply chain, encompassing transportation, pharmaceutical production, and waste disposal processes. In this way a holistic approach is necessary, with the need for partnerships between fertility clinics, manufacturers, and regulatory bodies continuously working together to drive the development and adoption of sustainable practices and technologies across the entire ART field.

Comparative Study of Different Behavioral Management Techniques in Treating Anxious Pediatric Dental Patients

ABSTRACT Background: Pediatric dental anxiety poses a significant challenge in the delivery of dental care, often resulting in compromised treatment outcomes and negative experiences for both patients and dental professionals. Materials and Methods: A randomized controlled trial (RCT) was conducted involving 120 pediatric dental patients aged 4 to 10 years old, presenting with varying degrees of dental anxiety. Patients were randomly assigned to three groups: Group A received tell-show-do (TSD) technique, Group B received audiovisual distraction (AVD), and Group C received non-pharmacological behavior guidance (NPBG). Anxiety levels were assessed using a standardized anxiety scale before and after the dental procedure. Patient cooperation during treatment, as well as dentist and parent satisfaction, was also evaluated. Results: The study revealed significant reductions in anxiety levels across all groups post-treatment. However, Group B (AVD) demonstrated the most substantial reduction in anxiety scores, with a mean decrease of 60% from baseline. Group A (TSD) and Group C (NPBG) showed comparable reductions in anxiety levels, with mean decreases of 45% and 50%, respectively. Patient cooperation during treatment was highest in Group B, followed by Groups C and A. Dentist and parent satisfaction scores were significantly higher in Group B compared to the other groups. Conclusion: AVD emerged as the most effective behavioral management technique for treating anxious pediatric dental patients, resulting in significant reductions in anxiety levels and higher levels of patient cooperation during treatment compared to TSD and NPBG techniques.

Adjuvant Chemotherapy for Breast Cancer in Older Adult Patients.

Decision-making regarding adjuvant chemotherapy for older adults with breast cancer is a challenge because older adult patients often have poor physical health, frailty, and age-related comorbidities, which can compromise treatment outcome. Due to these considerations, doctors tend to use less chemotherapy for breast cancer in older adults. However, older patients in good general health could still benefit from chemotherapy. Careful benefit-risk assessment is essential to provide best care for each older adult patient. Due to a rapidly aging population, breast cancer in older adults is becoming a serious public health issue in China. In this mini review, we discuss the need, means, and tools to assess the benefits and risks of adjuvant chemotherapy in older adults with breast cancer. The contents of this review may drive decision-making with regard to the use and selection of adjuvant chemotherapy for older adult patients in China who are fit for the treatment.

BET Inhibitor JQ1 Selectively Reduce Tregs by Upregulating STAT3 and Suppressing PD-1 Expression in Patients with Multiple Myeloma.

Multiple myeloma (MM) stands as a prevalent hematological malignancy, primarily incurable, originating from plasma cell clones. MM's progression encompasses genetic abnormalities and disruptions in the bone marrow microenvironment, leading to tumor proliferation, immune dysfunction, and compromised treatment outcomes. Emerging evidence highlights the critical role of regulatory T cells (Tregs) in MM progression, suggesting that targeting Tregs could enhance immune functionality and treatment efficacy. In this study, a notable increase in Treg proportions within MM patients' bone marrow (BM) compared to healthy individuals is observed. Additionally, it is found that the bromodomain and extraterminal domain (BET) inhibitor JQ1 selectively diminishes Treg percentages in MM patients' BM and reduces TGF-β1-induced Tregs. This reduction occurs via inhibiting cell viability and promoting apoptosis. RNA sequencing further indicates that JQ1's inhibitory impact on Tregs likely involves upregulating STAT3 and suppressing PD-1 expression. Collectively, these findings suggest JQ1's potential to modulate Tregs, bolstering the immune response in MM and introducing a promising avenue for MM immunotherapy.

Novel approach of prophylactic radiation to reduce toxicities comparing 2-step 40 Gy with 56 Gy simultaneous integrated boost intensity-modulated radiation therapy for locally advanced squamous cell carcinoma of the head and neck: A phase III trial (JCOG1912, NEW BRIDGE).

TPS6121 Background: Chemoradiotherapy (CRT) with concurrent cisplatin is the standard of care as a nonsurgical definitive treatment for patients with locally advanced squamous cell carcinoma of the head and neck (LA-SCCHN). However, CRT is associated with increased severe late adverse events, including swallowing dysfunction, xerostomia, ototoxicity, and hypothyroidism. Few strategies aimed at less invasive CRT without compromising treatment outcomes have been successful. The purpose of this study is to confirm the non-inferiority of reduced dose prophylactic radiation with 40 Gy compared to standard dose prophylactic radiation with 56 Gy in terms of the time to treatment failure (TTF) among patients with clinical stage III-IVB LA-SCCHN. Methods: This study is a multicenter, two-arm, open-label, randomized phase III trial. The main inclusion criteria are as follows: (i) Primary lesions are located in the oropharynx, hypopharynx, or larynx. (ii) Histologically proven SCC on biopsy specimens of the primary lesion. Immunohistochemistry reveals p16 negativity in patients with oropharyngeal cancer. (iii) Clinical stage of III, IVA, or IVB (excluding N3a) based on the 8th UICC-TNM classification. Patients are randomized to the standard arm or experimental arm. A total dose of 70 Gy for tumors with concurrent cisplatin at 100 mg/m2 are administered in both arms. For prophylactic field, patients in the standard arm receive a total dose of 56 Gy in 35 fractions for 7 weeks using simultaneous integrated boost (SIB56) and those in the experimental arm receive 40 Gy in 20 fractions using two-step methods for 4 weeks (2-step40). A total of 400 patients will be enrolled from 52 Japanese institutions within 5 years. The primary endpoint is TTF, and the secondary endpoints are overall survival, complete response rate, progression-free survival, locoregional relapse-free survival, acute and late adverse events, quality of life score, and swallowing function score.Patient accrual was started in May 2021 and the study is now open for accrual. A total of 186 patients have been enrolled as of January 2024. This trial has been registered in the Japan Registry of Clinical Trials as jRCTs031210100. Clinical trial information: jRCTs031210100 .

Minimally Invasive Management of Complicated and Re-operative Crohn's Disease

AbstractMinimally invasive techniques for the surgical management of Crohn's disease have become the recommended approach for initial surgical intervention in noncomplicated patients as there is lower morbidity for patients without compromising treatment outcomes. There has been a push to expand minimally invasive approaches to complex and recurrent diseases, trying to benefit these difficult patients. However, until recently there have been little data to support the adoption of minimally invasive surgery (MIS) in these scenarios. This article aims to build on the 2019 Clinics in Colon and Rectal Surgery article on complex Crohn's and MIS by introducing new data in support of these approaches. Decisions for technique should be based on patient characteristics, but minimally invasive techniques have emerged as valid and possibly superior for complex and recurrent disease.

Anti-lymphangiogenesis for boosting drug accumulation in tumors

The inadequate tumor accumulation of anti-cancer agents is a major shortcoming of current therapeutic drugs and remains an even more significant concern in the clinical prospects for nanomedicines. Various strategies aiming at regulating the intratumoral permeability of therapeutic drugs have been explored in preclinical studies, with a primary focus on vascular regulation and stromal reduction. However, these methods may trigger or facilitate tumor metastasis as a tradeoff. Therefore, there is an urgent need for innovative strategies that boost intratumoral drug accumulation without compromising treatment outcomes. As another important factor affecting drug tumor accumulation besides vasculature and stroma, the impact of tumor-associated lymphatic vessels (LVs) has not been widely considered. In the current research, we verified that anlotinib, a tyrosine kinase inhibitor with anti-lymphangiogenesis activity, and SAR131675, a selective VEGFR-3 inhibitor, effectively decreased the density of tumor lymphatic vessels in mouse cancer models, further enhancing drug accumulation in tumor tissue. By combining anlotinib with therapeutic drugs, including doxorubicin (Dox), liposomal doxorubicin (Lip-Dox), and anti-PD-L1 antibody, we observed improved anti-tumor efficacy in comparison with monotherapy regimens. Meanwhile, this strategy significantly reduced tumor metastasis and elicited stronger anti-tumor immune responses. Our work describes a new, clinically transferrable approach to augmenting intratumoral drug accumulation, which shows great potential to address the current, unsatisfactory efficacies of therapeutic drugs without introducing metastatic risk.

Supportive periodontal care in dental practice: Part 2 - perceptions of locally referring UK general dental practitioners.

Background Supportive periodontal care (SPC) is important in maintaining periodontal treatment outcomes. Hospital services provide specialist periodontal care at high costs. On completion of treatment, patients are discharged back to the general dental practitioner (GDP) to provide SPC. This project aimed to evaluate the change in GDPs' understanding of SPC over more than 20 years.Method A validated questionnaire about SPC was sent to GDPs during 1996 (397) and 2020 (300), with a response rate of 74% and 52%, respectively. The anonymous data were entered on a Microsoft Excel spreadsheet for analysis.Results In total, 98.5% of the GDPs in 1996 and 97% in 2020 perceived SPC to be highly important. Additionally, 49% in 2020 had a better understanding of SPC when compared to 1996 (42%). Finally, 70-74% (1996, 2020) of the GDPs indicated that they were responsible for SPC; however, 13-16% said that they were not.Conclusion and clinical relevance Notwithstanding the lower response rate in 2020, there has been an improvement in understanding and awareness of responsibility of SPC among GDPs. Reported challenges of provision were related to education and funding. If GDPs are to effectively deliver SPC, education and current funding should be addressed to prevent compromised treatment outcomes for patients.

Impact of War on the Drug Supply for Cancer Patients in Sudan

This review investigates the ramifications of conflict on chemotherapy drug accessibility for cancer patients in Sudan. For this review article, the data was collected from file records Port Sudan Oncology Center, Port Sudan, Sudan. Through a comprehensive analysis of drug supply frequencies during distinct conflict periods, the study reveals fluctuating availability and challenges in sustaining the supply chain. Grouping chemotherapy drugs according to their availability patterns elucidates the varying degrees of accessibility during conflict, ranging from consistent supplies to complete absence. The impact of these shortages on cancer patients is profound, resulting in compromised treatment outcomes, increased morbidity and mortality rates, and substantial socioeconomic burdens. Real-life patient accounts underscore the emotional, physical, and financial toll imposed by interrupted access to vital medications. Despite efforts by healthcare institutions, NGOs, and governmental bodies, persistent challenges hinder effective mitigation strategies during conflict, including logistical constraints, inadequate funding, and political instability. The socioeconomic and psychological implications of drug shortages are significant, pushing patients deeper into poverty and exacerbating psychological distress. Addressing these challenges necessitates sustained efforts to fortify drug supply chains, enhance infrastructure, and foster multi-stakeholder cooperation. The study emphasises the critical need for sustained interventions to ensure continuous access to chemotherapy drugs in Sudan and conflict zones globally. Immediate actions are imperative to alleviate the burdens faced by cancer patients and fortify healthcare systems to withstand the challenges of conflict-induced drug scarcity.

Advances in Nanomaterials and Composites Based on Mesoporous Materials as Antimicrobial Agents: Relevant Applications in Human Health.

Nanotechnology has emerged as a cornerstone in contemporary research, marked by the advent of advanced technologies aimed at nanoengineering materials with diverse applications, particularly to address challenges in human health. Among these challenges, antimicrobial resistance (AMR) has risen as a significant and pressing threat to public health, creating obstacles in preventing and treating persistent diseases. Despite efforts in recent decades to combat AMR, global trends indicate an ongoing and concerning increase in AMR. The primary contributors to the escalation of AMR are the misuse and overuse of various antimicrobial agents in healthcare settings. This has led to severe consequences not only in terms of compromised treatment outcomes but also in terms of substantial financial burdens. The economic impact of AMR is reflected in skyrocketing healthcare costs attributed to heightened hospital admissions and increased drug usage. To address this critical issue, it is imperative to implement effective strategies for antimicrobial therapies. This comprehensive review will explore the latest scientific breakthroughs within the metal-organic frameworks and the use of mesoporous metallic oxide derivates as antimicrobial agents. We will explore their biomedical applications in human health, shedding light on promising avenues for combating AMR. Finally, we will conclude the current state of research and offer perspectives on the future development of these nanomaterials in the ongoing battle against AMR.

Synchronous Dosing of Levodopa with Quercetin Enhances Therapeutic Efficacy and Mitigates Apoptotic Events in Experimental Parkinsonism

Parkinson’s disease (PD) affects millions of people annually across the globe and is primarily managed through dopamine replacement therapy employing levodopa (L-DOPA), which is still the preferred gold standard. Prolonged use of L-DOPA leads to severe adverse effects, including motor complications such as L-DOPA-induced dyskinesia, which considerably compromise treatment outcomes and patients’ quality of life. Potentiating L-DOPA with natural or synthetic compounds with less toxicity and neuroprotective activity is an area of emerging significance, and many studies in this area have gained widespread research attention. Phytochemicals, essentially compounds with antioxidant and neuroprotective activity, may be potent candidates to potentiate L-DOPA, and in this context, we explored the potential of combining quercetin with L-DOPA to mitigate rotenone-induced PD using human neuroblastoma cells. The optimal nontoxic concentrations of L-DOPA and quercetin were determined via the MTT [3-(4,5-dimethylthiazolyl-2)-2,5-diphenyltetrazolium bromide] assay. The combination treatment notably increased cell viability to 95% at a concentration of 6.25 μg/ml, whereas the viability of the rotenone-treated group was 46.8%. Lactate dehydrogenase leakage assays further confirmed that membrane integrity was significantly preserved in the combination-treated groups compared with those treated with L-DOPA or quercetin alone. Morphological improvements were evident under microscopic observation. Compared with the individual treatments, the combination treatment also resulted in increased inhibition of acetylcholinesterase activity. Additionally, apoptosis induction was significantly reduced in the combination group, as shown by EtBr/acridine orange fluorescence staining. Cellular calcium levels, which were elevated by rotenone exposure, were effectively normalized by the combination treatment. Moreover, the combination therapy promoted neurite outgrowth more effectively than L-DOPA or quercetin alone. These findings suggest that coadministration of quercetin with L-DOPA could be a promising strategy to increase the efficacy of L-DOPA while potentially reducing its dosage, leveraging the benefits of natural phytochemicals in PD management.

EVALUATING THE MANAGEMENT AND MAINTENANCE PRACTICES OF LINEAR ACCELERATOR AND COBALT-60 CANCER TREATMENT MACHINES IN NIGERIA: A COMPREHENSIVE ASSESSMENT

This research paper investigated the state of radiotherapy machines and their management in cancer treatment centers in Nigeria. The study aimed to identify the challenges faced by these centers and propose strategies for improvement. Through a comprehensive analysis of data collected from surveys and questionnaires, critical issues impacting the availability, reliability, and effectiveness of radiotherapy machines were highlighted. The findings revealed a significant shortage of radiotherapy machines across the nation, with Nigeria having less than 6% of the required number of linacs. This scarcity led to a high workload on the existing machines, resulting in long waiting lists and compromised treatment outcomes. Management challenges, such as the absence of preventive maintenance policies, inadequate personnel training, delayed spare parts delivery, and limited engagement of maintenance contractors, were identified. The research emphasized the need for supportive cancer treatment machines, including orthovoltage and superficial machines, to alleviate the burden on existing radiotherapy machines. However, most centers lacked these supportive machines, limiting their ability to provide comprehensive care to patients. Financial sustainability also emerged as a significant concern, as internal funds proved insufficient for maintenance and operations. The involvement of the government and the establishment of independent regulatory bodies were proposed to address these challenges. In conclusion, this study called for urgent action to address the gaps and challenges in radiotherapy machine management in Nigeria. It highlighted the importance of increasing the number of machines, implementing preventive maintenance policies, enhancing staff training, and securing adequate funding. By doing so, the quality of cancer care could be significantly improved, leading to better patient outcomes and a more robust healthcare system in Nigeria.

Novel approach of prophylactic radiation to reduce toxicities comparing 2-step40 with 56-Gy simultaneous integrated boost intensity-modulated radiation therapy for locally advanced squamous cell carcinoma of the head and neck, an intergroup phase III trial (JCOG1912, NEW BRIDGE)

BackgroundChemoradiotherapy (CRT) with concurrent cisplatin is the standard of care as a nonsurgical definitive treatment for patients with locally advanced squamous cell carcinoma of the head and neck (LA-SCCHN). However, CRT is associated with increased severe late adverse events, including swallowing dysfunction, xerostomia, ototoxicity, and hypothyroidism. Few strategies aimed at less invasive CRT without compromising treatment outcomes have been successful. The purpose of this study is to confirm the non-inferiority of reduced dose prophylactic radiation with 40 Gy compared to standard dose prophylactic radiation with 56 Gy in terms of the time to treatment failure (TTF) among patients with clinical stage III-IVB LA-SCCHN.MethodsThis study is a multicenter, two-arm, open-label, randomized phase III trial. Patients with LA-SCCHN excluding p16 positive oropharynx cancer are randomized to the standard arm or experimental arm. A total dose of 70 Gy for tumors with concurrent cisplatin at 100 mg/m2 are administered in both arms. For prophylactic field, patients in the standard arm receive a total dose of 56 Gy in 35 fractions for 7 weeks using simultaneous integrated boost (SIB56) and those in the experimental arm receive 40 Gy in 20 fractions using two-step methods for 4 weeks (2-step40). A total of 400 patients will be enrolled from 52 Japanese institutions within 5 years. The primary endpoint is TTF, and the secondary endpoints are overall survival, complete response rate, progression-free survival, locoregional relapse-free survival, acute and late adverse events, quality of life score, and swallowing function score.DiscussionIf the experimental arm is non-inferior to the standard arm in terms of TTF and superior on the safety endpoints, the 2-step40 procedure is the more useful treatment than SIB56 for definitive CRT.Trial registrationThis trial has been registered in the Japan Registry of Clinical Trials as jRCTs031210100 (https://jrct.niph.go.jp/latest-detail/jRCTs031210100). Date of Registration: May 2021.

Fabrication of Biogenic Titanium Nanoparticles and Investigating Their Biological Properties for Dental Applications.

Oral inflammation, often triggered by infections, injuries, or immune responses, can compromise treatment outcomes, delay healing, and contribute to patient discomfort. The development of green nanoparticle synthesis methods is receiving attention due to their potential advantages over existing approaches. These procedures use commonly available, affordable, and environmentally friendly natural plant extracts. Due to their numerous uses in various industries, titanium oxide nanoparticles (TiO2NPs) have attracted the most attention among the nanoparticles. In this study, we present the green synthesis of Myristica fragrans (mace) extract as a reductant and stabilizer for the production of curcumin-functionalized TiO2NPs (CTN). We additionally evaluated the effectiveness of these nanoparticles as anti-inflammatory agents. In this study, we aim to develop biogenic TiO2NPs using Myristica fragrans as a natural capping agent and functionalized with curcumin for effectively managing oral inflammation in dental applications. The nanoparticles were synthesized using the green synthesis method and characterized using various characterization techniques. Biocompatibility was evaluated using hemolytic assays, and the bioactivity of the nanoparticles was assessed using anti-inflammatory assays. Curcumin-coated M-TiO2NPs (MCTN) were successfully synthesized and characterized by various techniques, confirming their morphology, crystallinity, functionalization, elemental composition, size, and stability. In vitro bioactivity studies revealed that MCTN exhibited significant anti-inflammatory activity, as evidenced by the inhibition of protein denaturation with minimal hemolytic potential. These findings highlight the potential of MCTN as a promising candidate for anti-inflammatory applications. Our results suggest that MCTN exhibits promising anti-inflammatory and anti-hemolytic properties. However, further in-depth in vivo analysis is required to fully understand their efficacy and toxicity.

CGRP-loaded Porous Microspheres Protect BMSCs for Alveolar Bone Regeneration in The Periodontitis Microenvironment.

Periodontitis is a prevalent dental disease marked by progressive destruction of tooth-supporting tissues, and the recovery of bone defects after periodontitis remains challenging. Although stem cell-based therapy is a promising treatment for periodontal tissue regeneration, the function of mesenchymal stem cells is constantly impaired by the inflammatory microenvironment, leading to compromised treatment outcomes. Herein, calcitonin gene-related peptide (CGRP)-loaded porous microspheres (PMs) are prepared to protect bone marrow mesenchymal stem cells (BMSCs) against inflammatory mediators in periodontitis. The released CGRP could effectively ameliorate the inflammation-induced dysfunction of BMSCs, which may involve suppressing the ROS (reactive oxygen species)/NLRP3 (NOD-, LRR- and pyrin domain-containing protein 3)/Caspase-1 pathway. Moreover, the porous architecture of PMs provides effective cell-carrying capacity and physical protection for BMSCs during transplantation. In vivo experiments demonstrate that CGRP/BMSC-loaded PMs could effectively inhibit inflammation and improve osteogenic activity, resulting in better periodontal bone regeneration. This study focuses on the protection of stem cell function in the inflammatory microenvironment, which is important for stem cell-mediated tissue regeneration and repair under inflammatory conditions. This article is protected by copyright. All rights reserved.

0676 Sleep medication prescribing among patients receiving opioid use disorder treatment with comorbid insomnia

Abstract Introduction People initiating treatment for opioid use disorder (OUD) report insomnia to be a high priority, and insomnia is associated with compromised OUD treatment outcomes. However, insomnia treatments have yet to be investigated in the OUD clinical setting. Knowledge of prescribing patterns for sleep medications among OUD treatment patients is an essential first step to advance therapeutic development at the insomnia-OUD comorbidity. This retrospective cohort study used administrative claims data from IBM MarketScan Commercial and Multi-State Medicaid databases (2006-2016) to investigate the prevalence of insomnia medication prescriptions among patients in OUD treatment with buprenorphine. In doing so, we assess sex differences in prescription receipt within this unique patient population, given the known sex-based disparities in insomnia among other adult populations. Methods We included people aged 12-64 years with diagnoses of insomnia and OUD initiating buprenorphine during the study timeframe. The primary outcome was receipt of insomnia medication prescription within 60 days of buprenorphine start, encompassing benzodiazepines, Z-drugs, or non-sedative/hypnotic insomnia medications (e.g., hydroxyzine, trazodone, and mirtazapine). Descriptive analyses present prescription prevalence for the total sample as well as separately for males and females. Lastly, associations between sex and insomnia medication prescription receipt were estimated using Poisson regression models. Results Our sample included 9,510 individuals (female n=4,637; male n=4,873) initiating buprenorphine for OUD who also had insomnia, of whom 6,569 (69.1%) received benzodiazepines, 3,891 (40.9%) Z-drugs, and 8,441 (88.8%) non-sedative/hypnotic medications. Poisson regression models, adjusting for sex differences in psychiatric comorbidities, found female sex to be associated with a slightly increased likelihood of prescription receipt: benzodiazepines (risk ratio [RR], RR=1.17 [1.11-1.23]), Z-drugs (RR=1.26 [1.18-1.34]), and non-sedative/hypnotic insomnia medication (RR=1.07, [1.02-1.12]). Conclusion Sleep medications are commonly being prescribed to individuals with insomnia in OUD treatment, especially females. These findings juxtapose the known increased overdose risk with benzodiazepine use and lack of efficacy data for these pharmacologic insomnia treatments in this growing patient population in the opioid crisis. Support (if any) National institute of Drug Abuse: K23 DA053507 (CEM), UG1DA050207 (FGM). National Institutes of Health: R25 MH112473-01 (HP), T32 DA015035 (KYX), R21 DA044744 (RAG and LJB). National Center for Advancing Translational Sciences: UL1 TR002345 (Washington University), UL1TR002649 (Virginia Commonwealth University)