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Background: Near-infrared (NIR) phototheranostics provide promising noninvasive imaging and treatment for head and neck squamous cell carcinoma (HNSCC), capitalizing on its adjacency to skin or mucosal surfaces. Activated by laser irradiation, targeted NIR fluorophores can selectively eradicate cancer cells, harnessing the power of synergistic photodynamic therapy and photothermal therapy. However, there is a paucity of NIR bioprobes showing tumor-specific targeting and effective phototheranosis without hurting surrounding healthy tissues. Methods: We engineered a tumor-specific bifunctional NIR bioprobe designed to precisely target HNSCC and induce phototheranosis using bioconjugation of a cyclic arginine-glycine-aspartic acid (cRGD) motif and zwitterionic polymethine NIR fluorophore. The cytotoxic effects of cRGD-ZW800-PEG were measured by assessing heat and reactive oxygen species (ROS) generation upon an 808-nm laser irradiation. We then determined the in vivo efficacy of cRGD-ZW800-PEG in the FaDu xenograft mouse model of HNSCC, as well as its biodistribution and clearance, using a customized portable NIR imaging system. Results: Real-time NIR imaging revealed that intravenously administered cRGD-ZW800-PEG targeted tumors rapidly within 4 h postintravenous injection in tumor-bearing mice. Upon laser irradiation, cRGD-ZW800-PEG produced ROS and heat simultaneously and exhibited synergistic photothermal and photodynamic effects on the tumoral tissue without affecting the neighboring healthy tissues. Importantly, all unbound bioprobes were cleared through renal excretion. Conclusions: By harnessing phototheranosis in combination with tailored tumor selectivity, our targeted bioprobe ushers in a promising paradigm in cancer treatment. It promises safer and more efficacious therapeutic avenues against cancer, marking a substantial advancement in the field., Competing Interests: Competing interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. H.S.C. reports a relationship with Nawoo Vision and Ferrex Therapeutics: board membership, stock, and royalty., (Copyright © 2024 Hae Sang Park et al.)

Background: To establish the prevalence and patterns of prescribing to pregnant women in an Irish primary care setting., Methods: We reviewed electronic healthcare records routinely collected in primary care, of pregnant women attending nine Dublin-based General Practices affiliated to the Irish Primary Care Research Network (IPCRN) for antenatal care between January 2007 and October 2013 (n = 2,361 pregnancies)., Results: Excluding folic acid, 46.8% (n = 1,104) of pregnant women were prescribed at least one medication. Amoxicillin (11.1%, n = 263) and co-amoxiclav (8.0%, n = 190) were the most commonly prescribed medication followed by topical clotrimazole (4.9%, n = 117), salbutamol inhalers (4.1%, n = 96) and paracetamol (4.0%, n = 95). General Medical Services (GMS) patients were more likely to receive a prescription than private patients (OR 2.81; 95%CI (2.28, 3.47)). We applied the US FDA pregnancy-risk categories as a proxy measure of prescribing appropriateness, with FDA Category D and X medications considered inappropriate. FDA Category D drugs were prescribed in 5.9% (n = 140) of pregnancies. FDA Category X drugs were prescribed in 4.9% (n = 116) of pregnancies but after exclusion of oral contraceptives, progestogens, infertility treatments Category X medications were prescribed in 0.6% (n = 13) of pregnancies. After the initial antenatal consultation the prescribing prevalence of FDA Category D medications reduced to 4.7% (n = 110) and Category X to 3.1% (n = 72)., Conclusions: The overall prevalence of prescribing to pregnant women in our cohort is low compared to studies internationally, however similar levels of prescribing for FDA Category D and X were found. Following the initial antenatal consultation levels of prescribing of the FDA Category D and X medications reduced, however there is potential to further reduce their use in early pregnancy. The IPCRN database has provided valuable information on the current practice of antenatal prescribing within this pilot group of practices however it is limited by the absence of morbidity and pregnancy outcome data.

Background: Potentially inappropriate prescribing (PIP) in older people is common in primary care and can result in increased morbidity, adverse drug events, hospitalizations and mortality. The prevalence of PIP in Ireland is estimated at 36% with an associated expenditure of over €45 million in 2007. The aim of this paper is to describe the application of the Medical Research Council (MRC) framework to the development of an intervention to decrease PIP in Irish primary care., Methods: The MRC framework for the design and evaluation of complex interventions guided the development of the study intervention. In the development stage, literature was reviewed and combined with information obtained from experts in the field using a consensus based methodology and patient cases to define the main components of the intervention. In the pilot stage, five GPs tested the proposed intervention. Qualitative interviews were conducted with the GPs to inform the development and implementation of the intervention for the main randomised controlled trial., Results: The literature review identified PIP criteria for inclusion in the study and two initial intervention components - academic detailing and medicines review supported by therapeutic treatment algorithms. Through patient case studies and a focus group with a group of 8 GPs, these components were refined and a third component of the intervention identified - patient information leaflets. The intervention was tested in a pilot study. In total, eight medicine reviews were conducted across five GP practices. These reviews addressed ten instances of PIP, nine of which were addressed in the form of either a dose reduction or a discontinuation of a targeted medication. Qualitative interviews highlighted that GPs were receptive to the intervention but patient preference and time needed both to prepare for and conduct the medicines review, emerged as potential barriers. Findings from the pilot study allowed further refinement to produce the finalised intervention of academic detailing with a pharmacist, medicines review with web-based therapeutic treatment algorithms and tailored patient information leaflets., Conclusions: The MRC framework was used in the development of the OPTI-SCRIPT intervention to decrease the level of PIP in primary care in Ireland. Its application ensured that the intervention was developed using the best available evidence, was acceptable to GPs and feasible to deliver in the clinical setting. The effectiveness of this intervention is currently being tested in a pragmatic cluster randomised controlled trial., Trial Registration: Current controlled trials ISRCTN41694007.

Background: Potentially inappropriate prescribing in older people is common in primary care and can result in increased morbidity, adverse drug events, hospitalizations and mortality. In Ireland, 36% of those aged 70 years or over received at least one potentially inappropriate medication, with an associated expenditure of over €45 million.The main objective of this study is to determine the effectiveness and acceptability of a complex, multifaceted intervention in reducing the level of potentially inappropriate prescribing in primary care., Methods/design: This study is a pragmatic cluster randomized controlled trial, conducted in primary care (OPTI-SCRIPT trial), involving 22 practices (clusters) and 220 patients. Practices will be allocated to intervention or control arms using minimization, with intervention participants receiving a complex multifaceted intervention incorporating academic detailing, medicines review with web-based pharmaceutical treatment algorithms that provide recommended alternative treatment options, and tailored patient information leaflets. Control practices will deliver usual care and receive simple patient-level feedback on potentially inappropriate prescribing. Routinely collected national prescribing data will also be analyzed for nonparticipating practices, acting as a contemporary national control. The primary outcomes are the proportion of participant patients with potentially inappropriate prescribing and the mean number of potentially inappropriate prescriptions per patient. In addition, economic and qualitative evaluations will be conducted., Discussion: This study will establish the effectiveness of a multifaceted intervention in reducing potentially inappropriate prescribing in older people in Irish primary care that is generalizable to countries with similar prescribing challenges., Trial Registration: Current controlled trials ISRCTN41694007.