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Background: Immune checkpoint inhibitors (ICIs) offer a new treatment approach for cancer, with an improvement in patient survival. However, it remains unclear whether their use impacts the quality of life of treated patients. This study aims to compare the health-related quality of life (HRQoL) of patients treated with different anti-PD-1 and anti-PD-L1 drugs, including several single or combination therapies. Methods: This is a prospective observational study conducted with adult cancer patients who received at least one dose of anti-PD-1 or anti-PD-L1. The HRQoL of all adult patients was assessed using the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Core 30 module (QLQ-C30), version 3, Arabic version. Results: A total of 199 patients were found to be eligible for this study. Of these, 93 patients (82 on a single medication and 11 on multiple ICIs) completed the questionnaire, with a response rate of 46.7%. The majority of patients were treated with pembrolizumab (39.8%), followed by a smaller number treated with nivolumab (35.5%). Most of the patients were diagnosed with solid and advanced malignancies—88.2% (p = 0.023) and 87.1% (p = 0.021), respectively—with a significant difference between treatment groups. The median functioning score was 84.7%, with no significant difference between treatment groups (p = 0.752). Fatigue and pain were noted in >50% of patients, influencing the overall cohort's score related to these symptoms, with scores of 88.8% and 83.3%, respectively. Although a non-significant variation was found in the scores of all combined symptoms among all groups, ranging from 82.1% to 90.4% (p = 0.931), patients receiving anti-PD-1 + anti-PD-L1 tended to more frequently complain about fatigue, pain, dyspnea, and constipation and hence, exhibited the worst, yet non-significant, scores compared to those of the other groups, with p = 0.234, p = 0.79, p = 0.704, and p = 0.86, respectively. All combined groups scored 83.3% on the global health scale. Nevertheless, the nivolumab-treated patients scored 75%, which was the worst global health score compared with those of the other groups, but this score was not statistically significant (p = 0.809). Conclusions: Our findings revealed no significant difference in the impact of different ICIs on the HRQoL of cancer patients. However, a larger number of cases would be necessary to provide a robust analysis and to yield conclusive results. [ABSTRACT FROM AUTHOR]

This study aimed to enhance the hepatic targeting of 5‐fluorouracil (5‐FU) by tyloxapol (TYL) and nanoliposomes to promote drug efficacy and safety. The lipophilicity of 5‐FU was increased by cholesterol conjugation (5‐FUC). Nanoliposomes were prepared, characterized, and loaded with 5‐FU and 5‐FUC and injected into TYL‐treated male Wistar albino rats. After 4 h, LDL and hepatic homogenate were isolated, and the concentrations of 5‐FU and 5‐FUC were investigated in both specimens. The pharmacokinetic parameters of 5‐FU‐ and 5‐FUC‐loaded liposomes were also investigated. The present results revealed that the prepared liposomes have a nanoscale size, negative zeta potential, and prolonged drug release. TYL injection significantly elevated the plasma levels of nonhigh‐density lipoproteins, triacylglycerol (TAG), and total cholesterol (TC). The isolated LDL nanoparticles had a nanosized homogenous vesicle structure and a negative zeta potential. 5‐FUC‐loaded liposomes and TYL augmented 5‐FUC loading into LDL and hepatic tissues compared to that for 5‐FU. Moreover, the present results indicated that 5‐FUC‐loaded liposomes significantly improved the Cmax, Tmax, AUC, MRT, and t1/2 compared to those for the 5‐FUC solution and 5‐FU‐loaded liposomes. This study concluded that the triple approach of a lipophilic shift, nanoliposomes, and TYL is promising for enhancing drug bioavailability, LDL loading, and selective hepatic drug targeting. Practical Applications: 5‐Fluorouracil (5‐FU) is a hydrophilic anticancer medicine that elicits multiple side effects due to high doses, short half‐life, and nonspecific tissue distribution. In this study, 5‐FU was shifted into a lipophilic form (5‐FUC) by cholesterol conjugation. The 5‐FUC was loaded into a nanoliposome. Rats were injected with tyloxapol (TYL) to induce a temporary hyperlipidemia that produces a lipophilic milieu. The hyperlipidemia was confirmed physically by plasma milky appearance and biochemically by marked elevation of non‐HDL lipoproteins. Hyperlipidemia promotes 5‐FUC loading into VLDL‐LDL in vivo. The 5‐FUC level was determined in isolated LDL and liver tissues using HPLC analysis. The lipophilic shift, liposomal loading, and TYL improve pharmacokinetic parameters and bioavailability of 5‐FU with sustained action and hepatic targeting. This study opens a new avenue for endogenous drugs loading into lipoproteins as an approach for selective hepatic drug targeting. [ABSTRACT FROM AUTHOR]

Valsartan (Val) is an important antihypertensive medication with poor absorption and low oral bioavailability. These constraints are due to its poor solubility and dissolution rate. The purpose of this study was to optimize a mixed micelle system for the transdermal delivery of Val in order to improve its therapeutic performance by providing prolonged uniform drug levels while minimizing drug side effects. Thin-film hydration and micro-phase separation were used to produce Val-loaded mixed micelle systems. A variety of factors, including the surfactant type and drug-to-surfactant ratio, were optimized to produce micelles with a low size and high Val entrapment efficiency (EE). The size, polydispersity index (PDI), zeta potential, and drug EE of the prepared micelles were all measured. The in vitro drug release profiles were assessed using dialysis bags, and the permeation through abdominal rat skin was assessed using a Franz diffusion cell. All formulations had high EE levels exceeding 90% and low particle charges. The micellar sizes ranged from 107.6 to 191.7 nm, with average PDI values of 0.3. The in vitro release demonstrated a uniform slow rate that lasted one week with varying extents. F7 demonstrated a significant (p < 0.01) transdermal efflux of 68.84 ± 3.96 µg/cm2/h through rat skin when compared to the control. As a result, the enhancement factor was 16.57. In summary, Val-loaded mixed micelles were successfully prepared using two simple methods with high reproducibility, and extensive transdermal delivery was demonstrated in the absence of any aggressive skin-modifying enhancers. [ABSTRACT FROM AUTHOR]

Purpose: This study aimed to assess dentists' views of the utility of an unrestored shortened dental arch (SDA) compared to the utility of various prosthetic treatment options.Materials and Methods: A total of 142 dentists working at four sites in Riyadh, Saudi Arabia, were interviewed and presented with 18 scenarios for patients of different ages with SDAs that lost molar teeth. Participants were asked to indicate on a standardized visual analog scale (VAS) how they would value the health of the patient's mouth if the SDAs were left unrestored or restored with five prosthetic dental restorations.Results: With a utility value of 0.0 representing the worst possible health state for a mouth and 1.0 representing the best, dentists' mean utility value for unrestored SDAs was 0.43 (standard deviation [SD] = 0.28). For implant-supported fixed dental prostheses (ISFDPs), cobalt-chromium removable partial dentures (RPDs), acrylic RPDs, cantilever conventional fixed dental prostheses (CFDPs), and cantilever resin-bonded fixed dental prostheses (RBFDPs), the mean utility values were 0.64 (SD = 0.27), 0.54 (SD = 0.20), 0.48 (SD = 0.20), 0.42 (SD = 0.28), and 0.39 (SD = 0.27), respectively. Neither patient age nor dentists' clinical experience had an impact on dentists' perceptions of the utility of unrestored SDAs and outcomes of this treatment concept (P > .01).Conclusion: Restoration of SDAs by ISFDPs received the highest utility value among the surveyed group of dentists. Although the assigned value for unrestored SDAs was low, this value was comparable to the value of SDAs that were restored by acrylic RPDs or cantilever FDPs of either type. [ABSTRACT FROM AUTHOR]