Antibiotic-eluting scaffolds with responsive dual-release kinetics facilitate bone healing and eliminate S. aureus infection.

Osteomyelitis (OM) is a progressive, inflammatory infection of bone caused predominately by Staphylococcus aureus. Herein, we engineered an antibiotic-eluting collagen-hydroxyapatite scaffold capable of eliminating infection and facilitating bone healing. An iterative freeze-drying and chemical crosslinking approach was leveraged to modify antibiotic release kinetics, resulting in a layered dual-release system whereby an initial rapid release of antibiotic to clear infection was followed by a sustained controlled release to prevent reoccurrence of infection. We observed that the presence of microbial collagenase accelerated antibiotic release from the crosslinked layer of the scaffold, indicating that the material is responsive to microbial activity. As exemplar drugs, vancomycin and gentamicin-eluting scaffolds were demonstrated to be bactericidal, and supported osteogenesis in vitro. In a pilot murine model of OM, vancomycin-eluting scaffolds were observed to reduce S. aureus infection within the tibia. Finally, in a rabbit model of chronic OM, gentamicin-eluting scaffolds both facilitated radial bone defect healing and eliminated S. aureus infection. These results show that antibiotic-eluting collagen-hydroxyapatite scaffolds are a one-stage therapy for OM, which when implanted into infected bone defects simultaneously eradicate infection and facilitate bone tissue healing.

Liposomes-enabled cancer chemoimmunotherapy.

Chemoimmunotherapy is an emerging paradigm in the clinic for treating several malignant diseases, such as non-small cell lung cancer, breast cancer, and large B-cell lymphoma. However, the efficacy of this strategy is still restricted by serious adverse events and a high therapeutic termination rate, presumably due to the lack of tumor-targeted distribution of both chemotherapeutic and immunotherapeutic agents. Targeted drug delivery has the potential to address this issue. Among the most promising nanocarriers in clinical translation, liposomes have drawn great attention in cancer chemoimmunotherapy in recent years. Liposomes-enabled cancer chemoimmunotherapy has made significant progress in clinics, with impressive therapeutic outcomes. This review summarizes the latest preclinical and clinical progress in liposome-enabled cancer chemoimmunotherapy and discusses the challenges and future directions of this field.

Potential interventions and interactions of bioactive polyphenols and functional polysaccharides to alleviate inflammatory bowel disease - A review.

Inflammatory bowel disease is a multifaceted condition that is influenced by nutritional, microbial, environmental, genetic, psychological, and immunological factors. Polyphenols and polysaccharides have gained recognition for their therapeutic potential. This review emphasizes the biological effects of polyphenols and polysaccharides, and explores their antioxidant, anti-inflammatory, and microbiome-modulating properties in the management of inflammatory bowel disease (IBD). However, polyphenols encounter challenges, such as low stability and low bioavailability in the colon during IBD treatment. Hence, polysaccharide-based encapsulation is a promising solution to achieve targeted delivery, improved bioavailability, reduced toxicity, and enhanced stability. This review also discusses the significance of covalent and non-covalent interactions, and simple and complex encapsulation between polyphenols and polysaccharides. The administration of these compounds in appropriate quantities has proven beneficial in preventing the development of Crohn's disease and ulcerative colitis, ultimately leading to the management of IBD. The use of polyphenols and polysaccharides has been found to reduce histological scores and colon injury associated with IBD, increase the abundance of beneficial microbes, inhibit the development of colitis-associated cancer, promote the production of microbial end-products, such as short-chain fatty acids (SCFAs), and improve anti-inflammatory properties. Despite the combined effects of polyphenols and polysaccharides observed in both in vitro and in vivo studies, further human clinical trials are needed to comprehend their effectiveness on inflammatory bowel disease.

Preparation and characterization of astaxanthin-loaded liposomes by phytosterol oleate instead of cholesterol.

Hydrophobic bioactive compounds like astaxanthin (AST) exhibit poor water solubility and low bioavailability. Liposomes, which serve as nanocarriers, are known for their excellent biocompatibility and minimal immunogenicity. Traditionally, liposomes have been primarily constructed using phospholipids and cholesterol. However, the intake of cholesterol may pose a risk to human health. Phytosterol ester was reported to reduce level of cholesterol and improve properties of liposomes. In this study, phytosterol oleate was used to prepare liposomes instead of cholesterol to deliver AST (AST-P-Lip). The size range of AST-P-Lip was 100-220 nm, and the morphology was complete and uniform. In vitro studies showed that AST-P-Lip significantly enhanced the antioxidant activity and oral bioavailability of AST. During simulated digestion, AST-P-Lip protected AST from damage by gastric and intestinal digestive fluid. Additionally, AST-P-Lip had a good storage stability and safety. These results provide references for the preparation of novel liposomes and the delivery of bioactive compounds.

Assessment of acute, subacute genetic toxicities and immunomodulatory activity of palm (Trachycarpus fortunei) buds.

ETHNOPHARMACOLOGY RELEVANCE: Palm buds are a natural green resource of the forest, which are not only rich in nutrients but contain a large number of phenolic acids and flavonoids, among other components. It has a variety of biological activities such as antioxidant and uterine smooth muscle stimulation. AIM OF THE STUDY: To evaluate the safety of palm buds for use as a nutraceutical product and food by evaluating the toxicity, subacute toxicity and genotoxicity of the young palm buds. Also studied for its immune-enhancing activity. MATERIALS AND METHODS: Acute toxicity tests were performed in mice using the maximum tolerance method, and the manifestations of toxicity and deaths were recorded after administration of 10,000 mg/mL for 14 consecutive d (days) of observations. To assess subacute toxicity, mice were treated with palm buds (750, 1500, or 3000 mg/mL) daily for 28 days. The teratogenicity of palm buds was assessed by the Ames test, the mouse bone marrow cell micronucleus test, and the mouse spermatozoa malformation test. In addition, we evaluated the immune-enhancing ability of palm buds by the mouse carbon profile test, delayed-type metamorphosis reaction, and serum hemolysin assay. RESULTS: In the acute toxicity study, the Median Lethal Dose (LD50) was greater than 10,000 mg/kg bw in both male and female rats. There were also no deaths or serious toxicities in the subacute study. The no-observed-adverse-effect level (NOAEL) was 3000 mg/kg bw. However, the mice's food intake decreased after one week. The medium and high dose groups had a reducing effect on body weight in mice of both sexes. In addition, the changes in organ coefficients of the liver, kidney and stomach in male mice were significantly higher in the high-dose group (3.23 ± 0.35, 0.75 ± 0.05, 0.57 ± 0.05 g) than in the control group (2.94 ± 0.18, 0.58 ± 0.05, 0.50 ± 0.02 g). Hematological analyses showed that all the indices of the rats in each palm sprout dose group were within the normal range. The results of blood biochemical indicators showed that there was a significant reduction in TP in the blood of male mice in the high-dose group (44.6 ± 7.8 g/L) compared to the control group (58.3 ± 15.1 g/L). In histopathological analysis, none of the significant histopathological changes were observed. The results of the immunological experiment in mice showed that the liver coefficient and thymus coefficient of the high-dose group (8400 mg/kg) were significantly lower than the control group. There was no remarkable difference in auricle swelling between each dose palm bud group (1400, 2800, or 8400 mg/kg) and the control group. The anti-volume number of the high-dose group was significantly increased. CONCLUSION: Palm buds have non-toxic effects in vivo and have little effect on non-specific and cellular immunity in the test mice within the dose range of this experiment. The immunoenhancement in mice is mainly achieved through humoral immunity. In conclusion, our results suggest that palm buds are safe for use as healthcare products and food.

Assessing the potential fasting and postprandial mechanisms involved in the acute hypoglycemic and anti-hyperglycemic effects of four selected plants from Iran used in traditional Persian medicine.

ETHNOPHARMACOLOGICAL RELEVANCE: In traditional Persian medicine (TPM), people often use herbal infusions as a dosage form to treat diseases related to hyperglycemia, known as 'dam-kardeh'. Traditionally, herbal preparations of Eryngium bungei Boiss. (E. b), Tragopogon buphthalmoides (DC.) Boiss. (T. b), Salvia hydrangea DC. ex Benth. (S. h), and Juniperus polycarpos K. Koch. (J. p) are used to manage diabetes in Iran. However, there is no evidence of their effectiveness in controlling glucose levels and their mechanisms remain unclear. AIM OF THE STUDY: This study aimed to investigate whether traditional doses of plant infusions can have hypoglycemic and/or anti-hyperglycemic effects during fasting and/or postprandial states and establish the basis for future research on their potential mechanisms of action. MATERIALS AND METHODS: The effects of traditional doses of herbal extracts on blood glucose levels in STZ-NA-induced hyperglycemic rats were investigated in 2-h acute tests during fasting and postprandial states (with a glucose load). In addition, the potential inhibitory effect in vitro of enzymes involved in relevant pathways, such as gluconeogenesis (fructose-1,6-bisphosphatase, FBPase and glucose-6-phosphatase, G6Pase), carbohydrate breakdown (intestinal α-glucosidases), and insulin sensitivity (protein tyrosine phosphatase 1B, PTP-1B) was evaluated. Acute toxicity tests were carried out and HPLC-SQ-TOF was used to analyze the chemical profiles of the plant extracts. RESULTS: In the fasting state, T. b, S. h, and E. b were as effective as glibenclamide in lowering blood glucose levels in hyperglycemic rats. Moreover, all three suppressed G6Pase and FBPase enzymatic activity by 90-97% and 80-91%, respectively. On the other hand, significant postprandial hypoglycemic efficacy was observed for E. b, S. h, and T. b. Based on the AUC values, T. b caused a reduction comparable to the therapeutic efficacy of repaglinide. When investigating the possible mechanisms of action involved in this activity, E. b, S. h, and T. b showed significant inhibition of PTP-1B in vitro (>70%). Finally, all plant extracts showed no signs of acute toxicity. Several compounds that may contribute to biological activities were identified, including phenolic acids and flavonoid glycosides. CONCLUSIONS: The present study supports the traditional use of T. b, E. b and S. h for the control of diabetes in the fasting and postprandial state. Moreover, these plants were found to be rich in bioactive compounds with hypoglycemic and antihyperglycemic activities. On the other hand, J. p, showed a modest effect only in the fasting state and after 90 min. Further studies are needed to expand these results by analyzing the chemical composition and using complementary experimental models.

Current Review on Nanophytomedicines in the Treatment of Oral Cancer: Recent Trends and Treatment Prospects.

Cancer is one of the major life-threatening diseases in the world and oral cancer is the 8th most common type of deadly cancers in Asian countries. Despite many causes, tobacco is the main causative agent as 90% of oral cancer cases were due to daily consumption of tobacco and its products. The major drawback of the conventional therapies for oral cancer including chemotherapy, surgery and radiotherapy or combination of these is the dose limiting toxicity. Developments in technology and research led to new innovative discoveries in cancer treatments. In the past few decades, increased attention has been given to researches in alternative cancer treatment strategies using plants and plant products. Recently many anticancer drugs from natural products or phytochemicals were approved internationally. Due to the low bioavailability and poor solubility of phytochemicals, various research works on nano-carrier based drug delivery systems were exploited in the recent past to make them as promising anticancer agents. In the current review, an overview of oral cancer and its treatment, risk factors, missing links of conventional therapies, contribution of nanotechnology in cancer treatment and research on phytochemical based drug treatment and different polymeric nanoparticles were discussed briefly. The future prospects for the use of various types of polymeric nanoparticles applied in the diagnosis and treatment of oral cancer were also mentioned. The major concern of this review is to give the reader a better understanding on various types of treatment for oral cancer.

Recent Updates on Phytopharmaceuticals-Based Novel Phytosomal Systems and Their Clinical Trial Status: A Translational Perspective.

Phytopharmaceuticals are the newly termed herbal medicine, which includes standardized extract, bioactive fraction, and phytoconstituent. They have been practiced to cure, treat, and mitigate diseases. Phytopharmaceuticals have many health benefits, but their therapeutic efficacy is limited due to poor absorption, low bioavailability, and early elimination profile. A novel phospholipid complex is a newly introduced patented technology developed to incorporate the standardized plant extracts/fractions or water-soluble phytoconstituents into phospholipids to produce lipid compatible molecular complex, called phytosome, which improves their absorption and bioavailability. In herbal formulations, phytosome is the most advanced dosage form that has an upgraded absorption rate and enhanced pharmacokinetics compared with conventional products. The phospholipid complex results from hydrogen bonding between phospholipids and phytoconstituents, offering the maximum incorporation of herbal active ingredients into the lipidic layer and core. The increased therapeutic efficacy is due to the formation of amphiphilic phospholipid-complex of herbal medicine. This review highlights the role of phospholipids on delivery of herbal bioactives and natural extracts with particular emphasis on phytosomes. Moreover, the status of bioavailabilities, commercial products, patents, and clinical trials of phytosomal systems of phytopharmaceuticals were addressed.

The immunological and pharmacokinetic evaluation of Lipid-PLGA hybrid nanoparticle-based oxycodone vaccines.

The current opioid epidemic is one of the most profound public health crises facing the United States. Despite that it has been under the spotlight for years, available treatments for opioid use disorder (OUD) and overdose are limited to opioid receptor ligands such as the agonist methadone and the overdose reversing drugs such as naloxone. Vaccines are emerging as an alternative strategy to combat OUD and prevent relapse and overdose. Most vaccine candidates consist of a conjugate structure containing the target opioid attached to an immunogenic carrier protein. However, conjugate vaccines have demonstrated some intrinsic shortfalls, such as fast degradation and poor recognition by immune cells. To overcome these challenges, we proposed a lipid-PLGA hybrid nanoparticle (hNP)-based vaccine against oxycodone (OXY), which is one of the most frequently misused opioid analgesics. The hNP-based OXY vaccine exhibited superior immunogenicity and pharmacokinetic efficacy in comparison to its conjugate vaccine counterpart. Specifically, the hNP-based OXY vaccine formulated with subunit keyhole limpet hemocyanin (sKLH) as the carrier protein and aluminum hydroxide (Alum) as the adjuvant (OXY-sKLH-hNP(Alum)) elicited the most potent OXY-specific antibody response in mice. The induced antibodies efficiently bound with OXY molecules in blood and suppressed their entry into the brain. In a following dose-response study, OXY-sKLH-hNP(Alum) equivalent to 60 µg of sKLH was determined to be the most promising OXY vaccine candidate moving forward. This study provides evidence that hybrid nanoparticle-based vaccines may be superior vaccine candidates than conjugate vaccines and will be beneficial in treating those suffering from OUD.

Local delivery of carboplatin-loaded hydrogel and calcium carbonate enables two-stage drug release for limited-dose radiation to eliminate mouse malignant glioma.

Postoperative radiotherapy remains the gold standard for malignant glioma treatment. Clinical limitations, including tumor growth between surgery and radiotherapy and the emergence of radioresistance, reduce treatment effectiveness and result in local disease progression. This study aimed to develop a local drug delivery system to inhibit tumor growth before radiotherapy and enhance the subsequent anticancer effects of limited-dose radiotherapy. We developed a compound of carboplatin-loaded hydrogel (CPH) incorporated with carboplatin-loaded calcium carbonate (CPCC) to enable two-stage (peritumoral and intracellular) release of carboplatin to initially inhibit tumor growth and to synergize with limited-dose radiation (10 Gy in a single fraction) to eliminate malignant glioma (ALTS1C1 cells) in a C57BL/6 mouse subcutaneous tumor model. The doses of carboplatin in CPH and CPCC treatments were 150 µL (carboplatin concentration of 5 mg/mL) and 15 mg (carboplatin concentration of 4.1 µg/mg), respectively. Mice receiving the combination of CPH-CPCC treatment and limited-dose radiation exhibited significantly reduced tumor growth volume compared to those receiving double-dose radiation alone. Furthermore, combining CPH-CPCC treatment with limited-dose radiation resulted in significantly longer progression-free survival than combining CPH treatment with limited-dose radiation. Local CPH-CPCC delivery synergized effectively with limited-dose radiation to eliminate mouse glioma, offering a promising solution for overcoming clinical limitations.

Single-dose of integrated bilayer microneedles for enhanced hypertrophic scar therapy with rapid anti-inflammatory and sustained inhibition of myofibroblasts.

Hypertrophic scar (HS) tends to raised above skin level with high inflammatory microenvironment and excessive proliferation of myofibroblasts. The HS therapy remains challenging due to dense scar tissue which makes it hard to penetrate, and the side effects resulting from intralesional corticosteroid injection which is the mainstay treatment in clinic. Herein, bilayer microneedle patches combined with dexamethasone and colchicine (DC-MNs) with differential dual-release pattern is designed. Two drugs loaded in commercially available materials HA and PLGA, respectively. Specifically, after administration, outer layer rapidly releases the anti-inflammatory drug dexamethasone, which inhibits macrophage polarization to pro-inflammatory phenotype in scar tissue. Subsequently, inner layer degrades sustainedly, releasing antimicrotubular agent colchicine, which suppresses the overproliferation of myofibroblasts with extremely narrow therapeutic window, and inhibits the overexpression of collagen, as well as promotes the regular arrangement of collagen. Only applied once, DC-MNs directly delivered drugs to the scar tissue. Compared to traditional treatment regimen, DC-MNs significantly suppressed HS at lower dosage and frequency by differential dual-release design. Therefore, this study put forward the idea of integrated DC-MNs accompany the development of HS, providing a non-invasive, self-applicable, more efficient and secure strategy for treatment of HS.

Hemoglobin and total bilirubin may affect tacrolimus clearance in liver transplant patient following the early postoperative period: a case report.

BACKGROUND: Tacrolimus is a potent calcineurin inhibitor (CNI) that is principally used as a first-line immunosuppressant for the prophylaxis of allograft rejection in liver transplantation (LT) patients. In clinical practice, prescribing the optimal tacrolimus dosage is complicated by its narrow therapeutic index and high pharmacokinetic variability. Thus, performing therapeutic drug monitoring (TDM) of only tacrolimus may not provide optimal drug levels. However, other influential clinical factors affecting tacrolimus levels, such as hemoglobin (Hb), hematocrit, and total bilirubin (TBIL), should be considered while adjusting tacrolimus levels. This case report aims to introduce clinicians and their teams to taking the pharmacokinetic prediction equation into consideration for a better understanding of tacrolimus dosage adjustment during the early postoperative LT. CASE PRESENTATION: In this case report, an 18-year-old male patient of Thai ethnicity was admitted for orthotropic liver transplantation, and tacrolimus was prescribed as a cornerstone immunosuppressive agent. In the immediate postoperative period, which is the most challenging period in liver transplantation, the population pharmacokinetics predictive equation was clinically used to assist in dosage adjustment of tacrolimus by considering the significant clinical factors in this case. Hemoglobin and total bilirubin levels were deemed significant clinical factors affecting the oral clearance (CL/F) of tacrolimus. First, a decrease in the Hb concentration increases the free drug concentration and therefore increases the CL/F of tacrolimus. Second, an elevated TBIL decreases the biliary excretion of tacrolimus, resulting in a decrease in the CL/F of tacrolimus. Thus, dose optimization of tacrolimus would be accurate when taking the pharmacokinetic prediction equation into consideration. Moreover, the results may contribute to a better understanding of tacrolimus pharmacokinetic variability in each transplant patient during the immediate postoperative course. CONCLUSIONS: Hemoglobin and total bilirubin were significant clinical factors influencing the oral clearance of tacrolimus early after liver transplantation. A decrease in the hemoglobin concentration would increase the free drug concentration and therefore increase the oral clearance of tacrolimus. An elevated total bilirubin decreases the biliary excretion of tacrolimus, resulting in a decrease in the oral clearance of tacrolimus.

Population pharmacokinetic modeling of vedolizumab for graft-versus-host disease prophylaxis in adults with allogeneic hematopoietic stem cell transplant.

We aimed to characterize the population pharmacokinetics (PK) of vedolizumab for acute graft-versus-host disease prophylaxis in adults undergoing allogeneic hematopoietic stem cell transplantation (allo-HSCT) and assess potential clinically relevant covariates. Dosing, patient characteristics, and PK from a phase 1b, open-label, dose-finding study of vedolizumab 75 mg initial dose escalated to 300 mg and a phase 3 study of vedolizumab 300 mg in patients receiving allo-HSCT were analyzed using a two-compartment population PK model with linear elimination. Covariates included age, race, weight, sex, albumin, lymphocyte count, GvHD type, and concomitant medications. Weight, albumin, and lymphocyte count were time-varying covariates. Model selection was driven by goodness-of-fit criteria, precision of parameter estimates, and visual predictive checks. In 193 patients undergoing allo-HSCT, vedolizumab PK were well described by a two-compartment, linear PK model. Using reference covariate values, final parameter estimates (95% confidence intervals [CI]) were: clearance, 0.148 (0.136, 0.162) L/day; central volume of distribution, 3.12 (3.03, 3.21) L; intercompartmental clearance, 0.500 (0.408, 0.612) L/day; and peripheral volume of distribution, 3.95 (3.52, 4.44) L. Weight and albumin were the most important predictors of vedolizumab PK, with clearance decreasing by ≈20% for low body weight/high albumin and increasing by ≈30% for high body weight/low albumin. There was an inverse relationship between vedolizumab clearance and age, but no detectable effect for lymphocyte count or GvHD type. Post hoc analyses did not detect any relationship between vedolizumab PK and concomitant medications. In summary, the covariates studied did not have a clinically meaningful effect on the PK of vedolizumab.

Assessment of current practices and perceived effectiveness of injectable polynucleotide for enlarged facial pores among cosmetic physicians: A survey-based evaluation.

BACKGROUND: Polynucleotides stimulate collagen formation and are used clinically to enhance elasticity. In this study, we investigated current practices and perceived effectiveness of polynucleotide injection treatment for enlarged facial pores among cosmetic physicians. MATERIALS AND METHODS: A survey was developed to investigate clinicians' use and effectiveness of polynucleotides in the treatment of enlarged facial pores. This survey was distributed to clinicians at the Korean Aesthetic Surgery & Laser Society Autumn Symposium. RESULTS: A total of 407 physicians who used polynucleotides for enlarged facial pores were enrolled in the survey. Polynucleotides were used by 75.7%, 87.7%, and 72.2% of physicians for enlarged facial pores caused by excessive sebum production, reduced elasticity, and acne, respectively. Among those users, 81.4%, 83.8%, and 76.8% in those same categories, respectively, responded that polynucleotides were "very effective" or "effective." Furthermore, most clinicians combined polynucleotides with microneedle radiofrequency as energy-based devices and with botulinum toxin as injection therapy. CONCLUSION: This study highlights the widespread use and perceived efficacy of polynucleotide injection among cosmetic physicians in the Republic of Korea for enlarged facial pores due to excessive sebum production, reduced elasticity, and acne. Positive feedback from practitioners supports the benefits of using polynucleotides in enlarged facial pore treatment.

Pregnant individuals perspectives towards receiving COVID-19 vaccination during their pregnancy: an in-depth qualitative study.

Introduction: Pregnant individuals have an increased risk of severe illness from coronavirus disease 2019 (COVID-19) infection. Vaccination is an effective strategy to prevent severe illness and complications for pregnant individuals. Pregnant individuals are often excluded from research and remain hesitant to receive vaccination against COVID-19. It is pivotal to study factors related to vaccine uptake and hesitancy among pregnant individuals. We studied barriers and facilitators for pregnant individuals choice and motivation regarding vaccination against COVID-19 during pregnancy to aid future pregnant individuals in their decision to vaccinate against various infectious agents. Methods: In this qualitative study, pregnant individuals were interviewed between October 2021 and January 2022 using a semi-structured approach. A topic list was used to explore their feelings, perceptions and ideas regarding vaccination against COVID-19 during pregnancy. Interviews were transcribed verbatim and thematic analyses was performed using MAX QDA. Results: After nine interviews, saturation was reached. Three main themes were identified that influenced pregnant individuals choice and motivation regarding vaccination: health consequences, ambiguity of information and societal motivation. Health consequences mainly concerned the effect for their offspring, and the unknown long-term effects of COVID-19 vaccination. The advice from the Dutch institute for Public Health and Environment changed from not vaccinating pregnant individuals after release of the developed vaccine, to routinely vaccinating all pregnant individuals after research data were available from the United States of America (USA). This change of policy fuelled doubt and confusion for vaccination. Arguments in favor of vaccination from the social perspective were specific behaviour rules and restrictions due to the pandemic. E.g. without vaccination people were unable to travel abroad and having to take a COVID-19 test every time entering a public place. Conclusion: Pregnant individuals need clear, unambiguous information concerning health consequences, short- and long-term, particularly for their offspring, in the decision-making process regarding COVID-19 vaccination. Additionally, the societal perspective needs to be addressed. Besides the aforementioned themes, general counselling should focus on misperceptions of vaccine safety and the role of misinformation which are also important in the non-pregnant population. This study underlines the importance of including pregnant individuals in research programs to obtain specific information targeted to their needs.

The impact of attitude toward COVID-19 vaccine on intention to receive influenza vaccination: a multi-group comparison based on the influence of presumed influence model and spillover effects.

Introduction: Influenza vaccination is one of the most important strategies for preventing influenza. However, the influenza vaccination rate in China remains low. During the COVID-19 pandemic, people held different attitudes toward the COVID-19 vaccine. In the post-pandemic era, do the varying attitudes toward the COVID-19 vaccine affect the intention to receive influenza vaccination? Methods: Based on the influence of presumed influence (IPI) model and spillover effects, this study employed structural equation modeling for multi-group comparison to analyze questionnaires from 613 participants, using instruments such as the Perceived Media Influence on Others Scale (PMIO), the Susceptibility to Influenza Scale (SI), and the Attitude toward Influenza Vaccine Scale (AIV). Results: The key findings are as follows: (1) Information exposure to the influenza vaccine significantly influences perceived media influence on others. (2) Perceived media influence on others does not directly impact the intention to receive influenza vaccination but rather affects it through attitude toward the influenza vaccine. (3) Moreover, multi-group analyses revealed differences in the IPI model among audiences with different attitudes toward the COVID-19 vaccine. These differences demonstrated that prior attitudes toward the COVID-19 vaccine can influence attitudes toward similar influenza vaccines, thus demonstrating the existence of spillover effects. Conclusion: Attitude toward the COVID-19 vaccine can influence the intention to receive the influenza vaccination. Those with a negative attitude toward the COVID-19 vaccine are significantly influenced by susceptibility to influenza. Perceived media influence affects the intention to receive the influenza vaccination among those with a positive attitude toward the COVID-19 vaccine.

Potential therapeutic option for EGFR-mutant small cell lung cancer transformation: a case report and literature review.

Transformation from non-small cell lung cancer (NSCLC) to small cell lung cancer (SCLC) is rare and is associated with poor prognosis. However, the standard treatment protocols for patients with SCLC transformation remain unknown. Here, we report the case of a patient with advanced EGFR exon 19 deletion (19del) NSCLC who underwent SCLC transformation during targeted therapy. Biopsies and genetic testing were performed to adjust treatment regimens accordingly. The patient responded favorably to a combined treatment regimen comprising etoposide plus cisplatin chemotherapy and adebrelimab plus osimertinib. This case highlights the critical importance of acknowledging tumor heterogeneity in clinical decision-making and identifying potentially effective treatment options for patients with SCLC transformation. Additionally, we reviewed cases of the transformation of NSCLC to SCLC from 2017 to 2023.

Evaluation of the COVID-19 vaccine effectiveness on the outcomes of COVID 19 disease in Iran: a test-negative case-control study.

Introduction: This study measures the COVID-19 vaccine effectiveness (CVE) against hospital admission and severe COVID-19. Methods: This study is a test-negative case-control design using data from eight provinces in April, 2021 until March, 2022. The individuals were classified as cases and controls based on the results of the RT-PCR test for SARS-CoV-2 and matched based on the timing of the test being conducted as well as the timing of hospital admission. The measure of association was an odds ratio (OR) by univariate and multiple logistic regression. The multiple logistic regression has been carried out to take confounding factors and potential effect modifiers into account. The CVE was computed as CVE = (1 - OR)*100 with 95% confidence interval. Results: Among 19314 admitted patients, of whom 13216 (68.4%) were cases and 6098 (31.6%) were controls, 1313 (6.8%) died. From total, 5959 (30.8%) patients had received the vaccine in which one, two, and booster doses were 2443 (12.6%), 2796 (14.5Ùª), and 720 (3.7Ùª), respectively. The estimated adjusted effectiveness of only one dose, two doses and booter vaccination were 22% (95% CI: 14%-29%), 35% (95% CI: 29%-41%) and 33% (95% CI: 16%-47%), respectively. In addition, the adjusted vaccine effectiveness against severe outcome was 33% (95% CI: 19%- 44%), 34% (95% CI: 20%- 45%) and 20% (95% CI: -29%- 50%) for those who received one, two and booster vaccinations, respectively. Conclusion: Our study concluded that full vaccination, though less effective compared to similar studies elsewhere, decreased hospital admissions and deaths from COVID-19 in Iran, particularly during the Delta variant period, with an observed decline during the Omicron variant dominance.

Assessment of Albumin Usage Patterns and Appropriateness in a Comprehensive Cancer Centre: A retrospective study in Jordan.

Objectives: Albumin is commonly used for various indications; however, there is conflicting data regarding its appropriate use in different clinical cases. This study aimed to determine the pattern and appropriateness of albumin use among cancer patients at the King Hussein Cancer Center in Jordan. Methods: A retrospective analysis was conducted on adult cancer patients who were prescribed albumin between January 2019 and July 2020 in both outpatient and inpatient settings. Data collected included demographics, prescribing services, indications and dosing regimens. A literature review was performed using PubMed to assess the appropriateness of albumin indications and dosing regimens against current guidelines, drug information resources and the package insert. Results: Albumin was prescribed to 1,361 patients during the study period. Each patient received an average of 74.4 ± 89 g of albumin for an average of 2.6 ± 1.8 days. Albumin use was deemed appropriate in 69% of the patients. The critical care service accounted for the highest albumin consumption, with 37% of prescriptions for septic shock. Inappropriate use of albumin was most prevalent in the medical solid tumour services (40.8% of prescriptions), primarily for edema (28%). Conclusion: To the best of the author's knowledge, this study is the first to evaluate albumin use in a large cohort of oncology patients. Approximately one-third of the albumin prescriptions were considered inappropriate. Continuous education on appropriate usage and regular evaluations of guideline adherence are essential to ensure proper utilisation of albumin in cancer care.

Lubricating drops for contact lens discomfort in adults.

BACKGROUND: Contact lens discomfort is a symptom-based clinical diagnosis that affects 13% to 75% of contact lens wearers. The Tear Film and Ocular Surface Society defines contact lens discomfort as "a condition characterized by episodic or persistent adverse ocular sensations related to lens wear either with or without visual disturbance, resulting from reduced compatibility between the lens and ocular environment, which can lead to decreased wearing time and discontinuation from lens wear." Signs of the condition include conjunctival hyperemia, corneal and conjunctival staining, altered blinking patterns, lid wiper epitheliopathy, and meibomian gland dysfunction. Eye care specialists often treat contact lens discomfort with lubricating drops, including saline, although there is no clear evidence showing this treatment is effective and safe. OBJECTIVES: To evaluate the efficacy and safety of lubricating drops for ocular discomfort associated with contact lens wear in adults. SEARCH METHODS: We searched CENTRAL (which contains the Cochrane Eyes and Vision Trials Register), MEDLINE, Embase.com, two other databases, and two trials registries to May 2024, without date or language restrictions. SELECTION CRITERIA: We included parallel-group randomized controlled trials (RCTs) that evaluated lubricating drops, including saline, versus no treatment, or that evaluated lubricating drops versus saline, in adult contact lens wearers. We included studies regardless of publication status, language, or year of publication. DATA COLLECTION AND ANALYSIS: We applied standard Cochrane methodology. The critical outcome was contact lens discomfort. Important outcomes were corneal fluorescein staining and conjunctival redness. Adverse outcomes were incident microbial keratitis, inflammatory corneal infiltrates, and participant discontinuation. We assessed risk of bias for outcomes reported in the summary of findings table using the Cochrane risk of bias tool RoB 2, and we rated the certainty of the evidence using GRADE. MAIN RESULTS: We included seven RCTs conducted in the USA, Canada, Italy, and France. They randomized a total of 463 participants to lubricating drops, saline, or no treatment. Four trials evaluated lubricating drops and saline versus no treatment, but one of them provided no usable outcome data. Three trials evaluated lubricating drops versus saline. Study characteristics All trial participants were adults, and the mean age ranged from 25.7 years to 36.7 years. The proportion of women varied from 15% to 82%. The trials lasted between one and four weeks. Of the five trials that reported contact lens discomfort, we judged three at high risk of bias, and considered the other two had some risk of bias concerns. Lubricating drops (including saline) versus no treatment Lubricating drops compared with no treatment may reduce contact lens discomfort, measured on a 37-point scale (lower is better), but the evidence is very uncertain (mean difference [MD] -5.9 points, 95% confidence interval [CI] -3.74 to -8.05; 2 RCTs; 119 participants). One trial found no difference between lubricating drops and no treatment in "end-of-day" comfort. The trial that compared saline with no treatment provided no results for the control group. Two studies measured corneal fluorescein staining on a scale of 0 to 20 (lower is better). We found low-certainty evidence of little to no difference between lubricating drops and no treatment in changes in the extent (MD -0.15 points, 95% CI -0.86 to 0.56; 2 RCTs; 119 participants), depth (MD -0.01 points, 95% CI -0.44 to 0.42; 2 RCTs; 119 participants), or type (MD 0.04 points, 95% CI -0.38 to 0.46; 2 RCTs; 119 participants) of corneal fluorescein staining scores. Regarding conjunctival redness, measured on a scale of 0 to 4 (lower is better), there was low-certainty evidence of little to no difference between lubricating drops and no treatment in nasal region scores (MD 0.10, 95% CI -0.29 to 0.49; 1 RCT; 73 participants) and temporal region scores (MD 0.00, 95% CI -0.39 to 0.39; 1 RCT; 73 participants). No studies reported microbial keratitis or inflammatory corneal infiltrates, and no trials reported vision-threatening adverse events up to four weeks of treatment. All trials reported the proportion of participants who discontinued participation. In two trials, no participants left any treatment group. Our meta-analysis of another two studies suggests little difference in the number of people who dropped out of the lubricating treatment group versus the no treatment group (risk ratio [RR] 1.42, 95% CI 0.19 to 10.94; 138 participants; low-certainty evidence). Lubricating drops versus saline Lubricating drops may have little to no effect compared with saline on contact lens discomfort measured on a visual analog scale of 0 to 100 (lower is better), but the evidence is very uncertain (MD 9.5 points, 95% CI -4.65 to 23.65; 1 RCT; 39 participants). No studies reported corneal fluorescein staining or conjunctival redness. No studies reported microbial keratitis or inflammatory corneal infiltrates, and no trials reported vision-threatening adverse events up to four weeks of treatment. Our meta-analysis of three studies suggests little difference in the number of people who dropped out of the lubricating treatment group versus the saline group (RR 1.56, 95% CI 0.47 to 5.12; 269 participants; low-certainty evidence). AUTHORS' CONCLUSIONS: Very low-certainty evidence suggests that lubricating drops may improve contact lens discomfort compared with no treatment, but may have little or no effect on contact lens discomfort compared with saline. Low-certainty evidence also suggests that lubricating drops may have no unwanted effects that would lead to discontinuation over one to four weeks. Current evidence suggests that prescribing lubricating drops (including saline) to people with contact lens discomfort is a viable option. However, most studies did not assess patient-reported contact lens (dis)comfort using a validated instrument. Therefore, further well-designed trials are needed to generate high-certainty evidence on patient-reported outcomes as well as on longer-term safety outcomes.