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ESMO Open Jun 2024Paclitaxel resistance limits durability of response in patients with initial clinical benefit. Overexpression of spleen tyrosine kinase (SYK) has been proposed as a...
BACKGROUND
Paclitaxel resistance limits durability of response in patients with initial clinical benefit. Overexpression of spleen tyrosine kinase (SYK) has been proposed as a possible resistance mechanism. This phase I trial evaluated the safety and preliminary activity of the SYK inhibitor TAK-659 combined with paclitaxel in patients with advanced taxane-refractory solid tumors.
PATIENTS AND METHODS
Patients with advanced solid tumors and prior progression on taxane-based therapy received intravenous infusion of paclitaxel on days 1, 8, and 15 plus oral TAK-659 daily in 28-day cycles. The dose-escalation phase included six cohorts treated at different dose levels; the dose-expansion phase included patients with ovarian cancer treated at the highest dose level. Toxicity was graded using the National Cancer Institute Common Terminology Criteria for Adverse Events version 5.0. Efficacy was evaluated using Response Evaluation Criteria in Solid Tumors version 1.1.
RESULTS
Our study included 49 patients. Maximum tolerated dose was not reached, but higher rates of adverse events were observed at higher dose levels. There were no treatment-related deaths. The most common treatment-related adverse events of any grade were increased aspartate aminotransferase (n = 31; 63%), increased alanine aminotransferase (n = 26; 53%), decreased neutrophil count (n = 26; 53%), and decreased white blood cell count (n = 26; 53%). Most adverse events were either grade 1 or 2. In the 44 patients with evaluable disease, 12 (27%) had stable disease as the best overall response, including three patients with prolonged stable disease, and 4 patients (9%) achieved a partial response.
CONCLUSIONS
The combination of paclitaxel and TAK-659 showed preliminary activity possibly overcoming resistance to taxane-based therapy as well as a tolerable safety profile in patients with advanced solid tumors.
Topics: Humans; Paclitaxel; Female; Middle Aged; Aged; Neoplasms; Male; Adult; Antineoplastic Combined Chemotherapy Protocols; Drug Resistance, Neoplasm; Taxoids; Maximum Tolerated Dose; Syk Kinase
PubMed: 38914452
DOI: 10.1016/j.esmoop.2024.103486 -
PloS One 2024Public health guidance recommended that children who are 6 months or older be vaccinated against COVID-19 in June of 2022. In the U.S., 56% of children under 17 had not...
BACKGROUND
Public health guidance recommended that children who are 6 months or older be vaccinated against COVID-19 in June of 2022. In the U.S., 56% of children under 17 had not received the COVID-19 vaccination in 2023. We examine parents' willingness to vaccinate their children against COVID-19 using the theory of planned behavior in order to design effective strategies to promote vaccine uptake.
METHODS
The Philadelphia Community Engagement Alliance is part of an NIH community-engaged consortium focused on addressing COVID-19 disparities across the U.S. We surveyed 1,008 Philadelphia parents (mean age 36.86, SD 6.55; 42.3% racial/ethnic minorities) between September 2021 and February 2022, a period when guidance for child vaccination was anticipated. Structural Equation Modeling analysis examined associations between parental willingness and vaccine-related attitudes, norms, and perceived control. Covariates included parents' COVID-19 vaccination status, race/ethnicity, gender, and survey completion post-CDC pediatric COVID-19 vaccination guidelines. Subgroup analyses by race/ethnicity and gender were conducted.
RESULTS
Our model demonstrated good fit (χ2 = 907.37, df = 419, p<0.001; comparative fit index [CFI] = 0.951; non-normed fit index [NNFI] = 0.946; root mean square error of approximation [RMSEA] = 0.034 with 95% CI = 0.030-0.038). Attitudes ([Formula: see text] = 0.447, p<0.001) and subjective norms ([Formula: see text] = 0.309, p = 0.002) were predictors of intention. Racial/ethnic minority parents exhibited weaker vaccination intentions ([Formula: see text] = -0.053, p = 0.028) than non-Hispanic White parents.
CONCLUSIONS
Parents' attitudes and norms influence their vaccination intentions. Despite the survey predating widespread child vaccine availability, findings are pertinent given the need to increase and sustain pediatric vaccinations against COVID-19. Interventions promoting positive vaccine attitudes and prosocial norms are warranted. Tailored interventions and diverse communication strategies for parental subgroups may be useful to ensure comprehensive and effective vaccination initiatives.
Topics: Humans; Parents; Female; Male; COVID-19; COVID-19 Vaccines; Adult; Vaccination; Child; SARS-CoV-2; Surveys and Questionnaires; Vaccination Hesitancy; Philadelphia; Health Knowledge, Attitudes, Practice; Child, Preschool; Middle Aged; Adolescent
PubMed: 38913679
DOI: 10.1371/journal.pone.0305877 -
PloS One 2024In the first year of roll-out, vaccination for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) prevented almost 20 million deaths from coronavirus disease...
BACKGROUND
In the first year of roll-out, vaccination for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) prevented almost 20 million deaths from coronavirus disease 2019 (COVID-19). Yet, little is known about the factors influencing access to vaccination at the individual level within rural poor settings of low-income countries. The aim of this study was to examine determinants of vaccine receipt in rural India.
METHODS
A census of a rural village in Tamil Nadu was undertaken from June 2021 to September 2022. We surveyed 775 participants from 262 households. Household-level data on socioeconomic status (SES), water, sanitation, and hygiene practices, and individual-level demographic information, travel history, and biomedical data, including anthropometry, vital signs, and comorbidities, were collected. Logistic regression models with 5-fold cross-validation were used to identify the biomedical, demographic, and socioeconomic determinants of vaccine receipt and the timing of receipt within the first 30 days of eligibility. Vaccine ineligible participants were excluded leaving 659 eligible participants. There were 650 eligible participants with complete biomedical, demographic, and socioeconomic data.
RESULTS
There were 68.0% and 34.0% of individuals (N = 650) who had received one and two vaccine doses, respectively. Participants with household ownership of a permanent account number (PAN) or ration card were 2.15 (95% CI:1.32-3.52) or 3.02 (95% CI:1.72-5.29) times more likely to receive at least one vaccine dose compared to households with no ownership of such cards. Participants employed as housewives or self-employed non-agricultural workers were 65% (95% CI:0.19-0.67) or 59% (95% CI:0.22-0.76) less likely to receive at least one vaccine dose compared to salaried workers. Household PAN card ownership, occupation and age were linked to the timing of vaccine receipt. Participants aged ≤18 and 45-60 years were 17.74 (95% CI:5.07-62.03) and 5.51 (95% CI:2.74-11.10) times more likely to receive a vaccine within 30 days of eligibility compared to 19-44-year-olds. Biomedical factors including BMI, vital signs, comorbidities, and COVID-19 specific symptoms were not consistently associated with vaccine receipt or timing of receipt. No support was found that travel history, contact with COVID-19 cases, and hospital admissions influenced vaccine receipt or timing of receipt.
CONCLUSION
Factors linked to SES were linked to vaccine receipt, more so than biomedical factors which were targeted by vaccine policies. Future research should explore if government interventions including vaccine mandates, barriers to vaccine access, or peer influence linked to workplace or targeted vaccine promotion campaigns underpin these findings.
Topics: Humans; India; COVID-19 Vaccines; Female; Male; COVID-19; Rural Population; Adult; Middle Aged; Socioeconomic Factors; Adolescent; Vaccination; SARS-CoV-2; Young Adult
PubMed: 38913614
DOI: 10.1371/journal.pone.0305819 -
JAMA Network Open Jun 2024Major concerns regarding individuals who adhere to a vegan diet are whether they meet protein and essential amino acid recommendations and how reliant they are on...
IMPORTANCE
Major concerns regarding individuals who adhere to a vegan diet are whether they meet protein and essential amino acid recommendations and how reliant they are on ultraprocessed foods.
OBJECTIVES
To investigate whether individuals who adhere to a vegan diet meet protein and essential amino acid recommendations and, as secondary objectives, to determine ultraprocessed food intake and potential factors associated with inadequate protein intake in this population.
DESIGN, SETTING, AND PARTICIPANTS
This cross-sectional survey study was conducted between September 2021 and January 2023 in Brazil among male and female adults (aged 18 years or older) who adhered to a vegan diet recruited from social media platforms.
EXPOSURE
Adherence to a vegan diet and unprocessed and minimally processed foods and ultraprocessed food consumption.
MAIN OUTCOMES AND MEASURES
Protein and essential amino acid intake and food consumption by processing level were assessed using a 1-day food diary. Nutrient adequacy ratios were calculated by dividing nutrient intake by its recommendation (using scores truncated at 1) for each participant and then finding the mean across participants for each nutrient. The mean adequacy ratio was the mean of all nutrient adequacy ratios.
RESULTS
Of 1014 participants who completed the survey, 774 individuals (median [IQR] age, 29 [24-35] years; 637 female [82.3%]) were confirmed as adhering to a vegan diet and provided adequate food recalls, among whom 558 individuals reported body weight and so had relative protein and amino acid intake values available. The median (IQR) body mass index (calculated as weight in kilograms divided by height in meters squared) of participants was 22.6 (20.3-24.8). The nutrient adequacy ratio of protein was 0.93 (95% CI, 0.91-0.94); for essential amino acids, ratios ranged from 0.90 (95% CI, 0.89-0.92) for lysine to 0.98 (95% CI, 0.97-0.99) for phenylalanine and tyrosine. The mean adequacy ratio for protein and all amino acids was 0.95 (95% CI, 0.94-0.96). The median intake level was 66.5% (95% CI, 65.0%-67.9%) of total energy intake for unprocessed and minimally processed food and 13.2% (95% CI, 12.4%-14.4%) of total energy intake for ultraprocessed food. Adjusted logistic regression models showed that consuming protein supplements (odds ratio [OR], 0.06 [95% CI 0.02-0.14]; P < .001) or textured soy protein (OR, 0.32 [95% CI, 0.17-0.59]; P < .001) was associated with decreased odds of inadequate protein intake. Higher ultraprocessed food intake levels were also associated with decreased odds of inadequate protein intake (eg, fourth vs first quartile of intake: OR, 0.16 [95% CI, 0.07-0.33]; P < .001), and higher unprocessed and minimally processed protein intake levels were associated with increased odds of inadequate protein intake (eg, fourth vs first quartile of intake: OR, 12.42 [95% CI, 5.56-29.51]; P < .001).
CONCLUSIONS AND RELEVANCE
In this study, most individuals who adhered to a vegan diet attained protein and essential amino acid intake recommendations, largely based their diet of unprocessed and minimally processed food, and had a significantly lower proportion of ultraprocessed food intake compared with previous reports. Participants consuming less ultraprocessed food were more likely to have inadequate protein intake, suggesting a significant reliance on ultraprocessed proteins for this population.
Topics: Humans; Female; Male; Adult; Brazil; Cross-Sectional Studies; Dietary Proteins; Vegans; Young Adult; Diet, Vegan; Food Handling; Middle Aged; Eating; Amino Acids; Amino Acids, Essential
PubMed: 38913373
DOI: 10.1001/jamanetworkopen.2024.18226 -
Gynecological Endocrinology : the... Dec 2024Female sexual interest and arousal disorder (FSIAD) is the most prevalent female sexual dysfunction in the postmenopause. (Review)
Review
INTRODUCTION
Female sexual interest and arousal disorder (FSIAD) is the most prevalent female sexual dysfunction in the postmenopause.
OBJECTIVE
The aim of this review is to provide a summary of the currently available evidence on the use of testosterone in the treatment of FSIAD in postmenopausal women.
METHODS
A narrative review on the topic was performed. Only randomized controlled trials (RCTs) and systematic reviews and meta-analysis were considered. 123 articles were screened, 105 of them assessed for eligibility, and finally 9 were included in qualitative synthesis following the PRISMA declaration.
RESULTS
Current evidence recommends, with moderate therapeutic benefit, the use of systemic transdermal testosterone within the premenopausal physiological range in postmenopausal women with Hypoactive Sexual Desire Disorder (HSDD), the previous entity for low desire dysfunction, not primarily related to modifiable factors or comorbidities such as relationship or mental health problems. The available evidence is based on studies with heterogeneity on their design (different testosterone doses, routes of administration, testosterone use in combination and alone, sexual instruments of measurement). There is no data indicating severe short-term adverse effects, although long-term safety data is lacking.
CONCLUSIONS
Despite having testosterone as a valuable tool, therapeutic strategies are lacking in the pharmacological field of HSDD/FSIAD. Neuroimaging studies could provide valuable information regarding the sexual desire substrate and suggest the potential application of already approved drugs for women with a good safety profile. The use of validated instruments for HSDD in postmenopausal women, considering the level of distress, is necessary to be able to draw robust conclusions on the evaluated treatments.
Topics: Humans; Female; Testosterone; Sexual Dysfunctions, Psychological; Postmenopause; Libido
PubMed: 38913119
DOI: 10.1080/09513590.2024.2364220 -
Acta Oncologica (Stockholm, Sweden) Jun 2024Background and purpose: Capecitabine can be used as first-line treatment for advanced breast cancer. However, real-world data on efficacy of capecitabine in this...
UNLABELLED
Background and purpose: Capecitabine can be used as first-line treatment for advanced breast cancer. However, real-world data on efficacy of capecitabine in this setting is sparse. The purpose of the study is to evaluate outcomes of patients with Human Epidermal Growth Factor Receptor (HER2)-normal advanced breast cancer treated with capecitabine monotherapy as first-line treatment.
MATERIAL AND METHODS
The study utilized the Danish Breast Cancer Group (DBCG) database and was conducted retrospectively across all Danish oncology departments. Inclusion criteria were female patients, with HER2-normal advanced breast cancer treated with capecitabine monotherapy as the first-line treatment from 2010 to 2020. The primary endpoints were overall survival (OS) and progression-free survival (PFS).
RESULTS
A total of 494 patients were included. Median OS was 16.4 months (95% confidence interval [CI]: 14.5-18.0), and median PFS was 6.0 months (95% CI: 5.3-6.7). Patients with estrogen receptor (ER)-positive disease had significantly longer OS (median: 22.8 vs. 10.5 months, p < 0.001) and PFS (median: 7.4 vs. 4.9 months, p = 0.003), when compared to ER-negative patients. Stratifying by age, patients under 45 years displayed a median PFS of 4.1 months, while those aged 45-70 years and over 70 years had median PFS of 5.7 and 7.2 months, respectively (p = 0.01).
INTERPRETATION
In this nationwide study, the efficacy of capecitabine as a first-line treatment for HER2-normal advanced breast cancer is consistent with other, mainly retrospective, studies. However, when assessed against contemporary and newer treatments, its effectiveness appears inferior to alternative chemotherapies or targeted therapies.
Topics: Humans; Capecitabine; Female; Retrospective Studies; Breast Neoplasms; Middle Aged; Receptor, ErbB-2; Aged; Adult; Antimetabolites, Antineoplastic; Aged, 80 and over; Denmark; Progression-Free Survival; Receptors, Estrogen
PubMed: 38912829
DOI: 10.2340/1651-226X.2024.38886 -
International Journal of Chronic... 2024Current guidelines recommend triple therapy maintenance inhalers for patients with recurrent exacerbations of chronic obstructive pulmonary disease (COPD); however,...
PURPOSE
Current guidelines recommend triple therapy maintenance inhalers for patients with recurrent exacerbations of chronic obstructive pulmonary disease (COPD); however, these maintenance therapies are underutilized. This study aimed to understand how physicians make COPD treatment decisions, and how combination maintenance therapies are utilized in a real-world setting.
PATIENTS AND METHODS
This exploratory, hypothesis-generating, non-interventional study used a cross-sectional online survey that was administered to a sample of practicing physicians in the United States. The survey included five fictitious vignettes detailing common symptoms experienced by patients with COPD. Survey questions included factors physicians consider in their decisions, and perceived barriers to prescribing treatments. Repeated measures multivariable analyses were conducted to evaluate how likely physicians were to switch to triple therapy versus no change to patient's current maintenance therapy or change to another maintenance therapy.
RESULTS
In total, 200 physicians completed the survey. Cost of treatment and patient access to treatment were reported as the most common barriers physicians consider in their prescribing decisions. Physicians were more likely to switch a patient's maintenance inhaler to triple therapy versus no change to maintenance inhaler if they considered the patient's history of new symptoms, insurance status, and clinical guidelines in their decision. Physicians with more experience treating patients with COPD, and those who treat more patients with COPD per week, were more likely to switch to triple therapy versus no change to maintenance inhaler.
CONCLUSION
This study demonstrates the complexity of factors that can influence physicians' decisions when prescribing treatments for patients with COPD, including considerations of treatment cost, patient access and adherence, patient comorbidities, efficacy of current treatment, clinical guidelines, and provider's level of experience treating COPD. Further research may help elucidate the relative importance of the factors influencing physicians' decisions and inform what types of decision-support tools would be most beneficial.
Topics: Humans; Pulmonary Disease, Chronic Obstructive; Cross-Sectional Studies; Practice Patterns, Physicians'; Male; Clinical Decision-Making; Female; Middle Aged; United States; Health Care Surveys; Bronchodilator Agents; Administration, Inhalation; Nebulizers and Vaporizers; Drug Therapy, Combination; Attitude of Health Personnel; Treatment Outcome; Health Knowledge, Attitudes, Practice; Drug Costs; Lung; Aged; Practice Guidelines as Topic; Adult; Health Services Accessibility
PubMed: 38912054
DOI: 10.2147/COPD.S454877 -
PeerJ 2024The incidence of perioperative neurocognitive disorders (PND) is high, especially after cardiac surgeries, and the underlying mechanisms remain elusive. Here, we... (Observational Study)
Observational Study
OBJECTIVE
The incidence of perioperative neurocognitive disorders (PND) is high, especially after cardiac surgeries, and the underlying mechanisms remain elusive. Here, we conducted a prospective observational study to observe serum proteomics differences in PND patients after cardiac valve replacement surgery.
METHODS
Two hundred and twenty-six patients who underwent cardiac valve surgery were included. They were categorized based on scoring into non-PND group (group non-P) and PND group (group P'). The risk factors associated with PND were analyzed. These patients were further divided into group C and group P by propensity score matching (PSM) to investigate the serum proteome related to the PND by serum proteomics.
RESULTS
The postoperative 6-week incidence of PND was 16.8%. Risk factors for PND include age, chronic illness, sufentanil dosage, and time of cardiopulmonary bypass (CPB). Proteomics identified 31 down-regulated proteins and six up-regulated proteins. Finally, GSTO1, IDH1, CAT, and PFN1 were found to be associated with PND.
CONCLUSION
The occurrence of PND can impact some oxidative stress proteins. This study provided data for future studies about PND to general anaesthesia and surgeries.
Topics: Humans; Male; Prospective Studies; Female; Proteomics; Middle Aged; Heart Valve Prosthesis Implantation; Risk Factors; Cognitive Dysfunction; Aged; Postoperative Complications; Postoperative Cognitive Complications; Incidence; Propensity Score; Adult
PubMed: 38912047
DOI: 10.7717/peerj.17536 -
Frontiers in Immunology 2024The Nipah virus (NiV), a highly deadly bat-borne paramyxovirus, poses a substantial threat due to recurrent outbreaks in specific regions, causing severe respiratory and...
The Nipah virus (NiV), a highly deadly bat-borne paramyxovirus, poses a substantial threat due to recurrent outbreaks in specific regions, causing severe respiratory and neurological diseases with high morbidity. Two distinct strains, NiV-Malaysia (NiV-M) and NiV-Bangladesh (NiV-B), contribute to outbreaks in different geographical areas. Currently, there are no commercially licensed vaccines or drugs available for prevention or treatment. In response to this urgent need for protection against NiV and related infections, we developed a novel homotypic virus-like nanoparticle (VLP) vaccine co-displaying NiV attachment glycoproteins (G) from both strains, utilizing the self-assembling properties of ferritin protein. In comparison to the NiV G subunit vaccine, our nanoparticle vaccine elicited significantly higher levels of neutralizing antibodies and provided complete protection against a lethal challenge with NiV infection in Syrian hamsters. Remarkably, the nanoparticle vaccine stimulated the production of antibodies that exhibited superior cross-reactivity to homologous or heterologous . These findings underscore the potential utility of ferritin-based nanoparticle vaccines in providing both broad-spectrum and long-term protection against NiV and emerging zoonotic challenges.
Topics: Animals; Nipah Virus; Henipavirus Infections; Ferritins; Mesocricetus; Antibodies, Viral; Antibodies, Neutralizing; Nanoparticles; Viral Vaccines; Cricetinae; Vaccines, Virus-Like Particle; Female; Humans; Nanovaccines
PubMed: 38911870
DOI: 10.3389/fimmu.2024.1387811 -
Frontiers in Immunology 2024Vitamin E, which is also known as tocopherol, is a compound with a polyphenol structure. Its esterified derivative, Vitamin E succinate (VES), exhibits unique anticancer...
BACKGROUND
Vitamin E, which is also known as tocopherol, is a compound with a polyphenol structure. Its esterified derivative, Vitamin E succinate (VES), exhibits unique anticancer and healthcare functions as well as immunomodulatory effects. Natural polysaccharides are proved to be a promising material for nano-drug delivery systems, which show excellent biodegradability and biocompatibility. In this study, we employed a novel polysaccharide-vitamin E succinate polymer (BSP-VES) micelles to enhance the tumor targeting and anti-colon cancer effect of andrographolide (AG).
METHODS
BSP-VES polymer was synthesized through esterification and its structure was confirmed using 1H NMR. AG@BSP-VES was prepared via the dialysis method and the drug loading, entrapment efficiency, stability, and safety were assessed. Furthermore, the tumor targeting ability of AG@BSP-VES was evaluated through targeted cell uptake and imaging. The antitumor activity of AG@BSP-VES was measured using MTT assay, Live&Dead cell staining, and cell scratch test.
RESULTS
In this study, we successfully loaded AG into BSP-VES micelles (AG@BSP-VES), which exhibited good stability, biosafety and sustained release effect. In addition, AG@BSP-VES also showed excellent internalization capability into CT26 cells compared with NCM460 cells . Meanwhile, the specific delivery of AG@BSP-VES micelles into subcutaneous and colon tumors was observed compared with normal colon tissues during the whole experiment process (1-24 h). What's more, AG@BSP-VES micelles exhibited significant antitumor activities than BSP-VES micelles and free AG.
CONCLUSION
The study provides a meaningful new idea and method for application in drug delivery system and targeted treatment of colon cancer based on natural polysaccharides.
Topics: Micelles; Animals; Colonic Neoplasms; Diterpenes; Humans; Mice; Cell Line, Tumor; Polysaccharides; Antineoplastic Agents; Drug Delivery Systems; Xenograft Model Antitumor Assays; Drug Carriers; Nanoparticles; Nanoparticle Drug Delivery System; Mice, Nude; Mice, Inbred BALB C
PubMed: 38911867
DOI: 10.3389/fimmu.2024.1380229