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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 -
Public Health Research & Practice Jun 2024An asymptomatic COVID-19 rapid antigen testing (RAT) screening program was implemented in Victorian schools in January 2022, to support keeping schools open throughout...
BACKGROUND
An asymptomatic COVID-19 rapid antigen testing (RAT) screening program was implemented in Victorian schools in January 2022, to support keeping schools open throughout the pandemic. This study explored compliance with the program among caregivers from priority populations in Victorian mainstream and specialist schools.
METHODS
We conducted semi-structured interviews between 7-31 March 2022 with caregivers of school-aged children participating in the RAT program in Victoria. Participants were asked about awareness, acceptability, compliance, frequency, and barriers to testing. Recordings were transcribed and deductively analysed using a framework approach.
RESULTS
Fifty caregivers participated. They expressed confusion about the 'recommended' program, assuming it was mandatory. Caregivers wanted notification from schools of positive cases to increase motivation for compliance. Culturally and linguistically diverse (CALD) families were compliant; however, in-language resources were limited. Aboriginal or Torres Strait Islander (Koori) families tested less regularly and received information from their community rather than school. Caregivers of children living with disabilities reported behavioural challenges to testing, resulting in distress or non-compliance, and received non-specific information for their children.
CONCLUSIONS
To increase engagement with future surveillance programs, caregivers need clarity about optionality, conducting tests, reporting results, and timely notification of cases. Requirements unique to each priority population include: accurate in-language information for CALD caregivers, community-led communication for Koori caregivers, tailored information, less testing, and flexibility for caregivers of children living with a disability. Keeping schools open and having tailored strategies to ensure equitable access for priority populations are essential for future pandemic management.
PubMed: 38914416
DOI: 10.17061/phrp34232407 -
PloS One 2024This study aimed to measure the preferences for mental health support among health professionals, their willingness to support the mental health of colleagues and...
BACKGROUND
This study aimed to measure the preferences for mental health support among health professionals, their willingness to support the mental health of colleagues and associated factors.
METHOD
A descriptive cross-sectional study was performed from August to October 2022 within five hospitals located in Hanoi, Vietnam. A total of 244 health professionals participated in the study. Data on socio-economic status, health and COVID-19-related characteristics, Depression Anxiety Stress Scale (DASS-21); and preferences for mental health support services were collected by using a structured self-reported questionnaire. Multivariate logistic regression models were utilized to identify associated factors with the demand for mental support services.
RESULTS
13.9%, 17.1% and 8.6% reported having at least mild depression, anxiety and stress, respectively. There 13.9% did not seek any mental health support during the COVID-19 pandemic. The most common support included talking with friends (52.9%), family (50.8%), colleagues (47.6%) and using social networks/Internet (43.5%). There 31.1% had been aware of mental health services, but only 18.0% used this service at least once. Regarding preferences, 47.3% had a demand for mental support services, and the most preferred service was providing coping skills (25.9%), followed by skills to support others against mental problems (22.2%). Major sources of support included psychiatrists (34.4%), colleagues (29.1%) and family (27.9%). The main preferred channels for support included telephone/mobile phone (35.7%) and Internet (20.9%). Only 12.3% were willing to provide mental support for colleagues during the pandemic. Age, education, perceived mental health status, ever seeking any mental service, and DASS-21 depression score were associated with demand for mental support services.
CONCLUSION
This study found a lack of awareness of mental health services for health professionals, as well as moderate levels of demand for this service in this population. Raising awareness and developing tailored mental health support services are important to enhancing the mental well-being of health professionals in Vietnam to prepare for the next pandemic.
Topics: Humans; COVID-19; Vietnam; Male; Female; Adult; Cross-Sectional Studies; Health Personnel; Mental Health Services; Middle Aged; Depression; Mental Health; Anxiety; Pandemics; Surveys and Questionnaires; SARS-CoV-2; Stress, Psychological; Social Support
PubMed: 38913676
DOI: 10.1371/journal.pone.0305869 -
PloS One 2024This study aimed to determine differences in the hip abductor muscle activity during clam exercise at different hip flexion and femoral anteversion angles. Thirty...
This study aimed to determine differences in the hip abductor muscle activity during clam exercise at different hip flexion and femoral anteversion angles. Thirty healthy females were divided into two groups based on the femoral anteversion angle: the excessive femoral anteversion group and the normal group. Clam exercise was performed at three different hip flexion angles (60°, 45°, and 30°). Tensor fascia latae, gluteus medius, and superior portion of gluteus maximus activities were measured during the exercise, and the results were normalized to the activity during maximum voluntary isometric contraction to calculate the gluteal-to-tensor fascia latae muscle activation index. The superior portion of gluteus maximus activities at a hip flexion of 60° and 45° were greater than that at 30°. The excessive femoral anteversion group had a lower gluteal-to-tensor fascia latae muscle activation index than the normal group; the gluteal-to-tensor fascia latae muscle activation index for hip flexion at 60° was higher than that at 45°, and the gluteal-to-tensor fascia latae muscle activation index for hip flexion at 60° and 45° were higher than that at 30°. Therefore, the femoral anteversion angle and hip joint position were related to the activity of the hip abductor muscles during clam exercise. These findings may provide a rationale for instructing exercises to maximize the activity of the hip abductor muscles in individuals with an excessive femoral anteversion angle.
Topics: Humans; Female; Muscle, Skeletal; Hip Joint; Femur; Exercise; Range of Motion, Articular; Young Adult; Adult; Isometric Contraction; Electromyography
PubMed: 38913672
DOI: 10.1371/journal.pone.0305515 -
JAMA Network Open Jun 2024Recent evidence suggests that childhood levels of serum lipids, blood pressure, body mass index (BMI), and smoking contribute to adult risk of cardiovascular disease...
IMPORTANCE
Recent evidence suggests that childhood levels of serum lipids, blood pressure, body mass index (BMI), and smoking contribute to adult risk of cardiovascular disease (CVD). Evidence is lacking on whether this is independent of adult risk levels.
OBJECTIVE
To quantify direct and indirect effects of childhood risk factors on adult CVD via adulthood risk factors using mediation analysis, and to quantify their relative importance during different life-course stages using a life-course approach.
DESIGN, SETTING, AND PARTICIPANTS
This prospective cohort study followed participants from the US, Finland, and Australia from childhood (1970s-1990s) until 2019, with data on CVD risk factors in childhood and adulthood. Longitudinal childhood and adulthood risk factors were summarized to describe BMI, lipids, and blood pressure cumulatively. Childhood and adulthood smoking were assessed with questionnaires. Data analysis was performed May 2022 to August 2023.
MAIN OUTCOMES AND MEASURES
The primary outcomes were fatal and nonfatal cardiovascular events in adulthood. Mediation analysis was used to estimate the direct and indirect effects of the childhood risk factors with CVD events, reported as incidence rate ratios (RRs) and 95% CIs.
RESULTS
A total of 10 634 participants (4506 male participants [42.4%]; mean [SD] age at childhood visit, 13.3 [3.0] years; mean [SD] age at adulthood visit, 32.3 [6.0] years) were included in the cohort. The mean (SD) age at CVD event or censoring was 49.2 (7.0) years. The median (IQR) follow-up time was 23.6 (18.7-30.2) years. Childhood risk factors, (low-density lipoprotein cholesterol [LDL-C], total cholesterol [TC], triglycerides, systolic blood pressure [SBP], smoking, BMI, and a combined score of these) were associated with CVD. BMI (direct effect for incidence RR per 1 SD unit, 1.18; 95% CI, 1.05-1.34) and LDL-C (direct effect incidence RR, 1.16; 95% CI, 1.01-1.34) in particular were found to play an important role via direct pathways, whereas the indirect effects were larger for TC, triglycerides, SBP, and the combined score. Childhood smoking only affected CVD via adulthood smoking. Life-course models confirmed that for the risk of CVD, childhood BMI plays nearly as important role as adulthood BMI, whereas for the other risk factors and the combined score, adulthood was the more important period.
CONCLUSIONS AND RELEVANCE
In this cohort study of 10 634 participants, childhood risk factors were found to be associated both directly and indirectly to adult CVD, with the largest direct effect seen for BMI and LDL-C. These findings suggest that intervention for childhood risk factors, in particular BMI, is warranted to reduce incidence of adult CVD as it cannot be fully mitigated by risk factor management in adulthood.
Topics: Humans; Male; Cardiovascular Diseases; Female; Child; Prospective Studies; Heart Disease Risk Factors; Finland; Middle Aged; Adolescent; Adult; Body Mass Index; Australia; Smoking; Risk Factors; United States; Blood Pressure; Incidence
PubMed: 38913374
DOI: 10.1001/jamanetworkopen.2024.18148 -
JAMA Network Open Jun 2024There is significant concern regarding increasing long-term antidepressant treatment for depression beyond an evidence-based duration. (Randomized Controlled Trial)
Randomized Controlled Trial
IMPORTANCE
There is significant concern regarding increasing long-term antidepressant treatment for depression beyond an evidence-based duration.
OBJECTIVE
To determine whether adding internet and telephone support to a family practitioner review to consider discontinuing long-term antidepressant treatment is safe and more effective than a practitioner review alone.
DESIGN, SETTING, AND PARTICIPANTS
In this cluster randomized clinical trial, 131 UK family practices were randomized between December 1, 2018, and March 31, 2022, with remote computerized allocation and 12 months of follow-up. Participants and researchers were aware of allocation, but analysis was blind. Participants were adults who were receiving antidepressants for more than 1 year for a first episode of depression or more than 2 years for recurrent depression who were currently well enough to consider discontinuation and wished to do so and who were at low risk of relapse. Of 6725 patients mailed invitations, 330 (4.9%) were eligible and consented.
INTERVENTIONS
Internet and telephone self-management support, codesigned and coproduced with patients and practitioners.
MAIN OUTCOMES AND MEASURES
The primary (safety) outcome was depression at 6 months (prespecified complete-case analysis), testing for noninferiority of the intervention to under 2 points on the 9-item Patient Health Questionnaire (PHQ-9). Secondary outcomes (testing for superiority) were antidepressant discontinuation, anxiety, quality of life, antidepressant withdrawal symptoms, mental well-being, enablement, satisfaction, use of health care services, and adverse events. Analyses for the main outcomes were performed on a complete-case basis, and multiple imputation sensitivity analysis was performed on an intention-to-treat basis.
RESULTS
Of 330 participants recruited (325 eligible for inclusion; 178 in intervention practices and 147 in control practices; mean [SD] age at baseline, 54.0 [14.9] years; 223 women [68.6%]), 276 (83.6%) were followed up at 6 months, and 240 (72.7%) at 12 months. The intervention proved noninferior; mean (SD) PHQ-9 scores at 6 months were slightly lower in the intervention arm than in the control arm in the complete-case analysis (4.0 [4.3] vs 5.0 [4.7]; adjusted difference, -1.1; 95% CI, -2.1 to -0.1; P = .03) but not significantly different in an intention-to-treat multiple imputation sensitivity analysis (adjusted difference, -0.9 (95% CI, -1.9 to 0.1; P = .08). By 6 months, antidepressants had been discontinued by 66 of 145 intervention arm participants (45.5%) who provided discontinuation data and 54 of 129 control arm participants (41.9%) (adjusted odds ratio, 1.02; 95% CI, 0.52-1.99; P = .96). In the intervention arm, antidepressant withdrawal symptoms were less severe, and mental well-being was better compared with the control arm; differences were small but significant. There were no significant differences in the other outcomes; 28 of 179 intervention arm participants (15.6%) and 22 of 151 control arm participants (14.6%) experienced adverse events.
CONCLUSIONS AND RELEVANCE
In this cluster randomized clinical trial of adding internet and telephone support to a practitioner review for possible antidepressant discontinuation, depression was slightly better with support, but the rate of discontinuation of antidepressants did not significantly increase. Improvements in antidepressant withdrawal symptoms and mental well-being were also small. There were no significant harms. Family practitioner review for possible discontinuation of antidepressants appeared safe and effective for more than 40% of patients willing and well enough to discontinue.
TRIAL REGISTRATION
ISRCTN registry Identifiers: ISRCTN15036829 (internal pilot trial) and ISRCTN12417565 (main trial).
Topics: Humans; Female; Male; Antidepressive Agents; Middle Aged; Telephone; Adult; Internet; Depression; United Kingdom
PubMed: 38913372
DOI: 10.1001/jamanetworkopen.2024.18383 -
International Journal of Biomaterials 2024Periodontitis therapy employing nanomaterials with submicron sizes holds promise for enhancing osteogenesis and facilitating periodontal cell proliferation. This study...
INTRODUCTION
Periodontitis therapy employing nanomaterials with submicron sizes holds promise for enhancing osteogenesis and facilitating periodontal cell proliferation. This study aims to assess the potential of nanoparticle-based rice husk liquid smoke (-RHLS) in an animal model of periodontitis by evaluating the expression of osteoprotegerin (OPG), receptor activator of nuclear factor-k (RANK), and receptor activator of nuclear factor-k ligand (RANKL).
METHODS
Twenty-eight male Wistar rats were inoculated with 10 CFU/ml of in the sulcus mandibular incisor region to create periodontitis and subsequently treated with n-RHLS while the control with saline. Immunohistochemical staining was performed on the mandibular incisor to assess OPG, RANK, and RANKL expression 2 and 7 days after treatment.
RESULTS
OPG expression exhibited a significant increase at both 2 and 7 days, while RANKL expression decreased notably after 7 days of treatment using n-RHLS ( < 0.05). In contrast, RANK expression did not show significant differences compared to the control groups ( > 0.05).
CONCLUSION
Nanostructured liquid smoke derived from rice husk nanoparticles (-RHLS) demonstrates potential as a therapeutic agent for periodontitis, especially on OPG/RANK/RANKL expression, by modulating OPG and RANKL expression to support periodontal tissue health.
PubMed: 38912518
DOI: 10.1155/2024/5015893 -
Heliyon Jun 2024Dental follicle cells (DFCs) promote bone regeneration and Circular RNAs (circRNAs) play crucial roles in bone development and regeneration. Our previous study...
Dental follicle cells (DFCs) promote bone regeneration and Circular RNAs (circRNAs) play crucial roles in bone development and regeneration. Our previous study demonstrated the upregulation of circFgfr2 expression during the osteogenic differentiation of DFCs. However, the molecular mechanisms and functional roles of circFgfr2 in DFCs osteogenesis remain unclear. In this study, we aimed to investigate the subcellular localization of circFgfr2 in DFCs using fluorescence hybridization. investigations demonstrated that circFgfr2 overexpression promoted osteogenic differentiation, as evidenced by real-time quantitative polymerase chain reaction. By integrating the outcomes of bioinformatics analyses, dual luciferase reporter experiments, and chromatin isolation by RNA purification, we identified circFgfr2 as a sponge for miR-133a-3p, a key regulator of osteogenic differentiation. Moreover, miR-133a-3p suppressed osteogenic differentiation by targeting DLX3 and RUNX2 in DFCs. We validated that circFgfr2 promoted the osteogenic differentiation of DFCs through the miR-133a-3p/DLX3 axis. To further investigate the therapeutic potential of circFgfr2 in bone regeneration, we conducted experiments and histological analyses. Overall, these results confirmed the crucial role of circFgfr2 in promoting osteogenesis. In summary, our findings demonstrated that the circFgfr2/miR-133a-3p/DLX3 pathway acts as a cascade, thereby identifying circFgfr2 as a promising molecular target for bone tissue engineering.
PubMed: 38912473
DOI: 10.1016/j.heliyon.2024.e32498 -
Heliyon Jun 2024This study aimed to investigate the performance and reliability of data-driven models employing correlational feature analysis and clinical validation for predicting...
OBJECTIVES
This study aimed to investigate the performance and reliability of data-driven models employing correlational feature analysis and clinical validation for predicting periodontal disease.
METHODS
The 7th Korea National Health and Nutrition Examination Survey ( = 10,654) was used for correlation analysis to identify significant risk factors for periodontitis. Periodontal prediction models were developed with the selected factors and database, followed by internal validation with 5-fold cross-validation and 1000 bootstrap resampling. External validation was conducted with clinical data ( = 120) collected through self-reported questionnaires, clinical periodontal parameters, and radiographic image analysis. Predictive performance was assessed for logistics regression, support vector machine, random forest, XGBoost, and neural network algorithms using the area under the receiver operating characteristic curves (AUC) and other performance metrics.
RESULTS
Correlation analysis identified 16 features from over 1000 potential risk factors for periodontitis. The best data-driven model (XGBoost) showed AUC values of 0.823 and 0.796 for internal and external validations, respectively. Modeling with clinical data revealed those same measures to be 0.836 and 0.649, respectively. In addition, the data-driven model could predict other clinical periodontal parameters including severe bone loss (AUC = 0.813), gingival bleeding (AUC = 0.694), and tooth loss (AUC = 0.734). A patient case study about prognostic predictions revealed that the probability of periodontitis can be reduced by 6.0 % (stop smoking) and 0.6 % (stop drinking) on average.
CONCLUSIONS
Data-driven models for predicting periodontitis and other periodontal parameters were developed from 16 risk factors, demonstrating enhanced prediction performance and reproducibility in internal-external validations.
PubMed: 38912435
DOI: 10.1016/j.heliyon.2024.e32496 -
Frontiers in Public Health 2024The primary health care system provides an ideal setting for the integration of oral health into general health care as well as equitable access to oral health care....
INTRODUCTION
The primary health care system provides an ideal setting for the integration of oral health into general health care as well as equitable access to oral health care. However, the limited oral health knowledge of primary health care workers necessitates appropriate training before they can participate in health promotion efforts. This pilot training was designed to examine the impact of the Oral Health Education module for Nurses and Community Health Care Workers on their oral health awareness and referral practices.
METHODS
This study will utilize a quasi-experimental design (pre-and post with a non-equivalent control group) to assess the impact of a five-day pilot oral health education program on the knowledge and referral practices of Nurses and Community Health Workers in primary health care centers in three states in Nigeria-(Lagos, Oyo, and Kano). The training modules were developed based on the six iterative steps described in the intervention mapping framework - needs assessment, highlighting program objectives and outcomes, selection of theory and mode of intervention, designing program based on theory, designing implementation plans, and developing an evaluation plan. Only the intervention group will participate in the full educational training sessions but both groups will complete the pre-and post-intervention questionnaires.
DISCUSSION
This pilot training combined the standardized training modules from the recently launched " and a newly developed maternal and child oral health module by our group using an evidence-based approach. To the best of our knowledge, this is the first program to examine the impact of the standardized OpenWHO modules. The success of this training will lay the foundation for developing a sustained channel for providing oral health education at the primary health care level in Nigeria, West Africa, and Africa.
Topics: Humans; Nigeria; Pilot Projects; Community Health Workers; Oral Health; Nurses; Primary Health Care; Female; Health Knowledge, Attitudes, Practice; Adult; Male
PubMed: 38912270
DOI: 10.3389/fpubh.2024.1398869