Hallmarks of cancer stemness.

Cancer stemness is recognized as a key component of tumor development. Previously coined "cancer stem cells" (CSCs) and believed to be a rare population with rigid hierarchical organization, there is good evidence to suggest that these cells exhibit a plastic cellular state influenced by dynamic CSC-niche interplay. This revelation underscores the need to reevaluate the hallmarks of cancer stemness. Herein, we summarize the techniques used to identify and characterize the state of these cells and discuss their defining and emerging hallmarks, along with their enabling and associated features. We also highlight potential future directions in this field of research.

Slow art plus: developing and piloting a single session art gallery-based intervention for mental health promotion via a mixed method waitlist randomized control trial.

Introduction: The current study builds on the expertise of National Gallery Singapore and Nanyang Technological University Singapore (NTU) in developing and piloting an enhanced version of the Slow Art program, namely "Slow Art Plus" for mental health promotion. Methods: A single-site, open-label, waitlist Randomized Control Trial (RCT) design comprising of a treatment group and waitlist control group was adopted (ClinicalTrials.gov ID: NCT05803226). Participants (N = 196) completed three online questionnaires at three timepoints: baseline [T1], immediately post-intervention/s baseline [T2], post-intervention follow-up/immediately post-intervention [T3]. Qualitative focus groups were conducted to evaluate program acceptability. Results: A mixed model ANOVA was performed to understand intervention effectiveness between the immediate intervention group and waitlist control group. The analyses revealed a significant interaction effect where intervention group participants reported an improvement in spiritual well-being (p = 0.001), describing their thoughts and experiences (p = 0.02), and nonreacting to inner experiences (p = 0.01) immediately after Slow Art Plus as compared to the control group. Additionally, one-way repeated measure ANOVAs were conducted for the intervention group to evaluate maintenance effects of the intervention. The analyses indicated significant improvements in perceived stress (p < 0.001), mindfulness (p < 0.001) as well as multiple mindfulness subscales, active engagement with the world (p = 0.003), and self-compassion (p = 0.02) 1 day after the completion of Slow Art Plus. Results from framework analysis of focus group data revealed a total of two themes (1: Experiences of Slow Art Plus, 2: Insights to Effective Implementation) and six subthemes (1a: Peaceful relaxation, 1b: Self-Compassion, 1c: Widened Perspective, 2a: Valuable Components, 2b: Execution Requisites, 2c: Suggested Enhancements), providing valuable insights to the overall experience and implementation of the intervention. Discussion: Slow Art Plus represents a unique approach, offering a standardized, multimodal, single-session program that integrates mindfulness and self-compassion practices, as well as reflective and creative expressions with Southeast Asian art. It demonstrates potential in meeting the mental health needs of a wide range of individuals and could be readily incorporated into social prescribing initiatives for diverse populations.

Targeting AXL induces tumor-intrinsic immunogenic response in tyrosine kinase inhibitor-resistant liver cancer.

Hepatocellular carcinoma (HCC) is an aggressive malignancy without effective therapeutic approaches. Here, we evaluate the tumor-intrinsic mechanisms that attenuate the efficacy of immune checkpoint inhibitor (ICI) that is observed in patients with advanced HCC who progress on first-line tyrosine kinase inhibitor (TKI) therapy. Upregulation of AXL observed in sorafenib- and lenvatinib-resistant HCCs is correlated with poor response towards TKI and ICI treatments. AXL upregulation protects sorafenib-resistant HCC cells from oxidative stress, mitochondrial damage, and accompanying immunogenic cell death through suppressed tumor necrosis factor-α (TNF-α) and STING-type I interferon pathways. Pharmacological inhibition of AXL abrogates the protective effect and re-sensitizes TKI-resistant HCC tumors to anti-PD-1 treatment. We suggest that targeting AXL in combination with anti-PD-1 may provide an alternative treatment scheme for HCC patients who progress on TKI treatment.

Economic evaluation of oral ivermectin, alone or in combination with permethrin, versus permethrin, in the treatment of classic scabies in the Philippine Setting

Background and Objective@#Oral ivermectin is recommended as an alternative to topical permethrin in Japanese, European, and CDC-STI guidelines for treating classic scabies. The combination of oral ivermectin and topical permethrin is also used in some settings. Partial economic evaluations conducted in India and Egypt have conflicting results, and no cost-effectiveness analysis in the Philippines has compared ivermectin-based regimens to permethrin for scabies treatment. We aimed to determine the cost-effectiveness of oral ivermectin, alone or in combination with permethrin, compared to permethrin, in the treatment of Filipino adult patients with classic scabies.@*Methods@#We used a decision tree model to estimate the cost-effectiveness of two regimens, oral ivermectin alone or in combination with permethrin, compared with permethrin to treat adults and children aged five years and older with classic scabies in the outpatient setting from the household perspective in the Philippines. We estimated total costs and disability-adjusted life years (DALYs) over a one-month follow-up. Input parameters were obtained from secondary data, such as effect estimates for probabilities of clinical outcomes from a network meta-analysis, DALYs from the Global Burden of Disease 2019, and prevailing market cost in the Philippines (DPRI 2022 with recommended markup by DOH, and leading drugstores) as of August 2022. We computed for incremental cost-effectiveness ratio (ICER) and net monetary benefit (NMB) to determine which of the interventions are cost-effective. Univariate and probabilistic sensitivity analyses, and scenario analyses were conducted to assess the impact of parameter and structural uncertainty.@*Results@#Ivermectin-based regimens are suggested to be likely cost-saving compared to permethrin in the Philippine outpatient setting. Base case analysis showed that oral ivermectin had higher cost-savings (change in cost, -1,039.31; change in DALYS, 0.00027), while combination oral ivermectin/permethrin had higher DALYs averted (change in cost, PhP -1,019.78; change in DALYs, 0.00045), compared to permethrin. Combination oral ivermectin/permethrin (56%) was the most cost-effective, followed by oral ivermectin (44%) compared to permethrin (0%) through probabilistic sensitivity analysis. Estimates for ivermectin were sensitive to risk of cure for ivermectin vs permethrin using 1-way deterministic sensitivity analysis. Oral ivermectin was favored over combination oral ivermectin/permethrin at all thresholds based on the cost-effectiveness acceptability curve.@*Conclusion@#Both ivermectin-based regimens seem to be cost-saving compared to permethrin in the treatment of classic scabies in the Philippine outpatient setting. Clinicians may consider oral ivermectin, alone or in combination with permethrin as an alternative first-line or second-line treatment depending on patient preference, adverse event risk profile, availability, and economic capacity. This needs to be confirmed using primary data from Filipino patients to enhance the robustness of the findings and support evidence-based local decision-making in different settings. Less uncertainty in modelled parameters can give greater confidence in the results, which can be adopted for budget impact analysis and allow more rational resource allocation. Value of information analysis can be done to determine whether the expense of future RCTs or surveys in Filipinos to collect primary data is worth it. The cost of reducing uncertainty, if deemed worth the cost of further studies, may facilitate population-level decision-making and budget planning. Findings may further inform practice guideline development, coverage decisions, and national control program planning by providing the most cost-effective scabies intervention.

Effects of participatory 'A'rt-Based Activity On 'Health' of Older Community-Dwellers: results from a randomized control trial of the Singapore A-Health Intervention.

Introduction: The practice of participatory art has been found to support the promotion, prevention, and management of health across the lifespan. However, clinical trials investigating the benefits of creative activities curated with and conducted in museums among older adults in East Asia remains limited. Methods: The current research utilized a single-site, open-label randomized control trial (RCT) to evaluate a standardized Participatory 'A'rt-Based Activity On 'Health' of Older Community-Dwellers - the Singapore A-Health Intervention. Outcome measures include frailty as assessed by the Centre of Excellence on Longevity Self-administered Questionnaire, wellbeing as assessed by the Warwick-Edinburgh Mental Wellbeing Scales, and quality of life as assessed by the EuroQol-5D. 112 participants aged 60 and above were randomized into the intervention group (n = 56) or an inactive control group (n = 56). Participants completed four standardized online self-administered assessments at baseline, 5-week, 9-week and 12-week follow-up during the intervention period. Results: Linear mixed model analyses revealed no statistically significant differences between the intervention group and control group for all outcome measures. However, within the intervention group, a consistent significant reduction in frailty was observed across time from baseline to 9 weeks (MD -0.44, 95% CI -0.85 to -0.039, p = 0.032), 5-weeks to 9-weeks (MD -0.64, 95% CI -1.03 to -0.24, p = 0.002), and 5-weeks to 12-weeks (MD -0.51, 95% CI -0.91 to -0.10, p = 0.014). Moreover, the post-test mean wellbeing score in the intervention group significantly improved over time at 9-weeks (MD 1.65, 95% CI 0.09 to 3.22, p = 0.039) and 12-week (MD 2.42, 95% CI 0.67 to 4.16, p = 0.006) as compared to baseline scores. Discussion: The findings demonstrate the potential of a structured art and museum-based intervention as a resource for promoting health among aging populations. Such benefits transcend social, cultural, and societal contexts. Clinical trial registration: ClinicalTrial.gov, NCT05945589.

A qualitative examination on the implementation of participatory "A"rt-based activity on "Health" of older community-dwellers: what worked for the Singapore A-Health Intervention?

Introduction: Art and museum-based interventions are gaining increasing recognition for their potential as low-risk activities for older adults, offering numerous physical, cognitive, and emotional benefits. However, there remains a dearth of knowledge regarding the science of implementation as well as the factors and processes that contribute to their effectiveness from the perspectives of intervention participants. Methods: The current research draws on the qualitative evaluation data obtained from a larger mixed-method randomized control trial that evaluated a standardized Participatory "A"rt-Based Activity On "Health" of Older Community-Dwellers-the Singapore A-Health Intervention. Adopting a participatory action research approach, the primary objective is to critically examine the lived experiences and health impact of the Singapore A-Health Intervention with a secondary objective to uncover strategies for optimized implementation outcomes. All 56 participants who completed the intervention filled out a program evaluation survey and a nested sample of 30 participants completed a series of acceptability focus groups. Results: Descriptive analyses of the program evaluation survey data revealed that 96.2% of participants were satisfied with the overall experience of the Singapore A-Health intervention (M = 9.00, SD = 1.76), reported that the intervention positively impacted their quality of life (M = 8.90, SD = 1.43), and social wellbeing (M = 8.92, SD = 1.43). Thematic analysis with a grounded theory approach on the qualitative focus group data revealed three interrelated themes detailing how the Singapore A-Health Intervention contributed to positive health and wellbeing outcomes (1. A-Health Experience, 2. Wellbeing Outcomes, 3. Enabling Factors) and nine subthemes (1a. Intellectual Stimulation, 1b. Positive Stress, 1c. Peer Interaction, 2a. Interpersonal Bonds, 2b. Personal Growth, 2c. Mindful Living, 3a. Integrated Support, 3b. Session Design, 3c. Mode of Engagement). Discussion: This investigation provides important insights to the Singapore A-Health intervention's effectiveness for enhancing wellbeing among older adults, as well as the factors that enable successful program implementation. These findings offer a culturally unique perspective on the benefits of art and museum interventions, while underscoring the imperative need for strong partnership and collaborations among community stakeholders in supporting the health and wellbeing of ageing populations.

Beta-human chorionic Gonadotropin levels as early predictor for progression to Gestational Trophoblastic Neoplasia after molar pregnancy evacuation at a Philippine tertiary hospital / Philippine Journal of Obstetrics and Gynecology

Objective@#This study aimed to determine if the beta-human chorionic gonadotropin (hCG) levels during the first 5 weeks after a molar evacuation predict progression to gestational trophoblastic neoplasia (GTN).@*Materials and Methods@#This was a retrospective cohort study of complete mole cases managed at a Philippine tertiary hospital from January 2009 to December 2018. Extracted data were analyzed using applicable statistical tools. The level of significance was set at a P < 0.05 using two-tailed comparisons. @*Results@#One hundred and fifty-five complete patient records were available for review. Disease progression in 15.48% of cases while regression in 84.52% were noted. Uterine size was larger in those who eventually had postmolar GTN (t: −3.12, df: 32.64, P: 0.01). Analysis of the receiver operating characteristic curve showed that optimum cut-off levels for predicting GTN at 1, 3, and 5 weeks after evacuation were 4,152 mIU/ml (sensitivity: 50%, specificity: 94.7%, area under the curve [AUC]: 0.75), 804 mIU/ml (sensitivity: 62.5, specificity: 96.9%, AUC: 0.94), and 541 mIU/ml (70.8%, specificity: 97.7%, AUC: 0.96), respectively. @*Conclusion@#The level of hCG within the first 5 weeks after molar pregnancy evacuation is predictive of progression to GTN.

The effect of a two-day training and refresher program on the basic emergency obstetric and newborn care knowledge and skills of health workers in Legazpi City, Albay

@#<p style="text-align: justify;"><strong>Objectives:</strong> The availability of emergency obstetric and newborn care (EmONC) services is one of the key strategies in improving maternal health and achieving Sustainable Development Goal 3. Health staff knowledge and competency on these interventions are crucial to ensure the effective handling and management of obstetric and newborn emergencies. Health workers, despite having undergone formal training, require regular refresher courses to keep up with new, evidence-based information on EmONC intervention; and to ensure compliance with national and local referral guidelines. A two-day workshop was implemented to assess the knowledge and skills of health workers in Legazpi, Albay, regarding obstetric emergency cases and referral guidelines.</p><p style="text-align: justify;"><strong>Methods:</strong> A pretest was conducted on the first day to assess the knowledge of the participants. A series of lectures were given before administering a posttest at the end of these lectures. An Objective Structured Clinical Examination (OSCE) was conducted on the second day, which aimed to assess the skills of the participants.</p><p style="text-align: justify;"><strong>Results:</strong> The pretest findings indicated that the participants are generally knowledgeable about areas such as handwashing and prenatal care. Results of the posttest show that participants had difficulty with the category of referrals. Moreover, comparing the pretest and posttest scores, there is strong evidence that there is a difference in the median values of the pretest scores as compared to the posttest scores. The results of the OSCE also indicate the need for further training on partograph use and adherence to an EINC protocol. More than half of the participants passed all five parts of the OSCE.</p><p style="text-align: justify;"><strong>Conclusion:</strong> The workshop contributed to an improvement in the knowledge of health care workers in obstetric emergency cases. Skills-wise, more frequent training may need to be conducted to improve other competencies such as partograph utilization and the practice of EINC interventions.</p><p style="text-align: justify;"><strong>Key Words:</strong> emergency obstetric care, training, skilled birth attendants, knowledge, skills</p>

Analysis of trends in maternal mortalities in Bicol region using national health surveys and maternal death reviews / Philippine Journal of Obstetrics and Gynecology

Background@#Since 1976, Bicol Region had higher maternal mortality ratio (MMR) than the Philippine average and became the fourth region with the highest MMR in 2012. Looking at trends of maternal health outcomes and determining risk factors among mothers who died may guide interventions to reduce MMR.@*Objectives@#To determine the changes in maternal mortality ratio (MMR) in the Bicol region from 2004 to 2017 and determine the sociodemographic profile of pregnant women who died from 2015 to 2018. @*Materials and Methods@#A records review of Bicol?s Regional Field Health Services Information System from 2004 to 2017 and maternal death review reports from 2015 to 2018 was done. Changes in MMR was determined using Poisson regression. The sociodemographic characteristics and causes of maternal deaths were analyzed using frequencies and proportion. @*Results@#From 2004 to 2017, MMR of 100.9 remained higher than the regional target of 31.6. Significant reductions in MMR were achieved in 2007 to 2008 and in 2011 to 2012 wherein MMR ranged between 75.3 to 89.3. However, by the end of 2012, maternal deaths again increased which reached 122.5 in 2017. From the maternal death reviews, it was observed that 29.5% of maternal deaths were aged 35 years and above and 7.5% were less than 20 years old. Mothers who had more than five pregnancies were 30.1% of total deaths. In terms of place of death, 15.7% died at home or in-transit to referral facilities. Hemorrhage or hypertension-related causes were the leading reasons for maternal deaths. @*Conclusion@#Significant reduction in MMR was not sustained after 2012 and higher deaths were reported in the succeeding years. Maternal deaths can be further reduced by using a systems approach, by promoting family planning, and by strengthening service delivery networks to effectively manage hemorrhage and hypertension-related emergencies.

Insights on maternal health in the Philippines from National Health Surveys and Maternal Health Policies

@#<p style="text-align: justify;"><strong>Background</strong>: Teaching clinics provide low-cost health programs while offering valuable learning opportunities for student clinicians, which then contributes to increasing health care accessibility. To date, there is a paucity of literature exploring the satisfaction of patient seen in rehabilitation teaching clinics in developing countries. The Service Quality (ServQual) Scale is a valid and reliable tool that has been used to measure client satisfaction in different work settings and industries.<br /><br /><strong>Objectives</strong>: The aim of this study was to demonstrate the usefulness of ServQual <br />in measuring the satisfaction of clients in a rehabilitation teaching clinic in a developing country.<br /><br /><strong>Methodology</strong>: A cross-sectional survey was conducted for three months among CTS-AA (Clinic for Therapy Services- Adult and Adolescent Section) clients who are at least 18 years old; have attended at least three sessions; and can read. Prior to <br />administration in CTS-AA, the ServQual scale was translated to Filipino, validated<br />and pilot tested for reliability.<br /><br /><strong>Results</strong>: Thirty-two respondents were included in the analysis. there was no <br />statistically significant difference between the expectation and the perceptions <br />of the clients for the domains of reliability (z=1.799, p=0.0721),responsiveness (z=0.839, p=0.4013), assurance (z=1.914, p=0.0556) and empathy (z=1.772, p=0.0764). However, there was a statistically significant difference between the clients' perception and expectation for tangibles (z=4.117, p<0.0001) and between the overall client perception and expectation (z=4.086, p<0.0001).The overall ServQual score for CTS-AA is -0.3782.<br /><br /><strong>Conclusion</strong>: The ServQual has been shown to be useful in assessing the satisfaction of clients in rehabilitation clinics and the specific areas that needs improvement. The tool can still be further improved by including items on cost, relationship of students with supervisors and outcomes of treatment.</p>

Factors associated with non-compliance with anti-malarial treatment among malaria patients in Puerto Princesa, Palawan

OBJECTIVE: Malaria is a life-threatening, mosquito-borne disease that continues to cause numerous deaths worldwide. In the Philippines, malaria remains an important problem, with five provinces having >1000 cases of malaria a year. The objective of this cross-sectional analytical study was to determine the association of selected factors with non-compliance to anti-malarial treatment among malaria patients in Puerto Princesa, Palawan, specifically: perceived susceptibility to malaria, perceived seriousness and severity of malaria, perceived benefits of medication, perceived barriers to treatment compliance and cues to action.METHODS: Using an interviewer-administered structured questionnaire, 320 individuals diagnosed with and treated for malaria from January to October 2010 were interviewed regarding compliance to anti-malarial treatment and the factors related to compliance. Descriptive statistics and multiple logistic regression were used to analyze the data.RESULTS: The rate of non-compliance to anti-malaria treatment was 17% (95% Cl 12.1%-21.2%). After multivariate analysis using logistic regression, symptom perception as a cue to action and forgetfulness as a perceived barrier to treatment compliance were found to be significantly associated with non-compliance to treatment. The odds of non-compliance were three times higher for individuals who perceived that an improvement in symptoms implied cure of malaria. An individual who forgot to take at least one dose of medication was 17 times more likely to be non-compliant with treatment compared to someone who did not forget to take a single dose.CONCLUSION: Given the factors found to be associated with non­compliance to treatment, more effective ways of ensuring compliance with anti-malaria treatment may be explored e.g., doing directly observed treatment and utilizing treatment partners that may help address the problem of forgetfulness. The fact that symptom improvement is not equivalent to cure must be stressed when advising patients. Emphasizing compliance to treatment and the consequences of noncompliance when conducting patient education activities may also help boost treatment compliance.

Randomized, single-blinded comparison of efficacy, safety and tolerability of metronidazole 750mg - miconazole 200mg vaginal suppository vs. metronidazole 500mg - nystatin 100, 000 IU vaginal suppository in the treatment of bacterial vaginosis, vulvovaginal candidiasis, trichomoniasis, and mixed vaginal infections / Philippine Journal of Obstetrics and Gynecology

OBJECTIVE: This randomized, single-blind, two-arm controlled study compared the efficacy, safety, and tolerability of an intravaginal suppository preparation containing metronidazole 750mg + miconazole 200mg (Neopenotran Forte) with another vaginal preparation containing metronidazole 500 mg + nystatin 10000 IU (Flagystatin) in the treatment of bacterial vaginosis (BV), candidal and trichomonial vulvovaginitis (CVV, TV), mixed vaginitis and in the prevention of secondary candidal vulvovaginitis. MATERIALS AND METHODS: Women ages 18-45 years with chief complaints of abnormal vaginal discharge or vaginal/vulvar itching were examined and microbiologic confirmation of BV, VVC, TV or mixed infection was made. They were then randomly assigned to receive either treatment once daily (nightly) for 7 days. A total of 261 subjects had evaluable clinical and microbiological findings at the end of the study. Test of cure by Amsel criteria and Nugent score were performed twice after treatment. RESULTS: The overall test revealed that microbiological cure rate is significantly different between the two treatment groups. CONCLUSION: The odds of being cured microbiologically is 2.35 times more in the metronidazole 750mg + miconazole nitrate 200mg group compared to the metronidazole 500 mg + nystatin 10000 IU group. However, no significant difference in the clinical cure between the two groups was found. Both drugs are safe and convenient to use.

Descending necrotizing mediastinitis, a dreaded complication of acute tonsillitis

@#<p style="text-align: justify;"><strong>OBJECTIVES:</strong> To report a case of acute tonsillitis that subsequently developed descending necrotizing mediastinitis, and to discuss the signs and symptoms, differential diagnosis, pathophysiology, diagnostic criteria, ancillary procedures and management.<br /><br /><strong>METHODS:</strong><br /><strong>Design:</strong> Case Report</p> <p><strong>Setting:</strong> Tertiary Private and Government Hospital</p> <p><strong>Patient:</strong> One</p> <p style="text-align: justify;"><strong>RESULTS:</strong>  A 36-year-old woman was admitted with a 2-day history of sore throat and a diagnosis of acute exudative tonsillitis. She complained of sore throat accompanied by dyspnea, neck and chest pain which rapidly progressed to mediastinitis. She was transferred to a tertiary government hospital where video assisted thoracoscopic surgery with bilateral deloculation,  mediastinoscopy and bronchoscopy revealed purulent discharge from the right main stem bronchus with multiloculated effusion in the left lung and posterolateral loculated effusion in the right lung. Her condition improved and she was discharged after a month of antibiotic therapy.<br /><br /><strong>CONCLUSION: </strong>Acute tonsillitis seldom leads to a life-threatening complication such as mediastinitis. Descending necrotizing mediastinitis develops when acute tonsillar infection progresses and descends to the mediastinum. It is a surgical emergency which requires mediastinal drainage, thoracotomy and long-term antimicrobials. Clinicians who manage oropharyngeal infections should be aware of this rare but lethal complication which may occur even in non-immunocompromised individuals.</p>