by Mina Baek, Minjae Kim, Hae In Choi, Bert Binas, Junho Cha, Kyoung Hwa Jung, Sungkyoung Choi, Young Gyu Chai
The multikinase inhibitor sorafenib is the standard first-line treatment for advanced hepatocellular carcinoma (HCC), but many patients become sorafenib-resistant (SR). This study investigated the efficacy of another kinase inhibitor, regorafenib (Rego), as a second-line treatment. We produced SR HCC cells, wherein the PI3K-Akt, TNF, cAMP, and TGF-beta signaling pathways were affected. Acute Rego treatment of these cells reversed the expression of genes involved in TGF-beta signaling but further increased the expression of genes involved in PI3K-Akt signaling. Additionally, Rego reversed the expression of genes involved in nucleosome assembly and epigenetic gene expression. Weighted gene co-expression network analysis (WGCNA) revealed four differentially expressed long non-coding RNA (DElncRNA) modules that were associated with the effectiveness of Rego on SR cells. Eleven putative DElncRNAs with distinct expression patterns were identified. We associated each module with DEmRNAs of the same pattern, thus obtaining DElncRNA/DEmRNA co-expression modules. We discuss the potential significance of each module. These findings provide insights and resources for further investigation into the potential mechanisms underlying the response of SR HCC cells to Rego.To synthesise the composition and effectiveness of computer-based patient decision aid (PDAs) in interventions for patients with chronic diseases.
A systematic review with meta-analysis.
Five databases were searched, and only randomised controlled trials (RCTs)were included. This review was conducted with the PRISMA guidelines. The JBI Appraisal Tools for randomised trials were used to assess the risk of bias. We used the random-effects model to conduct meta-analyses. Evidence from RCTs was synthesised using standardised mean differences or mean differences. The GRADE system was employed to assess the certainty of evidence and recommendations. This study was registered on PROSPERO (number: CRD42022369340).
PubMed, Embase, Web of Science, CINAHL and Cochrane Library were searched for studies published before October 2022.
The review included 22 studies, and most computer-based PDAs reported information on the disease, treatment options, pros and cons and risk comparison and value clarification. The use of computer-based PDAs showed a significant effect on decision conflict and knowledge, but not on decision regret, satisfaction, self-efficacy, anxiety and quality of life. The overall GRADE certainty of evidence was low.
Although the quality of evidence was low, however, using computer-based PDAs could reduce decision conflict and enhance knowledge when making medical decisions. More research is needed to support the contention above.
Computer-based PDAs could assist health-care providers and patients in the shared decision-making process and improving the quality of decision-making.
This study adhered to PRISMA guidelines.
The emergence of novel infectious diseases has amplified the urgent need for effective prevention strategies, especially ones targeting vulnerable populations such as children. Factors such as the high incidence of both emerging and existing infectious diseases, delays in vaccinations, and routine exposure in communal settings heighten children's susceptibility to infections. Despite this pressing need, a comprehensive exploration of research trends in this domain remains lacking. This study aims to address this gap by employing text mining and modeling techniques to conduct a comprehensive analysis of the existing literature, thereby identifying emerging research trends in infectious disease prevention among children.
A cross-sectional text mining approach was adopted, focusing on journal articles published between January 1, 2003, and August 31, 2022. These articles, related to infectious disease prevention in children, were sourced from databases such as PubMed, CINAHL, MEDLINE (Ovid), Scopus, and Korean RISS. The data underwent preprocessing using the Natural Language Toolkit (NLTK) in Python, with a semantic network analysis and topic modeling conducted using R software.
The final dataset comprised 509 journal articles extracted from multiple databases. The study began with a word frequency analysis to pinpoint relevant themes, subsequently visualized through a word cloud. Dominant terms encompassed “vaccination,” “adolescent,” “infant,” “parent,” “family,” “school,” “country,” “household,” “community,” “HIV,” “HPV,” “COVID-19,” “influenza,” and “diarrhea.” The semantic analysis identified “age” as a key term across infection, control, and intervention discussions. Notably, the relationship between “hand” and “handwashing” was prominent, especially in educational contexts linked with “school” and “absence.” Latent Dirichlet Allocation (LDA) topic modeling further delineated seven topics related to infectious disease prevention for children, encompassing (1) educational programs, (2) vaccination efforts, (3) family-level responses, (4) care for immunocompromised individuals, (5) country-specific responses, (6) school-based strategies, and (7) persistent threats from established infectious diseases.
The study emphasizes the indispensable role of personalized interventions tailored for various child demographics, highlighting the pivotal contributions of both parental guidance and school participation.
The study provides insights into the complex public health challenges associated with preventing and managing infectious diseases in children. The insights derived could inform the formulation of evidence-based public health policies, steering practical interventions and fostering interdisciplinary synergy for holistic prevention strategies.
This paper examined the magnitude of differences in performance across domains of cognitive functioning between participants who attrited from studies and those who did not, using data from longitudinal ageing studies where multiple cognitive tests were administered.
Individual participant data meta-analysis.
Data are from 10 epidemiological longitudinal studies on ageing (total n=209 518) from several Western countries (UK, USA, Mexico, etc). Each study had multiple waves of data (range of 2–17 waves), with multiple cognitive tests administered at each wave (range of 4–17 tests). Only waves with cognitive tests and information on participant dropout at the immediate next wave for adults aged 50 years or older were used in the meta-analysis.
For each pair of consecutive study waves, we compared the difference in cognitive scores (Cohen’s d) between participants who dropped out at the next study wave and those who remained. Note that our operationalisation of dropout was inclusive of all causes (eg, mortality). The proportion of participant dropout at each wave was also computed.
The average proportion of dropouts between consecutive study waves was 0.26 (0.18 to 0.34). People who attrited were found to have significantly lower levels of cognitive functioning in all domains (at the wave 2–3 years before attrition) compared with those who did not attrit, with small-to-medium effect sizes (overall d=0.37 (0.30 to 0.43)).
Older adults who attrited from longitudinal ageing studies had lower cognitive functioning (assessed at the timepoint before attrition) across all domains as compared with individuals who remained. Cognitive functioning differences may contribute to selection bias in longitudinal ageing studies, impeding accurate conclusions in developmental research. In addition, examining the functional capabilities of attriters may be valuable for determining whether attriters experience functional limitations requiring healthcare attention.
Management of pressure sores can have various environmental effects; moreover, the COVID-19 pandemic notably affected efforts towards effective management of pressure sores. Some cases of COVID-19 infections require long-term hospitalization in the intensive care unit. Moreover, special protective equipment worn by physicians owing to the pandemic complicate wound management. In this study, we compared the pressure ulcer characteristics between isolated patients with and those without COVID-19 and evaluated the effects of isolation on pressure sores. From November 2022 to February 2023, patients who had pressure sores were included and their medical records were reviewed retrospectively. The experimental group included patients with confirmed COVID-19 infections, who received clinical treatment in an isolated unit. Wound characteristics in each group and associated risk factors were analysed. Fifty-four isolated patients with COVID-19 and 58 control patients were included. The Braden Scale score and Korea patient classification system-1 did not vary significantly between the two groups. However, the number of Grade I pressure sores in the COVID-19 isolation group was significantly lower than those in the control group (p < 0.001), while the number of lesions was significantly higher (p = 0.034). The mortality rate in the COVID-19 isolation group was higher than that in the control group (p = 0.008), and more patients were discharged with unhealed wounds (p = 0.004). A higher treatment effect on pressure sores may be expected if the disease is more actively managed. Moreover, the wound care systems for isolated patients with COVID-19 require further attention.
Previous animal studies have shown the anti-obesity effect of kimchi-derived probiotic lactic acid bacteria. However, only a few epidemiological studies have investigated the association between kimchi consumption and obesity. Therefore, we aim to assess this relationship in Korean adults.
Cross-sectional study.
The Health Examinees study was conducted from 2004 to 2013.
This study analysed 115 726 participants aged 40–69 years enrolled in the Health Examinees study in Korea.
Obesity was defined as body mass index ≥25 kg/m2, and abdominal obesity was defined as waist circumference ≥90 cm in men and ≥85 cm in women. Kimchi consumption was assessed by the validated food frequency questionnaire.
In men, total kimchi consumption of 1–3 servings/day was related to a lower prevalence of obesity (OR: 0.875 in 1–2 servings/day and OR: 0.893 in 2–3 servings/day) compared with total kimchi consumption of
Consumption of 1–3 servings/day of total kimchi was associated with a lower risk of obesity in men. Baechu kimchi was associated with a lower prevalence of obesity in men, and kkakdugi was associated with a lower prevalence of abdominal obesity in both men and women. However, since all results showed a ‘J-shaped’ association, it is recommended to limit excessive kimchi intake.
by Lisa Jung, Sonja Hillemacher, Inga Tiemann, Mascha Lepke, Dirk Hinrichs
In commercial laying hens, keel bone damage (KBD) is a severe health and welfare problem leading to pain, reduced mobility and decreased laying performance. Flocks of all production systems and hybrid lines can be affected. KBD is a multifactorial welfare issue and, among other factors, associated with a high laying performance which negatively affects the calcium deposit in the medullary bones. Therefore, mature hens of local breeds with much lower egg production than commercial hybrids may be expected to show less or even no keel bone damage. This study evaluates (i) the prevalence of KBD in local breeds, (ii) the difference in type and level of damages, and (iii) if roosters and pullets are also affected. In total, we palpated 343 mature hens, 40 pullets, and 18 roosters of 13 different local breeds and one commercial hybrid. The animals were kept on eight different farms in free-range or floor-housing systems. Our results showed that on average 44.2% of mature hens per local breed were affected by KBD (range: 11.1%-84.7%). We found deviation of less than 1 cm in 26.9%, deviations of more than 1 cm in 6.4% and palpable fractures in 23.8% of the mature hens of local breeds. The tip was damaged in 23.6% of the mature hens. Also, pullets and roosters were affected by KBD. Finally, we found that KBD also occurs in local breeds. Therefore, we conclude that even the low laying performance of local breeds does not prevent them from the occurrence of KBD.KBD in local breeds may rather be associated with genetics (breed) as well as management and housing. Thus, breeders of local breeds should include bone health as a selection trait. Owners of local breeds should also pay attention to the condition of the keel and ought to be trained about preventive measures.To examine the effects of spousal support and parent–nurse partnership on caregiver burden of parents of children with chronic disease.
With the trend of increasing the global number of children with chronic diseases, the parental caregiver burden has become increasingly prevalent.
Cross-sectional study.
The study participants included 115 parents of children diagnosed with chronic disease at a general hospital in South Korea. The study duration was 4 June 2021–30 April 2022. Self-reported measures included the parent–nurse partnership scale, the Korean version of the Parenting Alliance Inventory and the family caregiver burden scale. T-tests, ANOVA, Pearson's correlation coefficients and hierarchical linear multiple regression were conducted using IBM SPSS version 26.0. This study followed STROBE guideline.
Parental caregiver burden was significantly negatively associated with spousal support and parent–nurse partnership. Factors significantly influencing caregiver burden were parental alcohol consumption; child's inherited metabolic disease, cardiovascular disease, disease relating to haematological tumours or kidney disease diagnosis; child's health perceived as poor by parents; child's dependency perceived as high by parents; hospitalization recency; and low spousal support. These factors accounted for 65% of caregiver burden.
Parental caregiver burden was related to spousal support and parent–nurse partnership, but the primary factor affecting caregiver burden was spousal support.
The results highlighted the role of healthcare professionals in educating parents of children with chronic diseases to facilitate spousal support and have implications for nursing and community-based interventions to reduce parental caregiver burden. Furthermore, they underlined that policymakers and other stakeholders should pay attention to the parental caregiver burden through government-based, family-centered strategies.
Parents of children with chronic disease were recruited to perform the self-administered survey in the phase of data collection.
To investigate the association between older patients’ willingness to have one or more medications deprescribed and: (1) change in medications, (2) change in the appropriateness of medications and (3) implementation of prescribing recommendations generated by the electronic decision support system tested in the ‘Optimising PharmacoTherapy In the Multimorbid Elderly in Primary CAre’ (OPTICA) trial.
A longitudinal sub-study of the OPTICA trial, a cluster randomised controlled trial.
Swiss primary care settings.
Participants were aged ≥65 years, with ≥3 chronic conditions and ≥5 regular medications recruited from 43 general practitioner (GP) practices.
Patients’ willingness to have medications deprescribed was assessed using three questions from the ‘revised Patient Attitudes Towards Deprescribing’ (rPATD) questionnaire and its concerns about stopping score.
Medication-related outcomes were collected at 1 year follow-up. Aim 1 outcome: change in the number of long-term medications between baseline and 12 month follow-up. Aim 2 outcome: change in medication appropriateness (Medication Appropriateness Index). Aim 3 outcome: binary variable on whether any prescribing recommendation generated during the OPTICA medication review was implemented. We used multilevel linear regression analyses (aim 1 and aim 2) and multilevel logistic regression analyses (aim 3). Models were adjusted for sociodemographic variables and the clustering effect at GP level.
298 patients completed the rPATD, 45% were women and 78 years was the median age. A statistically significant association was found between the concerns about stopping score and the change in the number of medications over time (per 1-unit increase in the score the average number of medications use was 0.65 higher; 95% CI: 0.08 to 1.22). Other than that we did not find evidence for statistically significant associations between patients’ agreement with deprescribing and medication-related outcomes.
We did not find evidence for an association between most measures of patient agreement with deprescribing and medication-related outcomes over 1 year.
by Chung-Fang Tseng, Hsiao-Chen Lin, Chung-Yuh Tzeng, Jing-Yang Huang, Chih-Jung Yeh, James Cheng-Chung Wei
Kawasaki disease (KD) is an inflammatory vasculitis disorder of unknown etiology. It is a rare but fatal disease and the leading cause of acquired coronary heart disease in children under the age of 5 years. We examined the association of KD with the demographics of family members, parents’ characteristics, and perinatal factors in Taiwanese children. This nested case–control study used data from Taiwan’s Health and Welfare Data Science Center and initially included children born in Taiwan between January 1, 2006, and December 31, 2015 (n = 1,939,449); the children were observed for KD development before the age of 5 years (n = 7870). The control group consisted of children without KD who were matched with each KD case by sex and birth date at a ratio of 8:1. The odds ratio (ORs) of the aforementioned associations were estimated using conditional logistic regression. The risk of KD decreased in children with younger parents [Preterm birth complications are the most common cause of death in children under 5 years. The presence of multiple microorganisms and genital tract inflammation could be the common mechanism driving early onset of labour. South Africa has high levels of preterm birth, genital tract infections and HIV infection among pregnant women. We plan to investigate associations between the presence of multiple lower genital tract microorganisms in pregnancy and gestational age at birth.
This cohort study enrols around 600 pregnant women at one public healthcare facility in East London, South Africa. Eligible women are ≥18 years and at Chlamydia trachomatis and Neisseria gonorrhoeae, with treatment if test results are positive. At these visits, additional vaginal specimens are taken for: PCR detection and quantification of Trichomonas vaginalis, Candida spp., Mycoplasma genitalium, M. hominis, Ureaplasma urealyticum and U. parvum; microscopy and Nugent scoring; and for 16S ribosomal RNA gene sequencing and quantification. Pregnancy outcomes are collected from a postnatal visit and birth registers. The primary outcome is gestational age at birth. Statistical analyses will explore associations between specific microorganisms and gestational age at birth. To explore the association with the quantity of microorganisms, we will construct an index of microorganism load and use mixed-effects regression models and classification and regression tree analysis to examine which combinations of microorganisms contribute to earlier gestational age at birth.
This protocol has approvals from the University of Cape Town Research Ethics Committee and the Canton of Bern Ethics Committee. Results from this study will be uploaded to preprint servers, submitted to open access peer-reviewed journals and presented at regional and international conferences.
by Jung Min Cho
The credibility and wide usability of nutrition fact labels (NFLs) have increased due to the pandemic, which may lead to healthier nutritional choices. This cross-sectional study aimed to evaluate the association between NFL use and meeting the estimated average requirements (EARs) for vitamins and minerals not listed on NFLs during the prepandemic (2019, n = 6606) and pandemic periods (2020 and 2021, n = 12085) using KNHANES data. Household surveys, health behavior interviews, and health checkup examinations were conducted for all participants. Subjects were included in the unAware+noUse, Aware+noUse, and Aware+Use groups according to NFL usage, and nutritional intake was analyzed by the 24-hour recall method. Complex-sample multiple logistic regression analysis was used to determine the odds ratios (ORs) and 95% confidence intervals (CIs) for meeting the EARs according to NFL usage in the crude and adjusted (including metabolic conditions) models. The primary finding was that awareness and NFL use were associated with adequate intake above the EARs for vitamin A, vitamin B2, niacin, folate, Ca, Fe, and P; this association was more evident during the pandemic. After adjusting for covariates, during the pandemic, the ORs of meeting the EARs in the Aware+noUse group and Aware+Use group were 1.25 (CI 1.06–1.47) and 1.36 (CI 1.05–1.75) for vitamin A, 1.26 (CI 1.06–1.50) and 1.54 (CI 1.19–2.00) for vitamin B2, 1.32 (CI 1.13–1.56) and 1.46 (CI 1.15–1.85) for folate, and 1.46 (CI 1.06–2.00) and 1.73 (1.09–2.75) for P, respectively. Additionally, the ORs for niacin (1.21, 1.02–1.43) and Fe (1.29, 1.08–1.54) were significant in the Aware+noUse group, and that for Ca (1.39, 1.08–1.78) was significant in the Aware+Use group (all pFrom previous studies, we have shown that viable colony forming units of bacteria and bacterial biofilms are reduced after sequential treatment with a surfactant-based dressing. Here, we sought to test the impact on visible bacterial pigments and the ultrastructural impact following the sequential treatment of the same surfactant-based dressing. Mature Pseudomonas aeruginosa biofilms were grown on ex vivo porcine skin explants, and an imaging-based analysis was used to compare the skin with and without a concentrated surfactant. In explants naturally tinted by bacterial chromophores, wiping alone had no effect, while the use of a surfactant-based dressing reduced coloration. Similarly, daily wiping led to increased immunohistochemical staining for P. aeruginosa antigens, but not in the surfactant group. Confocal immunofluorescent imaging revealed limited bacterial penetration and coating of the dermis and loose pieces of sloughing material. Ultrastructural analysis confirmed that the biofilms were masking the extracellular matrix (ECM), but the surfactant could remove them, re-exposing the ECM. The masking of the ECM may provide another non-inflammatory explanation for delayed healing, as the ECM is no longer accessible for wound cell locomotion. The use of a poloxamer-based surfactant appears to be an effective way to remove bacterial chromophores and the biofilm coating the ECM fibres.
by David Röthlisberger, Katharina Tabea Jungo, Lukas Bütikofer, Rosalinde K. E. Poortvliet, Jacobijn Gussekloo, Sven Streit
BackgroundFalls and consequent injuries are prevalent in older adults. In this group, half of injury-related hospitalizations are associated with falls and the rate of falls increases with age. The evidence on the role of blood pressure and the use of antihypertensive treatment on the risk of falls remains unclear in oldest-old adults (≥85 years).
ObjectivesTo examine the association between systolic blood pressure (SBP) and incident falls with medical consequences in oldest-old adults and to analyse whether this association is modified by the use of antihypertensive treatments or the presence of cardiovascular disease.
MethodsWe analysed data from the Leiden 85-plus Study, a prospective, population-based cohort study with adults aged ≥85 years and a 5-year follow-up. Falls with medical consequences were reported by the treating physician of participants. We assessed the association between time-updated systolic blood pressure and the risk of falling over a follow-up period of five years using generalized linear mixed effects models with a binomial distribution and a logit link function. Subgroup analyses were performed to examine the role of antihypertensive treatment and the difference between participant with and without cardiovascular disease.
ResultsWe analysed data from 544 oldest-old adults, 242 (44.4%) of which used antihypertensives. In 81 individuals (15%) ≥1 fall(s) were reported during the follow-up period. The odds for a fall decreased by a factor of 0.86 (95% CI 0.80 to 0.93) for each increase in blood pressure by 10 mmHg. This effect was specific to blood pressure values above 130mmHg. We did not find any evidence that the effect would be modified by antihypertensive treatment, but that there was a tendency that it would be weaker in participants with cardiovascular disease (OR 0.81, 95% CI 0.72 to 0.90 per 10mmHg) compared to those without cardiovascular disease (OR 0.94, 95% CI 0.84 to 1.05 per 10mmHg).
ConclusionOur results point towards a possible benefit of higher blood pressure in the oldest-old with respect to falls independent of the use of antihypertensive treatments.
Chronic headache is a ‘silent’ neuropsychiatric systemic lupus erythematosus symptom with heterogeneous prevalence, potentially reaching 54.4%. It may reduce quality of life by increasing the likelihood of depression and sleep disturbance. While pharmacotherapy remains the first-line treatment, the current management is still challenging and needs other non-invasive modalities. An effective, tolerable and disease-specific treatment modality including transcranial direct current stimulation (tDCS) is considered to reduce the frequency of chronic headaches, including in SLE. Until recently, there was no standard protocol for tDCS in treating headaches.
SHADE is a single-centre randomised double-blind multiarm sham-controlled trial for adults with clinically stable SLE, chronic headaches and without history of traumatic brain injury, brain infection, stroke or brain tumour. Random allocation is conducted to 88 subjects into 3 treatment groups (administration at primary motor, primary sensory and dorsolateral prefrontal cortex) and control group in 1:1:1:1 ratio. The primary endpoint is reduced number of headache days after adjunctive tDCS. The secondary endpoints are reduced headache intensity, increased quality of life, increased sleep quality, decreased depression and reduced analgesics use. The outcome is measured monthly until 3-month postintervention using headache diary, 36-Item Short Form Survey, Chronic Headache Quality of Life Questionnaire, Pittsburgh Sleep Quality Index and Mini International Neuropsychiatry Interview version 10 (MINI ICD 10). Intention-to-treat analysis will be performed to determine the best tDCS electrode placement.
Ethical approval had been obtained from the local Institutional Review Board of Faculty of Medicine Universitas Indonesia. Results will be published through scientific relevant peer-reviewed journals.