Treatment Strategies Research Articles

Current findings on the antitumor effects of metformin on esophageal squamous cell carcinoma (Review).

Esophageal squamous cell carcinoma (ESCC) is an intractable type of cancer that requires novel therapeutic modalities, since the therapeutic outcomes are often inadequate, even in response to multidisciplinary treatment. The antitumor effect of metformin, an antidiabetic drug, has been reported in esophageal cancer; however, its effects are diverse. Since various multidisciplinary therapies are used in ESCC, the antitumor effect of metformin is expected to be synergistic in some treatment strategies. The present review summarizes the antitumor effects of metformin and discusses its use in combination with existing therapies. The present study reviewed relevant studies where the molecular targets of metformin (AMPK and inflammatory system signals) were described, followed by the classification and organization of its antitumor effects, and subsequently summarized the current research on its antitumor effects, especially in ESCC. A number of studies have reported that metformin prevents the development of ESCC and exerts its antitumor effects through various pathways. In addition, metformin has been shown to inhibit tumor growth, induce apoptosis, inhibit cancer cell invasion, migration and angiogenesis into the tumor, and decrease tumor malignancy, such as metastasis. Furthermore, it may modulate host tumor immunity in a tumor-suppressive manner and is expected to improve prognosis following treatment for ESCC. Notably, metformin may be beneficial in combination with chemotherapy, such as cisplatin, and radiation. By contrast, it has been shown to potentially induce resistance to 5-fluorouracil. Finally, the effects of metformin in combination with other therapies are discussed in the present study, and perspectives on the potential benefits of metformin for future ESCC treatment are presented. In conclusion, the present review may be useful in improving the understanding of the wide range of antitumor effects of metformin. Although some concerning points remain, using metformin in ESCC treatment could be promising. Notably, more knowledge needs to be accumulated regarding the effects of metformin on ESCC.

Digitoxin inhibits ICC cell properties via the NF‑κB/ST6GAL1 signaling pathway.

Intrahepatic cholangiocarcinoma (ICC) is a type of liver cancer associated with poor prognosis and increased mortality; the limited treatment strategy highlights the urgent need for investigation. Traditional Chinese Medicine (TCM), used alone or in combination with other treatments, can enhance therapeutic efficacy, improve life quality of patients and extend overall survival. In total, two rounds of screening of a TCM library of 2,538 active compounds were conducted using a Cell Counting Kit‑8 assay and ICC cell lines. Cell proliferation and migration abilities were assessed through colony formation, 5‑ethynyl‑2'‑deoxyuridine, would healing and Transwell assays. The impact of digitoxin (DT) on signaling pathways was initially investigated using RNA sequencing and further validated using reverse transcription‑quantitative PCR, western blotting, lectin blotting and flow cytometry. ICC cells stably overexpressing ST6 β‑galactoside α‑2,6‑sialyltransferase 1 (ST6GAL1) were generated through lentiviral transfection. It was shown that DT emerged as a highly effective anti‑ICC candidate from two rounds high‑throughput library screening. DT could inhibit the proliferation and migration of ICC cells by suppressing NF‑κB activation and reducing nuclear phosphorylated‑NF‑κB levels, along with diminishing ST6GAL1 mRNA and protein expression. The aforementioned biological effects and signal pathways of DT could be counteracted by overexpressing ST6GAL1 in ICC cells. In conclusion, DT suppressed ICC cell proliferation and migration by targeting the NF‑κB/ST6GAL1 signaling axis. The findings of the present study indicated the promising therapeutic effects of DT in managing ICC, offering new avenues for treatment strategies.

Automated Alzheimer’s disease detection and classification based on optimized deep learning models using MRI

Alzheimer’s disease (AD) is a devastating neurologic condition characterized by brain atrophy and neuronal loss, posing a significant global health challenge. Early detection is paramount to impede its progression. This study aims to construct an optimized deep learning (DL) framework for early AD detection and classification using magnetic resonance images (MRI) scans. The classification task involves distinguishing between four AD stages: mild demented (MD), very mild demented (VmD), moderate demented (MoD), and non-demented (ND). To achieve effective classification, three DL models (VGG16, InceptionV3, and ResNet50) are implemented and fine-tuned. A systematic evaluation is conducted to optimize hyper-parameters, with extensive experimentation. The results demonstrate superior classification performance of the customized DL models compared to state-of-the-art methods. Specifically, visual geometry group 16 (VGG16) achieves the highest accuracy of 95.85%, followed by ResNet50 with 89.38%, while InceptionV3 yields the lowest accuracy of 87.23%. This study highlights the critical role of selecting appropriate DL models and customizing them for accurate AD detection and classification across various stages, offering significant insights for advancing clinical diagnosis and treatment strategies.

Impact of gender in patients with device-related thrombosis after left atrial appendage closure - A sub-analysis from the multicenter EUROC-DRT-registry.

Device-related thrombosis (DRT) is a common finding after left atrial appendage closure (LAAC) and is associated with worse outcomes. As women are underrepresented in clinical studies, further understanding of sex differences in DRT patients is warranted. This sub-analysis from the EUROC-DRT-registry compromises 176 patients with diagnosis of DRT after LAAC. Women, who accounted for 34.7% (61/176) of patients, were older (78.0±6.7vs. 74.9±9.1 years, p=.06) with lower rates of comorbidities. While DRT was detected significantly later in women (173±267vs. 127±192 days, p=.01), anticoagulation therapy was escalated similarly, mainly with initiation of novel oral anticoagulant (NOAC), vitamin K antagonist (VKA) or heparin. DRT resolution was achieved in 67.5% (27/40) of women and in 75.0% (54/72) of men (p=.40). In the remaining cases, an intensification/switch of anticoagulation was conducted in 50.% (9/18) of men and in 41.7% (5/12) of women. Final resolution was achieved in 72.5% (29/40) cases in women, and in 81.9% (59/72) cases in men (p=.24). Women were followed-up for a similar time as men (779±520vs. 908±687 days, p=.51). Kaplan-Meier analysis revealed no difference in mortality rates in women (Hazard Ratio [HR]: 1.73, 95%-Confidence interval [95%-CI]:.68-4.37, p=.25) and no differences in stroke (HR:.83, 95%-CI:.30-2.32, p=.72) within 2 years after LAAC. Evaluation of risk factors and outcome revealed no differences between men and women, with DRT in women being diagnosed significantly later. Women should be monitored closely to assess for DRT formation/resolution. Treatment strategies appear to be equally effective.

Comparative analysis of heart failure prediction using machine learning models

Heart failure is a critical health problem worldwide, and its prediction is a major challenge in medical science. Machine learning has shown great potential in predicting heart failure by analyzing large amounts of medical data. Heart failure prediction with the help of machine learning classification algorithms involves the use of models such as decision trees, logistic regression, and support vector machines to identify and analyze potential risk factors for heart failure. By analyzing large datasets containing medical and lifestyle-related variables, these models can accurately predict the likelihood of heart failure occurrence in individuals. In our research, the heart failure prediction and comparison are done using Logistic Regression, KNN, SVM, decision tree and random forest The accurate identification of high-risk individuals enables early intervention and better management of heart failure, reducing the risk of mortality and morbidity associated with this condition. Overall, machine learning algorithms play a major role in improving the accuracy of heart failure risk assessment, allowing for more personalized and effective prevention and treatment strategies.

Residual cardiovascular risk post-PCI: imaging and treatment strategy

Residual cardiovascular risk post-PCI: imaging and treatment strategy

A new model of endotracheal tube biofilm identifies combinations of matrix-degrading enzymes and antimicrobials able to eradicate biofilms of pathogens that cause ventilator-associated pneumonia.

Ventilator-associated pneumonia is defined as pneumonia that develops in a patient who has been on mechanical ventilation for more than 48 hours through an endotracheal tube. It is caused by biofilm formation on the indwelling tube, which introduces pathogenic microbes such as Pseudomonas aeruginosa, Klebsiella pneumoniae and Candida albicans into the patient's lower airways. Currently, there is a lack of accurate in vitro models of ventilator-associated pneumonia development. This greatly limits our understanding of how the in-host environment alters pathogen physiology and the efficacy of ventilator-associated pneumonia prevention or treatment strategies. Here, we showcase a reproducible model that simulates the biofilm formation of these pathogens in a host-mimicking environment and demonstrate that the biofilm matrix produced differs from that observed in standard laboratory growth medium. In our model, pathogens are grown on endotracheal tube segments in the presence of a novel synthetic ventilated airway mucus medium that simulates the in-host environment. Matrix-degrading enzymes and cryo-scanning electron microscopy were employed to characterize the system in terms of biofilm matrix composition and structure, as compared to standard laboratory growth medium. As seen in patients, the biofilms of ventilator-associated pneumonia pathogens in our model either required very high concentrations of antimicrobials for eradication or could not be eradicated. However, combining matrix-degrading enzymes with antimicrobials greatly improved the biofilm eradication of all pathogens. Our in vitro endotracheal tube model informs on fundamental microbiology in the ventilator-associated pneumonia context and has broad applicability as a screening platform for antibiofilm measures including the use of matrix-degrading enzymes as antimicrobial adjuvants.

Tertiary Lymphoid Structures in Brain Metastases of Lung Cancer: Prognostic Significance and Correlation With Clinical Outcomes.

The prognosis of patients with brain metastases (BMs) originating from lung cancer remains poor, despite advancements in treatment strategies. The role of tertiary lymphoid structures (TLSs) within the tumor immune microenvironment of BMs has not been extensively explored. This study utilized patient-derived clinical samples from 17 patients with histologically confirmed BMs of lung cancer, undergoing surgical resection. Immunohistochemistry was employed to analyze the presence and characteristics of TLS and tumor-infiltrating lymphocytes (TILs) within BM tissues, correlating these with clinical outcomes. TLSs, albeit in their immature form, were identified within BM tissues, distinguishing them from their mature counterparts in primary lung cancer tissues. A significant correlation between TLS density (but not TIL density) and improved postoperative survival was observed, underscoring the potential of TLS density as an independent prognostic marker. Furthermore, TLS density did not correlate with the Graded Prognostic Assessment (GPA) index, suggesting its unique prognostic value beyond conventional predictors. Our findings reveal the presence of TLSs in lung cancer-derived BMs and highlight their prognostic significance, independent of the GPA index. The identification of TLS within the unique central nervous system tumor microenvironment offers new insights into the immune landscape of BMs and suggests potential avenues for immunotherapeutic interventions targeting these structures to improve patient outcomes.

Understanding Clinician Knowledge, Attitudes, and Practices Relating to Nonpharmaceutical Fentanyl and Harm Reduction.

Nonpharmaceutical fentanyl (NPF) is driving the national epidemic of opioid overdose deaths. Clinicians can play a role in fostering awareness of this growing risk and delivering interventions to reduce mortality. However, there is limited research assessing clinician knowledge, attitudes, and practices relating to NPF and harm reduction strategies. A 34-question survey was designed to assess knowledge, attitudes, and practices related to NPF and harm reduction strategies of adult and pediatric hospital-based and emergency clinicians at a single academic medical center. Results were summarized using descriptive statistics. Chi square and Fishers exact tests were used to compare groups. There were 136 survey responses. The majority (88%) of respondents correctly answered a question on NPF potency. Most respondents were aware that NPF exposure was very (84%) or somewhat likely (10%) for someone using illicit opioids and very (44%) or somewhat likely (46%) for nonopioid drugs. Respondents viewed overdose prevention as highly important for patients using illicit opioids (93%) and nonopioid drugs (86%) but few (21%) were very/extremely familiar with overdose prevention strategies and just over half (57%) were comfortable/very comfortable counseling about overdose prevention. There was wide variability in utilization of harm reduction/treatment strategies (7.3% frequently providing fentanyl test kits to 70% frequently prescribing naloxone). Higher levels of comfort and familiarity with overdose prevention were associated with more frequent counseling on harm reduction strategies. Pediatric-only clinicians had less familiarity (5% very/extremely familiar) and comfort (35% comfortable/very comfortable) with overdose prevention, and limited use of harm reduction strategies (0%-31% using each strategy frequently). While clinicians had knowledge and awareness of NPF and rated overdose prevention as highly important, utilization of harm reduction and treatment strategies was variable. This study highlights opportunities for education and system-based support to improve clinician-driven harm reduction practices for patients at risk of overdose.

Clinical prognostic factors to guide treatment strategy for HPV‑positive oropharyngeal cancer using treatment outcomes of induction chemotherapy: A real‑world experience.

The role of induction chemotherapy (IC) in locally advanced oropharyngeal cancer (OPC) remains debatable, and suitable candidates for de-escalation treatment in these patients have not been fully identified. Therefore, the present study aimed to identify high-risk candidates for human papillomavirus (HPV)-positive OPC by analyzing patients who underwent IC followed by chemoradiotherapy (CRT) to guide optimal treatment strategies. Patients diagnosed with stage III-IVA OPC and treated with a minimum of two cycles of IC followed by CRT, between 2004 and 2020, were retrospectively reviewed. All the patients were restaged according to the American Joint Committee on Cancer, 8th edition. The overall response rate and survival outcomes associated with clinical factors based on HPV status were analyzed using univariate and multivariate analyses. The present study analyzed 105 patients with a median age of 60 years (range, 40-76 years). Among 105 patients, 40 (38.1%) were HPV-negative and 65 (61.9%) HPV-positive. In all patients, survival outcomes were notably poorer in patients aged ≥60 years (P=0.006) and those who did not achieve complete response post-CRT (P<0.001), irrespective of the HPV status. The median relative dose intensity of IC was ≥80%, indicating adequate treatment, regardless of age. In contrast to patients with HPV-negative OPC, age ≥60 years (P=0.011) and T4 stage (P=0.019) emerged as substantial poor prognostic factors for survival outcomes in patients with HPV-positive OPC. Patients with HPV-positive OPC were categorized into three groups based on the number of clinical factors at diagnosis (such as age and T4 stage). The progression-free and overall survival showed significant stratification across each group as the number of high-risk factors increased despite IC and CRT. The findings indicated that patients with these high-risk factors require a cautious therapeutic strategy even when they are diagnosed with HPV-positive OPC, and the role of combined modality, including IC, will need to be investigated in a randomized trial to be routinely incorporated into clinical practice.

Clinical Outcomes and Treatment Strategy of Mirizzi's Syndrome Treated With Surgery.

There is currently no standardized treatment for Mirizzi's syndrome (MS). We aim to explore the surgical treatment strategy for MS by analyzing its clinical characteristics and treatment outcomes. This retrospective study analyzed the clinical data of 130 patients with MS who underwent surgery at our hospital from April 2013 to April 2020. The study population comprised 130 patients with MS, with an approximately balanced sex ratio and a median age of 58.5 years. The preoperative diagnostic rate was 82.3%. The diagnostic accuracy of ERCP was 92.5%, higher than that of MRCP and ultrasound. All patients underwent surgical treatment, with 74 cases of laparoscopic surgery, 43 cases of laparotomy, and 13 cases of laparoscopic surgery converted to laparotomy. A total of 23 patients experienced short-term and long-term complications after surgery, with a complication rate of 17.7%. There was no statistical difference between laparoscopic surgery and open surgery in terms of intraoperative hemorrhage, operative time, and postoperative complication rate. However, the length of hospital stay was shorter in the laparoscopic surgery compared to the open surgery, which was statistically different from each other. ERCP is the gold standard for the diagnosis of MS, especially for identifying the type of MS. ERCP plays an important role in both the preoperative and postoperative phases of MS. Our study demonstrated that laparoscopic surgery was a safe and feasible option for MS treatment, even requires less hospitalization than open surgery.

Current Cognitive-Based Strategies in OT Interventions for Chronic Pain

Abstract Date Presented 03/22/24 This study describes the most common and effective cognitive strategies that are used by OTR/Ls to address chronic pain. Additionally, this study represents the reason that OTR/Ls may not use cognitive strategies in treating chronic pain. Primary Author and Speaker: Naghmeh Gheidi Additional Authors and Speakers: Brandon McCauley Contributing Authors: Miranda Gajewski, Cody Cline, Olivia Griesbach, Maimee Vang, Rylee Petit, Breana Haag

Oral Piwi-Interacting RNA Delivery Mediated by Green Tea-Derived Exosome-Like Nanovesicles for the Treatment of Aortic Dissection.

Aortic dissection (AD) is a severe cardiovascular disease necessitating active therapeutic strategies for early intervention and prevention. Nucleic acid drugs, known for their potent molecule-targeting therapeutic properties, offer potential for genetic suppression of AD. Piwi-interacting RNAs, a class of small RNAs, hold promise for managing cardiovascular diseases. Limited research on these RNAs and AD exists. This study demonstrates that an antagomir targeting heart-apoptosis-associated piRNA (HAAPIR) effectively regulates vascular remodeling, mitigating AD occurrence and progression through the myocyte enhancer factor 2D (Mef2D) and matrix metallopeptidase 9 (MMP9) pathways. Green tea-derived plant exosome-like nanovesicles (PELNs) are used for oral administration of antagomir. The antagomir-HAAPIR-nanovesicle complex, after purification and optimization, exhibits a high packing rate, while the antagomir is resistant to enzyme digestion. Administered to mice, the complex targets the aortic lesion, reducing AD incidence and improving survival. Moreover, MMP9 and Mef2D expression decrease significantly, inhibiting the phenotypic conversion of human aortic smooth muscle cells. PELNs encapsulate the antagomir-HAAPIR complex, maintaining stability, mediating transport into the bloodstream, and delivering Piwi-interacting RNAs to AD sites. Thus, HAAPIR is a potential target for persistent clinical AD prevention and treatment, and nanovesicle-encapsulated nucleic acids offer a promising cardiovascular disease treatment, providing insights for other therapeutic targets.

Analysis of host factor networks during hepatitis B virus infection in primary human hepatocytes.

Chronic hepatitis B virus (HBV) infection affects around 250 million people worldwide, causing approximately 887,000 deaths annually, primarily owing to cirrhosis and hepatocellular carcinoma (HCC). The current approved treatments for chronic HBV infection, such as interferon and nucleos(t)ide analogs, have certain limitations as they cannot completely eradicate covalently closed circular DNA(cccDNA). Considering that HBV replication relies on host transcription factors, focusing on host factors in the HBV genome may provide insights into new therapeutic targets against HBV. Therefore, understanding the mechanisms underlying viral persistence and hepatocyte pathogenesis, along with the associated host factors, is crucial. In this study, we investigated novel therapeutic targets for HBV infection by identifying gene and pathway networks involved in HBV replication in primary human hepatocytes (PHHs). Importantly, our study utilized cultured primary hepatocytes, allowing transcriptomic profiling in a biologically relevant context and enabling the investigation of early HBV-mediated effects. PHHs were infected with HBV virion particles derived from HepAD38 cells at 80 HBV genome equivalents per cell (Geq/cell). For transcriptomic sequencing, PHHs were harvested 1, 2-, 3-, 5-, and 7days post-infection(dpi). After preparing the libraries, clustering and sequencing were conducted to generate RNA-sequencing data. This data was processed using Bioinformatics tools and software to analyze DEGs and obtain statistically significant results. Furthermore, qRT-PCR was performed to validate the RNA-sequencing results, ensuring consistent findings. We observed significant alterations in the expression patterns of 149 genes from days 1 to7 following HBV infection (R2 > 0.7, q < 0.05). Functional analysis of these genes identified RNA-binding proteins involved in mRNA metabolism and the regulation of alternative splicing during HBV infection. Results from qRT-PCR experiments and the analysis of two validation datasets suggest that RBM14 and RPL28 may serve as potential biomarkers for HBV-associated HCC. Transcriptome analysis of gene expression changes during HBV infection in PHHs provided valuable insights into chronic HBV infection. Additionally, understanding the functional involvement of host factor networks in the molecular mechanisms of HBV replication and transcription may facilitate the development of novel strategies for HBV treatment.

Mild phototherapy strategies for efficient treatment of bacterial keratitis while avoiding side effects

Bacterial keratitis (BK) is one of the most threatening ocular diseases, leading to stromal injury, corneal perforation, or even blindness. Avoiding side effect is necessary for efficient BK treatment. Herein, we develop GDY-Ag@AgCl heterojunction catalysts to achieve BK treatment via mild phototherapy strategy. Mild photothermal therapy (PTT) can greatly enhance the generation of ROS produced by photocatalytic therapy (PCT), which can decrease the dosage of photosensitizer, as well as solve the issue of uncontrolled local overheating and the accumulation of PTT agents, minimizing side effects and avoiding secondary injuries. The results demonstrate that lower dosage of PTT/PCT agents, and milder and controlled thermal effect of GDY-Ag@AgCl exhibits excellent inactivation performance against ampicillin-resistant Escherichia coli and methicillin-resistant Staphylococcus aureus (MRSA). Moreover, this phototherapy strategy not only achieves more effective treatment of BK induced by MRSA with no side effects but also shows a superior ability to alleviate inflammation. This strategy offers a safe and promising theragnostic approach for treating ocular drug-resistant bacterial infections.

Psychological distress, health-promoting lifestyle and sociodemographic factors in Honduran university students: a structural equation model.

This study sought to analyze an explanatory model on the relationship among sociodemographic factors, health-promoting lifestyle behaviors and psychological distress (depression, anxiety and stress) in college students. This is an observational, analytical and cross-sectional study conducted on a national sample of 4203 students who entered a macro university in Honduras in 2021, 2022 and 2023. We used a sociodemographic survey, the Health-Promoting Lifestyle Profile (HPLP-II) and the Depression, Anxiety and Stress Scales (DASS-21). Univariate analysis and a multivariate structural equation model were conducted. The average HPLP-II score was 117.45 (± 23.41), and the average DASS-21 score was 20.06 (± 14.16). The multivariate model showed a good data fit (comparative fit index = 0.951; Tucker-Lewis index = 0.957; root mean square error of approximation = 0.067 [90% CI = 0.067-0.068]). Results indicate that being a woman (β = 0.11; p < 0.001) and being enrolled in biological and health sciences (β = 0.09; p < 0.001) significantly predict HPLP-II scores. Furthermore, being a woman (β = 0.17; p < 0.001), age (β = 0.10; p < 0.001) and having pre-existing medical conditions (β = 0.16; p < 0.001) significantly explain part of the variance of DASS-21. A significant reverse relationship between health-promoting behavior and psychological distress was shown (r = -0.36; p < 0.001). This study identifies protective and risky sociodemographic factors linked to health-promoting lifestyle behaviors and psychological distress. Our findings have implications for developing comprehensive intervention policies and strategies to promote health in higher education settings.

Atrial fibrillation fact sheet in Korea 2024: part 2—stroke prevention in Korean patients with atrial fibrillation

ObjectiveAtrial fibrillation (AF) increases the risk of thromboembolic events, making oral anticoagulants (OACs) essential for high-risk patients. This fact sheet provides nationwide statistics on AF management for stroke prevention in Korea. We aimed to evaluate current anticoagulation treatment trends and strategies in Korea.MethodThe Korean national health claims database from the National Health Insurance Service was used. AF patients aged ≥ 18 years from 2013 to 2022 were included. OAC use, including warfarin and non-vitamin K antagonist OACs (NOACs), was tracked through prescription data. The rates of OAC use were calculated based on continued use, considering prescription dates and amounts. For patients with multiple encounters, the last encounter was used for analysis.ResultsDuring the study, 20.4% of strokes were accompanied by AF, with AF diagnosed within 6 months before or after the stroke. The number of patients diagnosed with AF after a stroke increased from 4893 in 2013 to 6978 in 2022. Among newly diagnosed AF patients requiring OACs, 51% were not prescribed OACs within 6 months. OAC treatment rates for high-risk AF patients increased from 44.6% in 2013 to 77.5% in 2022, with NOAC prescriptions rising significantly after 2015. Regional variations in OAC prescription rates were observed, with lower rates in suburban/rural areas than in urban regions (76.0% vs. 79.6%, p < 0.001).ConclusionsConsiderable strokes could have been prevented with earlier AF detection and OAC treatment through more intensive electrocardiogram screening.

Neurobiology and Treatment of Posttraumatic Stress Disorder.

The recent worldwide surge of warfare and hostilities exposes increasingly large numbers of individuals to traumatic events, placing them at risk of developing posttraumatic stress disorder (PTSD) and challenging both clinicians and service delivery systems. This overview summarizes and updates the core knowledge of the genetic, molecular, and neural circuit features of the neurobiology of PTSD and advances in evidence-based psychotherapy, pharmacotherapy, neuromodulation, and digital treatments. While the complexity of the neurobiology and the biological and clinical heterogeneity of PTSD have challenged clinicians and researchers, there is an emerging consensus concerning the underlying mechanisms and approaches to diagnosis, treatment, and prevention of PTSD. This update addresses PTSD diagnosis, prevalence, course, risk factors, neurobiological mechanisms, current standard of care, and innovations in next-generation treatment and prevention strategies. It provides a comprehensive summary and concludes with areas of research for integrating advances in the neurobiology of the disorder with novel treatment and prevention targets.

Brief Report: Evaluating the Efficacy of Psychobehavioral Interventions for Cardiovascular Risk Among People Living With HIV: A Systematic Review and Meta-Synthesis of Randomized Controlled Trials

Abstract: People with HIV (PWH) are disproportionately affected by cardiovascular disease (CVD). Psychobehavioral therapies are capable of targeting the pathophysiology underlying HIV-CVD comorbidity. This study synthesized findings from randomized controlled trials of psychobehavioral therapies for reducing CVD risk among PWH following Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Inclusion criteria were as follows: (1) used a randomized controlled trial design, (2) evaluated a cognitive–behavioral or mindfulness-based therapy, (3) sampled adults (age ≥18 years) with HIV, (4) measured a behavioral (eg, diet) or biological (eg, immune functioning) CVD risk factor, and (5) published in an English-language peer-reviewed journal. Electronic searches were conducted in 6 databases (eg, MEDLINE) using controlled vocabulary and free-text synonyms for HIV, psychobehavioral therapy, and CVD risk. Data were independently extracted with consensus reached. Outcomes were immune activation, tobacco smoking, stress, inflammation, and physical activity from 33 studies. There were stronger effects for psychobehavioral interventions compared with controls on CD4 [Hedge g = 0.262, 95% confidence interval (CI) = 0.127 to 0.396] and tobacco-smoking abstinence (Hedge g = 0.537, 95% CI = 0.215 to 0.86). There were no differences or insufficient data for stress, inflammation, or physical activity. No eligible studies examined psychobehavioral interventions on blood pressure, lipids, or weight in PWH. There is increasing importance to further invest in broader CVD risk reduction effort for PWH that include psychobehavioral intervention strategies.

Skill enactment and knowledge acquisition among community users of digital mental health interventions: qualitative study with thematic analysis.

The acquisition of knowledge and use of skills from digital mental health interventions (DMHIs) are considered important for effectiveness. However, our understanding of user experiences implementing skills learned from these interventions is limited, particularly outside of research trials. This qualitative study aimed to investigate how community users learn and apply knowledge and skills from DMHIs based on cognitive behavioural therapy (CBT) in daily life. The study also examined factors influencing the selection and use of skills and explored perceived changes in mental health resulting from the intervention. Thirteen adults aged 26 to 66 years (10 females) were recruited using social media advertising and participated in semi-structured interviews by telephone or videoconference. All participants were living in Australia and had used a digital CBT program within the past 3 months. Interviews lasted on average 45min. Transcripts were analysed using theoretical thematic analysis. Participants demonstrated high levels of program engagement. Findings were organised into three topics with six major themes. Participants reported that their chosen intervention reinforced existing knowledge and fostered new skills and insights (Topic 1, Theme 1: knowledge consolidation). Most described actively applying skills (Topic 1, Theme 2: active approach to skill enactment), although the extent of learning and range of skills enacted varied across participants. Influences on skill selection included the perceived relevance of intervention strategies to the user's needs and personal characteristics (Topic 2, Theme 1: relevance of intervention strategies), as well as the perceived or experienced effectiveness of those strategies (Topic 2, Theme 2: perceived and experienced benefit). Challenges to ongoing skill enactment included time scarcity, prioritisation difficulties, and lack of motivation (Topic 2, Theme 3: navigating time constraints and low motivation). Improvements in mental health were generally modest and attributed mainly to participants' proactive efforts (Topic 3, Theme 1: perceived changes). DMHIs may reinforce existing understanding of psychotherapeutic strategies, offer new knowledge, and encourage the application of skills in everyday life among community users who actively engage with these interventions. Future research should prioritise personalising DMHIs and investigating methods to optimise the acquisition, retention, and sustained application of knowledge and skills.