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BMJ Open Jul 2024University students are one of the most vulnerable populations for anxiety disorders worldwide. In Northern Ireland, anxiety disorders appear to be more common among the...
Cerina: cognitive-behavioural therapy-based mobile application for managing GAD symptoms among Ulster University Students in Northern Ireland - a protocol for a pilot feasibility randomised controlled trial.
INTRODUCTION
University students are one of the most vulnerable populations for anxiety disorders worldwide. In Northern Ireland, anxiety disorders appear to be more common among the university student population due to the population demographics across the region. Despite the need, these students show less inclination to access the widely available on-campus well-being services and other external professional services. Digital cognitive-behavioural therapy (CBT) aims to bridge this gap between the need for psychological help and access to it. However, challenges such as limited reach, low adoption, implementation barriers and poor long-term maintenance are mainstay issues resulting in reduced uptake of digital CBT. As a result, the potential impact of digital CBT is currently restricted. The proposed intervention 'Cerina' is a scalable CBT-based mobile app with an interactive user interface that can be implemented in university settings if found to be feasible and effective.
METHODS AND ANALYSIS
The study is a single-blind pilot feasibility randomised controlled trial aiming to test the feasibility and preliminary effects of Cerina in reducing Generalised Anxiety Disorder (GAD) symptoms. Participants are 90 Ulster University students aged 18 and above with self-reported GAD symptoms. They will be allocated to two conditions: treatment (ie, access to Cerina for 6 weeks) and a wait-list control group (ie, optional on-campus well-being services for 6 weeks). Participants in the wait-list will access Cerina 6 weeks after their randomisation and participants in both conditions will be assessed at baseline, at 3 (mid-assessment) and 6 weeks (postassessment). The primary outcome is the feasibility of Cerina (ie, adherence to the intervention, its usability and the potential to deliver a full trial in the future). The secondary outcomes include generalised anxiety, depression, worry and quality of life. Additionally, participants in both conditions will be invited to semistructured interviews for process evaluation.
ETHICS AND DISSEMINATION
Ethical approval for the study has been granted by the Ulster University Research Ethics Committee (ID: FCPSY-22-084). The results of the study will be disseminated through publications in scientific articles and presentations at relevant conferences and/or public events.
TRIAL REGISTRATION NUMBER
NCT06146530.
Topics: Humans; Cognitive Behavioral Therapy; Mobile Applications; Students; Pilot Projects; Feasibility Studies; Northern Ireland; Anxiety Disorders; Universities; Single-Blind Method; Male; Female; Young Adult; Randomized Controlled Trials as Topic; Adolescent; Quality of Life; Adult
PubMed: 38950994
DOI: 10.1136/bmjopen-2023-083554 -
International Journal of Gynecological... Jul 2024To identify characteristics associated with long-term progression-free survival (≥2 years) in patients with advanced ovarian cancer treated with niraparib first-line... (Randomized Controlled Trial)
Randomized Controlled Trial
OBJECTIVE
To identify characteristics associated with long-term progression-free survival (≥2 years) in patients with advanced ovarian cancer treated with niraparib first-line maintenance therapy in the phase III PRIMA/ENGOT-OV26/GOG-3012 study.
METHODS
In this post hoc analysis of PRIMA, patients randomized to niraparib were grouped based on investigator-assessed progression-free survival (progressive disease/censoring <2 years or ≥2 years after randomization). Variables assessed for predictive value were Eastern Cooperative Oncology Group performance status, International Federation of Gynecology and Obstetrics (FIGO) stage at diagnosis, clinical response to platinum-based chemotherapy, number of prior chemotherapy cycles, primary tumor location, body mass index, categorical age, debulking surgery type, number of baseline target lesions, number of baseline non-target lesions, /homologous recombination-deficiency status, residual disease status, and duration from end of chemotherapy to randomization. Logistic regression modeling using backward elimination (significance level=0.15) identified covariates associated with long-term progression-free survival (clinical cut-off date November 17, 2021).
RESULTS
Of 487 patients randomized to niraparib, 152 (31%) had progressive disease/censoring ≥2 years after randomization. Multivariable logistic regression modeling using backward elimination identified mutation/homologous recombination deficiency status (p<0.0001), FIGO stage (p=0.041), primary tumor location (p=0.095), and number of baseline non-target lesions (p=0.0001) to be associated with long-term progression-free survival. Patients significantly more likely to achieve progression-free survival of ≥2 years in the final model were those with - and -mutated/homologous recombination-deficient tumors or wild-type/not determined/homologous recombination-deficient tumors (vs wild-type/homologous recombination-proficient/not determined tumors), FIGO stage III (vs IV), and 0 or 1 baseline non-target lesions (vs ≥2 baseline non-target lesions).
CONCLUSIONS
The hypothesis-generating results of this analysis suggest that mutation/homologous recombination-deficiency status, FIGO stage, and number of baseline non-target lesions may predict progression-free survival of ≥2 years in patients with advanced ovarian cancer receiving niraparib first-line maintenance therapy.
TRIAL REGISTRATION NUMBER
NCT02655016.
Topics: Humans; Female; Indazoles; Piperidines; Progression-Free Survival; Ovarian Neoplasms; Middle Aged; Poly(ADP-ribose) Polymerase Inhibitors; Adult; Aged
PubMed: 38950925
DOI: 10.1136/ijgc-2024-005356 -
The Journal of Clinical Investigation Jul 2024Healthy adipose tissue is essential for normal physiology. There are 2 broad types of adipose tissue depots: brown adipose tissue (BAT), which contains adipocytes poised...
Healthy adipose tissue is essential for normal physiology. There are 2 broad types of adipose tissue depots: brown adipose tissue (BAT), which contains adipocytes poised to burn energy through thermogenesis, and white adipose tissue (WAT), which contains adipocytes that store lipids. However, within those types of adipose, adipocytes possess depot and cell-specific properties that have important implications. For example, the subcutaneous and visceral WAT confers divergent risk for metabolic disease. Further, within a depot, different adipocytes can have distinct properties; subcutaneous WAT can contain adipocytes with either white or brown-like (beige) adipocyte properties. However, the pathways that regulate and maintain this cell and depot-specificity are incompletely understood. Here, we found that the transcription factor KLF15 is required for maintaining white adipocyte properties selectively within the subcutaneous WAT. We revealed that deletion of Klf15 is sufficient to induce beige adipocyte properties and that KLF15's direct regulation of Adrb1 is a critical molecular mechanism for this process. We uncovered that this activity is cell autonomous but has systemic implications in mouse models and is conserved in primary human adipose cells. Our results elucidate a pathway for depot-specific maintenance of white adipocyte properties that could enable the development of therapies for obesity and associated diseases.
Topics: Animals; Mice; Kruppel-Like Transcription Factors; Adipocytes, White; Subcutaneous Fat; Humans; Mice, Knockout; Adipose Tissue, White; Male; Adipocytes, Beige
PubMed: 38949025
DOI: 10.1172/JCI172360 -
JPMA. the Journal of the Pakistan... Jun 2024To compare the effects of magnesium sulphate on the total dose of intravenous morphine consumption postoperatively following limb amputations along with rescue analgesia... (Randomized Controlled Trial)
Randomized Controlled Trial
OBJECTIVE
To compare the effects of magnesium sulphate on the total dose of intravenous morphine consumption postoperatively following limb amputations along with rescue analgesia requirement, pain scores and side effects.
METHODS
This prospective, triple-blinded, randomised controlled study was conducted from October 2021 to May 2022 at the Shaukat Khanum Memorial Cancer Hospital and Research Centre, Lahore, Pakistan, and comprised of patients scheduled for limb amputations. They were randomised into 2 equal groups. The anaesthesia protocol was uniform for all patients. Intervention group A was administered 30mg/kg loading dose and 10mg/kg/hr maintenance dose of magnesium sulphate intravenously, while patients in control group B received the same amount of plain isotonic saline. Morphine consumption, including that used for rescue analgesia and patient-controlled analgesia, was measured for 24 hours postoperatively. Numeric rating scale was used for the evaluation of postoperative pain in both groups at 15min, 1h, 2h, at discharge from the post-anaesthesia care unit and at 12h and 24h in the ward. Data was analysed using SPSS 23.
RESULTS
Of the 24 patients enrolled, the study was completed by 20(83.33%). There were 10(50%) patients in group A; 8(40%) males and 2(20%) females with mean age 24.8±14.14 years and mean surgery time 130.5±47.86 minutes. There were 10(50%) patients in group B; 8(40%) males and 2(20%) females with mean age 23.2±7.4 years and mean surgery time 117±23.85 minutes (p>0.05). Total morphine used over 24 hours in group A was 16±3.1 mg compared to 29.6±11.2 mg in group B (p<0.05). The time for first use of patient-controlled analgesia after arriving in the postanaesthesia care unit was significantly delayed in group A (72.2±24.95 minutes) compared to that in group B (25±26.68 minutes) (p<0.05). Pain scores were significantly higher in the group B at 15min compared to group A (p<0.05), but not at the rest of the time points (p>0.05).
CONCLUSIONS
Intravenous magnesium sulphate proved to be effective in lowering postoperative opioid requirement following limb amputations.
Topics: Humans; Pain, Postoperative; Magnesium Sulfate; Female; Male; Analgesics, Opioid; Adult; Morphine; Prospective Studies; Amputation, Surgical; Pain Measurement; Middle Aged; Analgesia, Patient-Controlled; Young Adult; Acute Pain
PubMed: 38948969
DOI: 10.47391/JPMA.9022 -
HemaSphere Jul 2024Twenty percent of children with T-cell lymphoblastic lymphoma (T-LBL) will relapse and have an extremely poor outcome. Currently, we can identify a genetically low-risk...
Twenty percent of children with T-cell lymphoblastic lymphoma (T-LBL) will relapse and have an extremely poor outcome. Currently, we can identify a genetically low-risk subgroup in pediatric T-LBL, yet these high-risk patients who need intensified or alternative treatment options remain undetected. Therefore, there is an urgent need to recognize these high-risk T-LBL patients through identification of molecular characteristics and biomarkers. By using RNA sequencing which was performed in 29/49 T-LBL patients who were diagnosed in the Princess Maxima Center for Pediatric Oncology between 2018 and 2023, we discovered a previously unknown high-risk biological subgroup of children with T-LBL. This subgroup is characterized by gene fusions, found in 21% of our T-LBL cohort (6/29). All patients presented with a large mediastinal mass, pleural/pericardial effusions, and absence of blasts in the bone marrow, blood, and central nervous system. Blood CCL17 (C-C Motif Chemokine Ligand 17, TARC) levels were measured at diagnosis in 26/29 patients, and all six patients with gene fusions patients exclusively expressed highly elevated blood CCL17 levels, defining a novel and previously not known clinically relevant biomarker for T-cell lymphoblastic lymphoma. Four out of these six patients relapsed during therapy, a fifth developed a therapy-related acute myeloid leukemia during maintenance therapy. These data indicate that T-LBL patients with a fusion have a high risk of relapse which can be easily identified using a blood CCL17 screening at diagnosis. Further molecular characterization through gene fusion analysis offers these patients the opportunity for treatment intensification or new treatment strategies.
PubMed: 38948925
DOI: 10.1002/hem3.117 -
International Journal of Chronic... 2024Exacerbations of chronic obstructive pulmonary disease (COPD) were reported less frequently during the COVID-19 pandemic. We report real-world data on COPD exacerbation...
BACKGROUND
Exacerbations of chronic obstructive pulmonary disease (COPD) were reported less frequently during the COVID-19 pandemic. We report real-world data on COPD exacerbation rates before and during this pandemic.
METHODS
Exacerbation patterns were analysed using electronic medical records or claims data of patients with COPD before (2017-2019) and during the COVID-19 pandemic (2020 through early 2022) in France, Germany, Italy, the United Kingdom and the United States. Data from each country were analysed separately. The proportions of patients with COPD receiving maintenance treatment were also estimated.
RESULTS
The proportion of patients with exacerbations fell 45-78% across five countries in 2020 versus 2019. Exacerbation rates in most countries were reduced by >50% in 2020 compared with 2019. The proportions of patients with an exacerbation increased in most countries in 2021. Across each country, seasonal exacerbation increases seen during autumn and winter in pre-pandemic years were absent during the first year of the pandemic. The percentage of patients filling COPD prescriptions across each country increased by 4.53-22.13% in 2019 to 9.94-34.17% in 2021.
CONCLUSION
Early, steep declines in exacerbation rates occurred in 2020 versus 2019 across all five countries and were accompanied by a loss of the seasonal pattern of exacerbation.
Topics: Humans; COVID-19; Pulmonary Disease, Chronic Obstructive; Disease Progression; Male; Female; Aged; Middle Aged; SARS-CoV-2; United States; France; United Kingdom; Pandemics; Italy; Time Factors; Seasons
PubMed: 38948907
DOI: 10.2147/COPD.S451009 -
Computational Psychiatry (Cambridge,... 2024Patients with anorexia nervosa (AN) typically hold altered beliefs about their body that they struggle to update, including global, prospective beliefs about their...
Patients with anorexia nervosa (AN) typically hold altered beliefs about their body that they struggle to update, including global, prospective beliefs about their ability to know and regulate their body and particularly their interoceptive states. While clinical questionnaire studies have provided ample evidence on the role of such beliefs in the onset, maintenance, and treatment of AN, psychophysical studies have typically focused on perceptual and 'local' beliefs. Across two experiments, we examined how women at the acute AN (N = 86) and post-acute AN state (N = 87), compared to matched healthy controls (N = 180) formed and updated their self-efficacy beliefs retrospectively (Experiment 1) and prospectively (Experiment 2) about their heartbeat counting abilities in an adapted heartbeat counting task. As preregistered, while AN patients did not differ from controls in interoceptive accuracy , they hold and maintain 'pessimistic' interoceptive, metacognitive self-efficacy beliefs after performance. Modelling using a simplified computational Bayesian learning framework showed that neither local evidence from performance, nor retrospective beliefs following that performance (that themselves were suboptimally updated) seem to be sufficient to counter and update pessimistic, self-efficacy beliefs in AN. AN patients showed lower learning rates than controls, revealing a tendency to base their posterior beliefs more on prior beliefs rather than prediction errors in both retrospective and prospective belief updating. Further explorations showed that while these differences in both explicit beliefs, and the latent mechanisms of belief updating, were not explained by general cognitive flexibility differences, they were explained by negative mood comorbidity, even after the acute stage of illness.
PubMed: 38948255
DOI: 10.5334/cpsy.109 -
Theranostics 2024Over the past two decades, metronomic chemotherapy has gained considerable attention and has demonstrated remarkable success in the treatment of cancer. Through chronic... (Review)
Review
Over the past two decades, metronomic chemotherapy has gained considerable attention and has demonstrated remarkable success in the treatment of cancer. Through chronic administration and low-dose regimens, metronomic chemotherapy is associated with fewer adverse events but still effectively induces disease control. The identification of its antiangiogenic properties, direct impact on cancer cells, immunomodulatory effects on the tumour microenvironment, and metabolic reprogramming ability has established the intrinsic multitargeted nature of this therapeutic approach. Recently, the utilization of metronomic chemotherapy has evolved from salvage treatment for metastatic disease to adjuvant maintenance therapy for high-risk cancer patients, which has been prompted by the success of several substantial phase III trials. In this review, we delve into the mechanisms underlying the antitumour effects of metronomic chemotherapy and provide insights into potential combinations with other therapies for the treatment of various malignancies. Additionally, we discuss health-economic advantages and candidates for the utilization of this treatment option.
Topics: Humans; Administration, Metronomic; Neoplasms; Tumor Microenvironment; Angiogenesis Inhibitors; Antineoplastic Agents; Animals; Antineoplastic Combined Chemotherapy Protocols
PubMed: 38948068
DOI: 10.7150/thno.95619 -
Genes & Diseases Sep 2024As the most prevalent and reversible internal epigenetic modification in eukaryotic mRNAs, -methyladenosine (mA) post-transcriptionally regulates the processing and... (Review)
Review
As the most prevalent and reversible internal epigenetic modification in eukaryotic mRNAs, -methyladenosine (mA) post-transcriptionally regulates the processing and metabolism of mRNAs involved in diverse biological processes. mA modification is regulated by mA writers, erasers, and readers. Emerging evidence suggests that mA modification plays essential roles in modulating the cell-fate transition of embryonic stem cells. Mechanistic investigation of embryonic stem cell maintenance and differentiation is critical for understanding early embryonic development, which is also the premise for the application of embryonic stem cells in regenerative medicine. This review highlights the current knowledge of mA modification and its essential regulatory contribution to the cell fate transition of mouse and human embryonic stem cells.
PubMed: 38947741
DOI: 10.1016/j.gendis.2023.101199 -
Cureus May 2024Brain metastasis is a rare complication of ovarian cancer, always found at the advanced stage. Even though different multimodal approaches are available, including...
Niraparib Maintenance Therapy for Brain Metastasis in Ovarian Endometrioid Adenocarcinoma With Peritoneal Carcinomatosis: A Comprehensive Case Study and Literature Review.
Brain metastasis is a rare complication of ovarian cancer, always found at the advanced stage. Even though different multimodal approaches are available, including surgical intervention and radiotherapy, there are no official guidelines for handling this serious complication. Poly(adenosine diphosphate-ribose) polymerase (PARP) inhibitors are a group of medications initially used for maintenance therapy in platinum-sensitive recurrent ovarian cancer. Niraparib has shown some efficacy in patients with brain metastasis due to its unique properties of penetrating the blood-brain barrier. Here, we present the case of a 51-year-old patient with advanced ovarian cancer with no germline breast cancer susceptibility gene (BRCA) mutations. Despite undergoing surgery and multiple rounds of chemotherapy, the patient's condition worsened, culminating in brain metastasis. Given her neurological issues, radiotherapy was not an option, prompting the initiation of a 300 mg dose of niraparib. To date, only sporadic case reports in the literature have described patients with ovarian cancer treated with niraparib and complicated by brain metastasis. Our case is unique because it is the first case of a patient with the endometrioid type of ovarian cancer.
PubMed: 38947662
DOI: 10.7759/cureus.61355