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Circulation Sep 2023Current clinical decision tools for assessing bleeding risk in individuals with atrial fibrillation (AF) have limited performance and were developed for individuals...
BACKGROUND
Current clinical decision tools for assessing bleeding risk in individuals with atrial fibrillation (AF) have limited performance and were developed for individuals treated with warfarin. This study develops and validates a clinical risk score to personalize estimates of bleeding risk for individuals with atrial fibrillation taking direct-acting oral anticoagulants (DOACs).
METHODS
Among individuals taking dabigatran 150 mg twice per day from 44 countries and 951 centers in this secondary analysis of the RE-LY trial (Randomized Evaluation of Long-Term Anticoagulation Therapy), a risk score was developed to determine the comparative risk for bleeding on the basis of covariates derived in a Cox proportional hazards model. The risk prediction model was internally validated with bootstrapping. The model was then further developed in the GARFIELD-AF registry (Global Anticoagulant Registry in the Field-Atrial Fibrillation), with individuals taking dabigatran, edoxaban, rivaroxaban, and apixaban. To determine generalizability in external cohorts and among individuals on different DOACs, the risk prediction model was validated in the COMBINE-AF (A Collaboration Between Multiple Institutions to Better Investigate Non-Vitamin K Antagonist Oral Anticoagulant Use in Atrial Fibrillation) pooled clinical trial cohort and the Quebec Régie de l'Assurance Maladie du Québec and Med-Echo Administrative Databases (RAMQ) administrative database. The primary outcome was major bleeding. The risk score, termed the DOAC Score, was compared with the HAS-BLED score.
RESULTS
Of the 5684 patients in RE-LY, 386 (6.8%) experienced a major bleeding event, within a median follow-up of 1.74 years. The prediction model had an optimism-corrected C statistic of 0.73 after internal validation with bootstrapping and was well-calibrated based on visual inspection of calibration plots (goodness-of-fit =0.57). The DOAC Score assigned points for age, creatinine clearance/glomerular filtration rate, underweight status, stroke/transient ischemic attack/embolism history, diabetes, hypertension, antiplatelet use, nonsteroidal anti-inflammatory use, liver disease, and bleeding history, with each additional point scored associated with a 48.7% (95% CI, 38.9%-59.3%; <0.001) increase in major bleeding in RE-LY. The score had superior performance to the HAS-BLED score in RE-LY (C statistic, 0.73 versus 0.60; for difference <0.001) and among 12 296 individuals in GARFIELD-AF (C statistic, 0.71 versus 0.66; for difference = 0.025). The DOAC Score had stronger predictive performance than the HAS-BLED score in both validation cohorts, including 25 586 individuals in COMBINE-AF (C statistic, 0.67 versus 0.63; for difference <0.001) and 11 945 individuals in RAMQ (C statistic, 0.65 versus 0.58; for difference <0.001).
CONCLUSIONS
In individuals with atrial fibrillation potentially eligible for DOAC therapy, the DOAC Score can help stratify patients on the basis of expected bleeding risk.
Topics: Humans; Atrial Fibrillation; Factor Xa Inhibitors; Dabigatran; Rivaroxaban; Anticoagulants
PubMed: 37621213
DOI: 10.1161/CIRCULATIONAHA.123.064556 -
Lakartidningen Apr 2024In the last 20 years there has been an increased interest in research on psychedelic compounds for treatment of psychiatric conditions such as depression, anxiety and... (Review)
Review
In the last 20 years there has been an increased interest in research on psychedelic compounds for treatment of psychiatric conditions such as depression, anxiety and substance use disorders. Despite existing treatments being efficacious for many patients, this is not the case for up to a third of the patients with depression. Additionally, treatments are often long and associated with side effects. This review focuses on the psychedelic compound psilocybin, a serotonin-2A-receptor agonist that has been seen to reduce depression and anxiety in patients after administration of only a single dose, with effects lasting several weeks. Recent findings from phase II studies suggest that psilocybin treatment for depression is safe and efficacious. A phase III study is currently recruiting. Whether psychedelics will become a part of standard healthcare remains to be seen, but findings do give rise to cautious optimism.
Topics: Humans; Hallucinogens; Psilocybin; Anxiety Disorders; Psychiatry
PubMed: 38572715
DOI: No ID Found -
Gastroenterology & Hepatology Jul 2023Tremendous effort has been put forth over the past 2 decades in understanding the pathophysiology of nonalcoholic fatty liver disease/nonalcoholic steatohepatitis...
Tremendous effort has been put forth over the past 2 decades in understanding the pathophysiology of nonalcoholic fatty liver disease/nonalcoholic steatohepatitis (NAFLD/NASH). Although multiple potential targets for drug development exist, there have been no approved therapies for NAFLD/NASH. Lipotoxicity, owing to increased delivery of fatty acids to the liver, and hepatic de novo lipogenesis are key drivers of disease pathogenesis. Moreover, genetics, environmental factors, and comorbid conditions converge to determine disease progression in individual patients. Given the complexity and heterogeneity of disease pathogenesis, numerous therapeutic targets have emerged and have been tested in clinical trials. Early trial failures have provided key lessons and foundational insights to move the field forward. Current ongoing phase 3 trials and emerging phase 2 trials are reasons for optimism, and 2 drugs, obeticholic acid and resmetirom, are being evaluated for accelerated approval by the US Food and Drug Administration this year. This article highlights key features of NASH pathophysiology and drug targets, the lessons learned from completed trials, and the current landscape of phase 2 and 3 clinical trials in NASH.
PubMed: 37771619
DOI: No ID Found -
BMC Psychiatry Aug 2023Previous studies suggested that childhood maltreatment is associated with poor health outcomes. While not everyone who experiences abuse as a child goes on to experience...
BACKGROUND
Previous studies suggested that childhood maltreatment is associated with poor health outcomes. While not everyone who experiences abuse as a child goes on to experience poor mental health, some traumatized people are grown to be more resilient than others. Few studies have examined the association between childhood maltreatment and adult resilience. This study aimed to determine different relationships between specific types and features of childhood maltreatment with adult resilience among Chinese with Major Depressive Disorder (MDD) and healthy controls (HCs).
METHODS
A total of 101 patients with MDD and 116 participants in the healthy control (HC) group from Zhumadian Psychiatric Hospital and its nearby communities were included in this analysis. Childhood maltreatment was assessed retrospectively using Childhood Trauma Questionnaire (CTQ). Adults' resilience was assessed by the Connor-Davidson Resilience Scale (CD-RISC). Generalized linear models were applied between childhood maltreatment (specific types and features) and resilience adjusting for covariates.
RESULTS
The total score of CD-RISC and factor scores of strength, optimism, and tenacity in the HC group were higher than those in the MDD group. CTQ total score had a negative association with optimism score among participants in MDD (β=-0.087, P < 0.001) and HC (β=-0.074, P = 0.023) groups. Higher emotional neglect (EN) score (β=-0.169, P = 0.001) and physical neglect (PN) score (β=-0.153, P = 0.043) were related to a worse optimism score in MDD group. Emotional abuse (EA) score was associated with a worse tenacity score (β=-0.674, P = 0.031) in MDD group. For participants in HC group, higher EN and PN scores were related to worse resilience scores (tenacity, strength, and optimism).
CONCLUSIONS
Patients with MDD showed lower optimism than HCs. Childhood maltreatment, especially childhood negect, independently contributed to optimism, with more severe childhood maltreatment predictive of worse performance of optimism. EA in childhood was also linked to worse tenacity in adult patients with MDD.
Topics: Adult; Child; Humans; Adverse Childhood Experiences; Depressive Disorder, Major; Emotional Abuse; Retrospective Studies; East Asian People
PubMed: 37648984
DOI: 10.1186/s12888-023-05124-w -
Frontiers in Psychiatry 2023This study aimed to investigate and compare the therapeutic outcomes of psychological capital between narrative therapy, cognitive-behavioral therapy, and play therapy...
AIM
This study aimed to investigate and compare the therapeutic outcomes of psychological capital between narrative therapy, cognitive-behavioral therapy, and play therapy in the context of hikikomori.
METHODS
This study included 502 hikikomori. Correlation analysis was performed to investigate the relationship between the three forms of therapy and psychological capital, while one-way ANOVA and independent samples -tests were performed to determine the differences in the outcomes of psychological capital between the three forms of therapies.
RESULTS
Results indicated that all three forms of therapy were significantly positively related to psychological capital. Moreover, while cognitive-behavioral therapy performed better in psychological capital (overall score) than the other two, cognitive-behavioral therapy performed better in the subscales "self-efficacy" and "resilience," while narrative therapy performed better in the "hope" and "optimism" subscales. Also, combining features of play therapy helped enhance the outcomes of narrative therapy and cognitive-behavioral therapy on psychological capital.
CONCLUSION
Owing to the varied outcomes of psychological capital among different therapies, the differential use of therapies to deal with the unique needs resultant of hikikomori helps achieve optimal results.
PubMed: 37608996
DOI: 10.3389/fpsyt.2023.1114170 -
Cancers Aug 2023Small cell lung cancer is an aggressive subtype of lung cancer with limited treatment options. Precision medicine has revolutionized cancer treatment for many tumor... (Review)
Review
Small cell lung cancer is an aggressive subtype of lung cancer with limited treatment options. Precision medicine has revolutionized cancer treatment for many tumor types but progress in SCLC has been slower due to the lack of targetable biomarkers. This review article provides an overview of emerging strategies for precision therapy in SCLC. Targeted therapies include targeted kinase inhibitors, monoclonal antibodies, angiogenesis inhibitors, antibody-drug conjugates, PARP inhibitors, and epigenetic modulators. Angiogenesis inhibitors and DNA-damaging agents, such as PARP and ATR inhibitors, have been explored in SCLC with limited success to date although trials are ongoing. The potential of targeting DLL3, a NOTCH ligand, through antibody-drug conjugates, bispecific T-cell engagers, and CAR T-cell therapy, has opened up new therapeutic options moving forward. Additionally, new research in epigenetic therapeutics in reversing transcriptional repression, modulating anti-tumor immunity, and utilizing antibody-drug conjugates to target cell surface-specific targets in SCLC are also being investigated. While progress in precision therapy for SCLC has been challenging, recent advancements provide optimism for improved treatment outcomes. However, several challenges remain and will need to be addressed, including drug resistance and tumor heterogeneity. Further research and biomarker-selected clinical trials are necessary to develop effective precision therapies for SCLC patients.
PubMed: 37627044
DOI: 10.3390/cancers15164016 -
International Journal of Molecular... Sep 2023Immunotherapy has emerged as an important approach for cancer treatment, but its clinical efficacy has been limited in prostate cancer compared to other malignancies.... (Review)
Review
Immunotherapy has emerged as an important approach for cancer treatment, but its clinical efficacy has been limited in prostate cancer compared to other malignancies. This review summarizes key immunotherapy strategies under evaluation for prostate cancer, including immune checkpoint inhibitors, bispecific T cell-engaging antibodies, chimeric antigen receptor (CAR) T cells, therapeutic vaccines, and cytokines. For each modality, the rationale stemming from preclinical studies is discussed along with outcomes from completed clinical trials and strategies to improve clinical efficacy that are being tested in ongoing clinical trials. Imperative endeavors include biomarker discovery for patient selection, deciphering resistance mechanisms, refining cellular therapies such as CAR T cells, and early-stage intervention were reviewed. These ongoing efforts instill optimism that immunotherapy may eventually deliver significant clinical benefits and expand treatment options for patients with advanced prostate cancer.
Topics: Male; Humans; Prostatic Neoplasms; Immunotherapy; Antibodies, Bispecific; Biomedical Research; Cell- and Tissue-Based Therapy
PubMed: 37762648
DOI: 10.3390/ijms241814347 -
Annals of Medicine and Surgery (2012) Nov 2023Depressive disorders are common mental illnesses characterized by persistent feelings of sadness, hopelessness, and loss of interest in activities. Self-esteem refers to...
BACKGROUND
Depressive disorders are common mental illnesses characterized by persistent feelings of sadness, hopelessness, and loss of interest in activities. Self-esteem refers to the appraisal of one's worth and personality, whereas optimism reflects a positive attitude and the expectation of positive outcomes. Therefore, the present study aims to determine the average self-esteem and optimism of patients with depression in 2022.
METHODS
The present study is a single center and prospective descriptive-analytical study in which 121 patients out of 154 participants with major depression using convenience sampling were studied. Recruitment started on 10 June 2022 and ended on 12 July 2022. Data were collected using a demographic questionnaire, the Rosenberg Self-Esteem Scale (RSES), and the Revised Life Orientation Test (LOT -R). Data analysis was performed using statistical tests and the Pearson correlation coefficient with SPSS software version 21.
RESULTS
The mean and SD of patients' self-esteem scores were 14.68±1.30, and the mean and SD for optimism scores were 9.90±1.68. Pearson correlation analysis showed that educational level had a significant inverse relationship with patients' self-esteem scores (=-0.009, =0.03), and sex had a significant relationship with patients' optimism scores (=0.175, =0.008).
CONCLUSION
Considering the importance of self-esteem and optimism in the recovery and return to society of patients with major depression, it is necessary to take measures to strengthen and increase self-esteem and optimism in these patients.
PubMed: 37915636
DOI: 10.1097/MS9.0000000000001263 -
Journal of Physiological Anthropology Jul 2023Hope and love are popular themes of literature and art in many human societies. The human physiology of love and hope is less well understood. This review presents... (Review)
Review
BACKGROUND
Hope and love are popular themes of literature and art in many human societies. The human physiology of love and hope is less well understood. This review presents evidence that the lack of love and/or hope delays growth disturbs development and maturation and even kills.
MAIN BODY
Love and hope intersect in promoting healthy human development. Love provides a sense of security and attachment, which are necessary for healthy physical, cognitive, and emotional development. Hope provides a sense of optimism and resilience in the face of adversity. Loving relationships can foster a sense of hope in individuals and in society by providing support systems during difficult times. Similarly, having a sense of hope can make it easier to form loving relationships by providing individuals with the confidence to connect with others. Hope and love are the fundamental basis of human biocultural reproduction, which is the human style of cooperation in the production, feeding, and care of offspring. Examples are given of the association between human growth in height with love and hope, including (1) the global "Long Depression" of 1873-1896, (2) "hospitalism" and the abuse/neglect of infants and children, (3) adoption, (4) international migration, (5) colonial conquest, and (6) social, economic, and political change in Japan between 1970 and 1990.
CONCLUSION
Overall, this review suggests that love and hope are both critical factors in promoting healthy human development and that they intersect in complex ways to support emotional well-being.
Topics: Child; Infant; Humans; Love; Japan
PubMed: 37443075
DOI: 10.1186/s40101-023-00330-7 -
Frontiers in Psychology 2023Although their perspectives and approaches vary, existing criminological theories are all based on the deterministic optimism that the crucial causes of criminal...
Although their perspectives and approaches vary, existing criminological theories are all based on the deterministic optimism that the crucial causes of criminal behavior must exist and can be uncovered. However, no key factor can fully explain the causes of criminal behavior. All factors that directly affect the occurrence of criminal behavior are important, and contingency is always at work. More feasible crime prevention and control measures can be proposed only considering the contingency factor. The aim of this study is to point out the limitations of the deterministic view of existing criminological theories that explain the causes of crime after knowing the results, and simultaneously to propose the contingency model with viable alternative solutions.
PubMed: 37599759
DOI: 10.3389/fpsyg.2023.1209619