Multimorbidity among people with HIV in regional New South Wales, Australia

Background: Multimorbidity is the co-occurrence of more than one chronic health condition in addition to HIV. Higher multimorbidity increases mortality, complexity of care and healthcare costs while decreasing quality of life. The prevalence of and factors associated with multimorbidity among HIV positive patients attending a regional sexual health service are described. Methods: A record review of all HIV positive patients attending the service between 1 July 2011 and 30 June 2012 was conducted. Two medical officers reviewed records for chronic health conditions and to rate multimorbidity using the Cumulative Illness Rating Scale (CIRS). Univariate and multivariate linear regression analyses were used to determine factors associated with a higher CIRS score. Results: One hundred and eighty-nine individuals were included in the study; the mean age was 51.8 years and 92.6% were men. One-quarter (25.4%) had ever been diagnosed with AIDS. Multimorbidity was extremely common, with 54.5% of individuals having two or more chronic health conditions in addition to HIV; the most common being a mental health diagnosis, followed by vascular disease. In multivariate analysis, older age, having ever been diagnosed with AIDS and being on an antiretroviral regimen other than two nucleosides and a non-nucleoside reverse transcriptase inhibitor or protease inhibitor were associated with a higher CIRS score. Conclusion: To the best of our knowledge, this is the first study looking at associations with multimorbidity in the Australian setting. Care models for HIV positive patients should include assessing and managing multimorbidity, particularly in older people and those that have ever been diagnosed with AIDS

Abnormal Corpus Callosum Integrity in Bipolar Disorder: A Diffusion Tensor Imaging Study

Objective: Abnormalities in the anterior interhemispheric connections provided by the corpus callosum (CC) have long been implicated in bipolar disorder (BID). In this study, we used complementary diffusion tensor imaging methods to study the structural integrity of the CC and localization of potential abnormalities in BD. Methods: Subjects included 33 participants with BID and 40 healthy comparison participants. Fractional anisotropy (FA) measures were compared between groups with region of interest (ROD methods to investigate the anterior, middle, and posterior CC and voxel-based methods to further localize abnormalities. Results: In ROI-based analyses, FA was significantly decreased in the anterior and middle CC in the BID group (p <.05). Voxel-based analyses similarly localized group differences to the genu, rostral body, and anterior midbody of CC (p <.05, corrected). Conclusion: The findings demonstrate abnormalities in the structural integrity of the anterior CC in BID that might contribute to altered interhemispheric connectivity in this disorder.National Institute of Mental Health (NIH)National Institute of Mental Health (NIH)[R01MH69747]National Institute of Mental Health (NIH)National Institute of Mental Health (NIH)[R01MH070902]National Institute of Mental Health (NIH)National Institute of Mental Health (NIH)[T32MH14276]National Institute of Mental Health (NIH)National Institute of Mental Health (NIH)[R01 EB006494]National Institute of Mental Health (NIH)[K23MH077914]National Institute of Mental Health (NIH)The Department of Veterans Affairs Career DevelopmentThe Department of Veterans Affairs Career DevelopmentMerit ReviewMerit ReviewResearch Enhancement Award Program (REAP)Research Enhancement Award Program (REAP)Attias Family FoundationAttias Family FoundationMarcia Simon KaplanMarcia Simon KaplanKlingenstein FoundationKlingenstein FoundationAlational InstitutesAlational InstitutesHealth (NIH)/National Center for Research Resources/Clinical and Translational Science AwardsHealth (NIH)/National Center for Research Resources/Clinical and Translational Science Awards[UL1RR024139-01]NIH/National Institute of Biomedical Imaging and Bioengineering[R01 EB006494]NIH/National Institute of Biomedical Imaging and Bioengineerin

Functional and Structural Connectivity Between the Perigenual Anterior Cingulate and Amygdala in Bipolar Disorder

Objective: Abnormalities in the morphology and function of two gray matter structures central to emotional processing, the perigenual anterior cingulate cortex (pACC) and amygdala, have consistently been reported in bipolar disorder (BD). Evidence implicates abnormalities in their connectivity in BD. This study investigates the potential disruptions in pACC-amygdala functional connectivity and associated abnormalities in white matter that provides structural connections between the two brain regions in BD. Methods: Thirty-three individuals with BD and 31 healthy comparison subjects (HC) participated in a scanning session during which functional magnetic resonance imaging (fMRI) during processing of face stimuli and diffusion tensor imaging (DTI) were performed. The strength of pACC-amygdala functional connections was compared between BD and HC groups, and associations between these functional connectivity measures from the fMRI scans and regional fractional anisotropy (FA) from the DTI scans were assessed. Results: Functional connectivity was decreased between the pACC and amygdala in the BD group compared with HC group, during the processing of fearful and happy faces (p < .005). Moreover, a significant positive association between pACC-amygdala functional coupling and FA in ventrofrontal white matter, including the region of the uncinate fasciculus, was identified (p < .005). Conclusion: This study provides evidence for abnormalities in pACC-amygdala functional connectivity during emotional processing in BD. The significant association between pACC-amygdala functional connectivity and the structural integrity of white matter that contains pACC-amygdala connections suggest that disruptions in white matter connectivity may contribute to disturbances in the coordinated responses of the pACC and amygdala during emotional processing in BD.National Institute of Mental Health (NIH)[R01MH69747]National Institute of Mental Health (NIH)National Institute of Mental Health (NIH)National Institute of Mental Health (NIH)[R01MH070902]National Institute of Mental Health (NIH)[T32MH1427G]National Institute of Mental Health (NIH)Clinical and Translational Science Award (CTSA), NIH National Center[UL1 RR0249139]Clinical and Translational Science Award (CTSA), NIH National CenterDepartment of Veterans Affairs Career Development (HPB), Merit Review (HPB) and Research Enhancement Award Program (REAP)Department of Veterans Affairs Career Development (HPB), Merit Review (HPB) and Research Enhancement Award Program (REAP)National Alliance for Research in Schizophrenia and Depression (Great Neck, New York)National Alliance for Research in Schizophrenia and Depression (Great Neck, New York)Attias Family FoundationAttias Family FoundationMarcia Simon KaplanMarcia Simon KaplanEthel F. Donaghzre Women`s Investigator ProgramEthel F. Donaghzre Women`s Investigator ProgramKlingenstein FoundationKlingenstein FoundationHoward Hughes Medical Institute FellowshipHoward Hughes Medical Institute Fellowshi

Race, Gene Expression Signatures, and Clinical Outcomes of Patients with High-Risk Early Breast Cancer

Importance: There has been little consideration of genomic risk of recurrence by breast cancer subtype despite evidence of racial disparities in breast cancer outcomes.Objective: To evaluate associations between clinical trial end points, namely pathologic complete response (pCR) and distant recurrence-free survival (DRFS), and race and examine whether gene expression signatures are associated with outcomes by race.Design, Setting, and Participants: This retrospective cohort study used data from the Investigation of Serial Studies to Predict Your Therapeutic Response With Imaging and Molecular Analysis 2 (I-SPY 2) multicenter clinical trial of neoadjuvant chemotherapy with novel agents and combinations for patients with previously untreated stage II/III breast cancer. Analyses were conducted of associations between race and short- and long-term outcomes, overall and by receptor subtypes, and their association with 28 expression biomarkers. The trial enrolled 990 female patients between March 30, 2010, and November 5, 2016, with a primary tumor size of 2.5 cm or greater and clinical or molecular high risk based on MammaPrint or hormone receptor (HR)-negative/ERBB2 (formerly HER2 or HER2/neu)-positive subtyping across 9 arms. This data analysis was performed between June 10, 2021, and October 20, 2022. Exposure: Race, tumor receptor subtypes, and genomic biomarker expression of early breast cancer.Main Outcomes and Measures: The primary outcomes were pCR and DRFS assessed by race, overall, and by tumor subtype using logistic regression and Cox proportional hazards regression models. The interaction between 28 expression biomarkers and race, considering pCR and DRFS overall and within subtypes, was also evaluated.Results: The analytic sample included 974 participants (excluding 16 self-reporting as American Indian or Alaska Native, Native Hawaiian or Other Pacific Islander, or multiple races due to small sample sizes), including 68 Asian (7%), 120 Black (12%), and 786 White (81%) patients. Median (range) age at diagnosis was 47 (25-71) years for Asian, 49 (25-77) for Black, and 49 (23-73) years for White patients. The pCR rates were 32% (n = 22) for Asian, 30% for Black (n = 36), and 32% for White (n = 255) patients (P =.87). Black patients with HR-positive/ERBB2-negative tumors not achieving pCR had significantly worse DRFS than their White counterparts (hazard ratio, 2.28; 95% CI, 1.24-4.21; P =.01), with 5-year DRFS rates of 55% (n = 32) and 77% (n = 247), respectively. Black patients with HR-positive/ERBB2-negative tumors, compared with White patients, had higher expression of an interferon signature (mean [SD], 0.39 [0.87] and -0.10 [0.99]; P =.007) and, compared with Asian patients, had a higher mitotic score (mean [SD], 0.07 [1.08] and -0.69 [1.06]; P =.01) and lower estrogen receptor/progesterone receptor signature (mean [SD], 0.31 [0.90] and 1.08 [0.95]; P =.008). A transforming growth factor β signature had a significant association with race relative to pCR and DRFS, with a higher signature associated with lower pCR and worse DRFS outcomes among Black patients only.Conclusions and Relevance: The findings show that women with early high-risk breast cancer who achieve pCR have similarly good outcomes regardless of race, but Black women with HR-positive/ERBB2-negative tumors without pCR may have worse DRFS than White women, highlighting the need to develop and test novel biomarker-informed therapies in diverse populations.</p