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Preclinical Evidence for the Use of Brexpiprazole + Antidepressant Treatment for Major Depressive Disorder and Post-Traumatic Stress Disorder: A Systematic Review
No full textPurpose: Brexpiprazole, when administered with antidepressant therapy, may provide additional benefits due to complementary actions on noradrenaline (norepinephrine), serotonin, and dopamine neurotransmitter systems. This review addressed the question: what information can preclinical studies provide on the use of brexpiprazole + antidepressant treatment? Methods: A systematic literature review was conducted to search for preclinical studies of brexpiprazole + antidepressant therapy that included a behavioral test relating to any psychiatric disorder. Ovid MEDLINE, Ovid Embase, and conference abstracts were searched (January 1, 2011–July 5, 2021). The statistically significant (p\u3c0.05) findings for brexpiprazole + antidepressant were extracted. Results: Of 296 records screened, nine articles were eligible, describing seven unique studies. In rodent models, including three models of depression (unpredictable chronic mild stress, social defeat stress, and lipopolysaccharide-induced depression), brexpipra-zole + selective serotonin reuptake inhibitor (SSRI) or serotonin–noradrenaline reuptake inhibitor (SNRI) consistently showed statistically significant benefits over vehicle on depression-like behaviors (forced swim test, tail suspension test, sucrose preference), whereas brexpiprazole and antidepressant monotherapies did not. In the predator scent stress model of post-traumatic stress disorder (PTSD), brexpiprazole + SSRI (escitalopram) showed a significant benefit over vehicle and/or monotherapy on anxiety-like behaviors (elevated plus-maze) and hyperalertness (acoustic startle response), whereas brexpiprazole and escitalopram monotherapies did not significantly differ from vehicle. In the fear conditioning model of PTSD, brexpiprazole showed significant improvements whether administered as monotherapy or in combination with escitalopram. Conclusion: Based on a small number of studies, the administration of brexpiprazole with an antidepressant appears to have a greater treatment effect than either brexpiprazole or antidepressant monotherapies in preclinical studies of depression-and PTSD-like behaviors. Thus, preclinical studies support evidence from randomized clinical trials for the therapeutic effects of adjunctive brexpiprazole in the treatment of major depressive disorder, and brexpiprazole in combination with sertraline in the treatment of PTSD. Funding: Otsuka/Lundbeck
Disparities Between Clinical Trial Recruitment and Real-World Demographics in Macular Edema Secondary to Retinal Vein Occlusion
No full textPurpose: Clinical trial cohorts frequently differ demographically from the overall population receiving treatment for the condition under study. Our study describes the racial, ethnic, and gender composition of the cohorts of retinal vein occlusion (RVO) macular edema (ME) clinical trials and compares this to the racial, ethnic, and gender composition of patients undergoing treatment for ME secondary to RVO from the (Intelligent Research in Sight) IRIS Registry. Design: Retrospective observational case series Subjects: Participants in RVO-ME clinical trials that met the following inclusion criteria: conducted in the United States of America, Phase III completed, data reported between January 1, 2000, and January 1, 2020, and demographic information reported with results. Methods: This study identified clinical trials by searching PubMed with the following search terms; “retinal vein occlusion” and “clinical trial” and by searching ClinicalTrials.gov with the search term “retinal vein occlusion.” Main Outcome Measures: The primary outcome was the enrollment fraction defined as the number of trial enrollees divided by the reference sample size of RVO patients undergoing treatment for ME from published IRIS Registry (Intelligent Research in Sight) data. Enrollment fraction was compared between different races, ethnicities, and genders. Results: Eight clinical trials met our inclusion criteria. Compared to the enrollment fraction of 7.69% among Whites, lower enrollment fractions were found in Black patients (4.32%, odds ratio [OR] 0.541, confidence interval [CI] 0.468-0.626, P \u3c .001) and Hispanic patients (3.38%, OR 0.420, CI 0.351-0.503, P \u3c .001), and higher enrollment fraction in Asian patients (10.68%, OR 1.436, CI 1.207-1.708, P \u3c .001). Men were more likely to enroll in the clinical trials compared to women (enrollment fraction, 7.69% vs 5.77%, respectively, OR 1.364, CI 1.273-1.462, P \u3c .001). Conclusions: RVO-ME clinical trials have a higher relative proportion of Asian, White and male subjects when compared to the population undergoing treatment for ME secondary to RVO. Further efforts should encourage clinical trial recruitment that is reflective of the RVO population undergoing treatment for ME to ensure generalizability of clinical trial results
Food Environments and Mental Health: Analyzing the Impact of Fast-Food Availability on U.S. Adults (2011-2016)
No full textThis study investigates the relationship between the availability of fast food in US territories and mental health outcomes. Utilizing a cross-sectional design, the study examines data from the 2011 and 2016 Behavioral Risk Factor Surveillance System (BRFSS) from the CDC, along with data from the U.S. Department of Agriculture’s Food Environment Atlas. The analysis included a nationally representative sample of 351,823 participants across all 50 US states. Multiple regression models examined the association between fast food availability and two primary mental health outcomes: the number of self-reported poor mental health days and the likelihood of being diagnosed with a depressive disorder by a medical provider. Findings of the study indicate that fast food availability was not a significant predictor of the number of poor mental health days reported in a month or being told you have a depressive disorder in both 2011 and 2016. However, several sociodemographic and health behavior variables—such as younger age, female gender, lower income and education levels, unemployment, smoking, lack of physical activity, and higher BMI were consistently and significantly associated with worse mental health outcomes. The number of poor mental health days increased from 2011 to 2016, highlighting a potential concern of declining mental well-being in the U.S. population. Secondary analysis revealed specific relationships in certain subgroups. For example, among employed individuals and college graduates, higher fast food availability was associated with more poor mental health days per month. While fast food availability alone may not be a predictor of mental health outcomes, this study highlights the importance and need for further longitudinal research to explore environmental influences on mental well-being over time
Culture and Other Direct Detection Methods to Diagnose Human Granulocytic Anaplasmosis
No full textObjectives: We sought to assess the performance of 3 laboratory tests on blood specimens for direct detection of Anaplasma phagocytophilum, the cause of human granulocytic anaplasmosis (HGA), in patients tested at a single medical institution in New York State. Methods: Direct tests included microscopic blood smear examination for intragranulocytic inclusions, polymerase chain reaction (PCR), and culture using the HL-60 cell line. The HGA cases testing positive by only 1 direct test were not included, unless HGA was confirmed by acute or convalescent serology using an indirect immunofluorescent assay. Results: From 1997 to 2009, 71 patients with HGA were diagnosed by at least 1 of the 3 direct test methods. For the subgroup of 55 patients who were tested using all 3 methods, culture was positive for 90.9% (50/55) vs 81.8% (45/55) for PCR vs 63.6% (35/55) for blood smear (P =.002). Most cultures (79.3%) were detected as positive within 1 week of incubation. Conclusions: Although using culture to detect A phagocytophilum is likely not amenable for implementation in most hospital laboratories, in our experience, culture had the highest yield among the direct tests evaluated
The Border Is Always Changing: A Mixed-Methods Study of Resilience Among Migrant Serving Organisations in the USA and Mexico
No full textThe Impact of Program and Geographic Signaling on Anesthesia Residency Applications, Interviews, and the Match
No full textBACKGROUND: Increased specialty competitiveness, alongside the inception of virtual interviews, has increased the number of applications submitted to the Electronic Residency Application Service (ERAS) in anesthesiology. ERAS introduced signals to provide applicants with a means to demonstrate interest in a select group of residency programs. In the 2023 to 2024 application cycle, anesthesiology applicants had the opportunity to send 5 gold and 10 silver signals in a tiered system. METHODS: This multicenter, cross-sectional (exempt) research survey was created by members of the executive council of the Association of Anesthesiology Core Program Directors (AACPD) and housed and distributed through REDCap and the University of Nebraska Medical Center. Publicly available contact information of anesthesiology core program directors was obtained from the Accreditation Council for Graduate Medical Education (ACGME) website and membership roster of the AACPD. In total, 174 anesthesiology programs were identified. A survey invitation was distributed on March 12, 2024, to all programs via e-mail with reminders. The survey closed on April 30, 2024. Survey responses were collected anonymously, with instructions to provide 1 response per program. All statistical summaries and analyses were performed using SAS 9.3 (SAS Institute). RESULTS: The survey was sent to all 174 identified programs, with a response rate of 48.9%. Small programs were defined as having \u3c44 residents, medium 44 to 62 residents, and large \u3e62 residents. Small programs received significantly fewer applications (median 1255) than medium (1420) and large (1558) programs (P =.0005). There was a statistically significant difference in the number of gold signals received based on program size, with large programs receiving significantly more than medium (169 vs 116, P =.0238) or small programs (168 vs 71, P \u3c.0001). Applicants sending gold signals were more likely to receive an interview compared to those who sent silver signals (56.7% vs 31%, P ≤.0001). Of the those interviewed, applicants who sent gold signals comprised 42% (28.7%-52.6%), whereas applicants who sent silver signals comprised 45.5% (33%-54.7%). Applicants who did not send a program signal but signaled geographically made up a smaller portion of the interview group at 3% (0%-15.4%). The percentage of matched residents sending gold signals made up 66.7% (47.1%-82.4%) of a program\u27s match list, whereas those sending silver signals were 25% (11.1%-33.3%) of the matched cohort. CONCLUSIONS: Anesthesiology applicants who sent program signals were selected for a large majority of available interview positions, and interviewed applicants who submitted gold and silver signals comprised the vast majority of matched resident cohorts
Sex-Specific Differences in Clinical Outcomes in Patients With Coronary Bifurcation Lesions
No full textCoronary bifurcation lesions are frequent challenging findings during percutaneous coronary intervention (PCI). Contemporary evidence has explored the potential sex-specific differences in patients undergoing PCI. In the present meta-analysis, we compared clinical outcomes of patients undergoing bifurcation PCI between women and men. Using the random-effects method, we compared the clinical outcomes of patients with a coronary bifurcation lesion following PCI between women and men. The results were reported using relative risk (RR) and 95% confidence interval (CI). Baseline comorbidities and mean age were compared between the 2 studied groups. Four observational studies comprising 30,684 patients (8898 women and 21,786 men) were included in the meta-analysis. Women were significantly older than men with a relatively higher prevalence of baseline comorbidities. After using adjusted data from 2 out of 4 available studies, performing PCI for bifurcation lesions in women was not associated with an increased risk of mortality (RR 1.33, 95% CI, 0.78–2.29), myocardial infarction (RR 1.22, 95% CI, 0.41–3.61), target lesion revascularization (RR 1.06, 95% CI, 0.40–2.81), stent thrombosis (RR 0.99, 95% CI, 0.09–10.52), and stroke (RR 1.19, 95% CI, 0.64–2.22). Women were at higher risk of major bleeding compared to male counterparts (RR 2.23, 95% CI, 1.73–2.89). The present study showed no difference in the risk of adverse clinical outcomes except the risk of bleeding between genders with coronary bifurcation lesions. Future studies with adjustment of age and baseline comorbidities are needed to confirm these findings
Endovascular Therapy versus Medical Management in Isolated Posterior Cerebral Artery Acute Ischemic Stroke: A Multinational Multicenter Propensity Score-Weighted Study
No full textBackground: Despite the proven effectiveness of endovascular therapy (EVT) in acute ischemic strokes (AIS) involving anterior circulation large vessel occlusions, isolated posterior cerebral artery (PCA) occlusions (iPCAo) remain underexplored in clinical trials. This study investigates the comparative effectiveness and safety of EVT against medical management (MM) in patients with iPCAo. Methods: This multinational, multicenter propensity score-weighted study analyzed data from the Multicenter Analysis of primary Distal medium vessel occlusions: effect of Mechanical Thrombectomy (MAD-MT) registry, involving 37 centers across North America, Asia, and Europe. We included iPCAo patients treated with either EVT or MM. The primary outcome was the modified Rankin Scale (mRS) at 90 days, with secondary outcomes including functional independence, mortality, and safety profiles such as hemorrhagic complications. Results: A total of 177 patients were analyzed (88 MM and 89 EVT). EVT showed a statistically significant improvement in 90-day mRS scores (OR = 0.55, 95% CI = 0.30–1.00, p = 0.048), functional independence (OR = 2.52, 95% CI = 1.02–6.20, p = 0.045), and a reduction in 90-day mortality (OR = 0.12, 95% CI = 0.03–0.54, p = 0.006) compared to MM. Hemorrhagic complications were not significantly different between the groups. Conclusion: EVT for iPCAo is associated with better neurological outcomes and lower mortality compared to MM, without an increased risk of hemorrhagic complications. Nevertheless, these results should be interpreted with caution due to the study’s observational design. The findings are hypothesis-generating and highlight the need for future randomized controlled trials to confirm these observations and establish definitive treatment guidelines for this patient population
Can “You” Write Me a Letter of Recommendation: Ethics of Self-Authored Letters of Recommendation
No full textThe Roles of Bitter and Sweet Taste Receptors in Food Allergy: Where Are We Now?
No full textFood allergy (FA) is a growing global concern, which contributes significantly to anaphylaxis and severe allergic reactions. Despite advancements in treatments like allergen immunotherapy and biologics, current approaches have notable limitations and there is a pressing need for new therapeutic strategies. Recent research into taste receptors has unveiled their potential role in FA, offering fresh perspectives for understanding and managing this condition. Taste receptors, particularly type 1 taste receptors (TAS1Rs/T1Rs, sweet taste receptors) and type 2 taste receptors (TAS2Rs/T2Rs, bitter taste receptors), are distributed not only in the oral cavity but also in various extra-oral tissues, and their interactions with immune responses are increasingly recognized. This review highlights the connections between taste receptors and FA, exploring how taste receptor mechanisms might contribute to FA pathogenesis and treatment. Taste receptors, especially TAS2Rs, which include multiple subtypes with varying ligand specificities, have been implicated in modulating allergic responses and could serve as targets for novel FA therapies. Additionally, compounds such as bitter agents and sweeteners that interact with taste receptors show promise in influencing FA outcomes. This review emphasizes the need for further research into the mechanisms of taste receptor involvement in FA and suggests that targeting these receptors could provide new avenues for therapeutic intervention in the future