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Introduction: Little research on the association of neighborhood environment with physical activity in resource-poor communities has been done. This study assessed changes in perceptions of the neighborhood environment and the association between those perceptions and physical activity in Mexican Americans on the Texas–Mexico border in an area where there would be community efforts to enhance pedestrian and cycling infrastructure and programming. Methods: We analyzed data from a population-based cohort of Mexican American individuals on the Texas–Mexico border. From 2008 to 2018, interviewer-administered questionnaires were used to collect perceptions of neighborhood environment and physical activity at baseline, 5- and 10-year follow-ups, and at other ancillary study visits, with an average of 3 data points per participant. We conducted multivariable longitudinal logistic regression analyses to assess if the changes in odds of positive perceptions of the neighborhood environment over the study years differed by physical activity patterns. Results: The sample (n = 1036) was mostly female (71%), born in Mexico (70%), and had no health insurance (69%). We saw improvements in the perceptions of several neighborhood environment attributes from 2008 to 2018, though we saw different longitudinal trajectories in these perceptions based on an individual's longitudinal physical activity patterns. By 2014–2018, we saw significantly higher positive perceptions of the neighborhood environment for those who consistently met physical activity guidelines compared with those who did not (adjusted rate ratio = 1.12, P =.049). Discussion: We found that perceptions of many neighborhood environment attributes improved between 2008 and 2018, and that overall positive perceptions were associated with consistently meeting physical activity guidelines over time. [ABSTRACT FROM AUTHOR]

BACKGROUND: There are several well-known treatments for Restless Legs Syndrome (RLS), including dopamine agonists (pramipexole, ropinirole, rotigotine), anticonvulsants (gabapentin and its analogs, pregabalin), oral or intravenous iron, opioids and benzodiazepines. However, in clinical practice, treatment is sometimes limited due to incomplete response or side effects and it is necessary to be aware of other treatment options for RLS, which is the purpose of this review. METHODS: We performed a narrative review detailing all of the lesser known pharmacological treatment literature on RLS. The review purposefully excludes well-established, well-known treatments for RLS which are widely accepted as treatments for RLS in evidence-based reviews. We also have emphasized the pathogenetic implications for RLS of the successful use of these lesser known agents. RESULTS: Alternative pharmacological agents include clonidine which reduces adrenergic transmission, adenosinergic agents such as dipyridamole, glutamate AMPA receptor blocking agents such as perampanel, glutamate NMDA receptor blocking agents such as amantadine and ketamine, various anticonvulsants (carbamazepine/oxcarbazepine, lamotrigine, topiramate, valproic acid, levetiracetam), anti-inflammatory agents such as steroids, as well as cannabis. Bupropion is also a good choice for the treatment of co-existent depression in RLS because of its pro-dopaminergic properties. DISCUSSION: Clinicians should first follow evidence-based review recommendations for the treatment of RLS but when the clinical response is either incomplete or side effects are intolerable other options can be considered. We neither recommend nor discourage the use of these options, but leave it up to the clinician to make their own choices based upon the benefit and side effect profiles of each medication.

Clonal haematopoiesis of indeterminate potential (CHIP) has been associated with many adverse health outcomes. However, further research is required to understand the critical genes and pathways relevant to CHIP subtypes, evaluate how CHIP clones evolve with time, and further advance functional characterisation and therapeutic studies. Large epidemiological studies are well placed to address these questions but often collect saliva rather than blood from participants. Paired saliva- and blood-derived DNA samples from 94 study participants were sequenced using a targeted CHIP-gene panel. The ten genes most frequently identified to carry CHIP-associated variants were analysed. Fourteen unique variants associated with CHIP, ten in DNMT3A, two in TP53 and two in TET2, were identified with a variant allele fraction (VAF) between 0.02 and 0.2 and variant depth ≥ 5 reads. Eleven of these CHIP-associated variants were detected in both the blood- and saliva-derived DNA sample. Three variants were detected in blood with a VAF > 0.02 but fell below this threshold in the paired saliva sample (VAF 0.008—0.013). Saliva-derived DNA is suitable for detecting CHIP-associated variants. Saliva can offer a cost-effective biospecimen that could both advance CHIP research and facilitate clinical translation into settings such as risk prediction, precision prevention, and treatment monitoring. [ABSTRACT FROM AUTHOR]

Previous research has revealed a strong link between the experience of childhood sexual abuse (CSA) and diabetes in adulthood. Moreover, research has shown that sexual minorities (SM) are exposed to adverse childhood experiences (ACEs) (i.e. CSA) and experience depression at higher rates than their heterosexual counterparts. Thus, it is imperative to further investigate the role of depression and the differential associations of exposure to ACEs with diabetes prevalence by sexual orientation. We explored sexual orientation disparities regarding the relationship between CSA and diabetes and examined the moderating role of depression. A total of 29,903 participants from the 2021 Behavioral Risk Factor Surveillance System (BRFSS) were included in this study. Secondary data analysis was conducted using the survey data, and weighted logistic regression and moderation analysis were performed. Heterosexuals who experienced CSA (AOR = 1.25; p <.05) and SM who experienced CSA (AOR = 2.13; p <.05) reported higher odds of having diabetes. Among heterosexuals, depression (AOR = 1.38; p <.001) was significantly associated with having diabetes. Additionally, depression was a significant moderator among heterosexuals with and without CSA. Further understanding of the impact of ACEs on diabetes among specific subgroups of SM should be assessed in future studies. [ABSTRACT FROM AUTHOR]

Objective: To explore the clinical utility of circulating tumor DNA (ctDNA) in esophageal adenocarcinoma (EAC) by developing a cost-effective and rapid technique utilising targeted amplicon sequencing. Summary of background data: Emerging evidence suggests that levels of ctDNA in the blood can be used to monitor treatment response and in the detection of disease recurrence in various cancer types. Current staging modalities for EAC such as computerised tomography of the chest/abdomen/pelvis (CT) and positron emission tomography (PET) do not reliably detect occult micro-metastatic disease, the presence of which signifies a poor prognosis. After curative-intent treatment, some patients are still at high risk of recurrent disease, and there is no widely accepted optimal surveillance tool for patients with EAC. Methods: Sixty-two patients with EAC were investigated for the presence of ctDNA using a tumor-informed approach. We designed a custom targeted amplicon sequencing panel of target specific primers covering mutational foci in 9 of the most commonly mutated genes in EAC. Serial blood samples were taken before and after neoadjuvant treatment (NAT), and during surveillance. Results: Somatic mutations were detected in pre-treatment biopsy samples of 55 out of 62 (89%) EAC patients. Mutations in TP53 (80%) were the most common. Out of these 55 patients, 20 (36%) had detectable ctDNA at baseline. The majority (90%) of patients with detectable ctDNA had either locally advanced tumors, nodal involvement or metastatic disease. In patients with locally advanced tumors, disease free survival (DFS) was more accurately stratified using pre-treatment ctDNA status [HR 4.34 (95% CI 0.93–20.21); P = 0.05] compared to nodal status on PET-CT. In an exploratory subgroup analysis, patients who are node negative but ctDNA positive have inferior DFS [HR 11.71 (95% CI 1.16-118.80) P = 0.04]. In blood samples taken before and following NAT, clearance of ctDNA after NAT was associated with a favourable response to treatment. Furthermore, patients who are ctDNA positive during post-treatment surveillance are at high risk of relapse. Conclusions: Our study shows that ctDNA has potential to provide additional prognostication over conventional staging investigation such as CT and PET. It may also have clinical utility in the assessment of response to NAT and as a biomarker for the surveillance of recurrent disease. [ABSTRACT FROM AUTHOR]

Objective: Current real-world health care cost information is needed to project future expenditures and inform policy. We estimated adults' 2019 health care costs in the United States (US) by age, sex, race/ethnicity, geographic region, and comorbidity., Methods: We aggregated and summarized health care costs in 2021 US dollars using claims data derived from Optum's de-identified Clinformatics® Data Mart database, which includes inpatient, outpatient, and prescription claims for commercial and Medicare Advantage beneficiaries nationwide., Results: A total of 9,227,901 adults were included in the analysis. The largest group represented was 71-75 years old (13%), female (53%), White (68%), received care in the South (41%), and had commercial health insurance (56%). There was a positive relationship between health care cost and age. Females had a 1.3-fold multiplicative increase in costs compared to males (95% CI 1.33-1.34). There were 92.5% of individuals who had health claims in the Northeast, 89.6% in the Midwest, 88.9% in the South, 77.1% in the West, and 12.7% with unknown geographic region. Patients with severe renal failure, heart failure, or metastatic cancer incurred the highest mean yearly costs ($139,844, $113,031, and $85,299, respectively). Metastatic cancer and severe renal failure were associated with a 5.3-fold multiplicative increase in costs compared with not having these conditions, after adjusting for potential confounders (95% CI, 5.26-5.41 and 4.98-5.16, respectively)., Conclusions: We identified patient characteristics and medical conditions that are associated with high health care cost burden and could benefit from tailored interventions. We provided detailed cost estimates to aid health care modeling, cost projection, and cost-minimizing interventions., (Copyright © 2024. Published by Elsevier Inc.)

Background: Asian American and Pacific Islander (AAPI) adults are an understudied group in terms of their mental health and mental healthcare needs. This has been complicated by the difficulty of recruiting adequate national samples of AAPI adults for research., Objective: This study aimed to analyze national data to examine the lifetime prevalence of major psychiatric disorders among AAPI adults relative to non-AAPI adults, as well as to identify and compare sociodemographic and clinical characteristics associated with lifetime suicide attempts among AAPI and non-AAPI adults., Methods: Cross-sectional data on 36,109 adults, including 1801 AAPI adults, from the National Epidemiological Survey of Alcohol and Related Conditions-III (NESARC-III), were analyzed with a series of chi-square and logistic regression analyses., Results: We found a significantly lower lifetime prevalence of mental health disorders in the AAPI versus the non-AAPI population nationally, including 2% of AAPI adults reporting lifetime suicide attempts as compared to about 5% of non-AAPI adults. Female sex and a history of major depressive disorder diagnosis were associated with lifetime suicide attempts in the AAPI and non-AAPI populations. Several unique factors were associated with having a history of suicide attempts in only the AAPI population, including a military service history and a diagnosis of panic disorder., Discussion: Our analysis demonstrated the significant sectors of the AAPI population that merit research, support, and intervention, including the AAPI veteran population. This study identifies several characteristics among AAPI adults that may make them particularly vulnerable to psychiatric problems and suicide risk, which may inform targeted prevention and efforts to provide culturally competent care to this population., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Ltd.)

Purpose: Molibresib is a selective, small molecule inhibitor of the bromodomain and extra-terminal (BET) protein family. This was an open-label, two-part, Phase I/II study investigating molibresib monotherapy for the treatment of hematological malignancies (NCT01943851)., Patients and Methods: Part 1 (dose escalation) determined the recommended Phase 2 dose (RP2D) of molibresib in patients with acute myeloid leukemia (AML), Non-Hodgkin lymphoma (NHL), or multiple myeloma. Part 2 (dose expansion) investigated the safety and efficacy of molibresib at the RP2D in patients with relapsed/refractory myelodysplastic syndrome (MDS; as well as AML evolved from antecedent MDS) or cutaneous T-cell lymphoma (CTCL). The primary endpoint in Part 1 was safety and the primary endpoint in Part 2 was objective response rate (ORR)., Results: There were 111 patients enrolled (87 in Part 1, 24 in Part 2). Molibresib RP2Ds of 75 mg daily (for MDS) and 60 mg daily (for CTCL) were selected. Most common Grade 3+ adverse events included thrombocytopenia (37%), anemia (15%), and febrile neutropenia (15%). Six patients achieved complete responses [3 in Part 1 (2 AML, 1 NHL), 3 in Part 2 (MDS)], and 7 patients achieved partial responses [6 in Part 1 (4 AML, 2 NHL), 1 in Part 2 (MDS)]. The ORRs for Part 1, Part 2, and the total study population were 10% [95% confidence interval (CI), 4.8-18.7], 25% (95% CI, 7.3-52.4), and 13% (95% CI, 6.9-20.6), respectively., Conclusions: While antitumor activity was observed with molibresib, use was limited by gastrointestinal and thrombocytopenia toxicities. Investigations of molibresib as part of combination regimens may be warranted., (©2022 The Authors; Published by the American Association for Cancer Research.)