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Journal of the National Cancer Institute Jun 2024Racial and ethnic minoritized groups report disproportionately lower trust in the healthcare system. Lower healthcare system trust is potentially related to increased...
BACKGROUND
Racial and ethnic minoritized groups report disproportionately lower trust in the healthcare system. Lower healthcare system trust is potentially related to increased exposure to racial discrimination in medical settings, but this association is not fully understood. We examined the association between racial discrimination in medical care and trust in the healthcare system among people with and without a personal cancer history.
METHODS
We examined racial discrimination and trust in a nationally representative American adult sample from the Health Information National Trends Survey 6. Racial discrimination was defined as any unfair treatment in healthcare based on race or ethnicity. Trust in the healthcare system (eg, hospitals and pharmacies) was grouped into low, moderate, and high trust. Multinomial logistic regression models were used to compare low and moderate trust relative to high trust in the healthcare system and estimate odds ratios (ORs) and 95% confidence intervals (CIs).
RESULTS
A total of 5,813 respondents (15% with a personal cancer history) were included 92% (n = 5,355) reported no prior racial discrimination experience during medical treatment. Prior experiences of racial discrimination were positively associated with low (OR = 6.12, 95% CI: 4.22-8.86) and moderate (OR = 2.70, 95% CI: 1.96-3.72) trust in the healthcare system, relative to high trust. Similar associations were observed when stratifying by personal cancer history.
CONCLUSION
Respondents who reported racial discrimination during medical encounters had lower trust in the healthcare system, especially respondents with a personal cancer history. Our findings highlight the need to address racial discrimination experiences during medical care to build patient trust and promote healthcare access.
PubMed: 38937274
DOI: 10.1093/jnci/djae154 -
ISA Transactions Jun 2024The missile integrated guidance and control (IGC) problem with seeker's asymmetric field-of-view (FOV) angle constraints is addressed. In the introduced model, the fin...
The missile integrated guidance and control (IGC) problem with seeker's asymmetric field-of-view (FOV) angle constraints is addressed. In the introduced model, the fin deflections controller is used to drive the body line-of-sight angle rate, which avoids the solving and tracking of aerodynamic angles in traditional IGC method. A novel fixed-time convergence virtual input based on the integral barrier Lyapunov function is designed to ensure the asymmetric FOV angle constraints are never violated. The virtual input is tracked by a new proposed pre-defined fixed time controller with adjustable initial convergence speed. The lumped uncertainty including aerodynamic coefficient and target maneuvering is coped by the fixed-time disturbance observer. It is proved that the closed-loop system states are converged to the bounded region in a fixed-time and the asymmetric FOV angle constraints are satisfied. The 6-degree of freedom flight simulations and comparisons verified the advantages of the proposed algorithm.
PubMed: 38937212
DOI: 10.1016/j.isatra.2024.06.004 -
The Lancet. Haematology Jul 2024The mainstay of treatment for early-stage follicular lymphoma is local radiotherapy, with a possible role for anti-CD20 monoclonal antibody (mAb). We aimed to evaluate...
Local radiotherapy and measurable residual disease-driven immunotherapy in patients with early-stage follicular lymphoma (FIL MIRO): final results of a prospective, multicentre, phase 2 trial.
BACKGROUND
The mainstay of treatment for early-stage follicular lymphoma is local radiotherapy, with a possible role for anti-CD20 monoclonal antibody (mAb). We aimed to evaluate the effect of these treatments using a measurable residual disease (MRD)-driven approach.
METHODS
This prospective, multicentre, phase 2 trial was conducted at 27 centres of the Fondazione Italiana Linfomi (FIL) in Italy. Eligible participants were adults (≥18 years) with newly diagnosed, histologically confirmed follicular lymphoma (stage I or II; grade I-IIIa). Patients were initially treated with 24 Gy involved-field radiotherapy over 12 days; those who were MRD-positive after radiotherapy or during follow-up received eight intravenous doses (1000 mg per dose; one dose per week) of the anti-CD20 mAb ofatumumab. The primary endpoint was the proportion of patients who were MRD-positive after involved-field radiotherapy and became MRD-negative after ofatumumab treatment. Patients were included in the primary endpoint analysis population if they were positive for BCL2::IGH rearrangement at enrolment in peripheral blood or bone marrow samples. MRD positivity was defined as the persistence of BCL2::IGH rearrangement in peripheral blood or bone marrow, assessed centrally by laboratories of the FIL MRD Network. The trial was registered with EudraCT, 2012-001676-11.
FINDINGS
Between May 2, 2015, and June 1, 2018, we enrolled 110 participants, of whom 106 (96%) were eligible and received involved-field radiotherapy. Of these, 105 (99%) were White, one (1%) was Black, 50 (47%) were male, and 56 (53%) were female. Of 105 participants in whom BCL2::IGH status was evaluable, 32 (30%) had a detectable BCL2::IGH rearrangement at baseline. After radiotherapy, 12 (40%) of 30 patients reached MRD-negative status, which was long-lasting (at least 36 or 42 months) in three (25%). In those who were MRD-positive after radiotherapy, ofatumumab induced MRD-negativity in 23 (92%; 95% CI 74-99) of 25 evaluable patients. After a median follow-up of 46·1 months (IQR 42·8-50·8), 14 (61%) of these 23 patients remain in complete response and are MRD-negative. The most common grade 3-4 adverse events were infusion-related reactions, observed in four patients.
INTERPRETATION
Local radiotherapy is frequently not associated with the eradication of follicular lymphoma. An MRD-driven, anti-CD20 monoclonal antibody consolidation enables molecular remission to be reached in almost all patients and is associated with a reduced incidence of relapse over time. A clinical advantage of an MRD-driven consolidation is therefore suggested.
FUNDING
AIRC Foundation for Cancer Research in Italy, Novartis International, and GlaxoSmithKline.
Topics: Humans; Lymphoma, Follicular; Male; Female; Neoplasm, Residual; Middle Aged; Aged; Prospective Studies; Adult; Immunotherapy; Neoplasm Staging; Antibodies, Monoclonal, Humanized; Aged, 80 and over
PubMed: 38937025
DOI: 10.1016/S2352-3026(24)00143-1 -
In Vivo (Athens, Greece) 2024Depression is associated with metabolic disorders, including non-alcoholic fatty liver disease (NAFLD). However, the mechanisms underlying the interaction between them...
BACKGROUND/AIM
Depression is associated with metabolic disorders, including non-alcoholic fatty liver disease (NAFLD). However, the mechanisms underlying the interaction between them are still poorly known.
MATERIALS AND METHODS
In this study, mice on a choline deficiency, L-amino acid-defined, high-fat diet (CDAHFD) developing steatosis were challenged with chronic restraint stress (CRS), a protocol widely used to induce depression. The development of depression and steatosis was evaluated using histopathology analysis, ELISA, q-PCR and Western Blot.
RESULTS
The contribution of the activated HPA axis to hepatic steatosis progress was fully established, which was validated using a hepatocyte model. Histopathological and biochemical analysis indicated that steatosis was exacerbated by CRS challenge, and behavioral tests indicated that the mice developed depression. Among the screened endocrinal pathways, the hypothalamic-pituitary-adrenal (HPA) axis was significantly activated and the synergistic effect of CDAHFD and CRS in activating the HPA axis was observed. In the hypothalamus, expression of corticotropin-releasing hormone (CRH) was increased by 86% and the protein levels of hypothalamic CRH were upregulated by 25% to 33% by CRS treatment. Plasma CRH levels were elevated by 45-56% and plasma adrenocorticotropic hormone (ACTH) levels were elevated by 29-58% by CRS treatment. In the liver, target genes of the HPA axis were activated, accompanied by disruption of the lipid metabolism and progression of steatohepatitis. The lipid metabolism in the Hepa1-6 cell line treated with endogenous corticosterone (CORT) was in accordance with the aforementioned in vivo responses.
CONCLUSION
Depression aggravated hepatic steatosis in CDAHFD-fed mice by activating the HPA axis. The risk of NAFLD development should be fully considered in depressive patients and improvement of psychotic disorders could be an etiological treatment strategy for them.
Topics: Animals; Hypothalamo-Hypophyseal System; Pituitary-Adrenal System; Mice; Depression; Disease Models, Animal; Non-alcoholic Fatty Liver Disease; Male; Mice, Inbred C57BL; Corticotropin-Releasing Hormone; Diet, High-Fat; Adrenocorticotropic Hormone; Liver; Fatty Liver; Corticosterone
PubMed: 38936893
DOI: 10.21873/invivo.13618 -
The American Journal of Cardiology Jun 2024Some patients with atrial fibrillation (AF), albeit less frequently, may regress from sustained to paroxysmal type.
BACKGROUND
Some patients with atrial fibrillation (AF), albeit less frequently, may regress from sustained to paroxysmal type.
OBJECTIVES
We sought to investigate how the regression of AF is associated with outcomes.
METHODS
Among the AF patients enrolled in the Fushimi AF Registry who were identified as having sustained AF at baseline, conversion of sustained to paroxysmal AF during follow-up was defined as AF regression. Major adverse cardiovascular events (MACE) were defined as a composite of cardiac death, myocardial infarction, ischemic stroke, systemic embolism, or hospitalization due to heart failure.
RESULTS
Among 2,261 patients with sustained AF at baseline, AF regression was observed in 214 (9.5%) patients over a median follow-up period of 5.8 years (1.78% per patient-year). The annual incidence of MACE in patients with AF regression was significantly lower than those without (3.47% vs. 6.59% per patient-year, P < 0.001; adjusted hazard ratio [HR], 0.53, 95% confidence interval [CI], 0.38-0.72). Furthermore, AF regression was significantly associated with reduced risk of MACE during and after the regression period from sustained to paroxysmal forms (during regression period: adjusted HR, 0.45; 95% CI, 0.22-0.90; after regression period: adjusted HR, 0.43; 95% CI, 0.26-0.67). The incidence of MACE was comparable between spontaneous regression (35/178: 19.7%) and therapy-associated regression (either receiving catheter ablation or antiarrhythmic drugs before the regression) (7/36: 19.4%) (P=0.98).
CONCLUSION
Regression of AF was associated with a lower incidence of adverse cardiovascular events. The risk of adverse events decreased significantly during the regression period and its reduction level persisted after regression.
CLINICAL TRIAL REGISTRATION
URL: http://www.umin.ac.jp/ctr/index.htm Unique identifier: UMIN000005834.
PubMed: 38936788
DOI: 10.1016/j.amjcard.2024.06.020 -
Journal of Stroke and Cerebrovascular... Jun 2024Mechanical thrombectomy (MT) is the standard of care for the treatment of acute ischemic stroke (AIS) with large vessel occlusion (LVO), but unfavorable outcomes remain...
INTRODUCTION
Mechanical thrombectomy (MT) is the standard of care for the treatment of acute ischemic stroke (AIS) with large vessel occlusion (LVO), but unfavorable outcomes remain common. Procedural arterial hypotension is associated with poor patient outcome. This study aimed to assess the impact of arterial hypotension "magnitude" (a combination of the depth, defined as the percentage relative to baseline arterial blood pressure, and the duration of hypotensive episodes)" during MT on neurological outcome.
METHODS
This is a monocentric retrospective study. Charts were reviewed between January 2018 and June 2021. "Patients were eligible if they were 18 years or older, anterior LVO was diagnosed on cerebral imaging" and MT performed under general anesthesia. Mean arterial pressure (MAP) was recorded every 5 minutes throughout the procedure, and the arterial hypotension "magnitude" was estimated by the area under the curve (AUC) for different thresholds of MAP drops.
MAIN OUTCOME MEASURE
The modified Rankin Scale (mRS) at 90 days.
MAIN RESULTS
Among the 117 patients analyzed, 46% had poor neurological outcome. Our study showed correlations between poor outcome and a greater procedural AUC of arterial hypotension for the different thresholds: 5% (k 0.18; 95% CI 0.06-0.30; P = 0.007), 10% (k 0.18; 95% CI 0.05-0.30; P = 0.008), 15% (k 0.18; 95% CI 0.04-0.30; P = 0.011), 20% (k 0.18; 95% CI 0.05-0.30; P = 0.010) and 30% (k 0.19; 95% CI 0.05-0.31; P = 0.010). This association persisted after controlling for age, baseline NIHSS score, and ASPECT score.
CONCLUSION
The magnitude of hypotension during MT under general anesthesia for AIS is an independent factor of poor outcome at 90 days. These associations have been observed in patients with mild and severe hypotensive episodes.
PubMed: 38936647
DOI: 10.1016/j.jstrokecerebrovasdis.2024.107838 -
Neurobiology of Disease Jun 2024The diagnosis of amyotrophic lateral sclerosis (ALS) is primarily clinical, supported by the electromyographic examination to reveal signs of lower motor neuron damage....
BACKGROUND
The diagnosis of amyotrophic lateral sclerosis (ALS) is primarily clinical, supported by the electromyographic examination to reveal signs of lower motor neuron damage. Identifying reliable markers of upper motor neuron (UMN) involvement is challenging. On this regard, the role of transcranial magnetic stimulation-induced motor-evoked potentials (TMS-MEPs), and its relationship with UMN burden, is still under investigation.
OBJECTIVE
To evaluate the ability of TMS-MEPs in delineating the neurophysiological UMN damage, and to determine the relationship between TMS-MEPs and [F]FDG-PET measures of neural dysfunction.
METHODS
We retrospectively selected 13 ALS patients who underwent, during the diagnostic process, the TMS-MEPs and [F]FDG-PET scans. Demographic and clinical data were collected. For the MEP evaluation, we considered normal MEP, absent MEP, or significantly increased central-motor-conduction-time. For [F]FDG-PET, we conducted voxel-wise analyses, both at single-subject and group levels, exploring hypometabolism and hypermetabolism patterns in comparison with a large dataset of healthy controls (HC).
RESULTS
Based on TMS-MEPs, we identified 4/13 patients with normal MEP in all limbs (GROUP-NO), while 9/13 had an abnormal MEP in at least one limb (GROUP-AB). Despite the [F]FDG-PET single-subject analysis revealed heterogenous expression of regional hypo- and hyper-metabolism patterns in the patients, the group-level analysis revealed a common hypometabolism, involving the precentral gyrus and the supplementary motor area, the paracentral lobule and the anterior cingulate cortex in the GROUP-AB. Moreover, exclusively for the GROUP-AB compared with HC, a relative hypermetabolism was observed in the right cerebellum, right inferior and middle temporal gyrus. The GROUP-NO showed no specific cluster of hypo- and hyper-metabolism compared to HC.
CONCLUSION
This study showed altered brain metabolism only in the ALS group with abnormal MEPs, suggesting an association between the two biomarkers in defining the UMN damage.
PubMed: 38936435
DOI: 10.1016/j.nbd.2024.106579 -
Journal of Public Health Management and... Jun 2024Chronic hepatitis B (CHB), caused by hepatitis B virus (HBV), is a risk factor for cirrhosis. The management of HBV-related cirrhosis is challenging, with guidelines...
CONTEXT
Chronic hepatitis B (CHB), caused by hepatitis B virus (HBV), is a risk factor for cirrhosis. The management of HBV-related cirrhosis is challenging, with guidelines recommending treatment initiation and regular monitoring for those affected.
OBJECTIVE
Our study characterized Kaiser Permanente Southern California patients with HBV-related cirrhosis and assessed whether they received recommended laboratory testing and imaging monitoring.
DESIGN
Retrospective cohort study.
SETTING AND PARTICIPANTS
We identified KPSC members aged ≥18 years with CHB (defined by 2, consecutive positive hepatitis B surface antigens ≥6 months apart) from 2008 to 2019. Of these patients, we further identified patients with potential HBV-related cirrhosis through ICD-10 code diagnosis, adjudicated via chart review.
MAIN OUTCOME MEASURES
Age, race/ethnicity, laboratory tests (eg, alanine aminotransferase [ALT]), and hepatocellular carcinoma (HCC) screening (based on standard screening recommendations via imaging) were described in those with HBV-related cirrhosis versus those without.
RESULTS
Among patients with CHB, we identified 65 patients with HBV-related cirrhosis over ~8 years. Diabetes was the most common comorbidity and was approximately 3 times more prevalent among patients with cirrhosis compared to patients without cirrhosis (21.5% vs. 7.1%). Of the 65 patients with cirrhosis, 72.3% (N = 47) received treatment. Generally, we observed that liver function tests (eg, ALT) were completed frequently in this population, with patients completing a median of 10 (6, 16) tests/year. All patients with cirrhosis had ≥1 ALT completed over the study period, and almost all cirrhotic patients (N = 64; 98.5%) had ≥1 HBV DNA test. However, the proportion of yearly imaging visits completed varied across the study years, between 64.0% in 2012 and 87.5% in 2009; overall, 35% (N = 23) completed annual imaging.
CONCLUSIONS
Our findings suggest that among patients with HBV-related cirrhosis, at the patient-level, completed imaging orders for HCC screening were sub-optimal. However, we observed adequate disease management practices through frequent liver function tests, linkage to specialty care, image ordering, and shared EHR between KPSC providers.
PubMed: 38936394
DOI: 10.1097/PHH.0000000000002001 -
Clinical Neurology and Neurosurgery Jun 2024The clinical importance of skeletal muscle characteristics for improving gait ability of stroke survivors is increasing. We aimed to examine the association between...
BACKGROUND
The clinical importance of skeletal muscle characteristics for improving gait ability of stroke survivors is increasing. We aimed to examine the association between muscle quantity and quality at discharge and changes in gait independence at the time of 1 year after discharge in patients with stroke.
METHODS
This prospective observational study included 100 patients with stroke who were admitted to a convalescent rehabilitation ward. We defined muscle quantity and quality operationally as muscle thickness and echo intensity observed in ultrasonography images, respectively, and measured quadriceps muscle on the paretic and non-paretic sides at the time of discharge. The outcome measured in our study was changes in gait independence 1 year after discharge, as assessed by the Functional Independence Measure gait assessment tool score.
RESULTS
Among the study participants, 23 (23.0 %) were assessed to have reduced gait independence, while 77 (77.0 %) were evaluated to have improved or maintained gait independence. Our multivariate logistic regression analysis revealed that only muscle quantity on the paretic side was significantly associated with an improvement or maintenance of gait independence (odds ratios 3.32; 95 % confidence interval 1.01-10.95; p = 0.049).
CONCLUSIONS
Our findings revealed that an improvement in gait independence 1 year after discharge was influenced by quadriceps muscle quantity on the paretic side at the time of discharge in patients with subacute stroke. This finding highlights the importance of lower limb muscle quantity on the paretic side as a clinically significant factor that influences the improvement in gait ability after hospital discharge.
PubMed: 38936176
DOI: 10.1016/j.clineuro.2024.108401 -
Medical Mycology Jun 2024The World Health Organization, in response to the growing burden of fungal disease, established a process to develop a fungal pathogen priority list. This systematic...
The World Health Organization, in response to the growing burden of fungal disease, established a process to develop a fungal pathogen priority list. This systematic review aimed to evaluate the epidemiology and impact of infections caused by Talaromyces marneffei, Coccidioides species, and Paracoccidioides species. PubMed and Web of Sciences databases were searched to identify studies published between 1 January 2011 and 23 February 2021 reporting on mortality, complications and sequelae, antifungal susceptibility, preventability, annual incidence, and trends. Overall, 25, 17, and 6 articles were included for T. marneffei, Coccidioides spp. and Paracoccidioides spp., respectively. Mortality rates were high in those with invasive talaromycosis and paracoccidioidomycosis (up to 21% and 22.7%, respectively). Hospitalization was frequent in those with coccidioidomycosis (up to 84%), and while the duration was short (mean/median 3-7 days), readmission was common (38%). Reduced susceptibility to fluconazole and echinocandins was observed for T. marneffei and Coccidioides spp., whereas >88% of T. marneffei isolates had minimum inhibitory concentration values ≤0.015 μg/ml for itraconazole, posaconazole, and voriconazole. Risk factors for mortality in those with talaromycosis included low CD4 counts (odds ratio 2.90 when CD4 count <200 cells/μl compared with 24.26 when CD4 count <50 cells/μl). Outbreaks of coccidioidomycosis and paracoccidioidomycosis were associated with construction work (relative risk 4.4-210.6 and 5.7-times increase, respectively). In the United States of America, cases of coccidioidomycosis increased between 2014 and 2017 (from 8232 to 14 364/year). National and global surveillance as well as more detailed studies to better define sequelae, risk factors, outcomes, global distribution, and trends are required.
Topics: Talaromyces; Humans; Paracoccidioides; Antifungal Agents; Coccidioides; World Health Organization; Mycoses; Paracoccidioidomycosis; Coccidioidomycosis; Microbial Sensitivity Tests
PubMed: 38935909
DOI: 10.1093/mmy/myad133