Benefits Of Therapy Research Articles

Extending localized passive heat therapy benefits for individuals with exercise intolerance.

Extending localized passive heat therapy benefits for individuals with exercise intolerance.

The Real-World Effectiveness of Antifungals in People with Cystic Fibrosis and Aspergillus-Positive Cultures.

The pathogenicity of Aspergillus in the cystic fibrosis (CF) airway is debated, leading to unclear clinical benefit of antifungal therapy for Aspergillus infection. To determine the real-world effectiveness of antifungal use in people with CF (PwCF) with Aspergillus species in the United States. We conducted a retrospective cohort study evaluating the association of antifungal use and respiratory outcomes in PwCF and Aspergillus positive cultures using the Cystic Fibrosis Foundation patient registry. Marginal structural models using inverse-probability treatment weighted estimators were used to test if antifungal exposure was associated with forced expiratory volume in one second percent predicted (FEV1pp) and pulmonary exacerbation rate, while controlling for fixed and time-varying confounders. We conducted sensitivity analyses on individuals with persistent Aspergillus and without concomitant allergic bronchopulmonary aspergillosis (ABPA). A total of 14,754 individuals with Aspergillus positive cultures between 2006 and 2019 were identified. Antifungals were prescribed to 3,575 (24.2%) unique PwCF during the study period. Antifungal use was not associated with FEV1pp (adjusted estimate -0.96 percentage points, 95% CI -2.21,0.29). Antifungal use was associated with 29% increased rate of pulmonary exacerbations requiring intravenous (IV) antibiotics (adjusted IRR=1.29, 95% CI 1.22, 1.37). In sensitivity analyses limited to individuals without ABPA< antifungals were associated with 1.88 lower FEV1pp (95% CI -3.35, -0.41) and an increased rate of pulmonary exacerbations (adjusted IRR= 1.30, 95% CI 1.21,1.40). Whereas, in patients with persistent Aspergillus and persistent Aspergillus without concomitant ABPA, antifungals were not associated with FEV1pp. Antifungal therapy in PwCF and Aspergillus positive cultures was not associated with improvements in FEV>1pp. While antifungal therapy was associated with increased risk for pulmonary exacerbations, this could reflect confounding by severity of disease. Randomized clinical trials examining the clinical efficacy of antifungals in Aspergillus infections are warranted.

Reviewing the effect of creative arts therapy on the development of cognitive and social skills in children and adolescents with autism spectrum disorder

Creative art therapy has been utilized for many years as a treatment regimen for certain mental disorders. Overall, results of studies on creative art therapy show a positive trend, with general improvements in mental health and reduction of neurological symptoms in the majority of cases. The results regarding the effectiveness of creative art therapies in treating autism spectrum disorder are unclear and varied, due to the range of symptoms involved in autism spectrum disorder, the effect of age on therapy, and the variety of creative art therapies available for use. Of all the creative art therapies chosen to review, music was the most investigated. The studies performed on music therapy showed positive results, however, a large-scale randomized controlled trial refuted the positive benefits, leading to an inconclusive overall result on the effectiveness of music therapy. Research on the benefits of creative art therapies for children with autism spectrum disorder is inconclusive. Studies generally demonstrate a positive effect on many different types of creative art therapies. However, these studies have major limitations in generalizability due to small sample sizes and their descriptive nature. Future research should focus on developing randomized controlled trial protocols that can be used on a larger scale to generate more definitive results on the benefits, or lack thereof, of creative art therapies. Research should also be performed on the effect of adolescence on creative art therapies, and whether targeting it at younger children with autism spectrum disorder would be more or less beneficial than targeting it towards adolescents.

Duration of Benefit and Risk of Dual Antiplatelet Therapy up to 72 Hours After Mild Ischemic Stroke and Transient Ischemic Attack.

Clopidogrel-aspirin initiated within 72 hours of symptom onset is effective in patients with mild ischemic stroke or transient ischemic attack (TIA) in the Intensive Statin and Antiplatelet Therapy for Acute High-risk Intracranial or Extracranial Atherosclerosis (INSPIRES) trial. Uncertainties remain about the duration of the treatment effect. This study aimed to assess duration of benefit and risk of clopidogrel-aspirin in these patients. The INSPIRES trial was a 2*2 factorial placebo-controlled randomized trial conducted in 222 hospitals in China. The 2 treatments did not interact and were evaluated separately. In this study, we performed secondary analyses based on antiplatelet treatment. All patients with mild stroke or TIA of presumed atherosclerotic cause within 72 hours of symptom onset enrolled in the trial were included. Patients were randomly assigned to receive clopidogrel-aspirin on days 1-21 followed by clopidogrel on days 22-90 or aspirin alone for 90 days. The primary efficacy outcome was major ischemic event which included the composite of ischemic stroke and nonhemorrhagic death. The primary safety outcome was moderate-to-severe bleeding. We estimated the risk difference between the 2 treatments for each stratified week. All 6,100 patients in the trial were included (3,050 in each group). The mean age was 65 years, and 3,915 patients (64.2%) were men. Compared with aspirin alone, the reduction of major ischemic events by clopidogrel-aspirin mainly occurred in the first week (absolute risk reduction [ARR] 1.42%, 95% CI 0.53%-2.32%) and remained in the second week (ARR 0.49%, 95% CI 0.09%-0.90%) and the third week (ARR 0.29%, 95% CI -0.05% to 0.62%). Numerical higher risk of moderate-to-severe bleedings in the clopidogrel-aspirin group was observed in the first 3 weeks (absolute risk increase 0.05% [95% CI -0.10% to 0.20%], 0.10% [95% CI -0.09% to 0.29%], and 0.18% [95% CI -0.03% to 0.40%] in the first, second, and third weeks, respectively). Among patients with mild ischemic stroke or high-risk TIA of presumed atherosclerotic cause, the net benefit of clopidogrel-aspirin initiated within 72 hours of symptom onset was pronounced in the first week and continued to a lesser degree in the following 2 weeks, outweighing the low, but ongoing hemorrhagic risk. ClinicalTrials.gov Identifier: NCT03635749. This study provides Class II evidence that among patients with mild ischemic stroke or high-risk TIA of presumed atherosclerotic cause, the net benefit of clopidogrel-aspirin initiated within 72 hours of symptom onset was pronounced in the first week and continued to a lesser degree in the following 2 weeks, outweighing the low but ongoing hemorrhagic risk.

7219 Ocular Findings in Jansen Metaphyseal Chondrodysplasia

Abstract Disclosure: F. Obiezu: None. K. Pan: None. A. Ninan: None. K.L. Roszko: None. L.S. Weinstein: None. C.R. Ferreira: None. R.I. Gafni: None. T. Magone De Quadros Costa: None. M.T. Collins: None. S. Jha: None. Jansen Metaphyseal Chondrodysplasia (JMC) is an ultra-rare disorder, with only 30 patients estimated to have the disease globally. It is caused by heterozygous pathogenic variants in PTHR1 that result in constitutive activation of parathyroid hormone type 1 receptor (PTHR1) signaling. A detailed description of craniofacial manifestations of the disease is lacking. Here we characterize the ophthalmological manifestations in patients with JMC. Six patients (4 males, 67%) with genetically confirmed JMC underwent a detailed ophthalmological evaluation, spectral-domain optical coherence tomography (OCT), craniofacial CT and 18F-NaF PET/CT scans. Median age at the time of the visit was 27.5 [IQR: 29] years. On physical examination, all patients were noted to have widely spaced eyes; 5 of the 6 had down slanted palpebral fissures, proptosis, or ptosis. Two patients had incomplete or defective closure of the eyelids (lagophthalmos), of which one had a history of progressive right facial nerve palsy with profuse epiphora. The second patient had central visual field defects, bilateral moderate optic disc pallor and bilateral retinal nerve fiber layer (RNFL) atrophy on OCT exam with bilateral optic canal narrowing on CT. Notably, comparison of these findings with a prior scan performed 5 years earlier showed progressive decrease in RNFL bilaterally. This patient had a history of prolonged intravenous bisphosphonate therapy, initiated in infancy for hypercalcemia and continued for over a decade. A third patient had normal vision, subtle temporal pallor of the optic nerve heads on dilated fundus exam, normal average RNFL, but decreased retinal ganglion cell layer analysis (GCA) on OCT. GCA was decreased in 4 of the 6 patients compared to age-matched reference range indicating a chronic optic nerve atrophic process. These data represent the first comprehensive report of the ophthalmologic findings in a cohort of patients with JMC. They demonstrate that patients with JMC have significant eye findings that appear to be more prevalent and pronounced with age. This suggests age-related, progressive optic neuropathy, which can be assessed by demonstrating OCT retinal GCA and RNFL loss and, may be a feature of JMC. The benefit and effect of long-term bisphosphonate therapy in patients with JMC remains unclear. Patients with JMC should undergo regular ophthalmologic examination including optic nerve OCT, visual field testing, and craniofacial imaging. Presentation: 6/1/2024

12338 Risk Of Retinopathy In Patients With Type 2 Diabetes On Semaglutide

Abstract Disclosure: A. Gupta: None. M. Nassar: None. H. Ghanim: None. Title: Risk of Retinopathy in Patients with Type 2 Diabetes on SemaglutideBackground: The use of semaglutide in patients with diabetic retinopathy (DR) has raised safety concerns. While previous studies, including a meta-analysis and the SUSTAIN trial, suggested an association between rapid HbA1c reduction and retinopathy progression, recent data question the increased risk with semaglutide. Our study investigates this risk of intensive therapy benefits for the prevention of DR. Methods: This retrospective cohort study utilized TriNetX electronic health records, analyzing 117,693,426 patients with type 2 diabetes mellitus (T2DM) on anti-hyperglycemic drugs. We divided patients into those with and without a history of retinopathy, further subdividing them by treatment (Semaglutide, Sitagliptin, and Empagliflozin). After matching for confounders, we analyzed the incidence and progression of retinopathy among 336,338 Semaglutide, 578,117 Sitagliptin, and 434,552 Empagliflozin patients without a history of DR, as well as a cohort with history. Results: In patients without a prior history of DR, semaglutide showed a significant reduction in DR incidence over three years compared to sitagliptin and empagliflozin (p&amp;lt;0.0001). However, in those with a history, the reduction was not statistically significant (p &amp;gt; 0.05). Patients with mild DR on Semaglutide experienced fewer progressions to severe stages (p&amp;lt;0.0001), while outcomes in severe cases were inconclusive.Discussion: Semaglutide may lower the risk of developing DR in patients with T2DM without a prior history of DR and potentially stabilize or improve mild conditions without worsening severe retinopathy. The observed effects could influence treatment choices, emphasizing the need for individualized patient management. Conclusion: Semaglutide appears safe regarding retinopathy risk in patients with T2DM, offering protective benefits in those without history and not exacerbating conditions in those with prior DR. This underscores the drug's potential for comprehensive diabetes management without compromising ocular health. Presentation: 6/3/2024

Comparison of subcutaneous and intravenous infliximab in patients with inflammatory bowel disease showed no differences in immunogenicity or treatment persistence at 1 year

BackgroundInfliximab (IFX) effectiveness in inflammatory bowel disease (IBD) can be impaired by antidrug antibodies (ADA). Subcutaneous IFX has a different pharmacokinetic profile compared with intravenous administration, potentially affecting immunogenicity.MethodsRetrospective audit...

A Patient-Relevant Measurement Strategy to Assess Clinical Benefit of Novel Therapies for Non-metastatic Cutaneous Squamous Cell Carcinoma.

Although cutaneous squamous cell carcinoma (CSCC) is the second most common type of skin cancer, research describing the patient experience is limited. This study sought to create a conceptual model of non-metastatic disease, to assess patient-reported outcome (PRO) instruments commonly used in CSCC against this model, and to develop a patient-relevant measurement strategy for evaluating the benefit of new therapies. Researchers conducted a literature review, a review of patient blogs, and interviews with dermatologists to draft the conceptual model. A total of 22 patients with CSCC participated in 60-min phone interviews, which were subsequently transcribed, coded, and analyzed; the conceptual model was thenupdated. PRO instruments used in CSCC were assessed for content validity on the basis of this. The CSCC patient experience includes physical symptoms, psychological impacts, and behavior changes. Existing PRO instruments were assessed against the conceptual model using targeted subdomains considered to be relevant for assessing clinical benefit. Four modules of the FACE-Q® Skin Cancer instrument, plus de novo items developed for concepts not assessed by the FACE-Q® [lesion symptoms, negative treatment effects (including symptomatic), and experience of care], provide the best coverage for the concepts of interest hypothesized to show the benefit of novel treatments. This research provides a comprehensive understanding of the experience of patients with non-metastatic CSCC, and the effects of its treatment. It also identifies unmet needs in a subgroup of patients reporting negative treatment experiences. Further cognitive debriefing and psychometric analysis of de novo items are warranted for applications in clinical research.

Assessment of Health-Related Quality of Life in Adults Living with HIV Attending Antiretroviral Clinics versus Traditional Healers' Offices in Bukavu City, Democratic Republic of the Congo.

The benefits of antiretroviral therapy (ART) for people living with HIV/AIDS (PLHIV) include immune system strengthening, viral load suppression, and improved health-related quality of life (HRQOL). This present study compares the HRQOL of PLHIV visiting ART clinics versus that of PLHIV attending traditional healers (THs)' offices, assesses the adherence of PLHIV to ART, identifies possible predictors of nonadherence of PLHIV to ART and HRQOL, and estimates the proportion of patients with HIV referred by THs to health centers in Bukavu. Between February and June 2023, a cross-sectional comparative study was conducted on 150 adult PLHIV attending ART clinics and 150 adult PLHIV visiting THs' offices in the 3 urban health zones of Bukavu. The World Health Organization Quality of Life questionnaire (WHOQOL-BREF) and a self-report questionnaire measuring ART adherence were used to collect the data. Regression models were used to identify the predictors of no adherence to ART and the HRQOL of PLHIV. Compared with those attending THs, PLHIV attending ART clinics had higher mean scores in all HRQOL domains. Approximately 84% of the participants were compliant with ART. The predictors associated with nonadherence to ART included illiterate participants [OR=23.3 (95% CI=1.23-439.5), p=0.004] and divorced or separated participants [OR=10.3 (95% CI=1.12-94.4), p=0.034]. The proportion of PLHIV referred to ART clinics by THs was only 10.7%. PLHIV visiting ART clinics had a better HRQOL than did PLHIV attending THs' offices. The rate of adherence to ART among PLHIV who attended ART clinics was high. It is recommended that PLHIV visiting THs be referred to ART clinics for improved HRQOL.

Dynamics of minimal residual disease and its clinical implications in multiple myeloma: A retrospective real-life analysis

BackgroundMinimal residual disease (MRD) testing is a promising approach to tailor the treatment of multiple myeloma (MM). However, several major concerns remain to be addressed before moving it into daily practice, most of which stem from the dynamic nature of the MRD status. Thus, it is crucial to understand the MRD dynamics and propose its clinical implications. MethodsWe retrospectively analysed the data of patients with newly diagnosed MM (NDMM) who had flow cytometry-based MRD tests at multiple time points after initiation of therapy. The impact of undetectable MRD (including attainment, duration and loss) on clinical outcomes was analysed. ResultsIn a cohort of 220 patients with NDMM, attainment of MRD− offered favourable outcomes (P < 0.0001 for both progression-free survival (PFS) and overall survival (OS)), regardless of baseline risk factors. Notably, MRD− duration ≥12 months was associated with an 83 % (95 % confidence interval (CI), 0.09−0.34; P < 0.0001) or 69 % (95 % CI, 0.13−0.76; P = 0.0098) reduction in risk of progression/death or death, while the longer MRD− was sustained, the better the outcome was. Loss of MRD− led to poor PFS (hazard ratio (HR) 0.01, 95 % CI 0–0.06, P < 0.0001) and OS (HR 0.03, 95 % CI 0–0.24, P = 0.0008). Most patients (70 %) who lost MRD− status carried high-risk cytogenetic abnormalities (HRCAs). While MRD− was temporally inconsistent with conventional therapeutic responses (eg ≥ complete remission or very good partial response), it predicted disease progression or recurrence more robustly than the latter. Last, the predictive value of the MRD status was independent of baseline risk factors (eg high-risk cytogenetic abnormality, International Staging System (ISS) or Revised (R-)ISS staging). ConclusionsLongitudinal assessment of MRD during the treatment course and follow-up is required for monitoring disease progression or relapse, to guide treatment decisions. Accordingly, a prospective study is currently ongoing to investigate the feasibility and benefit of the MRD-tailored therapy according to the longitudinal changes of the MRD status.

Inhibition of the Rho/MRTF pathway improves the response of BRAF-resistant melanoma to PD1/PDL1 blockade.

Metastatic cutaneous melanoma is a fatal skin cancer. Resistance to targeted and immune therapies limits the benefits of current treatments. Identifying and adding anti-resistance agents to current treatment protocols can potentially improve clinical responses. Myocardin-related transcription factor (MRTF) is a transcriptional coactivator whose activity is indirectly regulated by actin and the Rho family of GTPases. We previously demonstrated that development of BRAF inhibitor (BRAFi) resistance frequently activates the Rho/MRTF pathway in human and mouse BRAFV600E melanomas. In clinical trials, pretreatment with BRAFi reduces the benefit of immune therapies. We aimed to test the efficacy of concurrent treatment with our MRTF pathway inhibitor CCG-257081 and anti-PD1 in vivo and to examine its effects on the melanoma immune microenvironment. Because MRTF pathway activation upregulates the expression of immune checkpoint inhibitor genes/proteins, we asked whether CCG-257081 can improve the response to immune checkpoint blockade. CCG-257081 reduced the expression of PDL1 in BRAFi-resistant melanoma cells and decreased surface PDL1 levels on both BRAFi-sensitive and -resistant melanoma cells. Using our recently described murine vemurafenib-resistant melanoma model, we found that CCG-257081, in combination with anti-PD1 immune therapy, reduced tumor growth and increased survival. Moreover, anti-PD1/CCG-257081 co-treatment increased infiltration of CD8+ T cells and B cells into the tumor microenvironment and reduced tumor-associated macrophages. Here, we propose CCG-257081 as an anti-resistance and immune therapy-enhancing anti-melanoma agent.

Psychological and physiological benefits of horticultural therapy for Chinese older adults

Background Gardening as a leisure activity has been shown to be potentially beneficial for older adults, this study aimed to assess the physiological and psychological impacts of a specific horticultural activity, watering indoor plants, compared with playing a computer game - the Klondike Solitaire Card Game. Methods This crossover study included 100 older adults recruited from a nursing care facility for older people in Shanghai, China. They were allocated to either engage in watering indoor plants (horticultural group) or playing a computer game (control group). For the inclusion criteria, screening for cognitive function was conducted to exclude those with severe cognitive impairments, thereby focusing on those capable of participating fully in the study activities. Brainwave activities, blood pressure, and psychological states were measured through pre- and post-test questionnaires to evaluate the physiological and psychological effects. Results The activity of watering indoor plants was associated with significant reductions in both systolic and diastolic blood pressure, in contrast to the computer game activity. Additionally, participants in the horticultural group showed increased brainwave mean values, indicating heightened relaxation and focus, while decreases were observed in the control group. The experimental group reported reduced anxiety scores, along with increased feelings of comfort and relaxation, and also exhibited significantly higher meditation levels, which indicates a profound mental relaxation effect. Conclusion Our findings suggest that engaging in indoor horticultural activities, such as watering houseplants for 10 minutes, can reduce mental and physical stress levels in older adults.

Statin therapy is associated with lower risk of mortality among liver transplant candidates with metabolic dysfunction associated steatohepatitis

BackgroundStatin therapy is historically underutilized in patients with chronic liver disease. There is increasing evidence to support the use of statins in patients with cirrhosis, though data in decompensated patients are limited. The primary aim of this study was to evaluate the association between statin use and mortality in patients with advanced liver disease, comparing MASH and non-MASH cirrhosis. MethodsThis single-center retrospective cohort study included patients undergoing liver transplant (LT) evaluation at a large quaternary care center. Patients were categorized by etiology as metabolic dysfunction-associated steatohepatitis (MASH) or non-MASH cirrhosis. Statin use was defined as having an active prescription at the time of LT evaluation. The association between statin use and mortality was evaluated using multivariable Cox proportional hazard regression. ResultsThe study included 623 patients; 24% had MASH cirrhosis and 20% were prescribed a statin. Statin users were older, had a higher BMI and were more likely to have coronary artery disease. At the end of the study, statin use was associated with lower mortality among MASH patients (16% vs. 35%, p=0.010) and higher mortality among non-MASH patients (31% vs. 19%, p=0.066). After controlling for age (HR 1.05, 95% CI 1.00 – 1.10, p=0.039), MELD-Na (HR 1.07, 95% CI 1.04 – 1.11, p<0.001), BMI (HR 1.09, 95% CI 1.05 – 1.14, p<0.001), and CAD (HR 1.20, 95% CI 0.54 – 2.69, p=0.653), statin use conferred a 53% lower risk of death compared to no statin use in patients with MASH cirrhosis (HR 0.47, 95% CI 0.22 – 0.98, p=0.043). ConclusionsStatin use was associated with reduced mortality in patients with decompensated MASH cirrhosis undergoing LT evaluation, but increased mortality in those with non-MASH cirrhosis, particularly those with high-MELD-Na. These findings underscore the importance of reviewing individual patient characteristics and disease etiology when considering the benefits of statin therapy in patients with cirrhosis.

Does the use of stem-cell injection therapy benefit duration of healing in adults with large joint injuries?

Does the use of stem-cell injection therapy benefit duration of healing in adults with large joint injuries?

Towards a Better Prognosis in Patients with Systemic Sclerosis-Related Pulmonary Arterial Hypertension: Recent Developments and Perspectives.

Precapillary pulmonary hypertension (PH) is a significant complication of systemic sclerosis (SSc). It represents one of the leading causes of morbidity and mortality, correlating with a significantly dismal prognosis and quality of life. Despite advancements in the management of patients with pulmonary arterial hypertension associated with SSc (SSc-PAH), no significant improvement has been reported in survival of patients with precapillary SSc-PH associated with extensive lung parenchyma disease. International expert consensus and guidelines for the management of PH recommend annual screening of SSc patients for early detection of pre-capillary PH. The implementation of screening algorithms capable of identifying patients with a high likelihood of developing PH could help limit unnecessary right-heart catheterization procedures and prevent significant delay in diagnosis. Furthermore, early initiation of up-front combination targeted therapy in patients with PAH has shown increase in survival rates, indicating that timely and aggressive medical therapy is key for stabilizing and even improving functional class, hemodynamic parameters and 6 min walking distance (6MWD) in this population. Further research is warranted into the benefit of PAH-targeted therapies in patients with PH associated with lung disease. Lastly, we discuss the potential role of immunosuppression using biologic agents in the therapeutic management of precapillary PH in SSc patients.

Benefits of Extracorporeal Shock Wave Therapy to Reduce Spasticity in Cerebral Palsy and Stroke Patients

Background: Spasticity, a common issue in cerebral palsy and stroke patients, significantly impairs mobility and quality of life. Non-invasive treatments like Extracorporeal Shock Wave Therapy (ESWT) have been explored for spasticity reduction.Objective: To evaluate the effectiveness of ESWT in reducing spasticity in cerebral palsy (CP) and stroke patients using the Modified Ashworth Scale (MAS).Methods: A randomized controlled trial (RCT) was conducted on 28 spastic CP and stroke patients. Participants were divided into Group A (n = 14, ESWT combined with conventional physiotherapy) and Group B (n = 14, conventional physiotherapy only). ESWT was administered at 5 Hz frequency, 0.10 mJ/mm² energy flux density, and 1500 impulses per session for 30 minutes, 5 days a week, for 6 months. Spasticity was assessed using MAS pre- and post-intervention. Data were analyzed using IBM SPSS version 25.Results: The ESWT group showed a significant reduction in MAS scores from 3.21 ± 0.25 to 1.77 ± 0.37 (p &lt; 0.001), compared to the control group (3.10 ± 0.44 to 2.36 ± 0.60; p &lt; 0.001).Conclusion: ESWT significantly reduced spasticity in CP and stroke patients, demonstrating its potential as an adjunctive therapy.

Histopathologic pattern and molecular risk stratification are associated with prognosis in patients with stage IB lung adenocarcinoma.

The benefit of adjuvant therapy remains controversial in completely resected (R0) stage IB non-small cell lung cancer (NCLSC) patients. In this study, we aimed to explore potential prognostic factors in stage IB NSCLC patients. This study included 215 patients with R0 stage IB lung adenocarcinoma (LUAD) (tumor size: 3-4 cm). DNA sequencing was performed with surgical samples of 126 patients using a panel of 9 driver genes. The molecular risk stratification was assessed by a 14-gene quantitative polymerase chain reaction assay. Among the 215 patients, 67.9% had micropapillary/solid (MIP/SOL)-predominant tumors. Epidermal growth factor receptor (EGFR) mutations were detected in 75 of 126 patients (59.5%). MIP/SOL tumors harbored less common EGFR mutations than the other histologic patterns (50.6% vs. 79.5%, P=0.003). Molecular risk stratification was successfully assessed in 99 patients, of whom 37.4%, 26.3%, and 36.4% were high, intermediate, and low risk, respectively. The MIP/SOL pattern was associated with shorter disease-free survival (DFS) [hazard ratio (HR) =2.16, 95% confidence interval: 1.28-3.67; P=0.01]. The molecular high-risk patients had shorter DFS than the low- (HR =2.93, P=0.01) and intermediate-risk patients (HR =2.35, P=0.06). The prognostic value of molecular risk stratification was also significant in the MIP/SOL subset (median DFS high-risk: 45 months, low and intermediate risk: not reached; P=0.03). Our study showed that both the MIP/SOL pattern and molecular high-risk category were adverse prognostic factors in stage IB NSCLC patients. Our results suggest that combining histologic classification and molecular risk stratification may help to identify the subset of patients with poor prognosis.

Incidence of loss to follow-up and its predictors among HIV-infected under-five children after initiation of antiretroviral therapy in West Amhara Comprehensive Specialized Referral Hospitals, Northwest Ethiopia: a multicenter retrospective follow-up study

BackgroundLoss to follow-up (LTFU) among under-five children from HIV care profoundly affects the treatment outcomes of this vulnerable population. It is a major factor that negatively affects the benefits of antiretroviral therapy (ART). Current information about LTFU among HIV-positive under-five children on ART is essential for effective treatments. To far, nevertheless, limited research has been done in Ethiopia to address this issue. Thus, this study aimed to assess the incidence and predictors of LTFU among HIV-infected under-five children receiving ART in West Amhara Comprehensive Specialized Referral Hospitals.MethodsA multicenter institution-based retrospective follow-up study was conducted among 435 HIV-infected under-five children on ART selected by simple random sampling from January 1, 2010 to December 31, 2019, and data were collected between December 1, 2021, and January 31, 2022. A standardized data extraction tool adapted from the ART entry and follow-up forms was used. The event of interest for this study was LTFU, whereas the absence of LTFU was censored. Before being transferred to STATA version 14 for analysis, the data were entered into Epi-Data version 3.1. The Kaplan‒Meier curve was used to estimate an individual's survival-free probability at each specific point in time. The Cox proportional hazards model was used to identify predictors of LTFU.ResultsAmong the 420 records included in the final analysis, 30 (7.14%) of the individuals were LTFUs. The incidence rate of LTFU was 3.4 per 1000 person-months of observation (95% CI: 2.43–4.87). The survival probabilities of children after 12, 24, 36, and 48 months were 0.97, 0.92, 0.88, and 0.77, respectively. The independent predictors of LTFU were HIV infection in under-five children who lived in rural areas (AHR = 3.64; 95% CI: 1.41, 9.37), poor adherence to ART (AHR = 4.37; 95% CI: 1.59, 12.02), not receiving cotrimoxazole preventive therapy (AHR = 3.75; 95% CI: 1.39, 10.08), not receiving isoniazid prophylaxis (AHR = 3.4; 95% CI: 1.29, 9.01), and having a severe WHO clinical stage (AHR = 5.43; 95% CI: 1.38, 11.43).Conclusion and recommendationThe incidence of loss to follow-up was high, especially in the first two years after ART initiation. The risk of LTFU was greater for those who were rural residents, had poor adherence, lacked cotrimoxazole preventive therapy, not given isoniazid prophylaxis, and presented with WHO clinical stages III and IV. Therefore, clinicians should emphasize for cotrimoxazole preventive therapy and isoniazid prophylaxis, for those living in rural areas, who present with poor adherence and WHO clinical stages III and IV.

Antiplatelets for Cardiovascular Disease in Non-valvular AF with Rivaroxaban: A Subanalysis of the EXPAND Study.

In this subanalysis of the EXPAND study, we evaluated the risks and benefits of rivaroxaban plus antiplatelet therapy (APT) for patients with non-valvular atrial fibrillation (NVAF) complicated by stable coronary artery disease (CAD), ischemic stroke, or peripheral artery disease (PAD). From the EXPAND study population (n=7,141), patients with NVAF complicated by stable CAD (n=886), ischemic stroke (n=1,231), or PAD (n=160) were included. Patients complicated by any of them were set as ALL (n=2,030). Patients were all treated with rivaroxaban (10 or 15 mg/day) with (+) or without (-) APT. Efficacy outcomes were symptomatic stroke＋systemic embolism (SE), symptomatic stroke＋SE＋myocardial infarction＋cardiovascular death, and all-cause death. Safety outcomes included major and any bleeding. Hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated for differences between the APT(+) and APT(-) groups. There were no significant differences in the efficacy outcomes between the APT(+) and APT(-) groups in the ALL cohort or in the CAD and STROKE sub-cohorts. In the PAD subcohort, the HR [95% CI] for all-cause death in the APT(+) group increased (4.43 [1.05-18.71]; p=0.043). In the APT(+) group, the HR [95% CI] for any bleeding increased in the ALL cohort (1.28 [1.01-1.62]; p=0.044) and STROKE subcohort (1.42 [1.01-2.01]; p=0.047), and for major bleeding in the CAD subcohort (2.00 [1.01-3.93]; p=0.046). Rivaroxaban with APT did not reduce ischemic outcomes in patients with stable CAD or ischemic stroke; however, it did increase the risk of bleeding in patients with stable CAD or ischemic stroke.

GLP-1 Receptor Agonists and SGLT2 Inhibitors in Type 2 Diabetes: Pleiotropic Cardiometabolic Effects and Add-on Value of a Combined Therapy.

Glucagon-like peptide-1 receptor agonists (GLP-1RAs) and sodium-glucose cotransporter 2 inhibitors (SGLT2is) have proven efficacy and safety in randomized clinical trials and observational real-life studies. Besides improving glucose control, reducing body weight, and lowering arterial blood pressure (surrogate endpoints), the breakthroughs were the demonstration of a significant reduction in cardiovascular and renal events in patients with type 2 diabetes at high risk. GLP-1RAs reduce events linked to atherogenic cardiovascular disease (especially ischemic stroke) and also renal outcomes (FLOW trial with semaglutide), with a limited effect on heart failure. The most striking protective effects of SGLT2is were a marked reduction in hospitalization for heart failure and a remarkable reduced progression of chronic kidney disease. These benefits have been attributed to numerous pleiotropic effects beyond glucose-lowering action. Underlying mechanisms contributing to cardiovascular and renal protection are at least partially different between GLP-1RAs (mainly anti-atherogenic and vascular effects) and SGLT2is (mainly systemic and intrarenal hemodynamic changes). Thus, patients at high risk may benefit from complementary actions when being treated with a GLP-1RA/SGLT2i combination. Such combination has proven its efficacy on surrogate endpoints. Furthermore, posthoc subgroup analyses of cardiovascular outcome trials have suggested a greater cardiorenal protection in patients treated with a combination versus either monotherapy. The benefits of a combined therapy have been confirmed in a few retrospective cohort studies. A dedicated prospective trial comparing a combined therapy versus either monotherapy is ongoing (PRECIDENTD); however, several challenges still remain, especially the higher cost of a combined therapy and the worldwide underuse of either GLP-1RAs or SGLT2is in clinical practice, even in patients at high cardiorenal risk.