Initial Treatment Research Articles

Comparative Analysis of Ticagrelor and Clopidogrel Effects on Medication Adherence, Adverse Events, and Laboratory Parameters in Iranian Acute Coronary Syndrome Patients Post-PCI

Background: Acute coronary syndrome (ACS) remains a critical health concern, with patient outcomes significantly influenced by the selection of antiplatelet therapy post-percutaneous coronary intervention (PCI). Existing research suggests potential benefits of ticagrelor over clopidogrel in reducing cardiovascular events. However, there is limited comparative data within the Iranian population post-angiography. Objectives: This research aimed to compare laboratory findings, adherence rates, and side effects following the administration of ticagrelor and clopidogrel in ACS patients post-PCI. Methods: A case-control study was conducted to assess the impacts of antiplatelet therapy in 200 ACS patients undergoing PCI at Masih Daneshvari Hospital, Tehran, Iran. Patients were stratified into two groups, matched by age, gender, and type of cardiac disease. One group received clopidogrel, and the other received ticagrelor. Laboratory parameters, including HDL, LDL, and CRP, were evaluated at baseline and two months after treatment initiation. Additionally, adverse effects and medication adherence were assessed to evaluate the safety and efficacy of the two antiplatelet agents. Results: The study enrolled 200 ACS patients post-PCI, with 54% male and 46% female. The age range was 38 to 84 years, with a mean age of 63.07 ± 12.54 years. Of the patients, 76% had non-ST-elevation myocardial infarction (NSTEMI), while 24% had ST-elevation myocardial infarction (STEMI). Among STEMI patients, 56.25% were treated with fibrinolytics, and 43.75% underwent primary PCI. Common adverse events included dyspnea, bleeding, and gastrointestinal symptoms. Both the ticagrelor and clopidogrel groups showed reductions in LDL levels from baseline to the two-month follow-up. Conclusions: Ticagrelor and clopidogrel were both effective in reducing LDL levels after two months of treatment. However, ticagrelor demonstrated a more pronounced decrease in CRP levels, indicating potential anti-inflammatory benefits. These findings provide insight into antiplatelet therapy's role in managing ACS patients post-PCI.

Radio-Biological Confrontation in the Diagnosis of Invasive Aspergillosis: About Two Cases and Review of Literature

Invasive pulmonary aspergillosis due to Aspergillus fumigatus is an often serious mycosis, usually occurring in severely immunocompromised patients. It is accompanied by a high mortality rate due to its often difficult and late diagnosis. Diagnosis is based on early chest computed tomography and mycological examination of respiratory samples. Both patients had presented with acute respiratory distress, developing in a context of fever and deterioration of the general condition despite the initiation of broad-spectrum empirical treatment. In each of them, a chest CT scan was performed, objectifying atypical cavitary images not suggesting pulmonary aspergillosis. Cytobacteriological examination of sputum and search for Mycobacterium tuberculosis were negative. Serology for aspergillus antigens and a sample of bronchoalveolar lavage fluid for a mycological study were requested. Direct examination of bronchoalveolar lavage fluid was negative, but culture allowed the identification of Aspergillus fumigatus. Galactomannan testing was positive. Given these results, treatment with injectable voriconazole was initiated in our two cases. The evolution was marked by a clinical improvement of one patient and the death of the other patient. Invasive pulmonary aspergillosis is a major concern due to the frequency of its complications. Its diagnosis must be early to ensure adequate management for a better prognosis.

Mobile phone-based smoking-cessation intervention in patients with chronic diseases in China: a Sequential Multiple Assignment Randomized Trial (SMART).

Mobile phone-based interventions show promise for smoking cessation but often face low engagement. This study assessed the feasibility and preliminary effectiveness of a 2-phase, multi-component mobile phone-based smoking cessation intervention for patients with chronic diseases. This Sequential Multiple Assignment Randomized Trial (SMART) recruited smokers with chronic diseases from hospitals in Zhuhai, China. Participants received brief cessation advice and were randomized to personalized chat support (PCS, n=64) or group chat support (GCS, n=64) for 1 month. At 1-month, PCS non-responders (continuing smokers) were re-randomized to receive either multi-component optional support (MOS) or continued PCS for 2 months. GCS non-responders were re-randomized to receive PCS or continued GCS. Responders continued with their initial intervention for 2 months. Feasibility outcomes included eligibility, participation, retention, intervention engagement, and satisfaction. Preliminary effectiveness was assessed by abstinence rates among non-responders. Of 160 screened, 128 (all male, 46.1% aged≤39 years) participated. At 1-month, 51 and 53 non-responded to PCS and GCS, respectively. Of them, 26 were re-randomized to receive PCS-MOS and 26 to receive GCS-PCS. At 6-month, PCS-MOS showed a non-significant higher validated abstinence rate compared to PCS alone (11.5% vs. 4.2%, odds ratio [OR] 3.13, 95%CI 0.30-32.31, P=0.34), GCS-PCS showed a non-significant lower validated abstinence rate compared to GCS (0% vs. 11.1%, OR 0.50, 95%CI 0.15-1.67, P=0.26). This trial showed the feasibility of leveraging hospital visits as teachable opportunities and integrating mobile phone-based smoking cessation support into chronic disease management in China. Optional treatments alongside mobile support showed preliminary effectiveness.

Synergistic effects of rivaroxaban and hypothermia or acidosis on coagulation initiation measured with ROTEM®: a prospective observational study

BackgroundHypothermia and acidosis individually inhibit haemostasis. We designed this study with the aim to investigate whether rivaroxaban combined with hypothermia or acidosis exhibit synergistic inhibitory effects on haemostasis using ROTEM®.MethodsPatients with a clinical indication to start rivaroxaban treatment were prospectively included. Blood samples were collected before initiation of treatment and the day after. All blood samples were in vitro modified with respect to temperature (incubated and analysed at 28, 33, 37 and 40 degrees Celsius (°C)) and pH (6.8, 7.0, 7.2 and 7.4). The temperature and acidosis effects on the ROTEM EXTEM variables clotting time (CT), clot formation time (CFT) and alpha-angle (AA) were measured along with the individual effect of rivaroxaban on the same variables. The additive effect was calculated. The observed (potential synergistic) effects for the temperature and pH modified rivaroxaban samples on the same ROTEM variables, were registered. Differences between the additive and observed (potential synergistic) effects were analysed using matched non-parametric hypothesis testing.ResultsIn total, 13 patients were included. Hypothermia and rivaroxaban exhibited a synergistic effect on CT at 28 °C (p = 0.0002) and at 33 °C (p = 0.0007). The same applied for acidosis at pH 6.8 (p = 0.003) and pH 7.0 (p = 0.003). There were no signs of synergistic effects of rivaroxaban and temperature or acidosis on CFT. In AA there were signs of synergism at 28 °C (p = 0,001), but not at other tested temperatures or pH levels.ConclusionsThe combination rivaroxaban together with hypothermia or acidosis demonstrated inhibitory synergistic effects on haemostasis.Trial registrationThe study was retrospectively registered 2023-03-01 at ClinTrials.gov with NCT05669313.

Feasibility and Acceptability of Providing Cognitive Remediation in a Large USA System of Coordinated Specialty Care for Early Psychosis.

Multinational treatment guidelines support providing cognitive remediation to people recently diagnosed with schizophrenia, but the feasibility of implementing the treatment on a large scale is less well understood. This study took place between 2019 and 2023 at 14 clinics within a large network of programs providing early intervention services to people aged 16-30 experiencing nonaffective psychosis. Clinics were randomly assigned to deliver cognitive remediation as twice-weekly clinician-led groups (N = 5), cognitive remediation as once-weekly clinician-led groups with homework (N = 6), or treatment as usual (N = 3). All clinics screened for cognitive health need to guide treatment planning. Clinical teams (N = 11) received training to provide cognitive remediation. Program evaluation data were analysed for feasibility and acceptability. Screening for cognitive health needs was completed on 77% of the 1193 participants enrolled at the 11 clinics offering cognitive remediation. Clinicians identified cognitive difficulties in 53.9% (n = 496) of screened participants and referred 27% (n = 134) of these participants to cognitive remediation. Of referred participants, 77.6% (n = 104) initiated treatment, and n = 41 completed the treatment. The rate of referral was nearly double, and treatment initiation was significantly higher at programs delivering once-weekly (84.3%) than twice-weekly (64.4%) treatment but the difference in the rate of treatment completion was statistically nonsignificant. Satisfaction among treatment completers was high. Referrals to cognitive remediation required systemic support of a feasible cognitive health screening process. About a quarter of people with clinician-identified cognitive health needs were referred to cognitive remediation. Feasibility data suggest a flexible model of treatment delivery may facilitate implementation in this service setting.

Sputum and tongue swab molecular testing for the in-home diagnosis of tuberculosis in unselected household contacts: a cost and cost-effectiveness analysis.

Delayed and missed diagnosis are a persistent barrier to tuberculosis control, partly driven by limitations associated with sputum collection and an unmet need for decentralized testing. Household contact investigation with point-of-care testing of non-invasive specimens like tongue swabs are hitherto undescribed and may be a cost-effective solution to enable community-based active case finding. In-home, molecular point-of-care testing was conducted using sputum and tongue specimens collected from all household contacts of confirmed tuberculosis cases. A health economic assessment was executed to estimate and compare the cost and cost-effectiveness of different in-home, point-of-care testing strategies. Incremental cost effectiveness ratios of strategies utilizing different combination testing algorithms using sputum and/or tongue swab specimens were compared. The total implementation cost of delivering the standard of care for a 2-year period was $84 962. Strategies integrating in-home point-of-care testing ranged between $87 844 - $93 969. The cost-per-test for in-home, POC testing of sputum was the highest at $20·08 per test. Two strategies, Point-of-Care Sputum Testing and Point-of-Care Combined Sputum and Individual Tongue Swab Testing were the most cost-effective with ICERs of $543·74 and $547·29 respectively, both below a $2,760 willingness-to-pay threshold. An in-home, point-of-care molecular testing strategy utilizing combination testing of tongue swabs and sputum specimens would incur an additional 10.6% program cost, compared to SOC, over a 2-year period. The increased sample yield from tongue swabs combined with immediate result notification following, in-home POC testing would increase the number of new TB cases detected and linked to care by more than 800%. Evidence before this study: We searched PubMed for original research published between January 1, 1950 and June 30, 2024 that evaluated the cost-effectiveness of in-home POC molecular testing, as part of HCI strategies for tuberculosis. PubMed search terms used included ["household contact investigation" OR "household contact tracing"] AND "tuberculosis" AND "cost-effectiveness". The search revealed 8 studies, of which one was removed as HCIs were leveraged for the provision of short course preventative therapy and not tuberculosis testing. None of the studies were conducted in South Africa. All seven remaining studies relied on a hub-and-spoke model of sputum collection and transportation with sputum tested at a centralized laboratory facility. Although active case finding strategies like HCIs are endorsed by the WHO to improve early case detection and treatment initiation, limited research has been done to assess its cost-effectiveness in low- and middle-income countries.Added value of this study: To our knowledge, this is the first example of in-home molecular point-of-care (POC) testing as part of HCI. The use of primary data to estimate and compare the incremental cost effectiveness of different combination, in-home testing strategies utilizing alternative sample types equips policy makers with a selection of strategy options to choose from. The tradeoff between sample types with high collection yield and those with increased accuracy becomes evident in the economic analysis, highlighting the need to consider both yield and accuracy in effective clinical decision making and use-case development. The success of in-home, POC tongue swab testing of all contacts, irrespective of symptom presentation shows great promise for universal testing programs.Implications of all available evidence: Results from our economic modeling provide evidence in support for the integration of in-home, POC tuberculosis (TB) testing during HCI. The use of less invasive tongue swab samples to increase sample yield in the absence of sputum expectoration highlights the value of combination testing strategies. Immediate result notification resulting from rapid, in-home POC testing shows great promise for increasing early case detection and improving treatment uptake. In-home, POC testing strategies, when incorporated into HCI could curb ongoing community transmission and reduce the overall burden of TB. Considerations for adopting novel POC testing strategies in future active case finding programs like HCI should strongly be considered. We evaluated the cost-effectiveness of in-home, point-of-care TB testing of household contacts. The findings indicate that combined testing strategies using tongue swab and sputum specimens could significantly increase TB case detection, with modest additional program costs.

Mapping the Patient Experience in a Pediatric Hemophilia Unit: Our Patient Journey.

Background: Hemophilia is a rare X-linked bleeding disorder. Prophylaxis has improved outcomes, but there are still unmet needs to be addressed. The aim of this study was to develop a patient journey in pediatric patients with hemophilia, a visual tool that illustrates patients' relationship with the healthcare provider through time useful for identifying patient needs, potential concerns ("pain points"), and gaps in care. Methods: qualitative study in a pediatric hemophilia unit using a human-centered design methodology. First stage: discover and empathize: (a) semi-structured interviews to patients/families and stakeholders; (b) observation techniques ("shadowing") to patients/families and professionals. Second stage: analyzing the collected information to create the patient journey. Results: A preliminary "clinical journey" was built using information from eight interviews with professionals from the interdisciplinary hemophilia team. Interviews with patient association representatives, 13 patients/families, and six "shadowing" techniques with patients and professionals were used to compare the "clinical journey" with the patient's reported experience. Main "pain points" were detected before diagnosis, at diagnosis, during assimilation, at treatment initiation, during training, and when patients start asking about their condition. The empowerment process was detected as a potential moment to improve patient/family experiences. Conclusions: The patient journey helps to better understand patient/family experiences related to the disease in different scenarios. Caregivers and patient learning and empowerment processes are significant moments where the interdisciplinary team should focus to offer valuable solutions to improve outcomes. Further research is required in this area, particularly empirical research to amend or confirm the suggested patient journey.

Longitudinal monitoring of circulating tumor DNA to detect relapse early and predict outcome in early breast cancer.

Detection of molecular residual disease (MRD) allows for the identification of breast cancer patients at high-risk of recurrence, with the potential that early initiation of treatment at early stages of relapse could improve patient outcomes. The Invitae Personalized Cancer Monitoring™ assay (PCM) is a newly developed next-generation sequencing approach that utilizes up to 50 patient-specific, tumor-informed DNA variants, to detect circulating tumor DNA (ctDNA). The ability of the PCM assay to detect MRD before clinical relapse was evaluated. The cohort included 61 female patients with high-risk breast cancer who underwent neoadjuvant chemotherapy. Plasma samples were collected before and during neoadjuvant therapy, after surgery and during monitoring. PCM was used to detect ctDNA at each time point. The sensitivity to detect ctDNA in plasma from patients who relapsed during the monitoring phase was 76.9% (10/13). Specificity and positive predictive values were both 100% with all (10/61, 16%) of the patients who had ctDNA detected during the monitoring phase subsequently relapsing. Detection of ctDNA during monitoring was associated with a high-risk of future relapse (HR 37.2, 95% CI 10.5-131.9, p < 0.0001), with a median lead-time from ctDNA detection to clinical relapse of 11.7months. PCM detected ctDNA in patients who relapsed with a long lead-time over clinical relapse, shows strong association with relapse-free survival and may be used to identify patients at high-risk for relapse, allowing for earlier intervention.

Efficacy and determinants of response to inhaled treprostinil in pulmonary hypertension - interstitial lung disease

Inhaled treprostinil has shown to improve exercise capacity in patients with pulmonary hypertension-interstitial lung disease (PH-ILD). We evaluated the efficacy and determinants of favorable response to inhaled treprostinil at six months. MethodsOf the 106 patients screened, 42 were eligible for this retrospective single-center study. Assessments included rate of patients who achieved ≥30m improvement on 6-min walk test (6MWT), and death or transplantation rates at 6 months of treatment initiation. ResultsPatients were predominantly female (n = 26, 62 %) with autoimmune PH-ILD (n = 23, 55 %), and a median age of 68 (61, 75) years. Ten (38.5 %) patients achieved a distance increase ≥30 m in 6MWT. No statistically significant determinants of walking ≥30 m were noted on univariate analysis; however, responders had a lower right ventricular (RV) tissue Doppler S' velocity (9.2 [7.0, 11.0] vs. 11.9 [10.0, 14.4], p = 0.018) cm/s and evidence of pericardial effusion on baseline echocardiogram (82 % vs. 26 %, p = 0.003). PH-ILD patients who died or underwent transplantation were more likely to have progressive pulmonary fibrosis (PPF) (95 % vs 50 %, p < 0.001) ConclusionsIn real-world setting, treatment with inhaled treprostinil for six months increased the 6MWT by ≥ 30 m in about a third of PH-ILD patients. Lower RV tissue Doppler S' velocity and presence of pericardial effusion at baseline were associated with favorable response to inhaled treprostinil. PPF portends a poor survival in PH-ILD.

Effect of low-frequency alternating magnetic field on exopolysaccharide production and antioxidant capacity of Pleurotus citrinopileatus by submerged fermentation.

The objective of this study was to investigate the effect of low-frequency alternating magnetic field (LF-AMF) on the production of extracellular polysaccharide (EPS) by submerged fermentation of Pleurotus citrinopileatus. The fermentation conditions optimized by the central composite design method were as follows: fermentation time of 6.18days, temperature of 28.28°C, shaking speed of 149.04 r/min, and inoculum amount of 8.43%. Under these conditions, a LF-AMF was applied to the submerged fermentation of P. citrinopileatus. When the intensity of LF-AMF was 40 Gs, the initial intervention time was 24h after inoculation, and the treatment time was 6h at one time, the mycelial biomass of P. citrinopileatus increased by 11.30%, and the EPS yield increased by 23.09% compared with the fermentation without LF-AMF treatment. The morphology of mycelium after LF-AMF treatment was observed by scanning electron microscopy. It was found that the surface of mycelium was wrinkled, and the structure of mycelium was loose, which might be more conducive to the production of EPS. Mycelium diameter decreased, and ATPase activity increased, indicating that LF-AMF had a positive effect on the production of EPS by P. citrinopileatus fermentation. Moreover, LF-AMF could improve the permeability of the mycelial cell membrane, facilitate the exchange of intracellular and extracellular substances, and increase the metabolic capacity of P. citrinopileatus. In vitro antioxidant test of EPS showed that LF-AMF treatment also improved its antioxidant capacity.

Experiences and challenges of nurses in initiating antiretroviral drugs among adolescents living with HIV and AIDS in Thaba-Tseka, Lesotho

Background: Lesotho has the second-highest HIV and AIDS prevalence globally and is the country’s second leading cause of death. Despite increasing ART coverage, adolescents remain left behind and face high mortality because of delayed ART initiation. This study aimed to explore the experiences and challenges of nurses when initiating adolescents living with HIV on ART in Thaba-Tseka, Lesotho. Methods: A qualitative descriptive research design and twelve in-depth interviews were conducted among nurses from a hospital in the Thaba-Tseka district. Participants were selected purposively until data saturation was reached. Data were transcribed verbatim and analysed manually using the thematic analysis approach. The findings were presented in themes and sub-themes. Individual face-to-face interviews were conducted in English and Sesotho from May to August 2021. Results: The key findings in this study involved adolescents’ attendance at the health care facility, ART initiation process, HIV stigma influencing the uptake of ART, poor ART follow-up and socio-economic factors affecting adherence to ART. Conclusion: The themes uncovered in this study provide valuable insights into the gaps in ART initiation, and highlight the challenges encountered by nurses during this process among adolescents in Lesotho. The experiences and obstacles shared by nurses during ART initiation cover a range of issues, collectively demonstrating their engagement in HIV and ART care. These findings emphasise the critical role of policymakers and health care providers in devising customised ART initiation interventions for adolescents. Addressing these challenges will be crucial for enhancing ART uptake and adherence among adolescents living with HIV in Lesotho.

A case report of late detection of primary mediastinum herm cell tumor

Germ cell tumors are rare malignant neoplasms. Extragondal localization accounts for about 10% of all germ cell tumors, with up to 3% being mediastinal. The low incidence, along with a nonspecific clinical presentation, complicates initial diagnosis and leads to delays in diagnosis and the initiation of specific treatment. Primary care plays a crucial role in detecting such tumors and in patient routing. At the outpatient stage, the patient should be examined and referred to a specialized facility for specific treatment as quickly as possible. For differential diagnosis at the initial stages between mediastinal germ cell tumors and lymphoproliferative diseases, mediastinal sarcomas, thymomas, and others, monitoring tumor markers is necessary: alpha-fetoprotein (AFP), beta-human chorionic gonadotropin (beta-HCG), and lactate dehydrogenase (LDH). When these markers are elevated and time is critical, it is permissible to start specialized antitumor treatment without histological confirmation.Currently, it is also important to consider the role of the new coronavirus infection, which complicates differential diagnosis at the initial stages. This article presents a clinical case of late detection of a germ cell tumor and attempts to conduct systemic therapy in the context of the disease’s complicated progression.

Sarcoidosis: oral manifestations (case report)

Relevance. Sarcoidosis is a multisystem granulomatous disease of unknown origin, commonly presenting with bilateral hilar lymphadenopathy, pulmonary infiltrates, and involvement of the eyes, skin, gums, and oral mucosa. This clinical case illustrates the oral manifestations of this rare systemic disease. Gingival hypertrophy and soft tissue lesions on the lip mucosa were the initial signs of the condition. Following an extended diagnostic process, the patient underwent treatment by both a dentist and a rheumatologist, leading to a stable remission of the disease.Case description. This article presents a clinical case of sarcoidosis manifesting in the mouth as gingival hypertrophy and a soft tissue lesion on the upper lip. In most cases, a diagnosis of sarcoidosis is made before any oral symptoms appear. Diagnosing a systemic disease based on primary oral symptoms poses a unique challenge, as dental professionals may not always be familiar with the oral manifestations of systemic conditions. In cases of suspected sarcoidosis, the oral mucosa should be thoroughly examined, and systemic sarcoidosis should be considered in the differential diagnosis of granulomatous lesions in the mouth.Conclusion. Early initiation of treatment can significantly improve the patient's quality of life and prognosis.

Overall Survival in Real-World Patients with Unresectable Hepatocellular Carcinoma Receiving Atezolizumab Plus Bevacizumab Versus Sorafenib or Lenvatinib as First-Line Therapy: Findings from the National Veterans Health Administration Database.

Background/Objectives: This study evaluated comparative overall survival (OS) of United States veterans with unresectable hepatocellular carcinoma (uHCC) receiving first-line (1L) atezolizumab plus bevacizumab vs. sorafenib or lenvatinib, overall and across racial and ethnic groups. Methods: In this retrospective study, patients with uHCC who initiated atezolizumab plus bevacizumab (post-2020) or sorafenib or lenvatinib (post-2018) were identified from the Veterans Health Administration National Corporate Data Warehouse (1 January 2017-31 December 2022). Patient characteristics were evaluated in the year prior to 1L treatment initiation. Kaplan-Meier and multivariable Cox regression methods were used to compare OS starting from treatment between cohorts, both overall and by race and ethnicity. Results: Among the 1874 patients included, 405 (21.6%) received 1L atezolizumab plus bevacizumab, 1016 (54.2%) received sorafenib, and 453 (24.2%) received lenvatinib, with a median follow-up time of 8.5, 7.6, and 8.2 months, respectively. Overall, patients receiving atezolizumab plus bevacizumab had longer unadjusted median OS (12.8 [95% CI: 10.6, 17.1] months) than patients receiving sorafenib (8.0 [7.1, 8.6] months) or lenvatinib (9.5 [7.8, 11.4] months; both log-rank p < 0.001). After adjustment, atezolizumab plus bevacizumab was associated with a reduced risk of death by 30% vs. sorafenib (adjusted HR: 0.70 [95% CI: 0.60, 0.82]) and by 26% vs. lenvatinib (0.74 [0.62, 0.88]; both p < 0.001). OS trends in the White, Black, and Hispanic patient cohorts were consistent with that of the overall population. Conclusions: Atezolizumab plus bevacizumab was associated with improved survival outcomes compared with sorafenib and lenvatinib in patients with uHCC, both overall and across racial and ethnic subgroups.

Circulating miRNAs and Machine Learning for Lateralizing Primary Aldosteronism.

Distinguishing between unilateral and bilateral primary aldosteronism, a major cause of secondary hypertension, is crucial due to different treatment approaches. While adrenal venous sampling is the gold standard, its invasiveness, limited availability, and often difficult interpretation pose challenges. This study explores the utility of circulating microRNAs (miRNAs) and machine learning in distinguishing between unilateral and bilateral forms of primary aldosteronism. MiRNA profiling was conducted on plasma samples from 18 patients with primary aldosteronism taken during adrenal venous sampling on an Illumina MiSeq platform. Bioinformatics and machine learning identified 9 miRNAs for validation by reverse transcription real-time quantitative polymerase chain reaction. Validation was performed on a cohort consisting of 108 patients with known subdifferentiation. A 30-patient subset of the validation cohort involved both adrenal venous sampling and peripheral, the rest only peripheral samples. A neural network model was used for feature selection and comparison between adrenal venous sampling and peripheral samples, while a deep-learning model was used for classification. Our model identified 10 miRNA combinations achieving >85% accuracy in distinguishing unilateral primary aldosteronism and bilateral adrenal hyperplasia on a 30-sample subset, while also confirming the suitability of peripheral samples for analysis. The best model, involving 6 miRNAs, achieved an area under curve of 87.1%. Deep learning resulted in 100% accuracy on the subset and 90.9% sensitivity and 81.8% specificity on all 108 samples, with an area under curve of 86.7%. Machine learning analysis of circulating miRNAs offers a minimally invasive alternative for primary aldosteronism lateralization. Early identification of bilateral adrenal hyperplasia could expedite treatment initiation without the need for further localization, benefiting both patients and health care providers.

Malnutrition risk screening in adult oncology outpatients: An ASPEN systematic review and clinical recommendations.

Malnutrition screening is not widely practiced in outpatient cancer centers. This review aims to determine the validity of malnutrition screening tools and provide recommendations for clinical use. Studies identified by a systematic review assessed the general validity of screening tools in adult oncology outpatients from five databases through 2022. The American Society for Parenteral and Enteral Nutrition (ASPEN) convened a working group of members from the Academy of Nutrition and Dietetics, Academy of Oncology Nurse and Patient Navigators, American Cancer Society, American Society for Clinical Oncology, American Society for Nutrition, American Society for Radiation Oncology, Association of Cancer Care Centers, and Oncology Nursing Society to answer the following questions: (1) should clinicians screen for malnutrition, (2) which malnutrition screening tools are recommended, and (3) what are the clinical applications for malnutrition risk screening in adult oncology outpatients? Twenty of 738 studies met the criteria and were reviewed. Six screening tools with specific cut-points demonstrated validity and are recommended, including the Mini Nutritional Assessment (≤23.5), Malnutrition Screening Tool (MST; MST ≥ 2 and patient-led MST ≥ 2), Malnutrition Universal Screening Tool (MUST; MUST ≥ 1 and MUST ≥ 2), Nutrition Risk Screening-2002 (NRS-2002; NRS-2002 ≥ 2 and NRS-2002 ≥ 3), NUTRISCORE ≥ 5, and Patient-Generated Subjective Global Assessment Short Form (PG-SGA SF; PG-SGA SF ≥ 7 and PG-SGA SF ≥ 8). Six screening tools are valid for malnutrition risk identification in oncology ambulatory settings and recommended before treatment initiation and regularly thereafter, depending on treatment course. Research is needed to understand to what extent early diagnosis and management of malnutrition improves the clinical care of oncology patients.

Drug Survival of Dupilumab, Methotrexate, and Cyclosporine A in Children With Atopic Dermatitis

Dupilumab, methotrexate (MTX), and cyclosporine A (CsA) are valuable treatment options for pediatric patients with refractory moderate to severe atopic dermatitis (AD). Yet, comparative data on these treatments in pediatric patients are scarce. To evaluate drug survival of dupilumab, MTX, and CsA, and identify associated predictors in a multicenter daily practice cohort study of pediatric patients with AD. This multicenter daily practice cohort study included patients with AD aged 2 to 17 years treated with dupilumab, MTX, and/or CsA in 5 tertiary centers in the Netherlands between 2013 and 2023. Data were extracted from the prospective BioDay and TREAT Netherlands registries and electronic medical records. Dupilumab, MTX, CsA. Drug survival was analyzed using Cox proportional hazard regression models. Univariable and multivariable Cox regression analyses were conducted to identify variables associated with drug discontinuation. A total of 502 treatment episodes in 362 unique patients were included, comprising 192 dupilumab episodes, 94 MTX episodes, and 216 CsA episodes. Overall, the mean (SD) age at treatment initiation was 12.9 (3.8) years, and 272 treatment episodes (54.2%) in female patients. The 1-year, 2-year, and 3-year overall drug survival rates, respectively, were 84.1%, 72.3%, and 62.0% for dupilumab; 60.7%, 39.3%, and 25.3% for MTX; and 43.9%, 21.5%, and 10.4% for CsA. Ineffectiveness was the most frequent reason for drug discontinuation, accounting for 178 episodes (35.5%), mostly in patients treated with CsA, followed by adverse effects in 94 patients (18.7%). Treatment with MTX and treatment with CsA were independently associated with a higher risk for drug discontinuation due to ineffectiveness (hazard ratio [HR], 4.45 [95% CI, 2.38-8.34] and HR, 10.88 [95% CI, 6.23-19.02], respectively) and adverse effects (HR, 4.39 [95% CI, 2.05-9.39] and HR, 3.83 [95% CI, 1.85-7.92], respectively) compared to treatment with dupilumab. Patients aged 12 to 17 years starting systemic treatment were independently associated with a higher risk for drug discontinuation due to ineffectiveness (HR, 1.55 [95% CI, 1.10-2.20]) and adverse effects (HR, 2.39 [95% CI, 1.33-4.30]). This multicenter daily practice cohort study demonstrated a superior 1-year, 2-year, and 3-year overall drug survival for dupilumab, followed by MTX, with the lowest rates observed for CsA in pediatric patients with AD. This study also identified characteristics associated with discontinuation. These results provide insight into drug survival resulting from the effectiveness, safety, and tolerability of these systemic treatments in pediatric patients with AD and contribute to the optimization of patient outcomes.

Blood concentration monitoring and renal function changes during gentamicin administration for infective endocarditis: a retrospective observational study

BackgroundEstablished guidelines for monitoring gentamicin blood concentration are lacking; therefore, we focused on improving pharmacological interventions and ensuring their safety. We aimed to optimize gentamicin administration for infective endocarditis (IE) treatment.MethodsThe study involved adult patients diagnosed with IE and treated with gentamicin from January 2014 to December 2022. Clinical presentation and drug therapy regimen were comprehensively evaluated. We performed a retrospective chart review of the frequency of gentamicin dose adjustments and changes in renal function while on gentamicin. In addition, we attempted to extract risk factors for renal impairment using univariate analysis.ResultsOn average, a 7.1% decline [changed to − 6.7 ± 20.4 (standard deviation) mL/min/1.73 m2] in the estimated glomerular filtration rate was observed after gentamicin administration, but it was statistically insignificant. Notably, 58% of patients required dosage adjustments, with a subset requiring multiple adjustments. Among the cases in which dosage adjustments were made, 61% were within the first week of treatment. There were no patients with gentamicin levels below the target peak concentration. Furthermore, no independent risk factors were identified in patients requiring dose reduction.ConclusionsDose adjustment was necessary in many cases after treatment initiation. The time to dose adjustment varied widely. These findings highlight the importance of consistent blood concentration monitoring in patients of all demographics, at least weekly, and underscore that routine peak concentration assessments may not be essential when a 3 μg/mL target is maintained. This study provides information on monitoring gentamicin blood level, which can improve IE treatment safety.

Trajectories of disease evolution upon treatment initiation in systemic lupus erythematosus: results from four clinical trials of belimumab.

Upon commencement of therapy for active disease, patients with systemic lupus erythematosus (SLE) show varying evolution regarding disease activity measures and patient-reported outcomes (PROs). Our objective was to identify disease evolution trajectories to gain a deeper understanding of SLE progression, ultimately improving future trial design. Patients with ≥2 visits and available data on SLEDAI-2K, BILAG, PGA, FACIT-F, and glucocorticoid use were included in a post-hoc analysis of four randomised controlled trials of belimumab (BLISS-52, BLISS-76, BLISS-SC, EMBRACE). Growth mixture modelling identified latent classes. Among 2868 patients analysed, baseline median disease duration was 4.5 (IQR: 1.5-9.7) years and mean (± standard deviation) SDI 0.7 (±2.0), SLEDAI-2K 10.2 (±3.6), BILAG 17.0 (±7.8), PGA 1.5 (±0.5), FACIT-F 30.6 (±11.9), and prednisone dose 11.0 (±8.9) mg/day. In the initial model, glucocorticoid use and dose yielded high standard errors, indicating a weak link with the latent process. A refined model considered only clinical measures and FACIT-F, corrected for intervention and SDI; no other covariates improved the fit. Four classes best described disease evolution: highly active, responders; highly active, non-responders; moderately active, responders; moderately active, non-responders. LLDAS and DORIS remission attainment associated with latent classes. By linking disease activity measures with PROs, we identified four distinct trajectories describing SLE evolution following the initiation of therapy. This classification could be valuable for personalising treatment and guiding biological studies aimed at distinguishing patients with varying anticipated treatment responses, as no single clinical variable alone can predict disease progression.

Efficacy of vedolizumab and ustekinumab in pediatric-onset inflammatory bowel disease: A real-world multicenter study.

Vedolizumab and ustekinumab are effective in inducing and maintaining corticosteroid-free clinical remission (CFR) in adult patients with inflammatory bowel disease (IBD). This study describes the efficacy and safety of vedolizumab and ustekinumab in pediatric IBD. All patients ≤18 years of age with Crohn's disease (CD) or ulcerative colitis (UC) treated with vedolizumab or ustekinumab in three centers in Northern France were followed retrospectively. The primary outcome was CFR at Week 14 (W14). Twenty-five patients (9 CD, 16 UC) and 33 patients (28 CD, 5 UC) were started on vedolizumab and ustekinumab respectively between 2016 and 2021. All were previously treated with antitumor necrosis factor (TNF). The median time from diagnosis to treatment initiation was 21.0 (12.0-44.0) and 42.0 (22.0-73.5) months for vedolizumab and ustekinumab respectively. Among vedolizumab-treated patients, 36% were in CFR at W14, including 22% in CD and 44% in UC. At W52, 56% were in CFR, including 33% in CD and 69% in UC. Among ustekinumab-treated patients, 49% were in CFR at W14, including 54% in CD and 20% in UC. At W52, 55% were in CFR, including 57% in CD and 40% in UC. There was a significant increase in median growth velocity between W0 and W52 of +2 SD in vedolizumab-treated patients (p = 0.0002). Four adverse events were reported during vedolizumab treatment, none for ustekinumab-treated patients. Vedolizumab and ustekinumab appear to be effective in inducing and maintaining CFR in pediatric-onset IBD. Randomized controlled trials are needed to confirm these results.