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1.
Phys Rev Lett ; 133(3): 031601, 2024 Jul 19.
Artigo em Inglês | MEDLINE | ID: mdl-39094139

RESUMO

Various observables in different four-dimensional superconformal Yang-Mills theories can be computed exactly as Fredholm determinants of truncated Bessel operators. We exploit this relation to determine their dependence on the 't Hooft coupling constant. Unlike the weak coupling expansion, which has a finite radius of convergence, the strong coupling expansion is factorially divergent, necessitating the inclusion of nonperturbative, exponentially small corrections. We develop a method to systematically compute these corrections and discuss the resurgent properties of the resulting transseries.

2.
ACS Omega ; 9(30): 32881-32892, 2024 Jul 30.
Artigo em Inglês | MEDLINE | ID: mdl-39100325

RESUMO

Polyethylenimine (PEI) has been shown to be promising for direct air capture (DAC) of carbon dioxide and has potential for commercial scale-up globally. Laboratory scale processes include multiple steps, such as mixing, solvent extraction, vacuum application, sonication, and various flushes and activation steps. It is critical to properly control these operating parameters to achieve higher capture capacity as a result of the optimized material configuration. This study adopts previously published pelletization processes for PEI-infiltrated mesoporous foam silica (mesoporous silica foam) to uncover the adsorption mechanisms and optimize the associated fabrication steps, such as sonication, to achieve higher sorbent productivity. A high capture capacity was achieved at 46 °C for 75 wt % PEI loading (2.27 mmol/g) followed by PEI_MSF 70 (1.81 mmol/g) and PEI_MSF 80 (1.44 mmol/g). As part of the optimization, sonication parameters of frequency, amplitude, and time were modified for PEI_MSF 75 sorbent, which resulted in the highest uptake capacity of 3.04 mmol/g (sonicated at 40 kHz and a wave amplitude of 50% for 30 s). These preliminary results would tend to prove that sonication energy affects carbon capture capacity, although there is still a lack of understanding regarding the exact underlying mechanism, suggesting the need for further investigation. It is important to note that the present work is focused on the adsorption mechanisms and not desorption or durability of the capture performance. Ongoing research addresses these factors. This paper is intended to establish baseline DAC behavior of a promising capture medium and begins probing the optimization spectrum by considering the effects of sonication energy on adsorption. Ongoing work intends to address potential abbreviations of the full range of process steps and furthers the understanding of kinetics by considering the desorption and resorption attributes.

3.
Struct Heart ; 8(4): 100293, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-39100579

RESUMO

Background: The Navitor Investigational Device Exemption (IDE) study is a prospective, multicenter, global study assessing the safety and effectiveness of the Navitor valve in a population with severe, symptomatic aortic stenosis who are at high and extreme surgical risk. The impact of pre-existing conduction abnormalities and implantation technique on new permanent pacemaker implantation (PPI) for the Navitor platform is not fully understood. Therefore, the goal of this analysis was to investigate the associations between patient and procedural factors and the 30-day new PPI rate. Methods: A total of 260 patients who underwent implantation of a Navitor valve in the Navitor IDE study were reviewed. Patients with preprocedural permanent pacemakers (n = 28) were excluded. Baseline risk factors were assessed for statistical significance. Multivariable logistic regression analyses were performed to identify independent predictors of new PPI. Results: Mean age of the pacemaker-naïve population was 83.3 ± 5.2 years, 58.6% were female, average Society of Thoracic Surgeons score was 3.8% ± 1.9%, median frailty score was 1 (interquartile range 1, 2), and 17.7% were deemed at extreme surgical risk. Pre-existing first-degree atrioventricular block and right bundle branch block significantly increased the risk of new PPI postimplantation, whereas left bundle branch block did not. Membranous septum length in relation to noncoronary cusp implant depth was a significant predictor of new PPI, with higher rates of new PPI observed when noncoronary cusp implant depth exceeded membranous septum length. Analysis of implant depth alone revealed deeper implants were associated with a higher rate of new PPI, regardless of patient baseline conduction abnormality. Conclusions: The 30-day rate of new PPI in the Navitor IDE study is associated with patient pre-existing baseline conduction disturbances and implantation depth.

4.
J Control Release ; 2024 Aug 03.
Artigo em Inglês | MEDLINE | ID: mdl-39103055

RESUMO

The focus of nanoparticles in vivo trafficking has been mostly on their tissue-level biodistribution and clearance. Recent progress in the nanomedicine field suggests that the targeting of nanoparticles to immune cells can be used to modulate the immune response and enhance therapeutic delivery to the diseased tissue. In the presence of tumor lesions, monocytic-myeloid-derived suppressor cells (M-MDSCs) expand significantly in the bone marrow, egress into peripheral blood, and traffic to the solid tumor, where they help maintain an immuno-suppressive tumor microenvironment. In this study, we investigated the interaction between PAMAM dendrimers and M-MDSCs in two murine models of glioblastoma, by examining the cell-level biodistribution kinetics of the systemically injected dendrimers. We found that M-MDSCs in the tumor and lymphoid organs can efficiently endocytose hydroxyl dendrimers. Interestingly, the trafficking of M-MDSCs from the bone marrow to the tumor contributed to the deposition of hydroxyl dendrimers in the tumor. M-MDSCs showed different capacities of endocytosing dendrimers of different functionalities in vivo. This differential uptake was mediated by the unique serum proteins associated with each dendrimer surface functionality. The results of this study set up the framework for developing dendrimer-based immunotherapy to target M-MDSCs for cancer treatment.

5.
Int J Sports Phys Ther ; 19(7): 856-867, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38966826

RESUMO

Background: In 2020, the American Society of Shoulder and Elbow Therapists (ASSET) published an evidence-based consensus statement outlining postoperative rehabilitation guidelines following anatomic total shoulder arthroplasty (TSA). Purpose: The purpose of this study was to (1) quantify the variability in online anatomic TSA rehabilitation protocols, and (2) assess their congruence with the ASSET consensus guidelines. Methods: This study was a cross-sectional investigation of publicly available, online rehabilitation protocols for anatomic TSA. A web-based search was conducted in April 2022 of publicly available rehabilitation protocols for TSA. Each collected protocol was independently reviewed by two authors to identify recommendations regarding immobilization, initiation, and progression of passive (PROM) and active range of motion (AROM), as well as the initiation and progression of strengthening and post-operative exercises and activities. The time to initiation of various components of rehabilitation was recorded as the time at which the activity or motion threshold was permitted by the protocol. Comparisons between ASSET start dates and mean start dates from included protocols were performed. Results: Of the 191 academic institutions included, 46 (24.08%) had publicly available protocols online, and a total of 91 unique protocols were included in the final analysis. There were large variations seen among included protocols for the duration and type of immobilization post-operatively, as well as for the initiation of early stretching, PROM, AROM, resistance exercises, and return to sport. Of the 37 recommendations reported by both the ASSET and included protocols, 31 (83.78%) were found to be significantly different between groups (p\<0.05). Conclusion: Considerable variability was found among online post-operative protocols for TSA with substantial deviation from the ASSET guidelines. These findings highlight the lack of standardization in rehabilitation protocols following anatomic TSA. Level of Evidence: 3b.

6.
Schizophr Bull ; 2024 Jul 27.
Artigo em Inglês | MEDLINE | ID: mdl-39066666

RESUMO

BACKGROUND AND HYPOTHESIS: The Cognitive Model of Negative Symptoms is a prominent model that posits that defeatist performance beliefs (DPB) are a key psychological mechanism underlying negative symptoms in those with schizophrenia (SZ). However, the ecological validity of the model has not been established, and temporally specific evaluations of the model's hypotheses have not been conducted. This study tested the model's key hypotheses in real-world environments using ecological momentary assessment (EMA). STUDY DESIGN: Fifty-two outpatients with SZ and 55 healthy controls (CN) completed 6 days of EMA. Multilevel models examined concurrent and time-lagged associations between DPB and negative symptoms in daily life. STUDY RESULTS: SZ displayed greater DPB in daily life than CN. Furthermore, greater DPB were associated with greater concurrently assessed negative symptoms (anhedonia, avolition, and asociality) in daily life. Time-lagged analyses indicated that in both groups, greater DPB at time t led to elevations in negative symptoms (anhedonia, avolition, or asociality) at t + 1 above and beyond the effects of negative symptoms at time t. CONCLUSIONS: Results support the ecological validity of the Cognitive Model of Negative Symptoms and identify a temporally specific association between DPB and subsequent negative symptoms that is consistent with the model's hypotheses and a putative mechanistic pathway in Cognitive Behavioral Therapy for negative symptoms. Findings suggest that DPB are a psychological factor contributing to negative symptoms in real-world environments. Implications for measuring DPB in daily life and providing just-in-time mobile health-based interventions to target this mechanism are discussed.

7.
Neuromuscul Disord ; 42: 1-4, 2024 Jun 21.
Artigo em Inglês | MEDLINE | ID: mdl-38981343

RESUMO

We describe two anti-3­hydroxy-3-methyl-glutaryl-coenzyme A reductase (HMGCR) antibody-positive patients with treatment-responsive ophthalmoparesis. Patient 1 was a 53-year-old male with progressive proximal limb weakness, dysphagia, ptosis, and diplopia over 6 weeks and creatine kinase (CK) of 3,512 units/L. Patient 2 was a 55-year-old female with progressive proximal weakness, dysarthria, ptosis, diplopia, and dyspnea over 2 weeks with CK of 31,998 units/L. Both patients had normal thyroid studies and repetitive nerve stimulation, myopathic electromyography with fibrillation potentials, magnetic resonance imaging demonstrating abnormal enhancement of extraocular muscles, muscle biopsy showing necrotic myofibers, and positive anti-HMGCR antibodies. Patient 1 also had weakly positive anti-PM/Scl antibodies. Immunomodulatory therapies led to resolution of oculobulbar weakness and normalization of CK levels in both patients, while limb weakness resolved completely in patient 1 and partially in patient 2. These cases expand the phenotypic spectrum of anti-HMGCR antibody-associated myopathies to include subacute ophthalmoparesis with limb-girdle weakness and markedly elevated CK.

8.
Artigo em Inglês | MEDLINE | ID: mdl-39004211

RESUMO

OBJECTIVE: To examine the prevalence of preexisting articular bone pathology in patients with hip or knee pain due to osteoarthritis (OA) screened for fasinumab clinical trials. METHOD: This post-hoc analysis included patients with OA screened for three phase 3 fasinumab studies (NCT02683239, NCT03161093, NCT03304379). During screening, participants who met other clinical inclusion/exclusion criteria underwent radiography of knees, hips, and shoulders. Those with Kellgren-Lawrence grade (KLG) ≥ 2 for index joint and without an exclusionary finding proceeded to magnetic resonance imaging (MRI) of index, contralateral, and KLG ≥ 3 joints. Exclusionary findings included bone fragmentation/collapse, bone loss/resorption, osteonecrosis, and fracture, by either X-ray or MRI. Participants with extensive subchondral cysts were also excluded. Prevalence of abnormalities on radiographs and MRIs are reported. RESULTS: Of 27,633 participants screened, 21,997 proceeded to imaging. Of these, 1203 (5.5%) were excluded due to the presence of ≥ 1 joint with severe articular bone pathology (X-ray or MRI): bone fragmentation/collapse (2.60%), subchondral insufficiency fracture (SIF; 1.67%), osteonecrosis (1.11%), and significant bone loss (0.32%). Additionally, 3.13% screen-failed due to extensive subchondral cysts. More than half of the exclusions due to bone fragmentation/collapse (386/572), osteonecrosis (141/245) and significant bone loss (59/71), and approximately one third of SIF (133/367) and extensive subchondral cysts (229/689) were evident on X-rays. CONCLUSIONS: Approximately one in 20 participants with OA who met the clinical screening criteria for fasinumab phase 3 trials were later excluded due to preexisting severe articular bone pathology findings by X-ray or MRI.

9.
Artigo em Inglês | MEDLINE | ID: mdl-38971385

RESUMO

INTRODUCTION: Local failure rates after treatment for locally advanced non-small-cell lung cancer (NSCLC) remain high. Efforts to improve local control with uniform dose-escalation or dose-escalation to mid-treatment PET-avid residual disease have been limited by heightened toxicity. This trial aimed to refine response-based adaptive radiation (RT) and minimize toxicity by incorporating FDG-PET and V/Q SPECT imaging mid-treatment. METHODS: 47 patients with Stage IIA-III unresectable NSCLC were prospectively enrolled in this single-institution trial (NCT02492867). Patients received concurrent chemoradiation with personalized response-based adaptive RT over 30 fractions incorporating V/Q SPECT and FDG-PET. The first 21 fractions (46.2Gy at 2.2 Gy/fraction) were delivered to the tumor while minimizing dose to SPECT-defined functional lung. The plan was then adapted for the final 9 fractions (2.2-3.8Gy/fraction) up to a total of 80.4Gy, based on mid-treatment FDG-PET tumor response to escalate dose to residual tumor while minimizing dose to SPECT-defined functional lung. Non-progressing patients received consolidative carboplatin/paclitaxel or durvalumab. The primary endpoint of the study was ≥ grade 2 lung and esophageal toxicities. Secondary endpoints included time to local progression, tumor response, and overall survival. RESULTS: At one year post-treatment, the rates of grade 2 and grade 3 pneumonitis were 21.3% and 2.1%, respectively, with no difference in pneumonitis rates among patients who received and did not receive adjuvant durvalumab (p=0.74). While there were no grade 3 esophageal-related toxicities, 66.0% of patients experienced grade 2 esophagitis. 1- and 2-year local control rates were 94.5% (95% CI, 87.4% - 100%) and 87.5% (95% CI, 76.7% - 100%), respectively. Overall survival was 82.8% (95% CI, 72.6% -94.4%) at 1 year and 62.3% (95% CI, 49.6%-78.3%) at 2 years. CONCLUSIONS: Response-based adaptive dose-escalation accounting for tumor change and normal tissue function during treatment provided excellent local control, comparable toxicity to standard chemoradiation, and did not increase toxicity with adjuvant immunotherapy.

11.
Eur Neuropsychopharmacol ; 87: 18-23, 2024 Jul 17.
Artigo em Inglês | MEDLINE | ID: mdl-39024856

RESUMO

Roluperidone, a 5-HT2A, sigma2, and ɑ1A-adrenergic receptor antagonist, has proven efficacious for treating negative symptoms of schizophrenia in phase 2b and phase 3 clinical trials. Using network analysis, we demonstrated that the improvements observed in the phase 2b trial resulted from targeting avolition which was highly central and spurred a cascading effect of global negative symptom reductions when successfully treated. The current study aims to replicate these network findings using the phase 3 roluperidone clinical trial data. Participants included 496 schizophrenia patients with moderate to severe negative symptoms who were randomized to either roluperidone 32 mg/day (n =167), 64 mg/day (n = 162), or placebo (n = 167). Negative symptoms were assessed at baseline and weeks 2,4,8, and 12. Network intervention analysis (NIA) evaluated treatment-induced symptom changes over time to identify direct and indirect treatment effects. This analytic approach extends prior work by determining whether the symptoms with highest centrality have causal effects on the entire negative symptom construct and directly lead to symptom improvement. NIA indicated that the efficacious 64 mg/day dose of roluperidone had a direct effect on avolition, suggesting that changes in avolition propels treatment effects across the entire negative symptom constellation. These phase 3 findings replicated the phase 2b findings, indicating that from a network perspective, roluperidone achieves its effect by influencing the extent to which avolition drives other negative symptoms. These findings are relevant for understanding negative symptoms and how to treat them in neuropsychiatric disorders.

12.
Fam Syst Health ; 42(2): 151-156, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38990663

RESUMO

Despite high rates of pain-related concerns among primary care patients and associated increases in health care costs (Gore et al., 2012; Mills et al., 2016), psychological or behavioral treatments that are well suited for use in integrated primary care (IPC) settings remain sparsely implemented. Psychological treatment for chronic pain has been recommended for many years (Darnall, 2021; Institute of Medicine (US) Committee on Advancing Pain Research, Care and Education, 2011; Kligler et al., 2018), and the emphasis on the application of nonpharmacological treatment has intensified following concerns about opioid safety. There is abundant empirical support for the use of psychological treatment for chronic pain, such as cognitive behavioral therapy (CBT) in specialty settings (Williams et al., 2021). The evidence to support the use of "brief treatments" in IPC is in a comparatively early stage. The limited state of the research might suggest that brief behavioral intervention for chronic pain is years away from being ready for translation to everyday clinical practice. But why wait? We therefore conducted a focused narrative review of peer-reviewed research on brief psychotherapy for chronic pain in adults that could be feasibly employed in IPC settings through more widely adopted models, such as primary care behavioral health. (PsycInfo Database Record (c) 2024 APA, all rights reserved).


Assuntos
Dor Crônica , Atenção Primária à Saúde , Humanos , Dor Crônica/terapia , Dor Crônica/psicologia , Terapia Comportamental/métodos , Terapia Comportamental/normas , Prestação Integrada de Cuidados de Saúde/normas , Prestação Integrada de Cuidados de Saúde/tendências , Manejo da Dor/métodos , Manejo da Dor/normas , Terapia Cognitivo-Comportamental/métodos , Terapia Cognitivo-Comportamental/normas
13.
Neurology ; 103(3): e209559, 2024 Aug 13.
Artigo em Inglês | MEDLINE | ID: mdl-39018519

RESUMO

A 27-year-old woman with a known suprasellar dermoid cyst and stable idiopathic intracranial hypertension (IIH) presented with new monocular vision change and new-onset headaches. Formal visual field testing accurately identified progressive chiasmal compression due to her suprasellar dermoid cyst before radiographic change was appreciable on magnetic resonance imaging. Accurate interpretation of her visual field findings avoided the common pitfall of attributing new visual symptoms to her IIH diagnosis. This case highlights the value of recognizing visual field changes that localize to the chiasm even in patients with history of other ophthalmologic conditions.


Assuntos
Cisto Dermoide , Escotoma , Humanos , Feminino , Adulto , Cisto Dermoide/diagnóstico por imagem , Cisto Dermoide/complicações , Cisto Dermoide/cirurgia , Escotoma/etiologia , Escotoma/diagnóstico por imagem , Imageamento por Ressonância Magnética , Quiasma Óptico/diagnóstico por imagem , Quiasma Óptico/patologia , Pseudotumor Cerebral/diagnóstico por imagem , Pseudotumor Cerebral/complicações
14.
Infect Dis Ther ; 13(8): 1861-1876, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38961047

RESUMO

INTRODUCTION: This study aimed to assess the effects of a monoclonal antibody (mAb) combination on symptoms, daily function, and overall health-related quality of life. METHODS: We analyzed patient-reported outcomes data from symptomatic outpatients in a phase 1/2/3 trial. Patients with confirmed SARS-CoV-2 infection and ≥ 1 risk factor for severe COVID-19 received mAb treatment (casirivimab plus imdevimab 1200 mg) or placebo. Prespecified exploratory assessments included time to sustained symptoms resolution, usual health, and return to usual activities (assessed daily for 29 days). The trial was conducted from September 2020 to February 2021, prior to widespread COVID-19 vaccination programs and Omicron-lineage variants against which casirivimab + imdevimab is not active. RESULTS: In this analysis 736 outpatients received mAb and 1341 received placebo. Median time to sustained symptoms resolution was consistently shorter with mAb versus placebo (≥ 2 consecutive days: 14 vs 17 days, [nominal p = 0.0017]; ≥ 3 consecutive days: 17 vs 21 days, [nominal p = 0.0046]). Median time to sustained return to usual health and usual activities were both consistently shorter with mAb versus placebo (≥ 2 consecutive days: 12 vs 15 days [nominal p = 0.0001] and 9 vs 11 days [nominal p = 0.0001], respectively; ≥ 3 consecutive days: 14 vs 18 days [nominal p = 0.0003] and 10 vs 13 days [nominal p = 0.0041], respectively). CONCLUSIONS: mAb treatment against susceptible SARS-CoV-2 strains improved how patients feel and function, as evidenced by shortened time to sustained symptoms resolution and return to usual health and activities. Future studies are warranted to assess the patient experience with next generation mAbs. CLINICALTRIALS: GOV: Registration number, NCT04425629; Submission date June 11, 2020.

15.
Oncologist ; 2024 Jul 17.
Artigo em Inglês | MEDLINE | ID: mdl-39022993

RESUMO

INTRODUCTION: Personalized and tumor-informed circulating tumor DNA (ctDNA) testing is feasible and allows for molecular residual disease (MRD) identification in patients with pancreatic ductal adenocarcinoma (PDAC). METHODS: In this retrospective analysis of commercial cases from multiple US institutions, personalized, tumor-informed, whole-exome sequenced, and germline-controlled ctDNA levels were quantified and analyzed in patients with PDAC. Plasma samples (n = 1329) from 299 clinically validated patients were collected at diagnosis, perioperatively (MRD-window; within 2-12 weeks after surgery, before therapy), and during surveillance (>12 weeks post-surgery if no ACT or starting 4 weeks post-ACT) from November 2019 to March 2023. RESULTS: Of the initially diagnosed patients with stages I-III PDAC who went for resection, the median follow-up time from surgery was 13 months (range 0.1-214). Positive ctDNA detection rates were 29% (29/100) and 29.6% (45/152) during the MRD and surveillance windows, respectively. Positive ctDNA detection was significantly associated with shorter DFS within the MRD window (median DFS of 6.37 months for ctDNA-positive vs 33.31 months for ctDNA-negative patients; HR: 5.45, P < .0001) as well as during the surveillance period (median DFS: 11.40 months for ctDNA-positive vs NR for ctDNA-negative; HR: 12.38, P < .0001). Additionally, DFS was significantly better with KRAS wildtype status followed by KRASG12R (HR: 0.99, P = .97), KRASG12D (HR: 1.42, P = .194), and worse with KRASG12V (HR: 2.19, P = .002) status. In multivariate analysis, ctDNA detection at surveillance was found to be the most significant prognostic factor for recurrence (HR: 24.28, P < .001). CONCLUSIONS: Perioperative tumor-informed ctDNA detection in PDAC is feasible across all stages and is associated with patient survival outcomes.

16.
Foot Ankle Clin ; 29(3): 521-527, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-39068026

RESUMO

Noninferiority studies in surgery are, by their very nature, reductionist. They use multiple variables to generate a yes or no answer about the new device being tested. A binary outcome is appropriate for a regulatory agency such as the Food and Drug Administration, but the clinical situation is more nuanced. It is critical to understand the underlying philosophies and choices that go into trial design when a surgeon is recommending a new device. In the case of Cartiva, any of 3 reasonable alternative means of defining surgical success would have altered the final outcome of the MOTION trial. Additionally, using a more rigorous noninferiority margin rather than adding an additional cushion based upon the argument that motion alone had extra inherent value would have also led to failure of the trial to demonstrate noninferiority.


Assuntos
Artrodese , Humanos , Artrodese/métodos , Estudos de Equivalência como Asunto
17.
bioRxiv ; 2024 Jun 06.
Artigo em Inglês | MEDLINE | ID: mdl-38895268

RESUMO

Glioblastoma (GBM) is the most common malignant primary brain tumor, resulting in poor survival despite aggressive therapies. GBM is characterized by a highly heterogeneous and immunosuppressive tumor microenvironment (TME) made up predominantly of infiltrating peripheral immune cells. One significant immune cell type that contributes to glioma immune evasion is a population of immunosuppressive cells, termed myeloid-derived suppressor cells (MDSCs). Previous studies suggest that a subset of myeloid cells, expressing monocytic (M)-MDSC markers and dual expression of chemokine receptors CCR2 and CX3CR1, utilize CCR2 to infiltrate the TME. This study evaluated the mechanism of CCR2+/CX3CR1+ M-MDSC differentiation and T cell suppressive function in murine glioma models. We determined that bone marrow-derived CCR2+/CX3CR1+ cells adopt an immune suppressive cell phenotype when cultured with glioma-derived factors. Glioma secreted CSF1R ligands M-CSF and IL-34 were identified as key drivers of M-MDSC differentiation while adenosine and iNOS pathways were implicated in M-MDSC suppression of T cells. Mining a human GBM spatial RNAseq database revealed a variety of different pathways that M-MDSCs utilize to exert their suppressive function that are driven by complex niches within the microenvironment. These data provide a more comprehensive understanding of the mechanism of M-MDSCs in glioblastoma.

19.
J Clin Transl Endocrinol ; 36: 100352, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38860154

RESUMO

Objectives: To report the safety and side effects associated with taking verapamil for beta-cell preservation in children with newly-diagnosed T1D. Research Design and Methods: Eighty-eight participants aged 8.5 to 17.9 years weighing ≥ 30 kg were randomly assigned to verapamil (N = 47) or placebo (N = 41) within 31 days of T1D diagnosis and followed for 12 months from diagnosis, main CLVer study. Drug dosing was weight-based with incremental increases to full dosage. Side effect monitoring included serial measurements of pulse, blood pressure, liver enzymes, and electrocardiograms (ECGs). At study end, participants were enrolled in an observational extension study (CLVerEx), which is ongoing. No study drug is provided during the extension, but participants may use verapamil if prescribed by their diabetes care team. Results: Overall rates of adverse events were low and comparable between verapamil and placebo groups. There was no difference in the frequency of liver function abnormalities. Three CLVer participants reduced or discontinued medication due to asymptomatic ECG changes. One CLVerEx participant (18 years old), treated with placebo during CLVer, who had not had a monitoring ECG, experienced complete AV block with a severe hypotensive episode 6 weeks after reaching his maximum verapamil dose following an inadvertent double dose on the day of the event. Conclusions: The use of verapamil in youth newly-diagnosed with T1D appears generally safe and well tolerated with appropriate monitoring. We strongly recommend monitoring for potential side effects including an ECG at screening and an additional ECG once full dosage is reached.ClinicalTrials.gov number: NCT04233034.

20.
Artigo em Inglês | MEDLINE | ID: mdl-38846748

RESUMO

Learning personalized self-management routines is pivotal for people with type 1 diabetes (T1D), particularly early in diagnosis. Context-aware technologies, such as hybrid closed-loop (HCL) insulin pumps, are important tools for diabetes self-management. However, clinicians have observed that practices using these technologies involve significant individual differences. We conducted interviews with 20 adolescents and young adults who use HCL insulin pump systems for managing T1D, and we found that these individuals leverage both technological and non-technological means to maintain situational awareness about their condition. We discuss how these practices serve to infrastructure their self-management routines, including medical treatment, diet, and glucose measurement-monitoring routines. Our study provides insights into adolescents' and young adults' lived experiences of using HCL systems and related technology to manage diabetes, and contributes to a more nuanced understanding of how the HCI community can support the contextualized management of diabetes through technology design.

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