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1.
MicroPubl Biol ; 20242024.
Artigo em Inglês | MEDLINE | ID: mdl-38596360

RESUMO

Ant behavior relies on a collection of natural products, from following trail pheromones during foraging to warding off potential predators. How nervous systems sense these compounds to initiate a behavioral response remains unclear. Here, we used Caenorhabditis elegans chemotaxis assays to investigate how ant compounds are detected by heterospecific nervous systems. We found that C. elegans avoid extracts of the pavement ant ( Tetramorium immigrans ) and either osm-9 or tax-4 ion channels are required for this response. These experiments were conducted in an undergraduate laboratory course, demonstrating that new insights into interspecies interactions can be generated through genuine research experiences in a classroom setting.

3.
Pediatr Transplant ; 28(3): e14750, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38623880

RESUMO

BACKGROUND: Pediatric allogeneic hematopoietic cell transplant (allo-HCT) recipients are at risk for morbidity and mortality from human adenovirus (HAdV). HAdV can be detected in an asymptomatic state, referred to as infection or with signs or symptoms of illness, referred to as disease. Standardized case definitions are needed to distinguish infection from disease and allow for consistent reporting in both observational cohort studies and therapeutic clinical trials. METHODS: A working group of experts in virology, transplant infectious disease, and HCT was assembled to develop HAdV infection and disease definitions with the degree of certainty (i.e., possible, probable, and proven). Definitions were further refined through an iterative process and independently applied by two central review committees (CRCs) to 20 pediatric allo-HCT recipients with at least one HAdV-positive PCR. RESULTS: Initial HAdV infection and disease definitions were developed and updated through an iterative process after reviewing clinical and virological details for 81 subjects with at least one positive HAdV PCR detected in a clinical specimen. Independent application of final definitions to 20 HAdV positive allo-HCT recipients by two CRCs yielded similar number of HAdV infection or disease events but with variation of degree of certainty for some events. CONCLUSIONS: Application of definitions by a CRC for a study of HAdV infection and disease is feasible and can provide consistency in the assignment of outcomes. Definitions need further refinement to improve reproducibility and to provide guidance on determining clinical improvement or worsening after initial diagnosis of HAdV infection or disease.


Assuntos
Infecções por Adenovirus Humanos , Adenovírus Humanos , Transplante de Células-Tronco Hematopoéticas , Criança , Humanos , Infecções por Adenovirus Humanos/diagnóstico , Reprodutibilidade dos Testes , Transplante Homólogo , Estudos de Coortes
4.
medRxiv ; 2024 Apr 07.
Artigo em Inglês | MEDLINE | ID: mdl-38633788

RESUMO

Study Objectives: The study aimed to investigate sex differences in the relationship between sleep quality (self-report and objective) and cognitive function across three domains (executive function, verbal memory, and attention) in older adults. Methods: We analyzed cross-sectional data from 207 participants with normal cognition or mild cognitive impairment (89 males and 118 females) aged over 60. The relationship between sleep quality and cognitive performance was estimated using generalized additive models. Objective sleep was measured with the GT9X Link Actigraph, and self-reported sleep was measured with the Pittsburgh Sleep Quality Index. Results: We found that females exhibited stable performance of executive function with up to about 400 minutes of total sleep time, with significant declines in performance (p = 0.02) when total sleep time was longer. Additionally, a longer total sleep time contributed to lower verbal memory in a slightly non-linear manner (p = 0.03). Higher self-reported sleep complaints were associated with poorer executive function in females with normal cognition (p = 0.02). In males, a positive linear relationship emerged between sleep efficiency and executive function (p = 0.04), while self-reported sleep was not associated with cognitive performance in males with normal cognition. Conclusions: Our findings suggest that the relationships between sleep quality and cognition differ between older males and females, with executive function being the most influenced by objective and self-reported sleep. Interventions targeting sleep quality to mitigate cognitive decline in older adults may need to be tailored according to sex, with distinct approaches for males and females.

5.
J Chem Phys ; 160(16)2024 Apr 28.
Artigo em Inglês | MEDLINE | ID: mdl-38656446

RESUMO

This work describes optimizations of N-electron system wave functions by means of the simulated annealing technique within the doubly occupied configuration interaction framework. Using that technique, we minimize the energy variance of a Hamiltonian, providing determinations of wave functions corresponding to ground or excited states in an identical manner. The procedure that allows us to determine electronic spectra can be performed using treatments of restricted or unrestricted types. The results found in selected systems, described in terms of energy, spin, and wave function, are analyzed, showing the performance of each method. We also compare these results with those arising from more traditional approaches that minimize the energy, in both restricted and unrestricted versions, and with those obtained from the full configuration interaction treatment.

6.
Cell Rep ; 43(3): 113897, 2024 Mar 26.
Artigo em Inglês | MEDLINE | ID: mdl-38493478

RESUMO

Chromatin structure is regulated through posttranslational modifications of histone variants that modulate transcription. Although highly homologous, histone variants display unique amino acid sequences associated with specific functions. Abnormal incorporation of histone variants contributes to cancer initiation, therapy resistance, and metastasis. This study reports that, among its biologic functions, histone H3.1 serves as a chromatin redox sensor that is engaged by mitochondrial H2O2. In breast cancer cells, the oxidation of H3.1Cys96 promotes its eviction and replacement by H3.3 in specific promoters. We also report that this process facilitates the opening of silenced chromatin domains and transcriptional activation of epithelial-to-mesenchymal genes associated with cell plasticity. Scavenging nuclear H2O2 or amino acid substitution of H3.1(C96S) suppresses plasticity, restores sensitivity to chemotherapy, and induces remission of metastatic lesions. Hence, it appears that increased levels of H2O2 produced by mitochondria of breast cancer cells directly promote redox-regulated H3.1-dependent chromatin remodeling involved in chemoresistance and metastasis.


Assuntos
Neoplasias da Mama , Histonas , Humanos , Feminino , Histonas/metabolismo , Cromatina , Peróxido de Hidrogênio/farmacologia , Peróxido de Hidrogênio/metabolismo , Resistência a Múltiplos Medicamentos , Neoplasias da Mama/genética
7.
Contemp Clin Trials ; 138: 107466, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38331381

RESUMO

Hypertension control remains poor. Multiple barriers at the level of patients, providers, and health systems interfere with implementation of hypertension guidelines and effective lowering of BP. Some strategies such as self-measured blood pressure (SMBP) and remote management by pharmacists are safe and effectively lower BP but have not been effectively implemented. In this study, we combine such evidence-based strategies to build a remote hypertension program and test its effectiveness and implementation in large health systems. This randomized, controlled, pragmatic type I hybrid implementation effectiveness trial will examine the virtual collaborative care clinic (vCCC), a hypertension program that integrates automated patient identification, SMBP, remote BP monitoring by trained health system pharmacists, and frequent patient-provider communication. We will randomize 1000 patients with uncontrolled hypertension from two large health systems in a 1:1 ratio to either vCCC or control (usual care with education) groups for a 2-year intervention. Outcome measures including BP measurements, cognitive function, and a symptom checklist will be completed during study visits. Other outcome measures of cardiovascular events, mortality, and health care utilization will be assessed using Medicare data. For the primary outcome of proportion achieving BP control (defined as systolic BP < 130 mmHg) in the two groups, we will use a generalized linear mixed model analysis. Implementation outcomes include acceptability and feasibility of the program. This study will guide implementation of a hypertension program within large health systems to effectively lower BP.


Assuntos
Hipertensão , Medicare , Idoso , Humanos , Pressão Sanguínea , Determinação da Pressão Arterial , Atenção à Saúde , Hipertensão/diagnóstico , Hipertensão/terapia , Estados Unidos
9.
J Pediatric Infect Dis Soc ; 13(3): 159-185, 2024 Mar 19.
Artigo em Inglês | MEDLINE | ID: mdl-38339996

RESUMO

BACKGROUND: Since November 2019, the SARS-CoV-2 pandemic has created challenges for preventing and managing COVID-19 in children and adolescents. Most research to develop new therapeutic interventions or to repurpose existing ones has been undertaken in adults, and although most cases of infection in pediatric populations are mild, there have been many cases of critical and fatal infection. Understanding the risk factors for severe illness and the evidence for safety, efficacy, and effectiveness of therapies for COVID-19 in children is necessary to optimize therapy. METHODS: A panel of experts in pediatric infectious diseases, pediatric infectious diseases pharmacology, and pediatric intensive care medicine from 21 geographically diverse North American institutions was re-convened. Through a series of teleconferences and web-based surveys and a systematic review with meta-analysis of data for risk factors, a guidance statement comprising a series of recommendations for risk stratification, treatment, and prevention of COVID-19 was developed and refined based on expert consensus. RESULTS: There are identifiable clinical characteristics that enable risk stratification for patients at risk for severe COVID-19. These risk factors can be used to guide the treatment of hospitalized and non-hospitalized children and adolescents with COVID-19 and to guide preventative therapy where options remain available.


Assuntos
COVID-19 , Doenças Transmissíveis , Criança , Adulto , Humanos , Adolescente , SARS-CoV-2 , Consenso , Fatores de Risco
10.
JAMA Netw Open ; 7(2): e2355727, 2024 Feb 05.
Artigo em Inglês | MEDLINE | ID: mdl-38363571

RESUMO

Importance: COVID-19 in pediatric patients with acute lymphoblastic leukemia or lymphoma (ALL/LLy) has not been described in detail and may affect chemotherapy administration and long-term outcomes. Objective: To describe the clinical presentation of COVID-19 and chemotherapy modifications in pediatric patients with ALL/LLy. Design, Setting, and Participants: This is a retrospective case series of patients at St Jude Children's Research Hospital and its affiliate sites with newly diagnosed ALL/LLy who were treated on the Total XVII protocol (NCT03117751) between March 30, 2020, and June 20, 2022. Participants included patients aged 1 to 18 years who were receiving protocol chemotherapy. Acute symptoms and chemotherapy modifications were evaluated for 60 days after the COVID-19 diagnosis, and viral clearance, adverse events, and second SARS-CoV-2 infections were followed up during the 27-month study period. Exposures: SARS-CoV-2; all patients were screened at least weekly and at symptom onset and/or after known exposure to SARS-CoV-2. Main Outcomes and Measures: Description of the spectrum of COVID-19 illness and chemotherapy modifications. Results: Of 308 pediatric patients, 110 (36%) developed COVID-19 at a median age of 8.2 (IQR, 5.3-14.5) years. Sixty-eight patients (62%) were male. Most patients were in the continuation/maintenance phase of chemotherapy (101 [92%]). Severe disease was rare (7 [6%]) but was associated with older age, higher white blood cell counts at ALL/LLy diagnosis, lower absolute lymphocyte counts at COVID-19 diagnosis, abnormal chest imaging findings, and SARS-CoV-2 reinfection. Rare but serious thrombotic events included pulmonary embolism and cerebral venous sinus thrombosis (n = 1 for each). No multisystem inflammatory syndrome in children or death was seen. SARS-CoV-2 reinfection occurred in 11 patients (10%) and was associated with older age and with receiving standard or high-risk vs low-risk ALL/LLy therapy. Chemotherapy interruptions occurred in 96 patients (87%) and were longer for patients with severe disease, SARS-CoV-2 reinfection, and/or a COVID-19 diagnosis during the pre-Omicron variant period vs the post-Omicron period (after December 27, 2021). Conclusions and Relevance: In this case series of COVID-19 in pediatric patients with ALL/LLy, severe COVID-19 was rare, but chemotherapy administration was affected in most patients. Long-term studies are needed to establish the outcomes of COVID-19 in this population.


Assuntos
COVID-19 , Linfoma , Leucemia-Linfoma Linfoblástico de Células Precursoras , Humanos , Masculino , Criança , Pré-Escolar , Adolescente , Feminino , COVID-19/complicações , COVID-19/epidemiologia , SARS-CoV-2 , Estudos Retrospectivos , Teste para COVID-19 , Reinfecção , Leucemia-Linfoma Linfoblástico de Células Precursoras/complicações , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamento farmacológico , Leucemia-Linfoma Linfoblástico de Células Precursoras/epidemiologia , Linfoma/complicações , Linfoma/epidemiologia
11.
Entropy (Basel) ; 26(2)2024 Jan 31.
Artigo em Inglês | MEDLINE | ID: mdl-38392378

RESUMO

Quantum-key-distribution (QKD) networks are gaining importance and it has become necessary to analyze the most appropriate methods for their long-distance interconnection. In this paper, four different methods of interconnecting remote QKD networks are proposed. The methods are used to link three different QKD testbeds in Europe, located in Berlin, Madrid, and Poznan. Although long-distance QKD links are only emulated, the methods used can serve as a blueprint for the secure interconnection of distant QKD networks in the future. Specifically, the presented approaches combine, in a transparent way, different fiber and satellite physical media, as well as common standards of key delivery interfaces. The testbed interconnections are designed to increase the security by utilizing multipath techniques and multiple hybridizations of QKD and post-quantum cryptography (PQC) algorithms.

13.
Ambio ; 53(5): 746-763, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38355875

RESUMO

Partnerships in marine monitoring combining Traditional Ecological Knowledge and western science are developing globally to improve our understanding of temporal changes in ecological communities that better inform coastal management practices. A fuller communication between scientists and Indigenous partners about the limitations of monitoring results to identify change is essential to the impact of monitoring datasets on decision-making. Here we present a 5-year co-developed case study from a fish monitoring partnership in northwest Australia showing how uncertainty estimated by Bayesian models can be incorporated into monitoring management indicators. Our simulation approach revealed there was high uncertainty in detecting immediate change over the following monitoring year when translated to health performance indicators. Incorporating credibility estimates into health assessments added substantial information to monitoring trends, provided a deeper understanding of monitoring limitations and highlighted the importance of carefully selecting the way we evaluate management performance indicators.


Assuntos
Conservação dos Recursos Naturais , Animais , Incerteza , Teorema de Bayes , Austrália
14.
Nat Commun ; 15(1): 1020, 2024 Feb 03.
Artigo em Inglês | MEDLINE | ID: mdl-38310097

RESUMO

Understanding the interactions between small, submicrometer-sized colloidal particles is crucial for numerous scientific disciplines and technological applications. In this study, we employ optical tweezers as a powerful tool to investigate these interactions. We utilize a full image reconstruction technique to achieve high precision in characterizing particle pairs that enable nanometer-scale measurement of their positions. This approach captures intricate details and provides a comprehensive understanding of the spatial arrangement between particles, overcoming previous limitations in resolution. Moreover, our research demonstrates that properly accounting for optical binding forces to determine the intrinsic interaction potential is vital. We employ a discrete dipole approximation approach to calculate optical binding potentials and achieve a good agreement between the calculated and observed binding forces. We incorporate the findings from these simulations into the assessment of the intrinsic interaction potentials and validate our methodology by using short-range depletion attraction induced by micelles as an example.

15.
Pediatr Infect Dis J ; 2024 Feb 12.
Artigo em Inglês | MEDLINE | ID: mdl-38359358

RESUMO

BACKGROUND: Continuous infusion vancomycin (CIV) may benefit children who are unable to achieve therapeutic concentrations with intermittent vancomycin dosing and may facilitate outpatient administration by alleviating the burden of frequent dosing intervals. Previous studies have used variable dosing regimens and steady-state concentration goals. The purpose of this study was to evaluate the total daily dose (TDD) of CIV required to achieve therapeutic steady-state concentrations of 15-25 µg/mL in pediatric hematology/oncology patients. METHODS: A single-center retrospective study was performed for patients treated with CIV from January 2017 to June 2019. The primary outcome was the TDD required to achieve therapeutic steady-state concentrations on CIV. Secondary outcomes included time to reach therapeutic steady-state concentrations, CIV indications and adverse events associated with CIV. RESULTS: Data were collected for 71 courses of CIV in 60 patients. Median patient age was 4 years (range: 0.4-20 years). The median TDD required to achieve initial therapeutic concentrations was 50.3 mg/kg/d (interquartile range: 38.8-59.2) and was further divided into age-based cohorts. TDD in mg/kg was significantly lower in the older cohort (P < 0.001), but there was no statistically significant difference between age-based cohorts with TDD in mg/m2 (P = 0.97). Median time to achieve first therapeutic concentration was 19.3 hours (range: 8.6-72.3 hours). The most common indication for CIV was ease of outpatient administration (69.0%). Acute kidney injury incidence was minimal (4.2%). CONCLUSIONS: CIV is associated with rapid attainment of target concentrations in pediatric hematology/oncology patients and is safe and well tolerated.

16.
Arch Cardiol Mex ; 2024 Feb 02.
Artigo em Espanhol | MEDLINE | ID: mdl-38306475

RESUMO

Objective: To assess the association between coronary collateral circulation and ventricular contractile function in patients with non-reperfused acute myocardial infarction. Method: A retrospective and descriptive clinical study was conducted on patients with ST-elevation myocardial infarction (STEMI) at a reference cardiovascular center, from January 2006 to December 2022. Coronary angiographies and echocardiograms were reviewed to evaluate coronary collateral circulation and ventricular function, respectively. Patients were divided into groups based on the presence of collateral circulation. Both groups were compared and mortality during the index hospitalization was analyzed. Results: Out of a total of 14,985 patients with acute coronary syndrome, 8134 (54.3%) had the diagnosis of STEMI. We excluded 12,880, leaving a total of 2105 non-reperfused STEMI patients who underwent coronary angiography, revealing lesions. There were more patients without collateral circulation: 1547 (73.5%) vs. 558 (26.5%) (p = 0.025). Patients without collateral circulation had a higher left ventricular ejection fraction (median of 47% vs. 42%; p < 0.001). Mortality in patients with collateral circulation was higher compared to those without it (11.6% vs. 9.8%; p = 0.225), but statistical significance was not reached. Conclusions: Non-reperfused STEMI patients did not show protection from collateral circulation when assessing left ventricular systolic function. We did not find a difference in mortality compared to the population without development of collateral circulation.


Objetivo: Evaluar la asociación entre la circulación coronaria colateral y la función contráctil ventricular en pacientes con infarto agudo de miocardio no reperfundido. Método: Estudio observacional descriptivo y retrospectivo en pacientes con infarto agudo de miocardio con elevación del segmento ST (IAMCEST) en un centro cardiovascular de referencia, de enero de 2006 a diciembre de 2022. Se analizaron las coronariografías y los ecocardiogramas para evaluar la circulación coronaria colateral y la función ventricular, respectivamente. Se dividieron en grupos de acuerdo con la presencia de circulación colateral. Se compararon ambos grupos y se analizó la mortalidad durante la hospitalización del evento índice. Resultados: De 14,985 pacientes con síndrome coronario agudo, 8134 (54.3%) presentaron IAMCEST. Se excluyeron 12,880, quedando así 2105 pacientes con IAMCEST no reperfundidos y sometidos a coronariografía, revelando lesiones. Hubo más pacientes sin circulación colateral: 1547 (73.5%) vs. 558 (26.5%) (p = 0.025). Los pacientes sin circulación colateral presentaron una mayor fracción de eyección ventricular izquierda (mediana del 47% vs. 42%; p < 0.001). La mortalidad en los pacientes con circulación colateral fue mayor que en los pacientes sin ella (11.6% vs. 9.8%; p = 0.225), pero no se alcanzó significancia estadística. Conclusiones: Los pacientes con IAMCEST no reperfundidos no presentaron protección por la circulación colateral al evaluar la función sistólica ventricular izquierda. No se encontró diferencia en la mortalidad en comparación con la población sin desarrollo de circulación colateral.

17.
Ther Adv Infect Dis ; 11: 20499361231222134, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38188359

RESUMO

Background: Histoplasmosis is the second most frequent granulomatous disease in patients treated with tumor necrosis factor (TNF)-α inhibitors, second only to tuberculosis. However, there is limited information about pre-therapy screening procedures and the need for preventive treatments for patients who will start immunobiologicals. Methods: This is a cohort study that evaluated the prevalence of histoplasmosis in asymptomatic HIV-negative patients before initiation of TNF-α inhibitors by testing for Histoplasma antigen in urine samples. The patients included completed a 180-day follow-up after the initiation of the biologics to assess the onset of symptoms suggestive of histoplasmosis. Results: From January 2021 to December 2022, 54 patients who were prescribed a TNF-α inhibitor agent for treating autoimmune diseases in centers in southern Brazil were included. In the screening before therapy, the prevalence of a positive urinary Histoplasma antigen test was 14.8%. None of the 54 patients developed histoplasmosis after 6 months of immunobiological therapy, including the eight patients who tested positive. Conclusion: The prevalence of Histoplasma capsulatum infection in chronic patients may be higher than expected, but the impact of latent infection in asymptomatic patients is still uncertain, including those starting treatment with immunobiological drugs such as TNF-α inhibitors. Our study did not identify risk factors for the diagnosis of disseminated histoplasmosis in this group, including a positive result in an antigen test performed before immunobiological therapy. To date, there is no evidence to recommend routine antigen-based screening or preventive therapy for histoplasmosis before initiating a TNF-α inhibitor.


Using a urine test for fungal infection to screen people without symptoms who are about to start taking immunobiologic medications This study looked at the prevalence of histoplasmosis, a fungal infection, in asymptomatic patients who were about to start treatment with TNF-α inhibitors, which are medications used for autoimmune diseases. The researchers tested urine samples for Histoplasma antigen before the patients started the treatment and followed them for 180 days after starting the medication to see if they developed any symptoms of histoplasmosis. The study included 54 patients in southern Brazil, and they found that 14.8% of the patients tested positive for the Histoplasma antigen before starting the treatment. However, none of the patients, including those who tested positive, developed histoplasmosis during the 6-month follow-up. The researchers concluded that histoplasmosis infection may be more common in these patients than previously thought, but it's still not clear if asymptomatic patients with a positive antigen test will develop the infection when starting TNF-α inhibitor treatment. The study did not find any specific risk factors for developing histoplasmosis in this group of patients, and based on their findings, they did not recommend routine screening or preventive therapy for histoplasmosis before starting TNF-α inhibitor treatment.

18.
Life (Basel) ; 14(1)2024 Jan 08.
Artigo em Inglês | MEDLINE | ID: mdl-38255712

RESUMO

It has been reported that hyaluronic acid (HA) with a 35 kDa molecular weight (HA35) acts biologically to protect tissue from injury, but its biological properties are not yet fully characterized. This study aimed to evaluate the cellular effects and biodistribution of HA35 compared to HA with a 1600 kDa molecular weight (HA1600). We assessed the effects of HA35 and HA1600 on cell migration, NO and ROS generation, and gene expression in cultured macrophages, microglia, and lymphocytes. HA35 was separately radiolabeled with 99mTc and 125I and administered to C57BL/6J mice for in vivo biodistribution imaging. In vitro studies indicated that HA35 and HA1600 similarly enhanced cell migration through HA receptor binding mechanisms, reduced the generation of NO and ROS, and upregulated gene expression profiles related to cell signaling pathways in immune cells. HA35 showed a more pronounced effect in regulating a broader range of genes in macrophages and microglia than HA1600. Upon intradermal or intravenous administration, radiolabeled HA35 rapidly accumulated in the liver, spleen, and lymph nodes. In conclusion, HA35 not only exhibits effects on cellular bioactivity comparable to those of HA1600 but also exerts biological effects on a broader range of immune cell gene expression. The findings herein offer valuable insights for further research into the therapeutic potential of HA35 in inflammation-mediated tissue injury.

19.
Ann Am Thorac Soc ; 21(2): 296-307, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-37938917

RESUMO

Rationale: Randomized trials have shown inconsistent cardiovascular benefits from obstructive sleep apnea (OSA) therapy. Intermittent hypoxemia can increase both sympathetic nerve activity and loop gain ("ventilatory instability"), which may thus herald cardiovascular treatment benefit. Objectives: To test the hypothesis that loop gain predicts changes in 24-hour mean blood pressure (MBP) in response to OSA therapy and compare its predictive value against that of other novel biomarkers. Methods: The HeartBEAT (Heart Biomarker Evaluation in Apnea Treatment) trial assessed the effect of 12 weeks of continuous positive airway pressure (CPAP) versus oxygen versus control on 24-hour MBP. We measured loop gain and hypoxic burden from sleep tests and identified subjects with a sleepy phenotype using cluster analysis. Associations between biomarkers and 24-h MBP were assessed in the CPAP/oxygen arms using linear regression models adjusting for various covariates. Secondary outcomes and predictors were analyzed similarly. Results: We included 93 and 94 participants in the CPAP and oxygen arms, respectively. Overall, changes in 24-hour MBP were small, but interindividual variability was substantial (mean [standard deviation], -2 [8] and 1 [8] mm Hg in the CPAP and oxygen arms, respectively). Higher loop gain was significantly associated with greater reductions in 24-hour MBP independent of covariates in the CPAP arm (-1.5 to -1.9 mm Hg per 1-standard-deviation increase in loop gain; P ⩽ 0.03) but not in the oxygen arm. Other biomarkers were not associated with improved cardiovascular outcomes. Conclusions: To our knowledge, this is the first study suggesting that loop gain predicts blood pressure response to CPAP therapy. Eventually, loop gain estimates may facilitate patient selection for research and clinical practice. Clinical trial registered with www.clinicaltrials.gov (NCT01086800).


Assuntos
Apneia Obstrutiva do Sono , Humanos , Pressão Sanguínea , Apneia Obstrutiva do Sono/complicações , Polissonografia , Pressão Positiva Contínua nas Vias Aéreas , Hipóxia/complicações , Oxigênio , Biomarcadores
20.
medRxiv ; 2024 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-37546959

RESUMO

Background: Obesity is associated with obstructive sleep apnea (OSA) and cardiovascular risk. Positive airway pressure (PAP) is the first line treatment for OSA, but evidence on its beneficial effect on major adverse cardiovascular events (MACE) prevention is limited. Using claims data, the effects of PAP on mortality and incidence of MACE among Medicare beneficiaries with OSA were examined. Methods: A cohort of Medicare beneficiaries with ≥2 distinct OSA claims was defined from multi-state, state-wide, multi-year (2011-2020) Medicare fee-for-service claims data. Evidence of PAP initiation and utilization was based on PAP claims after OSA diagnosis. MACE was defined as a composite of myocardial infarction, heart failure, stroke, or coronary revascularization. Doubly robust Cox proportional hazards models with inverse probability of treatment weights estimated treatment effects controlling for sociodemographic and clinical factors. Results: Among 888,835 beneficiaries with OSA (median age 73 years; 43.9% women; median follow-up 1,141 days), those with evidence of PAP initiation (32.6%) had significantly lower all-cause mortality (HR [95%CI]: 0.53 [0.52-0.54]) and MACE incidence risk (0.90 [0.89-0.91]). Higher quartiles of annual PAP claims were progressively associated with lower mortality (Q2: 0.84 [0.81-0.87], Q3: 0.76 [0.74-0.79], Q4: 0.74 [0.72-0.77]) and MACE incidence risk (Q2: 0.92 [0.89-0.95], Q3: 0.89 [0.86-0.91], Q4: 0.87 [0.85-0.90]). Conclusion: PAP utilization was associated with lower all-cause mortality and MACE incidence among Medicare beneficiaries with OSA. Results might inform trials assessing the importance of OSA therapy towards minimizing cardiovascular risk and mortality in older adults.

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