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1.
Anesth Analg ; 2024 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-39405258

RESUMO

Congenital cardiac anesthesiologists practice in a unique environment with high risk for morbidity and mortality. Quality metrics can be used to focus clinical initiatives on evidence-based care and provide a target for local quality improvement measures. However, there has been no comprehensive review on appropriate quality metrics for congenital cardiac anesthesia to date. Members of the Quality and Safety Committee for the Congenital Cardiac Anesthesia Society proposed 31 possible candidate topics for metrics. Using a scoping review strategy, 3649 abstracts were reviewed with 30 articles meeting final criteria. Of these, 5 candidate metrics were unanimously proposed for local collection and national benchmarking efforts: use of a structured handover in the intensive care unit, use of an infection prevention bundle, use of blood conservation strategies, early extubation of cardiopulmonary bypass cases, and cardiac arrest under the care of a cardiac anesthesiologist. Many metrics were excluded due to a lack of primary data and perceived complexity beyond the scope of cardiac anesthesia practice. There is a need to develop more primary data including linking process measures with outcomes, developing risk-stratification for our patients, and collecting national data for benchmarking purposes.

2.
Int J Clin Pract ; 2024: 5877687, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38505696

RESUMO

Background: Over the last 25 years, clinical practice guidelines have emerged as a means to standardize and improve care. As pharmaceutical innovations develop, guidelines are updated to incorporate new interventions. However, the extent to which pharmacotherapies are represented as treatment options in guideline recommendations has not been well elucidated. This study aimed to quantify the role pharmacotherapy has played in clinical practice guidelines across a range of chronic diseases over the past 20 years. Methods: Clinical practice guidelines published from 2000 to 2021 were identified for five chronic diseases: ischemic heart disease (IHD), non-small cell lung cancer (NSCLC), chronic obstructive pulmonary disease (COPD), Alzheimer's disease (AD), and type 2 diabetes (T2D). Guidelines were reviewed and data on treatment recommendations were collected, including the type of intervention, line of therapy, and, for pharmacotherapies, year of regulatory approval and year of inclusion in guidelines. Results: In total, 92 clinical practice guidelines were reviewed. Among the 184 discrete recommended interventions across the five disease areas, 146 (79.3%) were pharmacotherapies, 21 (11.4%) were behavioral modifications, 6 (3.3%) were surgical interventions, and 11 (6%) were other interventions. Across guidelines, when a line of therapy was specified, behavioral modifications and pharmacotherapies were most frequently recommended as first-line interventions, whereas surgical interventions were more often recommended for subsequent lines of treatment. The time from regulatory approval of novel pharmacotherapies to inclusion in guideline recommendations varied considerably by disease area and geography. Conclusions: Across the reviewed disease areas, behavioral interventions and pharmacotherapies are shown to be critical components of clinical practice. Over the last 20 years, novel pharmaceutical innovations have been incorporated into clinical practice guideline recommendations; however, with varying speeds of adoption. Given the increasing pace of pharmacologic innovation, timely updates of clinical practice guidelines are critical to evolving the standard of care and practicing evidence-based medicine.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Diabetes Mellitus Tipo 2 , Neoplasias Pulmonares , Humanos , Diabetes Mellitus Tipo 2/tratamento farmacológico , Doença Crônica , Preparações Farmacêuticas
3.
Headache ; 63(4): 506-516, 2023 04.
Artigo em Inglês | MEDLINE | ID: mdl-36920123

RESUMO

OBJECTIVE: To characterize treatment decision-making processes and formalize consensus regarding key factors headache specialists consider in treatment decisions for patients with migraine, considering novel therapies. BACKGROUND: Migraine therapies have long been subject to binary classification, acute versus preventive, due to limitations of available drugs. The emergence of novel therapies that can be used more flexibly creates an opportunity to rethink this binary classification. To determine the role of these novel therapies in treatment, it is critical to understand whether existing guidelines reflect clinical practice and to establish consensus around factors driving management. METHODS: A three-round modified Delphi process was conducted with migraine clinical experts. Round 1 consisted of an online questionnaire; Round 2 involved an online discussion of aggregated Round 1 results; and Round 3 allowed participants to revise Round 1 responses, incorporating Round 2 insights. Questions elicited likelihood ratings (0 = highly unlikely to 100 = highly likely), rankings, and estimates on treatment decision-making. RESULTS: Nineteen experts completed three Delphi rounds. Experts strongly agreed on definitions for "acute" (median = 100, inter-quartile range [IQR] = 5) and "preventive" treatment (median = 90, IQR = 15), but noted a need for treatment customization for patients (median = 100, IQR = 6). Experts noted certain aspects of guidelines may no longer apply based on established tolerability and efficacy of newer acute and preventive agents (median = 91, IQR = 17). Further, experts agreed on a treatment category referred to as "situational prevention" (or "short-term prevention") for patients with reliable and predictable migraine triggers (median = 100, IQR = 10) or time-limited periods when headache avoidance is important (median = 100, IQR = 12). CONCLUSIONS: Using the modified Delphi method, a panel of migraine experts identified the importance of customizing treatment for people with migraine and the utility of "situational prevention," given the ability of new treatment options to meet this need and the potential to clinically identify patients and time periods when this approach would add value.


Assuntos
Transtornos de Enxaqueca , Humanos , Consenso , Transtornos de Enxaqueca/tratamento farmacológico , Técnica Delphi , Inquéritos e Questionários , Cefaleia
4.
J Physiol ; 600(22): 4939-4961, 2022 11.
Artigo em Inglês | MEDLINE | ID: mdl-36217719

RESUMO

We tested the hypothesis that N/OFQ neurones in the arcuate nucleus (N/OFQARC ) inhibit proopiomelanocortin (POMCARC ) neurones in a diet- and hormone-dependent manner to promote a more extensive rebound hyperphagia upon re-feeding following an 18 h fast. We utilized intact male or ovariectomized (OVX) female mice subjected to ad libitum-feeding or fasting conditions. N/OFQARC neurones under negative energy balance conditions displayed heightened sensitivity as evidenced by a decreased rheobase threshold, increased firing frequency, and increased burst duration and frequency compared to ad libitum-feeding conditions. Stimulation of N/OFQARC neurones more robustly inhibited POMCARC neurones under fasting conditions compared to ad libitum-feeding conditions. N/OFQARC inhibition of POMCARC neurones is hormone dependent as chemostimulation of N/OFQARC neurones from fasted males and OVX females produced a sizable outward current in POMCARC neurones. Oestradiol (E2 ) markedly attenuated the N/OFQ-induced POMCARC outward current. Additionally, N/OFQ tonically inhibits POMCARC neurones to a greater degree under fasting conditions than in ad libitum-feeding conditions as evidenced by the abrogation of N/OFQ-nociceptin opioid peptide (NOP) receptor signalling and inhibition of N/OFQ release via chemoinhibition of N/OFQARC neurones. Intra-arcuate nucleus application of N/OFQ further elevated the hyperphagic response and increased meal size during the 6 h re-feed period, and these effects were mimicked by chemostimulation of N/OFQARC neurones in vivo. E2 attenuated the robust N/OFQ-induced rebound hyperphagia seen in vehicle-treated OVX females. These data demonstrate that N/OFQARC neurones play a vital role in mitigating the impact of negative energy balance by inhibiting the excitability of anorexigenic neural substrates, an effect that is diminished by E2 in females. KEY POINTS: Nociceptin/orphanin FQ (N/OFQ) promotes increased energy intake and decreased energy expenditure under conditions of positive energy balance in a sex- and hormone-dependent manner. Here it is shown that under conditions of negative energy balance, i.e. fasting, N/OFQ inhibits anorexigenic proopiomelanocortin (POMC) neurones to a greater degree compared to homeostatic conditions due to fasting-induced hyperexcitability of N/OFQ neurones. Additionally, N/OFQ promotes a sustained increase in rebound hyperphagia and increase in meal size during the re-feed period following a fast. These results promote greater understanding of how energy balance influences the anorexigenic circuitry of the hypothalamus, and aid in understanding the neurophysiological pathways implicated in eating disorders promoting cachexia.


Assuntos
Estradiol , Pró-Opiomelanocortina , Masculino , Feminino , Camundongos , Animais , Pró-Opiomelanocortina/metabolismo , Estradiol/farmacologia , Peptídeos Opioides/farmacologia , Peptídeos Opioides/metabolismo , Metabolismo Energético , Hiperfagia , Nociceptina
5.
Future Oncol ; 18(30): 3419-3433, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-36098270

RESUMO

Background: Little is known about real-world outcomes for first-line and anti-PD-1 second-line treatment for advanced/metastatic esophageal squamous cell carcinoma (ESCC). Patients & methods: Retrospective data of advanced/metastatic ESCC patients treated between 2011 and 2021 were collected from Flatiron Health. Median duration of therapy (mDoT) and median overall survival (mOS) were evaluated for patients initiating first-line and anti-PD-1 second-line therapy. Results: Among patients receiving first-line therapy (n = 948), mDoT was 1.4 months and mOS was 16.0 months, with mOS of 16.0 and 18.0 months for the non-immunotherapy and immunotherapy cohorts, respectively. Among patients receiving anti-PD-1 second-line therapy (n = 60), mDoT was 5.7 months and mOS was 10.1 months. Conclusion: Patients with advanced/metastatic ESCC have short duration of therapy, and overall survival remains limited. This real-world study underscores the need for efficacious treatments for advanced/metastatic ESCC in the first- and second-line setting. Direct comparisons of emerging therapies in the real world are urgently needed.


Assuntos
Neoplasias Esofágicas , Carcinoma de Células Escamosas do Esôfago , Humanos , Carcinoma de Células Escamosas do Esôfago/tratamento farmacológico , Neoplasias Esofágicas/tratamento farmacológico , Estudos Retrospectivos , Resultado do Tratamento , Imunoterapia
6.
J Cardiothorac Vasc Anesth ; 36(12): 4347-4356, 2022 12.
Artigo em Inglês | MEDLINE | ID: mdl-36050214

RESUMO

OBJECTIVE: To address the current lack of specified data existing regarding the perioperative characteristics and outcomes in a novel patient population, which may bridge the current understanding of how patient characteristics and perioperative management may influence the postoperative hospital course before cardiac transplantation. DESIGN: A retrospective electronic chart review included all patients with failing single- ventricle (SV) physiology receiving ventricular assist device (VAD) support at a high-volume pediatric VAD center between April 5, 2010, and December 1, 2020, using institution-based electronic medical records for retrospective analysis. SETTING: At a single pediatric hospital. PARTICIPANTS: Fourteen pediatric patients with failing SV physiology receiving ventricular assist device therapy (SVAD). INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Preoperative, intraoperative, and postoperative patient demographic and medical data were obtained from prior inpatient progress notes, laboratory values, anesthetic records, cardiac catheterization reports, echocardiography reports, and postoperative surgical notes entered during inpatient encounters at the time of SVAD placement. Between April 5, 2010, and December 1, 2020, 16 VAD device implants supported 14 pediatric patients with failing SV physiology. Most patients presented with a preoperative diagnosis of hypoplastic left heart syndrome (N = 9, 64.3%). A total of 6 patients expired on VAD therapy (43%), 7 (50%) survived to receive a cardiac transplant, and 1 patient currently remains on device therapy. CONCLUSION: Although our institutional approach represents a single perspective, we anticipate that our experience institutional experience may prove helpful to others caring for peditric patients with single ventricle physiology undergoing ventricular assist device placement and promote collaborative efforts to improve their care.


Assuntos
Insuficiência Cardíaca , Transplante de Coração , Coração Auxiliar , Síndrome do Coração Esquerdo Hipoplásico , Humanos , Criança , Estudos Retrospectivos , Ecocardiografia , Insuficiência Cardíaca/cirurgia , Resultado do Tratamento
7.
Neuroendocrinology ; 111(1-2): 45-69, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-32028278

RESUMO

OBJECTIVE: We examined whether pituitary adenylate cyclase-activating polypeptide (PACAP) excites proopiomelanocortin (POMC) neurons via PAC1 receptor mediation and transient receptor potential cation (TRPC) channel activation. METHODS: Electrophysiological recordings were done in slices from both intact male and ovariectomized (OVX) female PACAP-Cre mice and eGFP-POMC mice. RESULTS: In recordings from POMC neurons in eGFP-POMC mice, PACAP induced a robust inward current and increase in conductance in voltage clamp, and a depolarization and increase in firing in current clamp. These postsynaptic actions were abolished by inhibitors of the PAC1 receptor, TRPC channels, phospholipase C, phosphatidylinositol-3-kinase, and protein kinase C. Estradiol augmented the PACAP-induced inward current, depolarization, and increased firing, which was abrogated by estrogen receptor (ER) antagonists. In optogenetic recordings from POMC neurons in PACAP-Cre mice, high-frequency photostimulation induced inward currents, depolarizations, and increased firing that were significantly enhanced by Gq-coupled membrane ER signaling in an ER antagonist-sensitive manner. Importantly, the PACAP-induced excitation of POMC neurons was notably reduced in obese, high-fat (HFD)-fed males. In vivo experiments revealed that intra-arcuate nucleus (ARC) PACAP as well as chemogenetic and optogenetic stimulation of ventromedial nucleus (VMN) PACAP neurons produced a significant decrease in energy intake accompanied by an increase in energy expenditure, effects blunted by HFD in males and partially potentiated by estradiol in OVX females. CONCLUSIONS: These findings reveal that the PACAP-induced activation of PAC1 receptor and TRPC5 channels at VMN PACAP/ARC POMC synapses is potentiated by estradiol and attenuated under conditions of diet-induced obesity/insulin resistance. As such, they advance our understanding of how PACAP regulates the homeostatic energy balance circuitry under normal and pathophysiological circumstances.


Assuntos
Núcleo Arqueado do Hipotálamo/fisiologia , Metabolismo Energético/fisiologia , Neurônios/fisiologia , Polipeptídeo Hipofisário Ativador de Adenilato Ciclase/fisiologia , Pró-Opiomelanocortina , Receptores de Polipeptídeo Hipofisário Ativador de Adenilato Ciclase/fisiologia , Canais de Potencial de Receptor Transitório/fisiologia , Animais , Núcleo Arqueado do Hipotálamo/efeitos dos fármacos , Fenômenos Eletrofisiológicos , Metabolismo Energético/efeitos dos fármacos , Feminino , Cobaias , Homeostase , Masculino , Camundongos , Camundongos Transgênicos , Neurônios/efeitos dos fármacos , Polipeptídeo Hipofisário Ativador de Adenilato Ciclase/genética , Polipeptídeo Hipofisário Ativador de Adenilato Ciclase/farmacologia , Receptores de Polipeptídeo Hipofisário Ativador de Adenilato Ciclase/efeitos dos fármacos , Canais de Potencial de Receptor Transitório/efeitos dos fármacos
8.
J Cardiovasc Magn Reson ; 23(1): 95, 2021 07 19.
Artigo em Inglês | MEDLINE | ID: mdl-34275477

RESUMO

BACKGROUND: Cardiac catheterization and cardiovascular magnetic resonance (CMR) imaging have distinct diagnostic roles in the congenital heart disease (CHD) population. Invasive CMR (iCMR) allows for a more thorough assessment of cardiac hemodynamics at the same time under the same conditions. It is assumed but not proven that iCMR gives an incremental value by providing more accurate flow quantification. METHODS: Subjects with CHD underwent real-time 1.5 T iCMR using a passive catheter tracking technique with partial saturation pulse of 40° to visualize the gadolinium-filled balloon, CMR-conditional guidewire, and cardiac structures simultaneously to aid in completion of right (RHC) and left heart catheterization (LHC). Repeat iCMR and catheterization measurements were performed to compare reliability by the Pearson (PCC) and concordance correlation coefficients (CCC). RESULTS: Thirty CHD (20 single ventricle and 10 bi-ventricular) subjects with a median age and weight of 8.3 years (2-33) and 27.7 kg (9.2-80), respectively,  successfully underwent iCMR RHC and LHC. No catheter related complications were encountered. Time taken for first pass RHC and LHC/aortic pull back was 5.1, and 2.9 min, respectively. Total success rate to obtain required data points to complete Fick principle calculations for all patients was 321/328 (98%). One patient with multiple shunts was an outlier and excluded from further analysis. The PCC for catheter-derived pulmonary blood flow (Qp) (0.89, p < 0.001) is slightly lower than iCMR-derived Qp (0.96, p < 0.001), whereas catheter-derived systemic blood flow (Qs) (0.62, p = < 0.001) was considerably lower than iCMR-derived Qs (0.94, p < 0.001). CCC agreement for Qp at baseline (C1-CCC = 0.65, 95% CI 0.41-0.81) and retested conditions (C2-CCC = 0.78, 95% CI 0.58-0.89) were better than for Qs at baseline (C1-CCC = 0.22, 95% CI - 0.15-0.53) and retested conditions (C2-CCC = 0.52, 95% CI 0.17-0.76). CONCLUSION: This study further validates hemodynamic measurements obtained via iCMR. iCMR-derived flows have considerably higher test-retest reliability for Qs. iCMR evaluations allow for more reproducible hemodynamic assessments in the CHD population.


Assuntos
Imageamento por Ressonância Magnética , Circulação Pulmonar , Cateterismo Cardíaco , Humanos , Espectroscopia de Ressonância Magnética , Valor Preditivo dos Testes , Reprodutibilidade dos Testes
9.
Ann Intern Med ; 173(10): 822-829, 2020 11 17.
Artigo em Inglês | MEDLINE | ID: mdl-32956597

RESUMO

DESCRIPTION: In June 2020, the U.S. Department of Veterans Affairs (VA) and U.S. Department of Defense (DoD) released a joint update of their clinical practice guideline for managing dyslipidemia to reduce cardiovascular disease risk in adults. This synopsis describes the major recommendations. METHODS: On 6 August to 9 August 2019, the VA/DoD Evidence-Based Practice Work Group (EBPWG) convened a joint VA/DoD guideline development effort that included clinical stakeholders and conformed to the Institute of Medicine's tenets for trustworthy clinical practice guidelines. The guideline panel developed key questions, systematically searched and evaluated the literature (English-language publications from 1 December 2013 to 16 May 2019), and developed 27 recommendations and a simple 1-page algorithm. The recommendations were graded by using the GRADE (Grading of Recommendations Assessment, Development and Evaluation) system. RECOMMENDATIONS: This synopsis summarizes key features of the guideline in 7 crucial areas: targeting of statin dose (not low-density lipoprotein cholesterol goals), additional tests for risk prediction, primary and secondary prevention, laboratory testing, physical activity, and nutrition.


Assuntos
Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Hiperlipidemias/tratamento farmacológico , Adesão à Medicação , Doenças Cardiovasculares/prevenção & controle , Dieta Mediterrânea , Exercício Físico , Humanos , Inibidores de Hidroximetilglutaril-CoA Redutases/administração & dosagem , Inibidores de Hidroximetilglutaril-CoA Redutases/efeitos adversos , Hipercolesterolemia/tratamento farmacológico , Hiperlipidemias/terapia , Guias de Prática Clínica como Assunto , Medição de Risco , Prevenção Secundária
10.
Int J Mol Sci ; 22(5)2021 Mar 08.
Artigo em Inglês | MEDLINE | ID: mdl-33800452

RESUMO

Energy homeostasis is regulated in coordinate fashion by the brain-gut axis, the homeostatic energy balance circuitry in the hypothalamus and the hedonic energy balance circuitry comprising the mesolimbcortical A10 dopamine pathway. Collectively, these systems convey and integrate information regarding nutrient status and the rewarding properties of ingested food, and formulate it into a behavioral response that attempts to balance fluctuations in consumption and food-seeking behavior. In this review we start with a functional overview of the homeostatic and hedonic energy balance circuitries; identifying the salient neural, hormonal and humoral components involved. We then delve into how the function of these circuits differs in males and females. Finally, we turn our attention to the ever-emerging roles of nociceptin/orphanin FQ (N/OFQ) and pituitary adenylate cyclase-activating polypeptide (PACAP)-two neuropeptides that have garnered increased recognition for their regulatory impact in energy homeostasis-to further probe how the imposed regulation of energy balance circuitry by these peptides is affected by sex and altered under positive (e.g., obesity) and negative (e.g., fasting) energy balance states. It is hoped that this work will impart a newfound appreciation for the intricate regulatory processes that govern energy homeostasis, as well as how recent insights into the N/OFQ and PACAP systems can be leveraged in the treatment of conditions ranging from obesity to anorexia.


Assuntos
Anorexia/metabolismo , Metabolismo Energético , Homeostase , Obesidade/metabolismo , Peptídeos Opioides/metabolismo , Polipeptídeo Hipofisário Ativador de Adenilato Ciclase/metabolismo , Caracteres Sexuais , Animais , Feminino , Humanos , Masculino , Nociceptina
11.
J Cardiovasc Magn Reson ; 22(1): 20, 2020 03 26.
Artigo em Inglês | MEDLINE | ID: mdl-32213193

RESUMO

BACKGROUND: Today's standard of care, in the congenital heart disease (CHD) population, involves performing cardiac catheterization under x-ray fluoroscopy and cardiac magnetic resonance (CMR) imaging separately. The unique ability of CMR to provide real-time functional imaging in multiple views without ionizing radiation exposure has the potential to be a powerful tool for diagnostic and interventional procedures. Limiting fluoroscopic radiation exposure remains a challenge for pediatric interventional cardiologists. This pilot study's objective is to establish feasibility of right (RHC) and left heart catheterization (LHC) during invasive CMR (iCMR) procedures at our institution in the CHD population. Furthermore, we aim to improve simultaneous visualization of the catheter balloon tip, MR-conditional guidewire, and cardiac/vessel anatomy during iCMR procedures. METHODS: Subjects with CHD were enrolled in a pilot study for iCMR procedures at 1.5 T with an MR-conditional guidewire. The CMR area is located adjacent to a standard catheterization laboratory. Using the interactive scanning mode for real-time control of the imaging location, a dilute gadolinium-filled balloon-tip catheter was used in combination with an MR-conditional guidewire to obtain cardiac saturations and hemodynamics. A recently developed catheter tracking technique using a real-time single-shot balanced steady-state free precession (bSSFP), flip angle (FA) 35-45°, echo time (TE) 1.3 ms, repetition time (TR) 2.7 ms, 40° partial saturation (pSAT) pre-pulse was used to visualize the gadolinium-filled balloon, MR-conditional guidewire, and cardiac structures simultaneously. MR-conditional guidewire visualization was enabled due to susceptibility artifact created by distal markers. Pre-clinical phantom testing was performed to determine the optimum imaging FA-pSAT combination. RESULTS: The iCMR procedure was successfully performed to completion in 31/34 (91%) subjects between August 1st, 2017 to December 13th, 2018. Median age and weight were 7.7 years and 25.2 kg (range: 3 months - 33 years and 8 - 80 kg). Twenty-one subjects had single ventricle (SV) anatomy: one subject was referred for pre-Glenn evaluation, 11 were pre-Fontan evaluations and 9 post-Fontan evaluations for protein losing enteropathy (PLE) and/or cyanosis. Thirteen subjects had bi-ventricular (BiV) anatomy, 4 were referred for coarctation of the aorta (CoA) evaluations, 3 underwent vaso-reactivity testing with inhaled nitric oxide, 3 investigated RV volume dimensions, two underwent branch PA stenosis evaluation, and the remaining subject was status post heart transplant. No catheter related complications were encountered. Average time taken for first pass RHC, LHC/aortic pull back, and to cross the Fontan fenestration was 5.2, 3.0, and 6.5 min, respectively. Total success rate to obtain required data points to complete Fick principle calculations for all patients was 331/337 (98%). Subjects were transferred to the x-ray fluoroscopy lab if further intervention was required including Fontan fenestration device closure, balloon angioplasty of pulmonary arteries/conduits, CoA stenting, and/or coiling of aortopulmonary (AP) collaterals. Starting with subject #10, an MR-conditional guidewire was used in all subsequent subjects (15 SV and 10 BiV) with a success rate of 96% (24/25). Real-time CMR-guided RHC (25/25 subjects, 100%), retrograde and prograde LHC/aortic pull back (24/25 subjects, 96%), CoA crossing (3/4 subjects, 75%) and Fontan fenestration test occlusion (2/3 subjects, 67%) were successfully performed in the majority of subjects when an MR-conditional guidewire was utilized. CONCLUSION: Feasibility for detailed diagnostic RHC, LHC, and Fontan fenestration test occlusion iCMR procedures in SV and BiV pediatric subjects with complex CHD is demonstrated with the aid of an MR-conditional guidewire. A novel real-time pSAT GRE sequence with optimized FA-pSAT angle has facilitated simultaneous visualization of the catheter balloon tip, MR-conditional guidewire, and cardiac/vessel anatomy during iCMR procedures.


Assuntos
Cateterismo Cardíaco/instrumentação , Cateteres Cardíacos , Cardiopatias Congênitas/diagnóstico , Imagem por Ressonância Magnética Intervencionista/instrumentação , Adolescente , Adulto , Criança , Pré-Escolar , Desenho de Equipamento , Estudos de Viabilidade , Feminino , Cardiopatias Congênitas/diagnóstico por imagem , Cardiopatias Congênitas/fisiopatologia , Cardiopatias Congênitas/terapia , Humanos , Lactente , Masculino , Imagens de Fantasmas , Projetos Piloto , Valor Preditivo dos Testes , Reprodutibilidade dos Testes , Adulto Jovem
12.
Heart Fail Clin ; 15(4): 497-507, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31472885

RESUMO

Heart failure (HF) is a significant cause of cardiovascular morbidity and mortality for women in the United States. There are clear sex-specific differences between men and women in etiology, disease progression, and outcomes. HF with preserved ejection fraction is the most common type of HF in women, with hypertensive heart disease playing a pivotal role in its etiology. The Practice Guidelines do not endorse sex-specific recommendations for standard medical therapy of HF management. Women are underrepresented in HF clinical trials, leading to a lacking evidence base supporting sex-specific therapy. Further studies are needed to evaluate targeted HF therapies in women.


Assuntos
Hipertensão , Progressão da Doença , Feminino , Insuficiência Cardíaca/etiologia , Insuficiência Cardíaca/fisiopatologia , Insuficiência Cardíaca/prevenção & controle , Humanos , Hipertensão/complicações , Hipertensão/fisiopatologia , Hipertensão/terapia , Fatores Sexuais , Volume Sistólico , Estados Unidos , Saúde da Mulher
13.
Molecules ; 23(2)2018 Feb 13.
Artigo em Inglês | MEDLINE | ID: mdl-29438314

RESUMO

An Gram negative strain of S. maltophilia, indigenous to environments contaminated by Cr(VI) and identified by biochemical methods and 16S rRNA gene analysis, reduced chromate by 100%, 98-99% and 92% at concentrations in the 10-70, 80-300, and 500 mg/L range, respectively at pH 7 and temperature 37 °C. Increasing concentrations of Cr(VI) in the medium lowered the growth rate but could not be directly correlated with the amount of Cr(VI) reduced. The strain also exhibited multiple resistance to antibiotics and tolerance and resistance to various heavy metals (Ni, Zn and Cu), with the exception of Hg. Hexavalent chromium reduction was mainly associated with the soluble fraction of the cell evaluated with crude cell-free extracts. A protein of molecular weight around 25 kDa was detected on SDS-PAGE gel depending on the concentration of hexavalent chromium in the medium (0, 100 and 500 mg/L). In silico analysis in this contribution, revealed the presence of the chromate reductase gene ChrR in S. maltophilia, evidenced through a fragment of around 468 bp obtained experimentally. High Cr(VI) concentration resistance and high Cr(VI) reducing ability of the strain make it a suitable candidate for bioremediation.


Assuntos
Proteínas de Bactérias/metabolismo , Cromo/metabolismo , Farmacorresistência Bacteriana Múltipla/genética , Oxirredutases/metabolismo , RNA Ribossômico 16S/genética , Stenotrophomonas maltophilia/efeitos dos fármacos , Antibacterianos/farmacologia , Proteínas de Bactérias/genética , Proteínas de Bactérias/isolamento & purificação , Biodegradação Ambiental , Cromo/farmacologia , Cobre/metabolismo , Cobre/farmacologia , Tolerância a Medicamentos , Expressão Gênica , Concentração de Íons de Hidrogênio , Testes de Sensibilidade Microbiana , Peso Molecular , Níquel/metabolismo , Níquel/farmacologia , Oxirredução , Oxirredutases/genética , Oxirredutases/isolamento & purificação , Filogenia , Stenotrophomonas maltophilia/classificação , Stenotrophomonas maltophilia/enzimologia , Stenotrophomonas maltophilia/genética , Temperatura , Zinco/metabolismo , Zinco/farmacologia
15.
J Nurse Pract ; 17(3): 265-266, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-36569404
16.
J Neuroendocrinol ; 36(1): e13357, 2024 01.
Artigo em Inglês | MEDLINE | ID: mdl-38056947

RESUMO

This study furthers the investigation of how pituitary adenylate cyclase activating polypeptide (PACAP) and the PAC1 receptor (PAC1R) regulate the homeostatic energy balance circuitry. We hypothesized that apoptotic ablation of PACAP neurones in the hypothalamic ventromedial nucleus (VMN) would affect both energy intake and energy expenditure. We also hypothesized that selective PAC1R knockdown would impair the PACAP-induced excitation in anorexigenic proopiomelanocortin (POMC) neurones and inhibition of orexigenic neuropeptide Y (NPY)/agouti-related peptide (AgRP) neurones in the hypothalamic arcuate nucleus (ARC). The results show CASPASE-3-induced ablation of VMN PACAP neurones leads to increased energy intake and meal frequency as well as decreased energy expenditure in lean animals. The effects were more robust in obese males, whereas we saw the opposite effects in obese females. We then utilized visualized whole-cell patch clamp recordings in hypothalamic slices. PAC1R knockdown in POMC neurones diminishes the PACAP-induced depolarization, increase in firing, decreases in energy intake and meal size, as well as increases in CO2 production and O2 consumption. Similarly, the lack of expression of the PAC1R in NPY/AgRP neurones greatly attenuates the PACAP-induced hyperpolarization, suppression of firing, decreases in energy intake and meal frequency, as well as increases in energy expenditure. The PACAP response in NPY/AgRP neurones switched from predominantly inhibitory to excitatory in fasted animals. Finally, the anorexigenic effect of PACAP was potentiated when oestradiol was injected into the ARC in ovariectomized females. This study demonstrates the critical role of anorexigenic VMN PACAP neurones and the PAC1R in exciting POMC and inhibiting NPY/AgRP neurons to control homeostatic feeding.


Assuntos
Polipeptídeo Hipofisário Ativador de Adenilato Ciclase , Pró-Opiomelanocortina , Animais , Masculino , Feminino , Pró-Opiomelanocortina/metabolismo , Polipeptídeo Hipofisário Ativador de Adenilato Ciclase/metabolismo , Neuropeptídeo Y/metabolismo , Proteína Relacionada com Agouti/metabolismo , Receptores de Polipeptídeo Hipofisário Ativador de Adenilato Ciclase/metabolismo , Núcleo Hipotalâmico Ventromedial/metabolismo , Núcleo Arqueado do Hipotálamo/metabolismo , Dieta , Neurônios/metabolismo , Obesidade/metabolismo
17.
Am Surg ; 90(9): 2212-2216, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-38768947

RESUMO

Background: In the setting of limited funding and high expectations for quality care, safety net hospitals play a crucial role in treating pediatric trauma patients. This study aimed to compare outcomes and hospitalization costs of pediatric trauma patients in safety net hospitals across the United States. Methods: The Nationwide Readmissions Database for 2016-2020 was queried for all patients under the age of 18 years hospitalized for traumatic injury. Patients admitted to safety net hospitals were propensity matched 1:1 to all other patients. The primary outcome was mortality. The secondary outcomes were readmission within 1-year, mean length of stay (LOS), total charges, and total hospitalization costs including readmissions. Results: There were 176,325 patients meeting inclusion criteria, and 30,869 were admitted to safety net hospitals. All safety net patients were successfully matched across predictors, and 61,738 patients were included. The overall mortality rate was 1.4% (n = 834), and the mortality risk was similar in safety net hospitals (OR 1.11 [.96-1.27] P = .15). The overall readmission rate, mean LOS, and mean total cost were similar for safety net hospitals when compared to all hospitals. However, the overall mean total charge was $78,724 (±$224,884) and was lower in safety net hospitals ($76,575 [±$198,342], P = .02). Discussion: Safety net hospitals deliver comparable outcomes as other health care facilities when caring for pediatric trauma patients. Notably, these hospitals appear to undercharge for their services, despite incurring similar costs in the process. These results shed light on the resilience of safety net hospitals in delivering quality and cost-effective care.


Assuntos
Custos Hospitalares , Tempo de Internação , Readmissão do Paciente , Provedores de Redes de Segurança , Ferimentos e Lesões , Humanos , Provedores de Redes de Segurança/economia , Criança , Masculino , Estados Unidos , Feminino , Adolescente , Readmissão do Paciente/estatística & dados numéricos , Readmissão do Paciente/economia , Ferimentos e Lesões/terapia , Ferimentos e Lesões/mortalidade , Ferimentos e Lesões/economia , Pré-Escolar , Tempo de Internação/estatística & dados numéricos , Lactente , Custos Hospitalares/estatística & dados numéricos , Estudos Retrospectivos , Bases de Dados Factuais
18.
Appl Clin Inform ; 15(1): 129-144, 2024 01.
Artigo em Inglês | MEDLINE | ID: mdl-38354837

RESUMO

BACKGROUND: Given the inequities in access to health care resources like COVID-19 vaccination, health systems should carefully consider how to reach underrepresented groups. Reflecting on vaccine rollout efforts holds insight on the role of community engagement and informatics support in promoting health equity. OBJECTIVES: This study aimed to assess the effectiveness of four outreach strategies deployed by University of Washington (UW) Medicine in improving vaccine equity over traditional vaccine scheduling online or by phone, we report on appointment scheduling and completion of appointments (i.e., vaccine administration) through (1) automated outreach to individuals from underrepresented groups, (2) temporary "pop-up" clinics in neighborhoods highly impacted by COVID-19, (3) vulnerable population clinics, and (4) mobile vaccine vans. METHODS: We conducted a 6-month retrospective analysis of electronic health records (EHR) to describe the sociodemographic characteristics of individuals who scheduled appointments using the outreach strategies and characteristics associated with a greater likelihood of vaccine administration based on appointment completion. To help explain trends in the EHR data, we engaged 10 health system leaders and staff who spearheaded the outreach strategies in follow-up conversations to identify qualitative insights into what worked and why. RESULTS: Compared with traditional scheduling, all outreach strategies except vulnerable population clinics had higher vaccine appointment completion rates, including automated outreach (N = 3,734 [94.7%], p < 0.001), pop-up clinics (N = 4,391 [96.0%], p < 0.001), and mobile vans (N = 4,198 [99.1%], p < 0.001); and lower cancellation rates, including automated outreach (N = 166 [1.1%], p < 0.001), pop-up clinics (N = 155 [0.6%], p < 0.001), and mobile vans (N = 0 [0%], p < 0.001). Qualitative insights emphasized ongoing community partnerships and information resources in successful outreach. CONCLUSION: Vaccine equity outreach strategies improved the proportion of patients who scheduled and completed vaccination appointments among populations disproportionately impacted by COVID-19. Engaging community partners and equity-focused informatics tools can facilitate outreach. Lessons from these outreach strategies carry practical implications for health systems to amplify their health equity efforts.


Assuntos
COVID-19 , Vacinas , Humanos , Vacinas contra COVID-19 , Estudos Retrospectivos , COVID-19/epidemiologia , COVID-19/prevenção & controle , Informática
19.
Am Surg ; 90(8): 2101-2103, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38565168

RESUMO

Venous thromboembolism (VTE) in pediatric trauma patients is under-investigated. The purpose of this study was to perform an evaluation of the risk factors for VTE after pediatric trauma, including readmissions across the United States. The Nationwide Readmissions Database for 2016-2020 was queried for all patients under the age of 18 years admitted for trauma. 276 670 patients were identified; 2063 (.8%) were diagnosed with VTE. Among those with VTE, 300 (15%) were identified during a readmission. Higher rates of VTE were seen in ages 15-17 years (n = 1,294, 1.3%, P < .001), penetrating injuries (n = 478, .9%, P < .001), and assault (n = 271, 2.7%, P < .001). The strongest risk factor for VTE was prolonged mechanical ventilation (OR 5.5 [4.9-6.3] P < .001). Our study found that a significant portion of post-traumatic VTE in children and teenagers occur during readmissions. A deeper understanding of the risk factors outlined here can guide enhanced clinical protocols, ensuring early detection and prevention of this complication.


Assuntos
Readmissão do Paciente , Tromboembolia Venosa , Ferimentos e Lesões , Humanos , Adolescente , Tromboembolia Venosa/epidemiologia , Tromboembolia Venosa/etiologia , Criança , Feminino , Masculino , Estados Unidos/epidemiologia , Fatores de Risco , Readmissão do Paciente/estatística & dados numéricos , Pré-Escolar , Ferimentos e Lesões/complicações , Ferimentos e Lesões/epidemiologia , Lactente , Bases de Dados Factuais , Estudos Retrospectivos , Respiração Artificial/estatística & dados numéricos
20.
Am Surg ; 90(9): 2249-2252, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-38871348

RESUMO

BACKGROUND: The rise of value-based purchasing has led to decreased compensation for hospital-acquired conditions, including surgical site infections (SSI). This study aims to assess the risk factors for SSI in children and teenagers undergoing gastrointestinal surgery across US hospitals. METHODS: The 2018-2020 Nationwide Readmissions Database was queried for patients undergoing gastrointestinal surgery under the age of 18. The primary outcome was SSI during index admission or readmission within a year. Comparison groups were elective, trauma, and emergent surgery based on anatomic location and urgency. Univariable comparison used chi-squared tests for relevant variables. Confounders were addressed through multivariable logistic regression with significant variables from univariable analysis. RESULTS: 113 108 total patients met the study criteria. The SSI rate during admission or readmission was 2.9% (n = 3254). Infections during admission and readmission were 1.4% (n = 1560) and 1.5% (n = 1694), respectively. The most common site was organ space (48.6%, n = 1657). Increased infection risk was associated with trauma (OR 1.80 [1.51-2.16] P < .001), emergency surgery (OR 1.31 [1.17-1.47] P < .001), large bowel surgery (OR 2.78 [2.26-3.43] P < .001), and those with three or more comorbidities (OR 2.03 [1.69-2.45] P < .001). Investor-owned hospitals (OR .65 [.56-.76] P < .001) and highest quartile income (OR .80 [.73-.88] P < .001) were associated with decreased infection risk. CONCLUSIONS: Pediatric patients undergoing gastrointestinal surgery face an elevated risk of SSI, especially in trauma and emergency surgeries, particularly with multiple comorbidities. Meanwhile, a reduced risk is observed in high-income and investor-owned hospital settings. Hospitals and surgeons caring for high risk patients should advocate for risk adjustment in value-based payment systems.


Assuntos
Comorbidade , Procedimentos Cirúrgicos do Sistema Digestório , Readmissão do Paciente , Fatores Socioeconômicos , Infecção da Ferida Cirúrgica , Humanos , Infecção da Ferida Cirúrgica/epidemiologia , Criança , Adolescente , Masculino , Feminino , Pré-Escolar , Fatores de Risco , Procedimentos Cirúrgicos do Sistema Digestório/efeitos adversos , Readmissão do Paciente/estatística & dados numéricos , Estados Unidos/epidemiologia , Lactente , Estudos Retrospectivos
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