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For the approval of a drug, the stability data must be submitted to regulatory authorities. Such analyses are often time-consuming and cost-intensive. Forced degradation studies are mainly carried out under harsh conditions in the dissolved state, often leading to extraneous degradation profiles for a solid drug. Oxidative mechanochemical degradation offers the possibility of generating realistic degradation profiles. In this study, a sustainable mechanochemical procedure is presented for the degradation of five active pharmaceutical ingredients (APIs) from the sartan family: losartan potassium, irbesartan, valsartan, olmesartan medoxomil, and telmisartan. High-resolution mass spectrometry enabled the detection of impurities already present in untreated APIs and allowed the elucidation of degradation products. Significant degradation profiles could already be obtained after 15-60 min of ball milling time. Many of the identified degradation products are described in the literature and pharmacopoeias, emphasizing the significance of our results and the applicability of this approach to predict degradation profiles for drugs in the solid state.
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Bencimidazoles , Compuestos de Bifenilo , Losartán , Telmisartán , Tetrazoles , Valsartán , Bencimidazoles/química , Bencimidazoles/análisis , Tetrazoles/química , Telmisartán/química , Valsartán/química , Losartán/química , Losartán/análisis , Compuestos de Bifenilo/química , Irbesartán/química , Irbesartán/análisis , Imidazoles/química , Benzoatos/química , Valina/química , Valina/análisis , Solventes/química , Estabilidad de MedicamentosRESUMEN
This paper details the development and validation of a temperature sensing methodology using an un-trimmed oscillator-based integrated sensor implemented in the 0.18-µm SOI XFAB process, with a focus on thermal monitoring in system-on-chip (SoC) based DC-DC converters. Our study identifies a quadratic relationship between the oscillator output frequency and temperature, which forms the basis of our proposed calibration mechanism. This mechanism aims at mitigating process variation effects, enabling accurate temperature-to-frequency mapping. Our research proposes and characterizes several trimming-free calibration techniques, covering a spectrum from zero to thirty-one frequency-temperature measurement points. Notably, the Corrected One-Point calibration method, requiring only a single ambient temperature measurement, emerges as a practical solution that removes the need for a temperature chamber. This method, after adjustment, successfully reduces the maximum error to within ±2.95 °C. Additionally, the Two-Point calibration method demonstrates improved precision with a maximum positive error of +1.56 °C at -15 °C and a maximum negative error of -3.13 °C at +10 °C (R2 value of 0.9958). The Three-Point calibration method performed similarly, yielding an R2 value of 0.9956. The findings of this study indicate that competitive results in temperature sensor calibration can be achieved without circuit trimming, offering a viable alternative or a complementary approach to traditional trimming techniques.
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Copper(I)-catalyzed domino reactions of 2-azido sulfoximines with 1-iodoalkynes yield fused triazolyl-containing benzothiadiazine-1-oxides. The protocol features the synthesis of two fused heterocyclic rings in one step with good to excellent yields and a broad functional group tolerance. Detailed mechanistic investigations indicate that a copper π-complex initiates a cycloaddition and oxidative C-N coupling reaction sequence. The results suggest an interrupted domino process involving an iodinated triazole as a key intermediate.
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An electro-mechanochemical protocol for the synthesis of vinylic sulfoximines has been developed. Utilising mechanochemically strained BaTiO3 nanoparticles, the catalytic active system is generated in situ by the reduction of copper(II) chloride. Various combinations of electron-donating and -withdrawing groups are tolerated, and the approach leads to products with difunctionalised double bonds in good to excellent yields. Attempts to add a sulfoximidoyl chloride to an alkyne proved difficult. Additions of a sulfonyl iodide to allenes and alkynes proceeded smoothly in the presence of silica gel without the need for activation by a piezoelectric material.
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Background: This great pandemic of COVID-19 has been a unique stressor that affected all communities in 2020. This study aims to examine the prevalence of anxiety and depression due to the COVID-19 pandemic in Saudi Arabia and to study the emotional cognition scale in the Kingdom of Saudi Arabia (KSA) in relation to the COVID-19 pandemic. Methodology: A descriptive cross-sectional study was conducted on 857 inhabitants randomly selected from the 13 administrative regions of Saudi Arabia, using a validated self-administrated questionnaire comprising six sections. The collected data were summarized and analyzed. Results: Among the majority of the studied participants, 377 (44.0%) were aged from 35 to less than 50 y. There were 489 (57.1%) females and 368 (42.9%) males, 616 (71.9%) Saudi nationals, 715 (83.4%) university-educated or postgraduate, 619 (72.2%) unmarried and 238 (27.8%) married, and 663 (77.4%) living in areas under partial lockdown. The resultant elevated total depression score was statistically significant (p<0.05) for the following: participants younger than 35y, females, Saudis, those with lower education levels, those who were married, students, those with work suspension during the COVID-19 pandemic, and amongst those who experienced complete lockdown. Among the majority of the studied participants, 355 (41.2%) showed mild depression, and 281(32.6) showed moderate anxiety, and were in the growth zone. In addition, the elevated total anxiety score was statistically significant (p<0.05) amongst the following; younger participants, females, Saudi nationals, those with lower educational levels, those who were unmarried, students, those with telework, and those with no curfew. Conclusion: The adverse mental health effects were more prevalent among particular groups of the population, such as females, adults under 35 years old, students, those with lower educational attainments, and those suffering from chronic illnesses. Anxiety was significantly correlated with depression. The practice of preventive measures, e.g., wearing masks, and social distancing to prevent the spread of COVID-19, may have had psychological benefits during the pandemic. Summary: We assessed the mental health status in Saudi Arabia during the first wave of the COVID-19 pandemic. Mild depression and moderate anxiety were prevalent problems, with many determinants and interrelations. Fear was the most infectious emotion, while happiness was the highest.
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BACKGROUND: On surface electrocardiographic (ECGs), it is difficult to differentiate Ito -mediated J waves, a repolarization phenomenon seen in J wave syndromes (JWS) from terminal QRS deflections that mimic J waves (pseudo J waves) in intraventricular conduction delay (IVCD), an abnormality in depolarization. We hypothesize that the difference between the "maximum QRS duration" inclusive of J point or terminal QRS deflections and the minimum QRS duration identified across a 12-lead ECG is significantly larger in Ito -mediated J waves, and can serve as a marker to make this distinction. METHODS: A retrospective analysis was performed on adults with ECGs consisting of one of the four following manifestations: J waves associated with hypothermia and early repolarization, and pseudo J waves associated with right bundle branch block (RBBB) and non-specific intraventricular conduction delay (NS-IVCD). All ECGs were assessed individually and the maximum and minimum discrete QRS deflections on 12-lead tracings, defined as "QRSmax " and QRSmin , were identified. The difference between "QRSmax " and QRSmin , designated as ∆QRS, was calculated and compared across the studied populations. RESULTS: A total of 60 patients consisting of 15 patients in each arm were included in the study. ΔQRS was significantly larger in the hypothermia and early repolarization groups, compared to RBBB and NS-IVCD (p < .0001), with the following mean ∆QRS: hypothermia 54.3 ± 13.7 ms, early repolarization pattern 47.3 ± 15.3 ms, RBBB 19.3 ± 6.5 ms, and NS-IVCD 16.0 ± 6.6 ms. CONCLUSION: ∆QRS may serve as a reliable ECG parameter for distinguishing Ito -mediated J waves from pseudo J waves produced by delayed intraventricular conduction.
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Bloqueo de Rama/fisiopatología , Electrocardiografía/métodos , Sistema de Conducción Cardíaco/fisiopatología , Hipotermia/fisiopatología , Adulto , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios RetrospectivosRESUMEN
Pyranopyrazole and its derivatives are classified to be a pharmacologically significant active scaffold for almost all modes of biological activities. In this work, An efficient, green, and facile three-component reaction for preparing pyrano[2,3-c]pyrazole derivatives via the condensation reaction of 5-methyl-2-phenyl-2,4-dihydro-3H-pyrazol-3-one, ethyl acetoacetate, and malononitrile in the presence of ZnO Nanoparticle. The products are produced with high yields and in shorter reaction times. It also is mild, safe, green, and environmentally friendly. The geometric parameters such as dipole moment, bond length, dihedral angles, total energy, heat of formation, atomic charges and energies at a highly accurate for prepared compounds were computed by Denisty Functional Theory along with the B3LYP functional. The newly synthesized compounds were screened for their anti-inflammatory and antioxidant activity. Some of the tested compounds displayed promising activities. The newly prepared compounds were found to be potent towards the antioxidant activity. Results indicated that compounds 11 and 12 exhibited significant (p ≥ 0.05) in vitro total antioxidant activity as 44.93 ± 0.15 and 39.60 ± 0.10 U/ML, respectively higher than standard ascorbic acid (29.40 ± 0.62).
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Antiinflamatorios no Esteroideos/farmacología , Antioxidantes/farmacología , Inhibidores de la Ciclooxigenasa/farmacología , Teoría Funcional de la Densidad , Inhibidores de la Lipooxigenasa/farmacología , Antiinflamatorios no Esteroideos/síntesis química , Antiinflamatorios no Esteroideos/química , Antioxidantes/síntesis química , Antioxidantes/química , Araquidonato 5-Lipooxigenasa/metabolismo , Catálisis , Inhibidores de la Ciclooxigenasa/síntesis química , Inhibidores de la Ciclooxigenasa/química , Relación Dosis-Respuesta a Droga , Humanos , Inhibidores de la Lipooxigenasa/síntesis química , Inhibidores de la Lipooxigenasa/química , Estructura Molecular , Estrés Oxidativo/efectos de los fármacos , Prostaglandina-Endoperóxido Sintasas/metabolismo , Piranos/síntesis química , Piranos/química , Piranos/farmacología , Pirazoles/síntesis química , Pirazoles/química , Pirazoles/farmacología , Especies Reactivas de Oxígeno/metabolismo , Relación Estructura-ActividadRESUMEN
N-acyl imidazolidinones, which are key intermediates in the stereoselective synthesis of amino acids by "self-regeneration of stereochemistry" methods, are classically made by only moderately diastereoselective methods. We now report that cyclization of pivaldimino-amides with phosgene in the presence of pyridine may be made fully diastereoselective for the trans-N-chloroformylimidazolidinones, and we detail the conformational features of the products. We show that despite the presence of the electrophilic carbamoyl chloride function the products show remarkable stability and may be deprotonated to form enolates with useful reactivity for the synthesis of amino acid derivatives.
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Both E- and Z-N'-alkenyl urea derivatives of imidazolidinones may be formed selectively from enantiopure α-amino acids. Generation of their enolate derivatives in the presence of K+ and [18]crown-6 induces intramolecular migration of the alkenyl group from N' to Cα with retention of double bond geometry. DFT calculations indicate a partially concerted substitution mechanism. Hydrolysis of the enantiopure products under acid conditions reveals quaternary α-alkenyl amino acids with stereodivergent control of both absolute configuration and double bond geometry.
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INTRODUCTION: Pharmacy is a very dynamic profession and the role of the pharmacist is improving with the expansion of the scope of services and the introduction of new subspecialties over time. Moving from being medication dispensers to outcome-oriented and patient-focused care providers; pharmacists will carry more responsibility and commitment to improve their knowledge and practice. Being updated and evidence-based is a key tool to achieve effective pharmaceutical care services. The primary purpose of this article is to highlight the concept of "evidence based pharmaceutical care" as professional practice to improve the quality of pharmaceutical care. METHODS: Literature for relevant evidence was searched by Medline (through PubMed), Cochrane library using the keywords: pharmaceutical care, evidence-based and pharmacy practice. Also a manual search through major journals for articles referenced in those located through PubMed was done. RESULTS AND DISCUSSION: There is strong data showing that pharmaceutical care lead to improvement in health outcomes and cost-effective therapy. More efforts, policies and qualified staff are needed to establish the "evidence-based pharmaceutical care" as new daily professional practice. Evidence to support pharmacists in their emerging role as care providers is available to improve the efficacy and quality of pharmaceutical care. Education and specialized training practicing evidence based approach are vital to prepare pharmacists to provide high quality pharmaceutical care. CONCLUSION: As care providers, pharmacists are effective in providing high quality patient care and being members in multidisciplinary clinical teams is needed to give them the opportunity. Evidence based pharmaceutical care is a natural and logical emerging concept in the modern pharmacy practice to achieve high quality and more effective pharmaceutical care but still more efforts and resources are needed to promote new attitude toward more professional career.
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BACKGROUND: Acute lower gastrointestinal bleeding (LGIB) is a common reason for hospital admission. However, the majority resolve spontaneously and only a minority require inpatient intervention. We aimed to describe the epidemiology and aetiology of acute LGIB admissions in our institution. We also aimed to validate the Oakland Score, which can identify patients at low risk of adverse outcome from LGIB, in our population and determine the proportion who could have safely avoided admission. METHODS: Using the prospective, validated Otago Clinical Audit database (DIVA), we searched for adult patients admitted to Dunedin Hospital with a primary diagnosis of LGIB between January 2013 and December 2020. We retrieved data to calculate the Oakland Score and details of inpatient treatment from the electronic patient record. We excluded patients admitted electively, admissions related to inflammatory bowel disease, and those with upper gastrointestinal bleeding. RESULTS: We identified 761 patients of which 501 met inclusion criteria (56% male, median age 76 years, 82% NZ European). Overall, 72% were managed with observation or diagnostic endoscopy, 32% received blood products, and 7% required haemostatic intervention to control bleeding. The area under the receiver operating characteristic curve for the Oakland Score was 0.85 (95% CI, 0.81-0.89). A cut-off score of ≤10 predicted a 95% probability of safely avoiding admission. This equates to saving 30 bed-days annually. CONCLUSION: The majority of patients admitted with LGIB are managed conservatively. The Oakland Score could be used as a stratification tool to safely reduce the admission rate.
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Hemorragia Gastrointestinal , Alta del Paciente , Adulto , Humanos , Masculino , Anciano , Femenino , Estudios Prospectivos , Nueva Zelanda/epidemiología , Medición de Riesgo , Hemorragia Gastrointestinal/diagnóstico , Hemorragia Gastrointestinal/epidemiología , Hemorragia Gastrointestinal/etiología , Enfermedad Aguda , Hospitales , Estudios RetrospectivosRESUMEN
Identifying a viable substitute for the limited array of current antifungal agents stands as a crucial objective in modern agriculture. Consequently, extensive worldwide research has been undertaken to unveil eco-friendly and effective agents capable of controlling pathogens resistant to the presently employed fungicides. This study explores the efficacy of Trichoderma isolates in combating tomato leaf spot disease, primarily caused by Alternaria alternata. The identified pathogen, A. alternata Alt3, was isolated and confirmed through the ITS region (OQ888806). Six Trichoderma isolates were assessed for their ability to inhibit Alt3 hyphal growth using dual culture, ethyl acetate extract, and volatile organic compounds (VOCs) techniques. The most promising biocontrol isolate was identified as T. afroharzianum isolate TRI07 based on three markers: ITS region (OQ820171), translation elongation factor alpha 1 gene (OR125580), and RNA polymerase II subunit gene (OR125581). The ethyl acetate extract of TRI07 isolate was subjected to GC-MS analysis, revealing spathulenol, triacetin, and aspartame as the main compounds, with percentages of 28.90, 14.03, and 12.97%, respectively. Analysis of TRI07-VOCs by solid-phase microextraction technique indicated that the most abundant compounds included ethanol, hydroperoxide, 1-methylhexyl, and 1-octen-3-one. When TRI07 interacted with Alt3, 34 compounds were identified, with major components including 1-octen-3-one, ethanol, and hexanedioic acid, bis(2-ethylhexyl) ester. In greenhouse experiment, the treatment of TRI07 48 h before inoculation with A. alternata (A3 treatment) resulted in a reduction in disease severity (16.66%) and incidence (44.44%). Furthermore, A3 treatment led to improved tomato growth performance parameters and increased chlorophyll content. After 21 days post-inoculation, A3 treatment was associated with increased production of antioxidant enzymes (CAT, POD, SOD, and PPO), while infected tomato plants exhibited elevated levels of oxidative stress markers MDA and H2O2. HPLC analysis of tomato leaf extracts from A3 treatment revealed higher levels of phenolic acids such as gallic, chlorogenic, caffeic, syringic, and coumaric acids, as well as flavonoid compounds including catechin, rutin, and vanillin. The novelty lies in bridging the gap between strain-specific attributes and practical application, enhancing the understanding of TRI07's potential for integrated pest management. This study concludes that TRI07 isolate presents potential natural compounds with biological activity, effectively controlling tomato leaf spot disease and promoting tomato plant growth. The findings have practical implications for agriculture, suggesting a sustainable biocontrol strategy that can enhance crop resilience and contribute to integrated pest management practices.
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Acetatos , Alternaria , Hypocreales , Cetonas , Solanum lycopersicum , Peróxido de Hidrógeno , EtanolRESUMEN
Sulfur(VI) fluoride motifs are important entities in organic chemistry. Typically, their syntheses involve the corresponding chlorides, which are often difficult to prepare and characterized by a poor storability due to the inherently weak S-Cl bond. Here, a single-step procedure for the preparation of sulfur(VI) fluorides starting from sulfonyl imidazoles as stable S(VI) reservoirs is described. By using a simple combination of AcOH and potassium bifluoride (KF2H), an imidazole-to-fluorine exchange furnishes a variety of sulfonyl, sulfonimidoyl, sulfoxyl, and sulfamoyl fluorides in good to excellent yields.
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BACKGROUND: Chronic steroid therapy is associated with higher vascular complication rates in patients undergoing transcatheter aortic valve replacement (TAVR). The effect of corticosteroids on aortic annular complications has not been directly assessed in this population. METHODS: A retrospective analysis of 1095 patients undergoing transfemoral TAVR was performed. Patients treated with chronic steroids at the time of the procedure (n = 99) were compared with those who received no steroids (n = 992). The primary outcome included a composite of aortic annular complications, defined as a combination of aortic annular rupture, aortic dissection/perforation, and left ventricular perforation. RESULTS: The primary outcome was significantly higher in the steroid group (4.0% vs 0.5%; P<.01). This finding was primarily driven by higher rates of acute annular rupture in the steroid group (2.0% vs 0.2%; P=.04). Steroid use was associated with higher rates of intraoperative cardiac arrest (5.1% vs 1.5%; P=.03), device capture/retrieval (4.0% vs 0.8%; P=.01), and emergent conversion to open heart surgery (4.0% vs 0.6%; P<.01). There were no differences with respect to in-hospital mortality, stroke, myocardial infarction, need for permanent pacemaker, bleeding complications, minor vascular complications, hospital length of stay, hospital 30-day readmission, or 30-day echocardiographic findings. Additionally, within the steroid group, there were no significant differences between balloon-expandable vs self-expanding TAVR prostheses with respect to composite aortic annular complications. CONCLUSION: Chronic steroid therapy increases the risk of aortic annular complications in patients undergoing TAVR, with detrimental consequences including intraoperative cardiac arrest and conversion to open heart surgery. Steroid use should be considered in patient selection and determination of procedural technique for TAVR.
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Estenosis de la Válvula Aórtica , Prótesis Valvulares Cardíacas , Reemplazo de la Válvula Aórtica Transcatéter , Válvula Aórtica/diagnóstico por imagen , Válvula Aórtica/cirugía , Estenosis de la Válvula Aórtica/diagnóstico , Estenosis de la Válvula Aórtica/cirugía , Prótesis Valvulares Cardíacas/efectos adversos , Humanos , Complicaciones Posoperatorias/epidemiología , Estudios Retrospectivos , Factores de Riesgo , Esteroides/efectos adversos , Reemplazo de la Válvula Aórtica Transcatéter/efectos adversos , Resultado del TratamientoRESUMEN
One of the tomato's acutely devastating diseases is Alternaria leaf spot, lowering worldwide tomato production. In this study, one fungal isolate was isolated from tomatoes and was assigned to Alternaria alternata TAA-05 upon morphological and molecular analysis of the ITS region and 18SrRNA, endoPG, Alt a1, and gapdh genes. Also, Urtica dioica and Dodonaea viscosa methanol leaf extracts (MLEs) were utilized as antifungal agents in vitro and compared to Ridomil, a reference chemical fungicide. The in vitro antifungal activity results revealed that Ridomil (2000 µg/mL) showed the highest fungal growth inhibition (FGI) against A. alternata (96.29%). Moderate activity was found against A. alternata by D. viscosa and U. dioica MLEs (2000 µg/mL), with an FGI value of 56.67 and 54.81%, respectively. The abundance of flavonoid and phenolic components were identified by HPLC analysis in the two plant extracts. The flavonoid compounds, including hesperidin, quercetin, and rutin were identified using HPLC in D. viscosa MLE with concentrations of 11.56, 10.04, and 5.14 µg/mL of extract and in U. dioica MLE with concentrations of 12.45, 9.21, and 5.23 µg/mL, respectively. α-Tocopherol and syringic acid, were also identified in D. viscosa MLE with concentrations of 26.13 and 13.69 µg/mL, and in U. dioica MLE, with values of 21.12 and 18.33 µg/mL, respectively. Finally, the bioactivity of plant extracts suggests that they play a crucial role as antifungal agents against A. alternata. Some phenolic chemicals, including coumaric acid, caffeic acid, ferulic acid, and α-tocopherol, have shown that they may be utilized as environmentally friendly fungicidal compounds.
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Fungicidas Industriales , Hesperidina , Sapindaceae , Solanum lycopersicum , Urtica dioica , Alternaria , Antifúngicos/farmacología , Ácidos Cumáricos , Metanol , Fenoles/química , Fenoles/farmacología , Extractos Vegetales/química , Extractos Vegetales/farmacología , Quercetina , Rutina , Urtica dioica/química , alfa-TocoferolRESUMEN
BACKGROUND: Although prior national reports have identified trends in the underutilization of transcatheter aortic valve replacement (TAVR) in Afro-American and Latino populations, racial and ethnic healthcare disparities in TAVR use in the State of Connecticut have not been previously reported. METHODS: We conducted a retrospective analysis of 1461 patients undergoing TAVR at our institute between from 2012 to 2020. Baseline demographics, procedural characteristics, clinical outcomes, median incomes and insurance coverage were compared between 1417 Caucasian and 44 minority patients, including 23 patients designated as Afro-American and 10 designated as Latino. Demographics of TAVR utilization at our institution were further compared to 6 additional Connecticut TAVR centers using Connecticut Hospital Association (CHA) ChimeData detailing hospital discharges for DRG 266 and 267. RESULTS: In comparison to Caucasian patients, minority cohorts were younger (75.7 ± 9.0 vs 81.5 ± 5.1 years, p < 0.001) and had more co-morbidities including diabetes (64% vs 34%, p < 001), coronary artery disease (95% vs 78%, p = 0.039), end stage renal disease requiring dialysis (9% vs 3%, p = 0.009) and atrial fibrillation (77% vs 62%, p = 0.041). The two groups did not differ with respect to other risk factors or co-morbidities, baseline echocardiographic or CTA findings, STS risk score, or procedural technique. Minority patients had a longer length of hospital stay (9.5 ± 9.0 vs 6.4 ± 6.9 days, p = 0.003), but did not differ with respect to procedural complications. Socioeconomic differences between the two groups included lower median incomes and higher rates of Medicaid or no insurance coverage for minority versus Caucasian patients. CHA ChimeData revealed a similar underutilization of TAVR in minority subgroups in the remaining 6 Connecticut TAVR centers. CONCLUSIONS: Despite statewide demographics describing 10.7% and 15.7% of the total population as Afro-American and Latino, respectively, only 3.0% of the total TAVR procedures performed at a large Connecticut health care facility were performed in minority subgroups. Despite having a higher burden of co-morbidities, minority patients had similar outcomes compared to Caucasian patients. Similar racial and ethnic disparities in TAVR utilization were confirmed statewide using CHA ChimeData.
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Estenosis de la Válvula Aórtica , Reemplazo de la Válvula Aórtica Transcatéter , Válvula Aórtica/diagnóstico por imagen , Válvula Aórtica/cirugía , Estenosis de la Válvula Aórtica/diagnóstico por imagen , Estenosis de la Válvula Aórtica/cirugía , Connecticut/epidemiología , Mortalidad Hospitalaria , Humanos , Estudios Retrospectivos , Factores de Riesgo , Reemplazo de la Válvula Aórtica Transcatéter/métodos , Resultado del Tratamiento , Estados Unidos/epidemiologíaRESUMEN
OBJECTIVES: This study aimed to perform the first meta-analysis of studies comparing transcarotid (TC) and trans-subclavian (TSc) transcatheter aortic valve replacement (TAVR). BACKGROUND: The safety and feasibility of a TC and a TSc approach for performing TAVR in patients with prohibitive femoral anatomy have been well described. The potential advantage of one approach over the other is yet to be ascertained. METHODS: A computerized literature search of key medical databases through September 2020 was performed. Randomized controlled trials (RCTs) and observational studies comparing TC and TSc TAVR with reported 30-day outcomes were considered. The primary endpoint was a composite of all-cause mortality, stroke, life-threatening, and/or major bleeding or major vascular complications. Statistical analysis using random-effects models to report the odds ratio (OR) with 95% confidence interval (CI) was performed. RESULTS: A total of 5 observational studies inclusive of 4164 patients (TC = 1788 and TSc = 2376) met the eligibility criteria. The average age of patients was 81.1 years. There was no difference in the occurrence of the composite endpoint between the groups at 30-days. A statistically insignificant trend towards higher rates of major vascular complications (OR 1.65; 95% CI 0.94-2.89; P = 0.08; I2 = 0%) and the need for permanent pacemaker placement was observed with the TSc approach. CONCLUSIONS: This meta-analysis of studies comparing TC and TSc TAVR showed similar 30-day outcomes between the 2 approaches. A notable trend towards higher rates of major vascular complications and the need for permanent pacemaker placement was observed with the TSc approach.
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Estenosis de la Válvula Aórtica , Reemplazo de la Válvula Aórtica Transcatéter , Anciano de 80 o más Años , Válvula Aórtica/diagnóstico por imagen , Válvula Aórtica/cirugía , Estenosis de la Válvula Aórtica/diagnóstico por imagen , Estenosis de la Válvula Aórtica/cirugía , Humanos , Factores de Riesgo , Factores de Tiempo , Reemplazo de la Válvula Aórtica Transcatéter/efectos adversos , Resultado del TratamientoRESUMEN
[Figure: see text].
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Estenosis de la Válvula Aórtica , Implantación de Prótesis de Válvulas Cardíacas , Reemplazo de la Válvula Aórtica Transcatéter , Válvula Aórtica/diagnóstico por imagen , Válvula Aórtica/cirugía , Estenosis de la Válvula Aórtica/diagnóstico por imagen , Estenosis de la Válvula Aórtica/cirugía , Implantación de Prótesis de Válvulas Cardíacas/efectos adversos , Humanos , Índice de Severidad de la Enfermedad , Volumen Sistólico , Reemplazo de la Válvula Aórtica Transcatéter/efectos adversos , Resultado del Tratamiento , Función Ventricular IzquierdaRESUMEN
The N-chloroformylimidazolidinone derivative of enantiopure l-alanine was deprotonated to form an enolate and functionalized with a series of allylic halides. Treatment of the resulting carbamoyl chlorides with potassium iodide led to cyclization of the allylic substituent onto the carbonyl group in an intramolecular aliphatic Friedel-Crafts-type acylation that corresponds to an aliphatic Bischler-Napieralski reaction. The product 3,4-dihydropyridinones were amenable to further functionalization, and finally hydrolysis, to deliver a series of enantio-enriched pipecolic acid derivatives.
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BACKGROUND: Previous reports described successful use of transcarotid and transsubclavian approaches for the performance of transcatheter aortic valve replacement (TAVR) in patients with severe aortic stenosis who cannot be treated with transfemoral access. The purpose of the present study was to compare these two alternative approaches with respect to safety, efficacy, and procedural efficiency. METHODS: A retrospective analysis of all TAVR procedures performed through either a transcarotid or a transsubclavian approach at a single tertiary care medical center between January 2016 and October 2018 was performed. Outcomes are reported in accordance with the Valve Academic Research Consortium definitions. RESULTS: During the study period, 33 patients had transcarotid TAVR and 38 patients had transsubclavian TAVR. Transcarotid patients were older (mean age, 82.9 ± 7.2 vs 78.1 ± 8.2 years; P = .012), but otherwise the two groups were not significantly different with respect to preoperative characteristics. Valve deployment was similar between the groups (100% vs 97%; P = .348). Procedure time was shorter with the transcarotid approach (110 ± 32 vs 134 ± 45 minutes; P = .014). There was a lower mean fluoroscopy air kerma in the transcarotid group (682.82 ± 713.48 mGy vs 2141 ± 2055 mGy; P < .001), although fluoroscopy dose-area product did not differ between the groups. There was no difference between the groups with respect to in-hospital or 30-day mortality (0% vs 3%; P = .355), stroke (3% vs 8%; P = .393), or vascular complication (3% vs 4%; P = .840). CONCLUSIONS: The transcarotid and the transsubclavian approaches have similar safety and efficacy outcomes. The transcarotid approach had a shorter procedure duration and a trend toward lower fluoroscopy duration and radiation exposure.