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INTRODUCTION/AIMS: Patients with amyotrophic lateral sclerosis (ALS) are susceptible to malnutrition, with appropriate management of nutritional interventions an active area of investigation. We sought to determine the impact of gastrostomy tube placement in ALS patients, exploring the correlation between forced vital capacity (FVC), malnutrition, and perioperative complications. METHODS: A retrospective review was performed of clinically diagnosed ALS patients treated at two multidisciplinary clinics (University of Kansas, University of Nebraska) from January 2009 to September 2020 who were referred for gastrostomy. Data collected included demographics, disease characteristics, and key gastrostomy related dates/outcomes. RESULTS: Two hundred thirty-nine patients were included with a median age of 65 years and median of 589 days from symptom onset to gastrostomy (interquartile range, 404-943). The population was predominantly Non-Hispanic White with bulbar-onset ALS. 30-day mortality was 4% and 30-day morbidity was 13%. Weight loss, body mass index, and predicted FVC at placement showed no increased 30-day morbidity or mortality association. Bulbar-onset ALS patients exhibited higher overall mortality postplacement than limb onset (odds ratio: 1.85, 95% confidence interval: 1.03-3.33). There was a 5% incidence of symptoms suggestive of refeeding syndrome. DISCUSSION: Rates of major/minor complications and 30-day mortality related to gastrostomy placement in our population were similar compared with prior studies in ALS. The lack of difference in outcomes based on FVC at procedure may suggest this is not predictive of outcome, or perhaps, high-quality perioperative respiratory management. Alternative reasons may account for the increased morbidity and mortality of gastrostomy placement in the ALS population.
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Esclerosis Amiotrófica Lateral , Nutrición Enteral , Gastrostomía , Humanos , Esclerosis Amiotrófica Lateral/terapia , Esclerosis Amiotrófica Lateral/complicaciones , Masculino , Femenino , Nutrición Enteral/métodos , Anciano , Estudios Retrospectivos , Persona de Mediana Edad , Resultado del Tratamiento , Desnutrición/etiología , Desnutrición/terapia , Capacidad Vital/fisiologíaRESUMEN
BACKGROUND: Advancements in arterial stenting technology have challenged prior notions favoring medical management for intracranial atherosclerotic disease (ICAD). Where previous conclusions were drawn from bare metal stent (BMS) technology, recent studies suggest drug-eluting stents (DES) are favorable due to their anti-proliferative effect, which reduces vascular remodeling. METHODS: We conducted a systematic review and meta-analysis of the literature prior to August 2023 reviewing all reports of ICAD treated with DES. Our target outcomes were incidence of any stroke, transient ischemic attack (TIA), or death within 30 days (postprocedural complications), ischemic stroke in the territory of the qualifying artery beyond 30 days (long-term complications), radiographically detected in-stent restenosis rate (ISR), and symptomatic ISR during follow-up. A subgroup analysis further stratified preprocedural mean stenosis above and below 70% into severe and moderate cohorts, respectively. RESULTS: PubMed, Web of Science, Cochrane and EMBASE query identified 527 candidate articles, from which 14 studies met inclusion criteria for a total of 607 patients and 640 ICAD lesions. Incidence of postprocedural complications was 7.3% (95% CI 3.9-11.7%) with subgroup analysis demonstrating significantly higher incidence in the severely stenotic group [9.0% (95% CI 4.7-14.5%)] than the moderately stenotic group [3.0% (95% CI 0.7-6.8%)]. Long-term complications were 1.2% (95% CI 0.4-2.3%). Radiographic ISR was 3.5% (95% CI 1.4-6.3%) and symptomatic ISR was 0.3% (95% CI 0.0-1.5%). CONCLUSIONS: Our systematic review and meta-analysis suggest that DES can effectively reduce the risk of ISR and may be a viable treatment modality to reduce long-term complications in refractory ICAD patients.
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Background: Pharmacy administrative claims data remain an accessible and efficient source to measure medication adherence for frequently hospitalized patient populations that are systematically excluded from the landmark drug trials. Published pharmacotherapy studies use medication possession ratio (MPR) and proportion of days covered (PDC) to calculate medication adherence and usually fail to incorporate hospitalization and prescription overlap/gap from claims data. To make the cacophony of adherence measures clearer, this study created a refined hospital-adjusted algorithm to capture pharmacotherapy adherence among patients with end-stage renal disease (ESRD). Methods: The United States Renal Data System (USRDS) registry of ESRD was used to determine prescription-filling patterns of those receiving new prescriptions for oral P2Y12 inhibitors (P2Y12-I) between 2011 and 2015. P2Y12-I-naïve patients were followed until death, kidney transplantation, discontinuing medications, or loss to follow-up. After flagging/censoring key variables, the algorithm adjusted for hospital length of stay (LOS) and medication overlap. Hospital-adjusted medication adherence (HA-PDC) was calculated and compared with traditional MPR and PDC methods. Analyses were performed with SAS software. Results: Hospitalization occurred for 78% of the cohort (N = 46 514). The median LOS was 12 (interquartile range [IQR] = 2-34) days. MPR and PDC were 61% (IQR = 29%-94%) and 59% (IQR = 31%-93%), respectively. After applying adjustments for overlapping coverage days and hospital stays independently, HA-PDC adherence values changed in 41% and 52.7% of the cohort, respectively. When adjustments for overlap and hospital stay were made concurrently, HA-PDC adherence values changed in 68% of the cohort by 5.8% (HA-PDC median = 0.68, IQR = 0.31-0.93). HA-PDC declined over time (3M-6M-9M-12M). Nearly 48% of the cohort had a ≥30 days refill gap in the first 3 months, and this increased over time (P < .0001). Conclusions: Refill gaps should be investigated carefully to capture accurate pharmacotherapy adherence. HA-PDC measures increased adherence substantially when adjustments for hospital stay and medication refill overlaps are made. Furthermore, if hospitalizations were ignored for medications that are included in Medicare quality measures, such as Medicare STAR program, the apparent reduction in adherence might be associated with lower quality and health plan reimbursement.
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BACKGROUND: About 50% of all hospitalized fragility fracture cases in older Americans are hip fractures. Approximately 3/4 of fracture-related costs in the USA are attributable to hip fractures, and these are mostly covered by Medicare. Hip fracture patients with dementia, including Alzheimer's disease, have worse health outcomes including longer hospital length of stay (LOS) and charges. LOS and hospital charges for dementia patients are usually higher than for those without dementia. Research describing LOS and acute care charges for hip fractures has mostly focused on these outcomes in trauma patients without a known pre-admission diagnosis of osteoporosis (OP). Lack of documented diagnosis put patients at risk of not having an appropriate treatment plan for OP. Whether having a diagnosis of OP would have an effect on hospital outcomes in dementia patients has not been explored. We aim to investigate whether having a diagnosis of OP, dementia, or both has an effect on LOS and hospital charges. In addition, we also report prevalence of common comorbidities in the study population and their effects on hospital outcomes. METHODS: We conducted a cross-sectional analysis of claims data (2012-2013) for 2175 Medicare beneficiaries (≥65 years) in the USA. RESULTS: Compared to those without OP or dementia, patients with demenia only had a shorter LOS (by 5%; P = .04). Median LOS was 6 days (interquartile range [IQR]: 5-7), and the median hospital charges were $45,100 (IQR: 31,500 - 65,600). In general, White patients had a shorter LOS (by 7%), and those with CHF and ischemic heart disease (IHD) had longer LOS (by 7 and 4%, respectively). Hospital charges were 6% lower for women, and 16% lower for White patients. CONCLUSION: This is the first study evaluating LOS in dementia in the context of hip fracture which also disagrees with previous reporting about longer LOS in dementia patients. Patients with CHF and IHD remains at high risk for longer LOS regardless of their diagnosis of dementia or OP.
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Fracturas de Cadera , Osteoporosis , Anciano , Anciano de 80 o más Años , Estudios Transversales , Femenino , Fracturas de Cadera/diagnóstico , Fracturas de Cadera/epidemiología , Fracturas de Cadera/terapia , Humanos , Tiempo de Internación , Masculino , Medicare , Osteoporosis/diagnóstico , Osteoporosis/epidemiología , Osteoporosis/terapia , Estados Unidos/epidemiologíaRESUMEN
BACKGROUND: Trends and clinical factors associated with prescribing choices for oral P2Y12 inhibitors (P2Y12-I) remain unknown for patients on chronic dialysis, i.e., with end-stage renal disease (ESRD). METHODS: From 2011-2014 U.S. Renal Data System registry, we identified 36,542 ESRD patients who received new prescriptions for P2Y12-I (median age 64.0 years and 54% males). Of the cohort, 93% were receiving hemodialysis and 7% on peritoneal dialysis. We analyzed trends and investigated clinical factors associated with specific P2Y12-I prescribed. RESULTS: Clopidogrel was prescribed for 95%, prasugrel for 3%, and ticagrelor for 2%. Clopidogrel was favored for those ≥75 years (18% of cohort). Compared to Caucasians, African Americans (36% of cohort) and Hispanics (19% of cohort) were less likely to receive prasugrel and ticagrelor (P<0.05). Patients receiving hemodialysis versus peritoneal dialysis were less likely to receive prasugrel over clopidogrel, adjusted odds ratio (aOR) 0.67 (0.55-0.82). Each additional year of dialysis decreased the odds of receiving prasugrel over clopidogrel, aOR 0.91 (0.85-0.98). History of atrial fibrillation reduced the odds of receiving ticagrelor or prasugrel over clopidogrel, aOR 0.69 (0.54-0.89) and 0.73 (0.60-0.89), respectively. Concomitant oral anticoagulant use was not associated with choice of P2Y12-I. Occurrence of non-ST segment elevation myocardial infarction or percutaneous coronary intervention within the 6-month period prior to the index date favored ticagrelor over prasugrel, aOR 1.31 (1.06-1.62) and 1.29 (1.01-1.66), respectively. However, prescribing trends favoring ticagrelor over prasugrel were not observed for deployment of drug-eluting, or multiple coronary stents. CONCLUSION: Between 2011 and 2014, clopidogrel remained the most common P2Y12-I whereas ticagrelor and prasugrel remained underutilized in ESRD patients. Prescribing practices for these drugs were based upon clinically approved indication for their use in the general population as well as perceived complexity of an ESRD patient including demographics, dialysis-related factors and comorbidities. Comparative effectiveness studies involving ESRD patients are needed to prove that ticagrelor and prasugrel are just as safe and effective as clopidogrel before clinicians can make informed decisions for choice of P2Y12-I in this patient population.
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Enfermedades Cardiovasculares/tratamiento farmacológico , Clopidogrel/administración & dosificación , Fallo Renal Crónico/terapia , Inhibidores de Agregación Plaquetaria/administración & dosificación , Pautas de la Práctica en Medicina/tendencias , Clorhidrato de Prasugrel/administración & dosificación , Antagonistas del Receptor Purinérgico P2Y/administración & dosificación , Diálisis Renal , Ticagrelor/administración & dosificación , Administración Oral , Adolescente , Adulto , Anciano , Enfermedades Cardiovasculares/sangre , Enfermedades Cardiovasculares/diagnóstico , Enfermedades Cardiovasculares/mortalidad , Toma de Decisiones Clínicas , Clopidogrel/efectos adversos , Prescripciones de Medicamentos , Utilización de Medicamentos/tendencias , Femenino , Humanos , Fallo Renal Crónico/diagnóstico , Fallo Renal Crónico/mortalidad , Masculino , Persona de Mediana Edad , Selección de Paciente , Diálisis Peritoneal , Inhibidores de Agregación Plaquetaria/efectos adversos , Clorhidrato de Prasugrel/efectos adversos , Prevalencia , Antagonistas del Receptor Purinérgico P2Y/efectos adversos , Sistema de Registros , Diálisis Renal/efectos adversos , Diálisis Renal/mortalidad , Estudios Retrospectivos , Medición de Riesgo , Factores de Riesgo , Ticagrelor/efectos adversos , Factores de Tiempo , Resultado del Tratamiento , Estados Unidos , Adulto JovenRESUMEN
OBJECTIVE: Hook of hamate fracture, the most common swing-related wrist fracture, is commonly seen in high-level athletes. The fracture is rarely diagnosed on routine wrist radiographs, thus generally requiring CT or MR for diagnosis. Surgical excision has a high success rate, however diagnostic delay contributes to a high complication rate. Radiographic signs of hook of hamate fracture have been published, but uncertainty of the diagnostic accuracy limits application. The purpose of this study is to determine accuracy and interobserver reliability of radiographic signs of hook of hamate. MATERIALS AND METHODS: This retrospective case-control study evaluated wrist radiographs of 50 patients, including 24 positive and 26 negative, for hook of hamate fracture, each proven by CT or MR. Five reviewers performed blinded, randomized evaluation of radiographs documenting whether the hook of hamate was normal or fractured, and if fractured, the radiographic signs present (ring sign, ghostly shadow, and diffuse sclerosis) and views that contributed to diagnosis. RESULTS: Radiographic signs demonstrated high sensitivity (85%; 95% CI: 77-91), specificity (92%; 95% CI: 86-96), and accuracy (89%; 95% CI: 84-92) with substantial interobserver reliability (k = 0.652). The ring sign was the most sensitive radiographic sign. Diagnosis was most often supported by the oblique view (38%) and rarely the lateral view (15%). CONCLUSIONS: Radiographic signs of hook of hamate fracture on routine radiographs can accurately and reliably diagnose hook of hamate fractures. Evaluation for discontinuity of the cortical ring will optimize sensitivity, allowing for timely diagnosis and treatment, and a reduction of complications.
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Fracturas Óseas/diagnóstico por imagen , Hueso Ganchoso/diagnóstico por imagen , Hueso Ganchoso/lesiones , Imagen por Resonancia Magnética , Tomografía Computarizada por Rayos X , Traumatismos de la Muñeca/diagnóstico por imagen , Adulto , Traumatismos en Atletas/diagnóstico por imagen , Estudios de Casos y Controles , Femenino , Humanos , Masculino , Persona de Mediana Edad , Reproducibilidad de los Resultados , Estudios Retrospectivos , Sensibilidad y EspecificidadRESUMEN
PURPOSE: To determine whether treating benign biliary strictures via a stricture protocol reduced the probability of developing symptomatic recurrence and requiring surgical revision compared to nonprotocol treatment. MATERIALS AND METHODS: A stricture protocol was designed to include serial upsizing of internal/external biliary drainage catheters to a target maximum dilation of 18-French, optional cholangioplasty at each upsizing, and maintenance of the largest catheter for at least 6 months. Patients were included in this retrospective analysis if they underwent biliary ductal dilation at a single institution from 2005 to 2016. Forty-two patients were included, 25 women and 17 men, with an average age of 51.9 years (standard deviation ± 14.6). Logistic regression models were used to determine the probability of symptomatic recurrence and surgical revision by stricture treatment type. RESULTS: Twenty-two patients received nonprotocol treatment, while 20 received treatment on a stricture protocol. After treatment, 7 (32%) patients in the nonprotocol group experienced clinical or laboratory recurrence of a benign stricture, whereas only 1 patient in the stricture protocol group experienced symptom recurrence. Patients in the protocol group were 8.9 times (95% confidence interval [CI] = 1.4-175.3) more likely to remain symptom free than patients in the nonprotocol group. Moreover, patients in the protocol group had an estimated 89% reduction in the probability of undergoing surgical revision compared to patients receiving nonprotocol treatment (odds ratio = .11, 95% CI = .01-.73). CONCLUSIONS: Establishing a stricture protocol may decrease the risk of stricture recurrence and the need for surgical revision when compared to a nonprotocol treatment approach.
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Colestasis/cirugía , Protocolos Clínicos , Drenaje/métodos , Cateterismo/instrumentación , Constricción Patológica , Dilatación , Femenino , Humanos , Masculino , Persona de Mediana Edad , Recurrencia , Reoperación , Estudios Retrospectivos , Factores de Riesgo , Resultado del TratamientoRESUMEN
Increasing radiologic exam volume and complexity necessitates leveraging advanced hardware solutions to optimize workflow efficiency. We evaluated radiologist satisfaction of a programmable 13-button non-conventional mouse compared to a conventional three-button mouse in daily interpretation workflow following a brief 2-day trial period. A prospective study was conducted with radiology staff and residents in a tertiary care center from 2015 to 2016. A survey was distributed prior to and after a tutorial and a 2-day non-conventional mouse trial period. The post-survey evaluated usage time, device settings, satisfaction, preferences, and perceived efficiency of both mice. Descriptive analyses, correlations, the Sign test, and the Wilcoxon signed-rank test were used to evaluate responses. Fifty-nine participants completed pre- and post-surveys. Several (41%, n = 24) had prior experience with a non-conventional mouse. Prior to the trial, one third of all participants (35.6%, n = 21) reported being satisfied or very satisfied with their conventional mouse. After spending an average of 9.8 h using the non-conventional mouse, there were no statistically significant changes in overall satisfaction with either conventional or non-conventional mice (p = 0.84 and p = 0.39, respectively). However, 76.3% (n = 45) agreed/somewhat agreed they preferred to use the non-conventional mouse in their daily workflow as opposed to the conventional mouse. The non-conventional mouse was also perceived as more efficient (66.1%, n = 39), required less time (62.7%, n = 37) and effort (74.6%, n = 44) to view images, allowed for easier manipulation of windows/images (76.3%, n = 45), and was more comfortable to use (78.0%, n = 46). Although there were no statistically significant shifts in overall satisfaction, participants reported a higher level of satisfaction, perceived efficiency, and preference for a non-conventional 13-button mouse compared to a conventional three-button mouse following a brief, 2-day trial period.
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Interpretación de Imagen Asistida por Computador/instrumentación , Satisfacción Personal , Radiólogos/estadística & datos numéricos , Radiología/instrumentación , Interfaz Usuario-Computador , Estudios de Cohortes , Eficiencia , Diseño de Equipo , Femenino , Humanos , Masculino , Estudios Prospectivos , Flujo de TrabajoRESUMEN
Healthy eating is a challenge for most college students, and students in the field of veterinary medicine are no exception. Health experts have recommended that universities emphasize the importance of healthy eating and promote healthy eating habits among students. However, before we can begin offering targeted interventions to promote healthy eating strategies and behaviors, we must first understand students' current strategies used for making healthy eating choices, self-reported eating habits, and perceptions of diet quality. Thus, the purpose of this study was to understand veterinary medical students' perceptions of current diet quality and to characterize their strategies for making healthy eating choices. Results indicate veterinary medical students employ a wide range of strategies and behaviors for healthy eating, yet few students reported eating a diet of poor quality. We conclude that while most students report eating a relatively healthy diet, variation in strategies used suggests room for improvement for many. This article discusses potential intervention strategies to promote healthy eating among veterinary students.
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Conducta Alimentaria , Motivación , Estudiantes de Medicina/psicología , Adulto , Animales , Educación en Veterinaria , Femenino , Humanos , Masculino , North Carolina , Encuestas y CuestionariosRESUMEN
The Centers for Disease Control (CDC) declares exercise to be one of the most important activities one can do to improve health. The benefits of exercise are well documented and include both physiologic and psychological health. Given the current landscape of wellness issues in veterinary medical education, it is necessary that students engage in exercise activities to manage stress and increase overall health. Therefore, to develop targeted interventions with the greatest likelihood for success, it is first necessary to understand what motivates veterinary medical students to exercise given their unique situational and environmental factors. This study is the first to explore this issue systematically in veterinary medical education, thus it is the authors' hope that the findings from this research will help identify exercise-related wellness interventions that could be implemented in veterinary medical schools.
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Ejercicio Físico , Motivación , Estudiantes de Medicina/psicología , Adulto , Animales , Educación en Veterinaria , Femenino , Humanos , Masculino , North Carolina , Encuestas y Cuestionarios , Adulto JovenRESUMEN
The Centers for Disease Control (CDC) declares exercise to be one of the most important activities one can do to improve health. The benefits of exercise are well documented and include both physiologic and psychological health. Given the current landscape of wellness issues in veterinary medical education, it is necessary that students engage in exercise activities to manage stress and increase overall health. Therefore, to develop targeted interventions with the greatest likelihood for success, it is first necessary to understand what motivates veterinary medical students to exercise given their unique situational and environmental factors. This study is the first to explore this issue systematically in veterinary medical education, thus it is the authors' hope that the findings from this research will help identify exercise-related wellness interventions that could be implemented in veterinary medical schools.
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We compared changes in academic achievement across 3years between children in elementary schools receiving the Academic Achievement and Physical Activity Across the Curriculum intervention (A+PAAC), in which classroom teachers were trained to deliver academic lessons using moderate-to-vigorous physical activity (MVPA) compared to a non-intervention control. Elementary schools in eastern Kansas (n=17) were cluster randomized to A+PAAC (N=9, target ≥100min/week) or control (N=8). Academic achievement (math, reading, spelling) was assessed using the Wechsler Individual Achievement Test-Third Edition (WIAT-III) in a sample of children (A+PAAC=316, Control=268) in grades 2 and 3 at baseline (Fall 2011) and repeated each spring across 3years. On average 55min/week of A+PACC lessons were delivered each week across the intervention. Baseline WIAT-III scores (math, reading, spelling) were significantly higher in students in A+PAAC compared with control schools and improved in both groups across 3years. However, linear mixed modeling, accounting for baseline between group differences in WIAT-III scores, ethnicity, family income, and cardiovascular fitness, found no significant impact of A+PAAC on any of the academic achievement outcomes as determined by non-significant group by time interactions. A+PAAC neither diminished or improved academic achievement across 3-years in elementary school children compared with controls. Our target of 100min/week of active lessons was not achieved; however, students attending A+PAAC schools received an additional 55min/week of MVPA which may be associated with both physical and mental health benefits, without a reduction in time devoted to academic instruction.
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Éxito Académico , Curriculum , Ejercicio Físico , Niño , Femenino , Humanos , Kansas , Masculino , Instituciones Académicas , EstudiantesRESUMEN
In Drosophila melanogaster, the iab-4/iab-8 locus encodes bi-directionally transcribed microRNAs that regulate the function of flanking Hox transcription factors. We show that bi-directional transcription, temporal and spatial expression patterns and Hox regulatory function of the iab-4/iab-8 locus are conserved between fly and the beetle Tribolium castaneum. Computational predictions suggest iab-4 and iab-8 microRNAs can target common sites, and cell-culture assays confirm that iab-4 and iab-8 function overlaps on Hox target sites in both fly and beetle. However, we observe key differences in the way Hox genes are targeted. For instance, abd-A transcripts are targeted only by iab-8 in Drosophila, whereas both iab-4 and iab-8 bind to Tribolium abd-A. Our evolutionary and functional characterization of a bi-directionally transcribed microRNA establishes the iab-4/iab-8 system as a model for understanding how multiple products from sense and antisense microRNAs target common sites.
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Drosophila melanogaster/genética , MicroARNs/genética , Transcripción Genética , Tribolium/genética , Animales , Línea Celular , Mapeo Cromosómico , Evolución Molecular , Regulación del Desarrollo de la Expresión Génica , Genes Homeobox , Genes de Insecto , Sitios Genéticos , MicroARNs/metabolismo , Filogenia , Interferencia de ARNRESUMEN
Introduction: Oral P2Y12 inhibitors (P2Y12-I) are commonly used antiplatelet drugs in patients with end-stage kidney disease (ESKD) on chronic dialysis. Although gaps in prescription refills are quite common in patients with ESKD, it remains unclear whether P2Y12-I prescription refill patterns are associated with adverse clinical outcomes. Methods: We used the United States Renal Data System (USRDS) registry for patients with ESKD to capture new P2Y12-I prescriptions from 2011 to 2015. The primary exposure was prescription refill patterns and the primary outcome was all-cause death. Results: Among the 31,243 patients with new P2Y12-I prescription, median age was 64 years; 54% were male; and 39% were Caucasian, 37% African American, and 18% Hispanic. We observed 3 P2Y12-I refill patterns as follows: continuous users (45.1%), noncontinuous users (3.6%), and users with ≥30 days refill gap (51.4%). Prescription refill pattern with ≥30 days refill gap (vs. continuous use) was associated with all-cause death (adjusted hazard ratio [HR]: 1.18; 95% confidence interval [CI]: 1.13-1.23). Age and race were the most important risk factors associated with prescription refill pattern. African Americans (vs. Caucasians) were more likely to demonstrate ≥30 days refill gap, (adjusted odds ratio [OR]: 1.43; 95% CI: 1.36-1.51). In addition, younger patients (vs. older) were more likely to demonstrate ≥30 day refill gap (adjusted OR/decade: 0.9; 95% CI: 0.89-0.92). Conclusion: Nonadherence to P2Y12-I prescriptions is quite common, and disproportionately affects minorities. Younger individuals with ESKD are independently associated with a higher risk of death. The odds of having a refill gap are decreasing for older patients who are more compliant than younger patients. Future studies should investigate whether phenotyping subgroups of patients with ESKD based on prescription refill patterns can help in improving adverse clinical outcomes.
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Circadian clocks provide an internal measure of external time allowing organisms to anticipate and exploit predictable daily changes in the environment. Rhythms driven by circadian clocks have a temperature compensated periodicity of approximately 24 hours that persists in constant conditions and can be reset by environmental time cues. Computational modelling has aided our understanding of the molecular mechanisms of circadian clocks, nevertheless it remains a major challenge to integrate the large number of clock components and their interactions into a single, comprehensive model that is able to account for the full breadth of clock phenotypes. Here we present a comprehensive dynamic model of the Neurospora crassa circadian clock that incorporates its key components and their transcriptional and post-transcriptional regulation. The model accounts for a wide range of clock characteristics including: a periodicity of 21.6 hours, persistent oscillation in constant conditions, arrhythmicity in constant light, resetting by brief light pulses, and entrainment to full photoperiods. Crucial components influencing the period and amplitude of oscillations were identified by control analysis. Furthermore, simulations enabled us to propose a mechanism for temperature compensation, which is achieved by simultaneously increasing the translation of frq RNA and decreasing the nuclear import of FRQ protein.
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Relojes Circadianos/fisiología , Péptidos y Proteínas de Señalización del Ritmo Circadiano/fisiología , Proteínas Fúngicas/fisiología , Modelos Biológicos , Neurospora crassa/fisiología , Sensación Térmica/fisiología , Simulación por Computador , Retroalimentación Fisiológica/fisiologíaRESUMEN
The photoreceptor and PAS/LOV protein VIVID (VVD) modulates blue-light signaling and influences light and temperature responses of the circadian clock in Neurospora crassa. One of the main actions of VVD on the circadian clock is to influence circadian clock phase by regulating levels of the transcripts encoded by the central clock gene frequency (frq). How this regulation is achieved is unknown. Here we show that VVD interacts with complexes central for circadian clock and blue-light signaling, namely the WHITE-COLLAR complex (WCC) and FREQUENCY-interacting RNA helicase (FRH), a component that complexes with FRQ to mediate negative feedback control in Neurospora. VVD interacts with FRH in the absence of WCC and FRQ but does not seem to control the exosome-mediated negative feedback loop. Instead, VVD acts to modulate the transcriptional activity of the WCC.
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Ritmo Circadiano/fisiología , Proteínas de Unión al ADN/fisiología , Proteínas Fúngicas/fisiología , Neurospora crassa/fisiología , Neurospora crassa/efectos de la radiación , ARN Helicasas/fisiología , Factores de Transcripción/fisiología , Secuencia de Bases , Núcleo Celular/metabolismo , Ritmo Circadiano/genética , Citoplasma/metabolismo , Proteínas de Unión al ADN/genética , Retroalimentación Fisiológica , Proteínas Fúngicas/genética , Regulación Fúngica de la Expresión Génica , Genes Fúngicos , Luz , Modelos Biológicos , Neurospora crassa/genética , Fotorreceptores Microbianos/genética , Fotorreceptores Microbianos/fisiología , ARN Helicasas/genética , ARN de Hongos/genética , ARN de Hongos/metabolismo , ARN Mensajero/genética , ARN Mensajero/metabolismo , Transducción de Señal , Factores de Transcripción/genéticaRESUMEN
Both the APOE ε4 and TOMM40 rs10524523 ("523") genes have been associated with risk for Alzheimer's disease (AD) and neuroimaging biomarkers of AD. No studies have investigated the relationship of TOMM40'523-APOE ε4 on the structural complexity of the brain in AD individuals. We quantified brain morphology and multiple cortical attributes in individuals with mild cognitive impairment (MCI) and AD, then tested whether APOE ε4 or TOMM40 poly-T genotypes were related to AD morphological biomarkers in cognitively unimpaired (CU) and MCI/AD individuals. We identified several AD-specific phenotypes in brain morphology and found that TOMM40 poly-T short alleles are associated with early, AD-specific brain morphological differences in healthy aging. We observed decreased cortical thickness, sulcal depth, and fractal dimension in CU individuals with the poly-T short alleles. Moreover, in MCI/AD participants, the APOE ε4 (TOMM40 L) individuals had a higher rate of gene-related morphological markers indicative of AD. Our data suggest that TOMM40'523 is associated with early brain structure variations in the precuneus, temporal, and limbic cortices.
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Enfermedad de Alzheimer , Humanos , Haplotipos , Enfermedad de Alzheimer/diagnóstico por imagen , Enfermedad de Alzheimer/genética , Apolipoproteína E4/genética , Genotipo , Fenotipo , Biomarcadores , Proteínas del Complejo de Importación de Proteínas Precursoras MitocondrialesRESUMEN
Background: The COVID-19 pandemic resulted in implementation of restrictive public health policies requiring people to limit or avoid interaction with others. These policies also had an economic impact. Individuals with multiple sclerosis (MS) already experience higher incidences of depression, anxiety, social isolation, and job loss, and the continuing pandemic may exacerbate these. Methods: Between November 2, 2020, and February 12, 2021, 233 individuals with MS completed the Hospital Anxiety and Depression Scale, the modified Medical Outcomes Study Social Support Survey, the Centers for Disease Control/National Institutes of Health Common Data Element Repository economic impact questions, and study team-designed questions about social and family relationships and adherence to public health policies. Results: Study participants reported high rates of mask wearing, good hand hygiene, and limited interactions with those outside their homes. They felt isolated from family they did not live with, friends, and coworkers. The frequency of conflicts with their spouses/partners increased "a little" among 20% of respondents, but overall relationships with housemates were "unchanged" or "a little better." Ninety-one percent of participants reported experiencing no financial impact. On the Hospital Anxiety and Depression Scale, 16.0% of 218 respondents reported depressive symptoms and 26.8% of 216 reported symptoms of anxiety above the commonly accepted clinically significant cutoff points. Only 3.4% of participants reported contracting SARS-CoV-2. Conclusions: During the first year of the pandemic, this study found no pronounced impact on the emotional, social, or economic stability of the individuals with MS it surveyed. It seems that these study participants adapted to the restrictions created by the pandemic and, by adhering to guidelines, protected themselves from contracting SARS-CoV-2.
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INTRODUCTION: Circulatory-respiratory death declaration is a common duty of physicians, but little is known about the amount of education and physician practice patterns in completing this examination. METHODS: An online survey of physicians was conducted evaluating the rate of formal training and specific examination techniques used in the pronouncement of circulatory-respiratory death. Data, including the level of practice, training received in a formal death declaration, and examination components, were collected. RESULTS: Respondents were attending physicians (52.4%), residents (30.2%), fellows (10.7%), and interns (6.7%). Most respondents indicated they had received no formal training in death pronouncement; however, most reported self-perceived competence. When comparing examination components used by the study's cohort, 95 different examination combinations were used for death pronouncement. CONCLUSIONS: Formal training in death pronouncement was uncommon and clinical practice varied. Implementation of formal training and standardization of the examination are necessary to improve physician competence and reliability in death declarations.
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INTRODUCTION: Although oral P2Y12 inhibitors (P2Y12-Is) are one of the most commonly prescribed medication classes in patients with end stage kidney disease on dialysis (ESKD), scarce data exist regarding their benefits and risks. METHODS: We compared effectiveness and safety of clopidogrel, prasugrel, and ticagrelor in a longitudinal study using the United States Renal Data System registry of Medicare beneficiaries with ESKD. Individuals who filled new P2Y12-I prescriptions between 2011 and 2015 were included and followed until death or censoring. The primary exposure variable was P2Y12-I assignment. The primary outcome variable was death. Secondary outcomes included cardiovascular (CV) death, coronary revascularization, and gastrointestinal (GI) hemorrhage. Survival analyses were performed after propensity matching. RESULTS: Of 44,619 patients with ESKD who received P2Y12-Is, 95% received clopidogrel (n = 42,523), 3% prasugrel (n = 1205), and 2% ticagrelor (n = 891). To balance baseline differences, propensity-matching was performed: 1:6 for prasugrel (n = 1189) versus clopidogrel (n = 7134); 1:4 for ticagrelor (n = 880) versus clopidogrel (n = 3520); and 1:1 for ticagrelor versus prasugrel (n = 880). Prasugrel was associated with a reduced risk for death versus clopidogrel and ticagrelor (adjusted hazard ratio [HR] = 0.82; 95% CI: 0.73-0.93 and 0.78; 95% CI: 0.64-0.95). Compared with clopidogrel, prasugrel reduced risk for coronary revascularization (HR = 0.91; 95% CI: 0.86-0.96). There were no differences in GI hemorrhage between P2Y12-Is. CONCLUSION: In patients with ESKD, prasugrel compared with others reduced risk of death possibly by reducing risk for coronary revascularizations and without worsening gastrointestinal hemorrhage. Future trials are imperative to compare efficacy and safety of P2Y12-Is in patients with ESKD.