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1.
EMBO Mol Med ; 2024 Aug 05.
Artículo en Inglés | MEDLINE | ID: mdl-39103698

RESUMEN

Chemotherapy, the standard of care treatment for cancer patients with advanced disease, has been increasingly recognized to activate host immune responses to produce durable outcomes. Here, in colorectal adenocarcinoma (CRC) we identify oxaliplatin-induced Thioredoxin-Interacting Protein (TXNIP), a MondoA-dependent tumor suppressor gene, as a negative regulator of Growth/Differentiation Factor 15 (GDF15). GDF15 is a negative prognostic factor in CRC and promotes the differentiation of regulatory T cells (Tregs), which inhibit CD8 T-cell activation. Intriguingly, multiple models including patient-derived tumor organoids demonstrate that the loss of TXNIP and GDF15 responsiveness to oxaliplatin is associated with advanced disease or chemotherapeutic resistance, with transcriptomic or proteomic GDF15/TXNIP ratios showing potential as a prognostic biomarker. These findings illustrate a potentially common pathway where chemotherapy-induced epithelial oxidative stress drives local immune remodeling for patient benefit, with disruption of this pathway seen in refractory or advanced cases.

2.
Clin Neuropharmacol ; 47(4): 134-139, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39008544

RESUMEN

OBJECTIVE: Lance-Adams syndrome is a rare and debilitating disorder characterized by successful cardiopulmonary resuscitation resulting in myoclonus activity. Alcohol withdrawal seizures from alcohol use disorder may further exacerbate Lance-Adams syndrome. We aim to present a case of Lance-Adams syndrome complicated by alcohol withdrawal seizures and successfully treated with a combination of valproate, clonazepam, and gabapentin. MATERIALS AND METHODS: The patient's electronic medical record, direct patient care experiences, and a comprehensive literature search were used for this case report. We report a 41-year-old male patient with Lance-Adams syndrome with concurrent alcohol use disorder. Treatment was improved when adding gabapentin for alcohol use disorder treatment, alongside combination antiepileptic therapy. A PubMed search was conducted to examine Lance-Adams syndrome case reports of successful combination antiepileptic therapy, with a secondary evaluation of patients with concurrent alcohol use disorder. RESULTS: The literature search yielded 18 articles, which resulted in 21 individual cases in which combination antiepileptic drug therapy was successful in treating myoclonus secondary to Lance-Adams syndrome; however, none of the case reports utilized gabapentin synergistically. One case described Lance-Adams syndrome complicated by alcohol consumption and similar to our patient, the patient used alcohol to abolish myoclonic activity. CONCLUSIONS: To the best of our knowledge, this is the first case report documenting a patient with Lance-Adams syndrome and concurrent alcohol use disorder, with a positive effect of gabapentin use. Gabapentin, when used for alcohol use disorder treatment, may be an appropriate adjunct agent in the management of patients receiving combination antiepileptic therapy for the treatment of Lance-Adams syndrome.


Asunto(s)
Convulsiones por Abstinencia de Alcohol , Anticonvulsivantes , Quimioterapia Combinada , Gabapentina , Humanos , Gabapentina/uso terapéutico , Masculino , Adulto , Anticonvulsivantes/uso terapéutico , Convulsiones por Abstinencia de Alcohol/tratamiento farmacológico , Convulsiones por Abstinencia de Alcohol/complicaciones , Sinergismo Farmacológico , Ácido Valproico/uso terapéutico , Clonazepam/uso terapéutico , Mioclonía/tratamiento farmacológico , Mioclonía/etiología
3.
Epidemiol Infect ; 152: e78, 2024 May 06.
Artículo en Inglés | MEDLINE | ID: mdl-38705587

RESUMEN

In September 2023, the UK Health Security Agency identified cases of Salmonella Saintpaul distributed across England, Scotland, and Wales, all with very low genetic diversity. Additional cases were identified in Portugal following an alert raised by the United Kingdom. Ninety-eight cases with a similar genetic sequence were identified, 93 in the United Kingdom and 5 in Portugal, of which 46% were aged under 10 years. Cases formed a phylogenetic cluster with a maximum distance of six single nucleotide polymorphisms (SNPs) and average of less than one SNP between isolates. An outbreak investigation was undertaken, including a case-control study. Among the 25 UK cases included in this study, 13 reported blood in stool and 5 were hospitalized. One hundred controls were recruited via a market research panel using frequency matching for age. Multivariable logistic regression analysis of food exposures in cases and controls identified a strong association with cantaloupe consumption (adjusted odds ratio: 14.22; 95% confidence interval: 2.83-71.43; p-value: 0.001). This outbreak, together with other recent national and international incidents, points to an increase in identifications of large outbreaks of Salmonella linked to melon consumption. We recommend detailed questioning and triangulation of information sources to delineate consumption of specific fruit varieties during Salmonella outbreaks.


Asunto(s)
Brotes de Enfermedades , Intoxicación Alimentaria por Salmonella , Humanos , Portugal/epidemiología , Masculino , Adulto , Femenino , Reino Unido/epidemiología , Persona de Mediana Edad , Niño , Adolescente , Estudios de Casos y Controles , Adulto Joven , Anciano , Preescolar , Intoxicación Alimentaria por Salmonella/epidemiología , Intoxicación Alimentaria por Salmonella/microbiología , Cucumis melo/microbiología , Salmonella/genética , Salmonella/aislamiento & purificación , Salmonella/clasificación , Lactante , Anciano de 80 o más Años , Filogenia
4.
Ment Health Clin ; 14(2): 92-96, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38694886

RESUMEN

Introduction: Studies indicate that long-acting injectable antipsychotics (LAIAs) reduce the risk of relapse and hospitalization compared with oral antipsychotics (APs) in adults. Oral formulations of APs are well-studied in the pediatric population, but little is known regarding the off-label use of LAIAs in this population. Methods: This retrospective chart review evaluated readmission rates for pediatric patients admitted to a psychiatric ward in a large academic hospital between January 1, 2015, and December 1, 2022, requiring AP therapy. The experimental group included patients initiated on LAIA therapy, and the control group included patients initiated on a new oral AP. Patients were matched by several clinical factors. Results: Each group consisted of 38 patients. For the primary outcome, hospital readmission rates at 3 months, the LAIA group had a 13.2% readmission rate compared with 26.3% in the comparator group (p = .153). In months 4 through 6, there was a 5.3% versus 15.8% readmission rate, respectively (p = .139). In months 7 through 12, it was 7.9% versus 18.4% (p = .179). There were significantly fewer cumulative readmissions at the 1-year mark in the LAIA group (N = 9, 23.7%) compared with the oral AP group (N = 18, 47.4%) (p = .031). No statistically significant differences were seen in hospital length of stay although results numerically favored LAIA. Discussion: In a pediatric population, the administration of an LAIA when compared with the oral equivalent resulted in numerically fewer hospital readmissions, decreased length of stay, and fewer adverse effects, but these effects were not statistically significant except for cumulative readmissions at 1 year.

5.
Immunity ; 57(5): 1141-1159.e11, 2024 May 14.
Artículo en Inglés | MEDLINE | ID: mdl-38670113

RESUMEN

Broadly neutralizing antibodies (bnAbs) targeting the hemagglutinin (HA) stem of influenza A viruses (IAVs) tend to be effective against either group 1 or group 2 viral diversity. In rarer cases, intergroup protective bnAbs can be generated by human antibody paratopes that accommodate the conserved glycan differences between the group 1 and group 2 stems. We applied germline-engaging nanoparticle immunogens to elicit a class of cross-group bnAbs from physiological precursor frequency within a humanized mouse model. Cross-group protection depended on the presence of the human bnAb precursors within the B cell repertoire, and the vaccine-expanded antibodies enriched for an N55T substitution in the CDRH2 loop, a hallmark of the bnAb class. Structurally, this single mutation introduced a flexible fulcrum to accommodate glycosylation differences and could alone enable cross-group protection. Thus, broad IAV immunity can be expanded from the germline repertoire via minimal antigenic input and an exceptionally simple antibody development pathway.


Asunto(s)
Anticuerpos Neutralizantes , Anticuerpos Antivirales , Virus de la Influenza A , Vacunas contra la Influenza , Infecciones por Orthomyxoviridae , Vacunación , Animales , Ratones , Humanos , Anticuerpos Antivirales/inmunología , Vacunas contra la Influenza/inmunología , Virus de la Influenza A/inmunología , Anticuerpos Neutralizantes/inmunología , Infecciones por Orthomyxoviridae/inmunología , Infecciones por Orthomyxoviridae/prevención & control , Glicoproteínas Hemaglutininas del Virus de la Influenza/inmunología , Sustitución de Aminoácidos , Linfocitos B/inmunología , Gripe Humana/inmunología , Gripe Humana/prevención & control , Anticuerpos ampliamente neutralizantes/inmunología
6.
AIDS Behav ; 28(4): 1401-1414, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38170275

RESUMEN

People living with HIV (PLH) who live in rural areas of the United States (US) face more challenges to obtaining medical care and suffer higher mortality rates compared to non-rural PLH. Compared with younger PLH, older PLH (age 50+) also face additional challenges to maintaining their health and wellbeing. Despite the heightened barriers to receiving care and remaining adherent to treatment among older rural PLH, few interventions to increase viral suppression and improve quality of life exist for this population. We pilot-tested four remotely-delivered interventions-group-based social support, group-based stigma-reduction, individual strengths-based case management, and individual technology detailing-aimed to improve care engagement and quality of life in rural older PLH in the southern US. Participants (N = 61, Mage = 58, 75% male) completed surveys and self-collected blood specimens at baseline and 3 months; in between, they were randomized to 0-4 interventions. We assessed feasibility, acceptability, and preliminary impact on medication adherence, viral suppression, quality of life, depressive symptoms, and hypothesized mediating mechanisms. More than 80% participated in assigned intervention(s), and 84% completed the study. Interventions were highly acceptable to participants, with more than 80% reporting they would recommend interventions to peers. More than 80% found the social support and case management interventions to be relevant and enjoyable. We found promising preliminary impact of interventions on quality of life, medication adherence, depressive symptoms, internalized stigma, and loneliness. Remotely-delivered interventions targeting rural older PLH are feasible to conduct and acceptable to participants. Larger scale study of these interventions is warranted.


RESUMEN: A pesar de las múltiples barreras para la adherencia a la medicación y la recepción de atención entre las personas mayores de zonas rurales que viven con el VIH, existen pocas intervenciones para mejorar la supresión viral y la calidad de vida para esta población. Realizamos pruebas piloto de intervenciones realizadas de forma remota (grupos de apoyo social, grupos de reducción del estigma, manejo de casos basado en los puntos fuertes y "technology detailing") entre las personas que viven con el VIH en zonas rurales del sur de Estados Unidos. Los participantes (N = 61, Medad = 58, 75% hombres) completaron encuestas y recolectaron muestras de sangre al inicio y a los 3 meses; en el medio, fueron asignados al azar a 0­4 intervenciones. Evaluamos la viabilidad, la aceptabilidad y el impacto preliminar. Más del 80% participó en la(s) intervención(es) y el 84% completó el estudio. Las intervenciones fueron muy aceptables para los participantes; más del 80% consideró que las intervenciones de apoyo social y gestión de casos eran relevantes y agradables. Las intervenciones tuvieron un impacto preliminar prometedor sobre la calidad de vida, la adherencia a la medicación, los síntomas depresivos, el estigma y la soledad. Las intervenciones realizadas a distancia dirigidas a las personas que viven con el VIH en zonas rurales de edad avanzada son viables y aceptables, y se justifica un estudio a mayor escala.


Asunto(s)
Infecciones por VIH , Calidad de Vida , Humanos , Masculino , Anciano , Persona de Mediana Edad , Femenino , Estudios de Factibilidad , Infecciones por VIH/tratamiento farmacológico , Infecciones por VIH/epidemiología , Apoyo Social , Población Rural
7.
Br J Cancer ; 129(12): 1877-1892, 2023 12.
Artículo en Inglés | MEDLINE | ID: mdl-37794178

RESUMEN

Thioredoxin-interacting protein (TXNIP) is commonly considered a master regulator of cellular oxidation, regulating the expression and function of Thioredoxin (Trx). Recent work has identified that TXNIP has a far wider range of additional roles: from regulating glucose and lipid metabolism, to cell cycle arrest and inflammation. Its expression is increased by stressors commonly found in neoplastic cells and the wider tumor microenvironment (TME), and, as such, TXNIP has been extensively studied in cancers. In this review, we evaluate the current literature regarding the regulation and the function of TXNIP, highlighting its emerging role in modulating signaling between different cell types within the TME. We then assess current and future translational opportunities and the associated challenges in this area. An improved understanding of the functions and mechanisms of TXNIP in cancers may enhance its suitability as a therapeutic target.


Asunto(s)
Neoplasias , Tiorredoxinas , Humanos , Proteínas Portadoras/genética , Proteínas Portadoras/metabolismo , Glucosa , Inflamación , Neoplasias/inmunología , Neoplasias/metabolismo , Oxidación-Reducción , Tiorredoxinas/metabolismo , Microambiente Tumoral
8.
Euro Surveill ; 28(43)2023 10.
Artículo en Inglés | MEDLINE | ID: mdl-37883039

RESUMEN

Routine laboratory surveillance has identified an unprecedented and ongoing exceedance of Cryptosporidium spp. across the United Kingdom, notably driven by C. hominis transmission, since 14 August 2023. Information from 477 reported cases in England and Wales, followed up with a standardised exposure questionnaire as of 25 September 2023, identified foreign travel in 250 (54%) of 463 respondents and swimming in 234 (66%) of 353 cases. A significant, common exposure has not yet been identified in first analyses.


Asunto(s)
Criptosporidiosis , Cryptosporidium , Humanos , Cryptosporidium/genética , Criptosporidiosis/diagnóstico , Criptosporidiosis/epidemiología , Reino Unido/epidemiología , Inglaterra/epidemiología , Gales/epidemiología
9.
Acad Psychiatry ; 47(6): 589-590, 2023 12.
Artículo en Inglés | MEDLINE | ID: mdl-37704879
10.
Am J Manag Care ; 29(8): 424-428, 2023 08.
Artículo en Inglés | MEDLINE | ID: mdl-37616149

RESUMEN

OBJECTIVES: To evaluate the appropriateness of the medication management for anyone who might have been affected by the Horizon New Jersey Health Medicaid Health Maintenance Organization (HNJH Medicaid HMO) formulary update from empagliflozin to ertugliflozin and to then optimize drug selection and monitoring. STUDY DESIGN: This is a single-center, 2-phase, pilot project led by 2 pharmacy students and the lead clinical pharmacist at a federally qualified health center in Trenton, New Jersey. METHODS: The primary outcome of the study is the number and percentage of patients whose prescription was changed inappropriately from empagliflozin to ertugliflozin. Secondary outcomes include the number and percentage of patients whose prescription was changed inappropriately because of failure to consider cardiovascular history and/or missed renal function checks and whether pharmacists were able to optimize therapy. Data were generated from electronic health record reports and analyzed in Microsoft Excel. RESULTS: A total of 126 unique patients were identified as receiving empagliflozin and/or ertugliflozin and 16 patients were switched from empagliflozin to ertugliflozin, all of whom had HNJH Medicaid HMO. Thirteen of the 16 (81.3%) patients were managed inappropriately based on their history of cardiovascular disease or inappropriate renal monitoring. Pharmacists recommended 22 interventions for patients who received empagliflozin and/or ertugliflozin, and all recommendations were accepted by providers. CONCLUSIONS: Following the HNJH Medicaid HMO's coverage update from empagliflozin to ertugliflozin, some patients received inappropriate therapy and providers accepted clinical pharmacists' recommendations to optimize therapy.


Asunto(s)
Compuestos Bicíclicos Heterocíclicos con Puentes , Farmacéuticos , Estados Unidos , Humanos , Proyectos Piloto
11.
Nat Commun ; 14(1): 5249, 2023 08 28.
Artículo en Inglés | MEDLINE | ID: mdl-37640732

RESUMEN

Low affinity is common for germline B cell receptors (BCR) seeding development of broadly neutralizing antibodies (bnAbs) that engage hypervariable viruses, including HIV. Antibody affinity selection is also non-homogenizing, insuring the survival of low affinity B cell clones. To explore whether this provides a natural window for expanding human B cell lineages against conserved vaccine targets, we deploy transgenic mice mimicking human antibody diversity and somatic hypermutation (SHM) and immunize with simple monomeric HIV glycoprotein envelope immunogens. We report an immunization regimen that focuses B cell memory upon the conserved CD4 binding site (CD4bs) through both conventional affinity maturation and reproducible expansion of low affinity BCR clones with public patterns in SHM. In the latter instance, SHM facilitates target acquisition by decreasing binding strength. This suggests that permissive B cell selection enables the discovery of antibody epitopes, in this case an HIV bnAb site.


Asunto(s)
Vacunas contra el SIDA , Infecciones por VIH , Humanos , Animales , Ratones , Linfocitos B , Células B de Memoria , Receptores de Antígenos de Linfocitos B/genética , Anticuerpos ampliamente neutralizantes , Antígenos VIH , Ratones Transgénicos , Infecciones por VIH/prevención & control
12.
Ment Health Clin ; 13(1): 18-24, 2023 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-36891480

RESUMEN

Introduction: Diabetes and depression may present concurrently, and clinical pharmacists are well equipped to manage these conditions. Clinical pharmacists were grant funded to implement a diabetes-focused randomized controlled trial in a Federally Qualified Health Center. The objective of this analysis is to evaluate if glycemic control and depressive symptoms improve for patients with diabetes and depression with additional management from clinical pharmacists compared with those receiving the standard of care. Methods: This is a post hoc subgroup analysis of a diabetes-focused randomized controlled trial. Pharmacists enrolled patients with type 2 diabetes mellitus (T2DM) and a glycated hemoglobin (A1C) greater than 8% and randomly assigned them to 1 of 2 cohorts, one managed by the primary care provider alone and one with additional care from the pharmacist. Pharmacists completed encounters with patients who have T2DM with or without depression to comprehensively optimize pharmacotherapy while tracking glycemic and depressive outcomes throughout the study. Results: A1C improved from baseline to 6 months in patients with depressive symptoms who received additional care from pharmacists by -2.4 percentage points (SD, 2.41) compared with a -0.1 percentage point (SD, 1.78) reduction in the control arm (P .0081), and there was no change in depressive symptoms. Discussion: Patients with T2DM and depressive symptoms experienced better diabetes outcomes with additional pharmacist management compared with a similar cohort of patients with depressive symptoms, managed independently by primary care providers. These patients with diabetes and comorbid depression received a higher level of engagement and care from the pharmacists, which led to more therapeutic interventions.

13.
WMJ ; 122(5): 377-379, 2023 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-38180928

RESUMEN

INTRODUCTION: The novel coronavirus (COVID-19) is a respiratory illness that may cause neuropsychiatric sequelae, including persistent psychotic symptoms. CASE PRESENTATION: A 70-year-old White man with no prior psychiatric history presented with altered mental status, Cotard's syndrome, and rigid delusions of poverty and homelessness 6 weeks after recovering from a mild case of COVID-19. After extensive medical workup revealed no organic etiology, he was treated for psychotic symptoms with an atypical antipsychotic, an antidepressant, and electroconvulsive therapy, with improvement over time. DISCUSSION: While COVID-19 is primarily a respiratory disease, some individuals may develop new-onset psychiatric or neuropsychiatric symptoms without prior psychiatric history. CONCLUSIONS: To our knowledge, this is the only published case of post-COVID-19 psychotic symptoms treated with electroconvulsive therapy. As the pandemic continues, the total impact of COVID-19 on psychotic symptoms remains to be seen.


Asunto(s)
Antipsicóticos , COVID-19 , Trastornos Mentales , Masculino , Humanos , Anciano , Deluciones , SARS-CoV-2
14.
J Am Pharm Assoc (2003) ; 62(3): 775-782.e3, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35027281

RESUMEN

BACKGROUND: There is a growing shortage of primary care physicians. Pharmacists can fill the gap, and interdisciplinary teams are being evaluated as part of health care reform. OBJECTIVE: This study aimed to determine whether adding a pharmacist to an interprofessional health team will improve diabetes outcomes. METHODS: In this 2-phase pilot study, Medicaid-eligible patients with diabetes were randomized to receive standard of care (control arm) or standard of care plus the care of a pharmacist (intervention arm) for 12 months (phase 1). The primary outcome was change in glycated hemoglobin (A1C) from baseline. Secondary outcomes included identifying and correcting medication therapy problems (MTPs) for comorbid conditions, adherence to preventive care visits, health care utilization, self-rated health, and satisfaction surveys. After phase 1, patients in the control arm who did not achieve an A1C of < 8% were eligible to enroll into phase 2 where they received treatment with a pharmacist for 6 months. RESULTS: Of the 239 patients enrolled, 122 completed phase 1. At 12 months, intervention patients' mean A1C was 1.85 percentage point (pp) below baseline versus 0.94 pp for control (between-group difference 0.91 pp; P = 0.0218). Most control patients (79%) who completed phase 1 and enrolled into phase 2 improved their A1C by more than 1 pp (P < 0.01). The pharmacists completed 806 patient visits and identified 2638 MTPs. Intervention patients were more adherent to preventive care visits with nutrition (P = 0.043), ophthalmology (P = 0.002), and dentistry (P = 0.007). For intervention patients, 78% rated their experience with the pharmacist as excellent whereas, for control patients, 37% rated their experience with their provider as excellent. CONCLUSION: Pharmacist comanagement of patients with diabetes can significantly improve glucose control and patient satisfaction. Creative payment models were used to include pharmacists in the interprofessional patient care team.


Asunto(s)
Diabetes Mellitus Tipo 2 , Farmacéuticos , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Hemoglobina Glucada/análisis , Humanos , Cumplimiento de la Medicación , Proyectos Piloto
15.
JAMA Netw Open ; 4(6): e216105, 2021 06 01.
Artículo en Inglés | MEDLINE | ID: mdl-34086036

RESUMEN

Importance: Although early fluid administration has been shown to lower sepsis mortality, positive fluid balance has been associated with adverse outcomes. Little is known about associations in non-intensive care unit settings, with growing concern about readmission from excess fluid accumulation in patients with sepsis. Objective: To evaluate whether positive fluid balance among non-critically ill patients with sepsis was associated with increased readmission risk, including readmission for heart failure. Design, Setting, and Participants: This multicenter retrospective cohort study was conducted between January 1, 2012, and December 31, 2017, among 57 032 non-critically ill adults hospitalized for sepsis at 21 hospitals across Northern California. Kaiser Permanente Northern California is an integrated health care system with a community-based population of more than 4.4 million members. Statistical analysis was performed from January 1 to December 31, 2019. Exposures: Intake and output net fluid balance (I/O) measured daily and cumulatively at discharge (positive vs negative). Main Outcomes and Measures: The primary outcome was 30-day readmission. The secondary outcomes were readmission stratified by category and mortality after living discharge. Results: The cohort included 57 032 patients who were hospitalized for sepsis (28 779 women [50.5%]; mean [SD] age, 73.7 [15.5] years). Compared with patients with positive I/O (40 940 [71.8%]), those with negative I/O (16 092 [28.2%]) were older, with increased comorbidity, acute illness severity, preexisting heart failure or chronic kidney disease, diuretic use, and decreased fluid administration volume. During 30-day follow-up, 8719 patients (15.3%) were readmitted and 3639 patients (6.4%) died. There was no difference in readmission between patients with positive vs negative I/O (HR, 1.00; 95% CI, 0.95-1.05). No association was detected between readmission and I/O using continuous, splined, and quadratic function transformations. Positive I/O was associated with decreased heart failure-related readmission (HR, 0.80 [95% CI, 0.71-0.91]) and increased 30-day mortality (HR, 1.23 [95% CI, 1.15-1.31]). Conclusions and Relevance: In this large observational study of non-critically ill patients hospitalized with sepsis, there was no association between positive fluid balance at the time of discharge and readmission. However, these findings may have been limited by variable recording and documentation of fluid intake and output; additional studies are needed to examine the association of fluid status with outcomes in patients with sepsis to reduce readmission risk.


Asunto(s)
Fluidoterapia/métodos , Alta del Paciente/estadística & datos numéricos , Sepsis/epidemiología , Sobrevivientes/estadística & datos numéricos , Equilibrio Hidroelectrolítico , Adulto , Anciano , California , Femenino , Insuficiencia Cardíaca/epidemiología , Humanos , Masculino , Persona de Mediana Edad , Readmisión del Paciente/estadística & datos numéricos , Estudios Retrospectivos , Sepsis/terapia
16.
Orthopedics ; 44(3): 166-171, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-33416896

RESUMEN

Soft tissue sarcomas are rare malignancies that are often presumed to be benign and are resected without the typical preoperative workup, such as imaging or biopsy. These unplanned resections occur in approximately 30% of all cases and frequently require further morbid treatments, resulting in worse oncologic outcomes. A retrospective review was performed of all patients who presented to a tertiary sarcoma center with a diagnosis of sarcoma between 1996 and 2017. In-depth chart reviews were performed for the 2600 patients who were identified, with 836 having a primary diagnosis of soft tissue sarcoma in an upper or lower extremity. Data collected included histologic features, grade, size, resection status, demographic features, referral information, metastatic disease, morbid procedures, and mortality rate. Patients were divided into 2 groups based on whether the tumor size was greater or less than 5 cm. This classification was in keeping with the guideline of referring patients to a tertiary sarcoma center for workup for tumors "larger than a golf ball." The difference in the rate of unplanned resection for tumors measuring less than 5 cm (41.6%) and those measuring 5 cm or greater (18.8%) was statistically significant (P<.001), with smaller tumors more likely to undergo unplanned resection, in keeping with the success of the "golf ball rule." The rate of metastatic disease for unplanned resection for tumors measuring 5 cm or greater (50.7%) was significantly greater than that for tumors measuring less than 5 cm (19.7%) (P<.001). The authors found a great deal of morbidity associated with unplanned resection, regardless of tumor size. Before resection is planned, delineation is required beyond tumor size. [Orthopedics. 2021;44(3):166-171.].


Asunto(s)
Reoperación/estadística & datos numéricos , Sarcoma/patología , Sarcoma/cirugía , Adulto , Anciano , Biopsia , Humanos , Masculino , Persona de Mediana Edad , Morbilidad , Metástasis de la Neoplasia , Estudios Retrospectivos , Sarcoma/mortalidad
17.
Curr Drug Targets ; 22(5): 505-538, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-32814524

RESUMEN

We describe herein the therapeutic targets involved in Alzheimer's disease as well as the available drugs and their synthetic routes. Bioactive compounds under development are also exploited to illustrate some recent research advances on the medicinal chemistry of Alzheimer's disease, including structure-activity relationships for some targets. The importance of multi-target approaches, including some examples from our research projects, guides new perspectives in search of more effective drug candidates. This review comprises the period between 2001 and early 2020.


Asunto(s)
Enfermedad de Alzheimer , Preparaciones Farmacéuticas , Enfermedad de Alzheimer/tratamiento farmacológico , Inhibidores de la Colinesterasa/farmacología , Humanos , Ligandos , Relación Estructura-Actividad
18.
Am J Manag Care ; 26(5): e162-e165, 2020 05 01.
Artículo en Inglés | MEDLINE | ID: mdl-32436685

RESUMEN

OBJECTIVES: To implement a project of linked pharmacist-provider new patient visits and then evaluate the impact on the productivity of the provider and pharmacist. STUDY DESIGN: A clinical pharmacist was integrated into the workflow at 2 sites (sites A and B) of Henry J. Austin Health Center, a federally qualified health center, so that new patients were scheduled to see the pharmacist in a 15-minute encounter immediately before a 15-minute encounter with the primary care provider. METHODS: Reports generated in the electronic health record were downloaded into Microsoft Excel for statistical analysis. Two-sample 2-tailed t tests assuming unequal variances were used to evaluate changes in the mean number of appointments checked in and canceled before and after the project's implementation to study provider productivity, the primary study outcome. Descriptive statistics were used to report the pharmacist's productivity. RESULTS: Statistically significant increases in the number of checked-in new patient visits and in all visits of any type were observed at site A; however, these changes were not observed at site B. CONCLUSIONS: The linked visits between the pharmacist and provider allowed for increased provider productivity at 1 of the sites. Based on these results and provider feedback from both sites, this project was viewed as a positive initiative. Scheduling challenges were a barrier to project success at site B.


Asunto(s)
Farmacéuticos/organización & administración , Atención Primaria de Salud/organización & administración , Proveedores de Redes de Seguridad/organización & administración , Citas y Horarios , Eficiencia Organizacional , Registros Electrónicos de Salud , Humanos , Rol Profesional
19.
Am J Med ; 133(8): 969-975.e2, 2020 08.
Artículo en Inglés | MEDLINE | ID: mdl-32007455

RESUMEN

BACKGROUND: Hip fracture is common in the elderly, many of whom are on anticoagulation. However, data are limited on outcomes with anticoagulation reversal in patients undergoing hip fracture surgery. METHODS: Adults ≥60 years old on oral anticoagulation who underwent hip fracture surgery at 21 hospitals in Northern California from 2006 to 2016 were identified through electronic databases. Outcomes were compared among patients treated and untreated with anticoagulation reversal preoperatively. RESULTS: Of 1984 patients on oral anticoagulation who underwent hip fracture surgery, 1943 (97.9%) were on warfarin and 41 (2.1%) were on direct oral anticoagulants. Reversal agents were administered to 1635 (82.4%). Compared to a watch-and-wait strategy, patients receiving reversal agents were more likely to be white, male, comorbid, and with higher admission and preoperative international normalized ratios (P <0.001 for all comparisons). No difference for 30-day mortality was detected between reversal vs non-reversal (7.8% vs 6.0%, respectively; hazard ratio [HR], 1.30 [95% confidence interval (CI), 0.82-2.07]). For secondary outcomes, reversal was associated with higher risk of delirium (8.6% vs 4.9%, risk ratio [RR], 1.77 [95% CI, 1.08-2.89]) and increased mean length of stay (6.4 vs 5.8 days, P <0.05). After adjustment, associations were no longer significant for delirium (RR 1.60, 95% CI, 0.97-2.65) or length of stay (mean difference 0.08, 95% CI, -0.55-0.71). No associations were detected between reversal and other secondary outcomes. CONCLUSION: No significant associations were found between reversal agents and 30-day mortality or other outcomes in patients on oral anticoagulation who underwent hip fracture surgery. Further investigation is needed.


Asunto(s)
Anticoagulantes/efectos adversos , Antifibrinolíticos/uso terapéutico , Factores de Coagulación Sanguínea/uso terapéutico , Pérdida de Sangre Quirúrgica/prevención & control , Fracturas de Cadera/cirugía , Hemorragia Posoperatoria/prevención & control , Cuidados Preoperatorios/métodos , Negro o Afroamericano , Anciano , Anciano de 80 o más Años , Anticuerpos Monoclonales Humanizados/uso terapéutico , Artroplastia de Reemplazo de Cadera , Asiático , Transfusión Sanguínea , Estudios de Cohortes , Delirio/epidemiología , Inhibidores del Factor Xa/efectos adversos , Femenino , Fijación Interna de Fracturas , Hispánicos o Latinos , Humanos , Relación Normalizada Internacional , Tiempo de Internación , Masculino , Mortalidad , Procedimientos Ortopédicos , Plasma , Complicaciones Posoperatorias , Hemorragia Posoperatoria/inducido químicamente , Modelos de Riesgos Proporcionales , Estudios Retrospectivos , Factores Sexuales , Vitamina K/uso terapéutico , Warfarina/efectos adversos , Población Blanca
20.
J Arthroplasty ; 34(7S): S17-S23, 2019 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-30982761

RESUMEN

BACKGROUND: Postoperative urinary retention (POUR) is common. Selective alpha-1 adrenergic antagonists, such as tamsulosin, are effective for treating urinary retention. The purpose of this study is to determine whether perioperative prophylactic tamsulosin reduces the incidence of POUR following total hip and knee arthroplasty. METHODS: Male patients 35 years of age and older undergoing primary total hip or knee arthroplasty at a single center from 2015 to 2018 were eligible for inclusion. Patients were randomized to receive tamsulosin 0.4 mg or placebo daily for 5 days preoperatively, the morning of surgery, and the first postoperative day. The incidence of POUR was determined during the postoperative hospitalization. RESULTS: A total of 176 patients were enrolled in the study. Two patients were withdrawn prior to randomization. The remaining 174 were randomized to tamsulosin (n = 87) or placebo (n = 87). After an additional 43 patients were withdrawn prior to surgery, 131 patients completed the study (tamsulosin, n = 64; placebo, n = 67). A total of 42 patients (32.1%) developed POUR, with 18 cases (28.1%) in the tamsulosin group and 24 cases (35.8%) in the placebo group (P = .345), resulting in an odds ratio of 0.701 and a risk difference of 7.69%. CONCLUSION: Prophylactic tamsulosin did not reduce the incidence of POUR after hip and knee arthroplasty compared to placebo. The odds ratio indicates an approximately 30% decreased odds of developing POUR in the tamsulosin group, albeit not statistically significant. Tamsulosin does not appear to be effective as a prophylactic measure for reducing POUR in male hip and knee arthroplasty patients.


Asunto(s)
Artroplastia de Reemplazo de Rodilla/efectos adversos , Complicaciones Posoperatorias , Tamsulosina/administración & dosificación , Cateterismo Urinario/efectos adversos , Retención Urinaria/prevención & control , Adulto , Anciano , Método Doble Ciego , Humanos , Extremidad Inferior , Masculino , Persona de Mediana Edad , Oportunidad Relativa , Periodo Perioperatorio , Periodo Posoperatorio , Periodo Preoperatorio , Factores de Riesgo , Resultado del Tratamiento , Retención Urinaria/etiología
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