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1.
Int J Cancer ; 153(8): 1501-1511, 2023 10 15.
Artículo en Inglés | MEDLINE | ID: mdl-37357950

RESUMEN

We evaluated the safety, tolerability, pharmacokinetics and antitumor activity of barecetamab monotherapy and combination cetuximab therapy in patients with advanced solid cancers, especially head and neck cancer (HNC). Part 1 was a 3 + 3 dose-escalation study in which 15 patients received barecetamab at 1, 3, 5, 10 and 20 mg/kg intravenously (IV) on days 1 and 28 and weekly in patients with advanced solid cancer. Part 2 was a dose-expansion study including two patient groups with advanced HNC, including six patients receiving barecetamab at 20 mg/kg IV every 3 weeks and 12 patients receiving barecetamab and cetuximab (400 mg/m2 on day 1 followed by 250 mg/m2 every week). No dose-limiting toxicities (DLTs) were observed. Maximum serum target engagement was reached with trough levels of doses ≥3 mg/kg IV weekly. Common adverse drug reactions were diarrhea, stomatitis, dermatitis acneiform and decreased appetite. One durable complete response of more than 17 months was observed, and the overall response and disease control rates were 36.4% (4/11) and 81.1% (9/11), respectively, in the combination therapy group. In conclusion, DLT was not observed in barecetamab at 1 to 20 mg/kg. The recommended phase II dose was determined to be 20 mg/kg triweekly. Barecetamab and in cetuximab combination was well tolerated and demonstrated meaningful antitumor effects.


Asunto(s)
Antineoplásicos , Neoplasias de Cabeza y Cuello , Humanos , Anticuerpos Monoclonales/efectos adversos , Antineoplásicos/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/farmacocinética , Cetuximab/efectos adversos , Neoplasias de Cabeza y Cuello/tratamiento farmacológico , Neoplasias de Cabeza y Cuello/etiología , Dosis Máxima Tolerada
2.
Cancer ; 129(19): 2966-2974, 2023 10 01.
Artículo en Inglés | MEDLINE | ID: mdl-37246414

RESUMEN

BACKGROUND: Salivary duct carcinoma (SDC) is uncommon but is the most aggressive subtype of salivary gland carcinomas. The high positivity rate for human epidermal growth factor receptor 2 (HER2) led to an investigation of the efficacy of HER2-targeted agents. Docetaxel-PM (polymeric micelle) is a low-molecular-weight, nontoxic, biodegradable, and docetaxel-loaded micellar formulation. Trastuzumab-pkrb is a biosimilar to trastuzumab. METHODS: This was a multicenter, single-arm, open-label phase 2 study. Patients with HER2-positive (immunohistochemistry [IHC] score of ≥2+ and/or HER2/chromosome enumeration probe 17 [CEP17] ratio of ≥2.0) advanced SDCs were enrolled. Patients received docetaxel-PM (75 mg/m2 ) and trastuzumab-pkrb (8 mg/kg in the first cycle and 6 mg/kg in subsequent cycles) every 3 weeks. Primary end point was objective response rate (ORR). RESULTS: A total of 43 patients were enrolled. The best objective responses were partial response in 30 (69.8%) patients and stable disease in 10 (23.3%) patients, leading to an ORR of 69.8% (95% confidence interval [CI], 53.9-82.8) and a disease control rate of 93.0% (80.9-98.5). Median progression-free survival, duration of response, and overall survival were 7.9 (6.3-9.5), 6.7 (5.1-8.4), and 23.3 (19.9-26.7) months, respectively. Patients with HER2 IHC score of 3+ or HER2/CEP17 ratio ≥2.0 demonstrated better efficacies compared to those with HER2 IHC score of 2+. Thirty-eight (88.4%) patients experienced treatment-related adverse events (TRAE). Because of TRAE, nine (20.9%), 14 (32.6%), and 19 (44.2%) patients required temporary discontinuation, permanent discontinuation, or dose reduction, respectively. CONCLUSIONS: The combination of docetaxel-PM and trastuzumab-pkrb demonstrated promising antitumor activity with a manageable toxicity profile in HER2-positive advanced SDC. PLAIN LANGUAGE SUMMARY: Salivary duct carcinoma (SDC) is uncommon but is the most aggressive subtype of salivary gland carcinomas. SDC shares morphological and histological similarities with invasive ductal carcinoma of breast, which led to an investigation of hormonal receptor and human epidermal growth factor receptor 2 (HER2)/neu expression status in SDC. In this study, patients with HER2-positive SDC were enrolled and treated with combination of docetaxel-polymeric micelle and trastuzumab-pkrb. Promising antitumor activities were shown with objective response rate of 69.8%, disease control rate of 93.0%, median progression-free survival of 7.9 months, median duration of response of 6.7 months, and median overall survival of 23.3 months.


Asunto(s)
Neoplasias de la Mama , Carcinoma Ductal , Humanos , Femenino , Docetaxel/uso terapéutico , Micelas , Anticuerpos Monoclonales Humanizados/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Trastuzumab/uso terapéutico , Receptor ErbB-2/genética , Receptor ErbB-2/metabolismo , Glándulas Salivales/metabolismo , Neoplasias de la Mama/tratamiento farmacológico
3.
MMWR Morb Mortal Wkly Rep ; 72(44): 1173-1182, 2023 Nov 03.
Artículo en Inglés | MEDLINE | ID: mdl-37917558

RESUMEN

Tobacco product use during adolescence increases the risk for lifelong nicotine addiction and adverse health consequences. CDC and the Food and Drug Administration analyzed data from the 2023 National Youth Tobacco Survey to assess tobacco product use patterns among U.S. middle school (grades 6-8) and high school (grades 9-12) students. In 2023, 10.0% of middle and high school students (2.80 million) reported current (i.e., past 30-day) use of any tobacco product. Current use of any tobacco product by high school students declined by an estimated 540,000, from 2.51 million in 2022 to 1.97 million in 2023. From 2022 to 2023, current e-cigarette use among high school students declined from 14.1% to 10.0%. Among middle and high school students, e-cigarette products were the most used tobacco product in 2023 (7.7%; 2.13 million), followed by cigarettes (1.6%), cigars (1.6%), nicotine pouches (1.5%), smokeless tobacco (1.2%), other oral nicotine products (1.2%), hookahs (1.1%), heated tobacco products (1.0%), and pipe tobacco (0.5%). Among students who had ever used an e-cigarette, 46.7% reported current use. In 2023, among students reporting current e-cigarette use, 89.4% used flavored products and 25.2% used an e-cigarette daily; the most commonly reported brands were Elf Bar, Esco Bars, Vuse, JUUL, and Mr. Fog. Given the number of middle and high school students that use tobacco products, sustained efforts to prevent initiation of tobacco product use among young persons and strategies to help young tobacco users quit are critical to reducing U.S. youth tobacco product use.


Asunto(s)
Sistemas Electrónicos de Liberación de Nicotina , Productos de Tabaco , Tabaquismo , Estados Unidos/epidemiología , Humanos , Adolescente , Nicotina , Encuestas Epidemiológicas , Estudios Transversales , Uso de Tabaco/epidemiología , Estudiantes
4.
AJR Am J Roentgenol ; 220(1): 134-140, 2023 01.
Artículo en Inglés | MEDLINE | ID: mdl-35920705

RESUMEN

BACKGROUND. Radiology informatics systems and clinical decision support tools in the electronic health record (EHR) can be leveraged to help impact ordering patterns in response to the ongoing global iodinated contrast media shortage. OBJECTIVE. The purpose of our study was to assess the impact of EHR order entry-based interventions, implemented as part of a health system's response to the global contrast media shortage, on contrast-enhanced CT utilization. METHODS. This retrospective study included 79,259 patients who underwent CT at a large multisite health system between April 1, 2022, and July 3, 2022. Two EHR-based interventions were implemented as part of the health system's response to the global contrast media shortage. A first EHR-based intervention on May 10, 2022, entailed creating an alert that appeared in a sidebar after any contrast-enhanced body CT orders, indicating the present shortage and recommending alternate imaging modalities. A second EHR-based intervention on May 16, 2022, required referrers to enter detailed clinical information for all contrast-enhanced body CT orders, which radiologists used when protocoling examinations. Data regarding CT orders and examinations performed were extracted from the electronic data warehouse. RESULTS. During the preintervention, first postintervention, and second postintervention periods, the mean number of patients who underwent contrast-enhanced CT per weekday was 726, 689, and 639, respectively (p for preintervention vs second postintervention periods, < .001). During the three periods, the mean number of patients who underwent CT per weekday was 1350, 1323, and 1314 (p < .001). During the three periods, the mean number of patients who underwent contrast-enhanced body CT per weekday was 561, 532, and 492 (p < .001). During the three periods, the mean number of orders for CT with IV contrast media per weekday was 154, 143, and 131 (p < .001). During the three periods, the mean number of orders for CT without IV contrast media per weekday was 196, 202, and 221 (p < .001). CONCLUSION. EHR order entry-based interventions implemented in response to the global contrast media shortage significantly reduced contrast-enhanced CT utilization in a large health system. CLINICAL IMPACT. The findings indicate the ability to rapidly achieve changes in ordering clinician behavior and subsequent clinical practice using systemwide EHR changes.


Asunto(s)
Registros Electrónicos de Salud , Radiología , Humanos , Medios de Contraste , Estudios Retrospectivos , Tomografía Computarizada por Rayos X
5.
Nicotine Tob Res ; 25(9): 1610-1613, 2023 08 19.
Artículo en Inglés | MEDLINE | ID: mdl-37279928

RESUMEN

INTRODUCTION: This manuscript examines prevalence of awareness and use of nicotine pouches among U.S. middle and high school students by sociodemographic characteristics and other tobacco product use and characterizes nicotine pouch and other tobacco product use behaviors among current nicotine pouch users. AIMS AND METHODS: Data are from the 2021 National Tobacco Youth Survey, a cross-sectional, school-based survey of middle and high school students (N = 20 413; overall response rate: 44.6%), which included questions on nicotine pouches in 2021 for the first time. Prevalence estimates, 95% confidence intervals, and estimated population counts were assessed for nicotine pouch awareness, ever use, and current (past 30 days) use, and for use behaviors related to nicotine pouches (frequency of use, flavor(s) used) and other tobacco products (ever, current, frequency of use) among current nicotine pouch users. RESULTS: Over one-third of students (35.5%) had ever heard of nicotine pouches. An estimated 1.9% (490 000) reported ever using them, while 0.8% (200 000) reported current use. Among current nicotine pouch users, 61.6% reported flavored nicotine pouch use, 64.2% reported current e-cigarette use, and 52.6% used multiple (≥2) tobacco products. Current use of nicotine pouches was common among current smokeless tobacco users (41.3%). CONCLUSIONS: Overall, in 2021, while relatively few students had ever tried nicotine pouches or currently used them, more than one-third had heard of them. Current nicotine pouch users tended to use other tobacco products, particularly e-cigarettes and smokeless tobacco. Given previous rapid increases in youth uptake of e-cigarettes, it is important to continue monitoring nicotine pouch use among young people. IMPLICATIONS: This study's findings provide an important baseline for future monitoring of nicotine pouch awareness and use among middle and high school students. Emerging tobacco products, particularly those that are flavored, widely available, discreet, and inexpensive have the potential to attract youth. Given the potential of these products to appeal to young people, ongoing monitoring of nicotine pouch use behaviors is important to inform public health and regulatory efforts.


Asunto(s)
Sistemas Electrónicos de Liberación de Nicotina , Productos de Tabaco , Humanos , Adolescente , Estados Unidos/epidemiología , Nicotina , Estudios Transversales , Uso de Tabaco/epidemiología
6.
MMWR Morb Mortal Wkly Rep ; 71(45): 1429-1435, 2022 Nov 11.
Artículo en Inglés | MEDLINE | ID: mdl-36355596

RESUMEN

Tobacco use* is the leading cause of preventable disease, disability, and death among adults in the United States (1). Youth use of tobacco products in any form is unsafe, and nearly all tobacco use begins during youth and young adulthood (2). The Food and Drug Administration (FDA) and CDC analyzed data from the 2022 National Youth Tobacco Survey (NYTS) to estimate current (past 30-day) use of eight tobacco products among U.S. middle (grades 6-8) and high school (grades 9-12) students. In 2022, approximately 11.3% of all students (representing 3.08 million persons) reported currently using any tobacco product, including 16.5% of high school and 4.5% of middle school students (2.51 million and 530,000 persons, respectively). Electronic cigarettes (e-cigarettes) were the most commonly used tobacco product among high school (14.1%; 2.14 million) and middle school (3.3%; 380,000) students. Approximately 3.7% of all students (representing 1 million persons) reported currently smoking any combustible tobacco product. Current use of any tobacco product was higher among certain population groups, including 13.5% of non-Hispanic American Indian or Alaska Native (AI/AN)† students; 16.0% of students identifying as lesbian, gay, or bisexual (LGB); 16.6% of students identifying as transgender; 18.3% of students reporting severe psychological distress; 12.5% of students with low family affluence; and 27.2% of students with low academic achievement. Implementation of comprehensive evidence-based tobacco control strategies, combined with FDA regulation, is important for preventing and reducing youth tobacco product use (1,2).


Asunto(s)
Sistemas Electrónicos de Liberación de Nicotina , Productos de Tabaco , Tabaquismo , Adolescente , Adulto , Femenino , Humanos , Estados Unidos/epidemiología , Adulto Joven , Encuestas Epidemiológicas , Uso de Tabaco/epidemiología , Tabaquismo/epidemiología , Estudiantes
7.
BMC Health Serv Res ; 22(1): 705, 2022 May 26.
Artículo en Inglés | MEDLINE | ID: mdl-35619126

RESUMEN

BACKGROUND: Health insurance claims data offer a unique opportunity to study disease distribution on a large scale. Challenges arise in the process of accurately analyzing these raw data. One important challenge to overcome is the accurate classification of study outcomes. For example, using claims data, there is no clear way of classifying hospitalizations due to a specific event. This is because of the inherent disjointedness and lack of context that typically come with raw claims data. METHODS: In this paper, we propose a framework for classifying hospitalizations due to a specific event. We then tested this framework in a private health insurance claims database (Symphony) with approximately 4 million US adults who tested positive with COVID-19 between March and December 2020. Our claims specific COVID-19 related hospitalizations proportion is then compared to nationally reported rates from the Centers for Disease Control by age. RESULTS: Across all ages (18 +) the total percentage of Symphony patients who met our definition of hospitalized due to COVID-19 was 7.3% which was similar to the CDC's estimate of 7.5%. By age group, defined by the CDC, our estimates vs. the CDC's estimates were 18-49: 2.7% vs. 3%, 50-64: 8.2% vs. 9.2%, and 65 + : 14.6% vs. 28.1%. CONCLUSIONS: The proposed methodology is a rigorous way to define event specific hospitalizations in claims data. This methodology can be extended to many different types of events and used on a variety of different types of claims databases.


Asunto(s)
COVID-19 , Adulto , COVID-19/epidemiología , Bases de Datos Factuales , Hospitalización , Humanos , Seguro de Salud
8.
Molecules ; 26(3)2021 Jan 26.
Artículo en Inglés | MEDLINE | ID: mdl-33530645

RESUMEN

The research on resveratrol (1) has been conducted intensively over a long time due to its proven antioxidant activity and disease-fighting capabilities. Many efforts have also been made to increase these biological effects. In the present study, six new extended aromatic resveratrol analogues containing naphthalene (2) and its bioisosteres quinoline (3 and 4), isoquinoline (5) quinoxaline (6) and quinazoline (7) scaffolds were designed and synthesized using an annulation strategy. The antioxidant and anti-inflammatory activities of these compounds were investigated. All compounds showed better antioxidant activity than resveratrol in ABTS assay. As for the anti-inflammatory test, 5 and 7 exhibited better activity than resveratrol. It is worth noting that nitrogen substitution on the extended aromatic resveratrol analogues has a significant impact on cell viability. Taking the antioxidant activities and NO inhibition activities into consideration, we conclude that isoquinoline analogue 5 may qualify for the further investigation of antioxidant and anti-inflammatory therapy. Furthermore, our study results suggest that in order to improve the biological activity of polyphenolic compounds, extended aromaticity and nitrogen substitution strategy could be a viable method for the design of future drug candidates.


Asunto(s)
Antioxidantes/síntesis química , Interleucina-1beta/genética , Interleucina-6/genética , Lipopolisacáridos/efectos adversos , Resveratrol/análogos & derivados , Estilbestroles/síntesis química , Animales , Antiinflamatorios/química , Antiinflamatorios/farmacología , Antioxidantes/química , Antioxidantes/farmacología , Supervivencia Celular/efectos de los fármacos , Regulación de la Expresión Génica/efectos de los fármacos , Isoquinolinas/química , Ratones , Naftalenos/química , Quinazolinas/química , Quinolinas/química , Quinoxalinas/química , Células RAW 264.7 , Resveratrol/química , Estilbestroles/química , Estilbestroles/farmacología , Relación Estructura-Actividad
9.
Oncologist ; 25(1): e186-e193, 2020 01.
Artículo en Inglés | MEDLINE | ID: mdl-31492766

RESUMEN

BACKGROUND: The efficacy of epidermal growth factor (EGF) receptor (EGFR) inhibitors in patients with non-small cell lung cancer (NSCLC), pancreatic cancer (PC), or colorectal cancer (CRC) has been demonstrated. However, dermatological reactions to these inhibitors can cause significant physical and psychosocial discomfort. The objective of the present study was to evaluate the efficacy of EGF ointment for EGFR inhibitor-related skin adverse events (ERSEs). MATERIALS AND METHODS: This placebo-controlled, double-blind, multicenter, pilot phase III trial enrolled patients with NSCLC, PC, or CRC treated with EGFR inhibitors. Patients with grade ≥2 ERSEs were included. Patients were randomized to three treatment arms: arm 1, placebo; arm 2, 1 ppm of EGF ointment; and arm 3, 20 ppm of EGF ointment. Patients applied ointment to their skin lesions twice daily. RESULTS: Efficacy evaluation was available for 80 patients (9 for PC, 28 for NSCLC, and 43 for CRC). Responses were 44.4% in arm 1, 61.5% in arm 2, and 77.8% in arm 3. There was a linear correlation between EGF concentrations and responses (p = .012). Quality of life (QoL) was assessed for 74 patients. Maximum changes in composite scores by Skindex-16 after treatment were significantly different among arms (mean ± SD: -5.2 ± 8.6 for arm 1, -11.7 ± 14.2 for arm 2, and - 18.6 ± 17.7 for arm 3; p = .008). EGF arms showed significant improvement in emotions (p = .005) and functioning (p = .044) scores over the placebo arm. CONCLUSION: EGF ointment is effective for managing ERSEs. It can also improve patients' QoL compared with placebo. Clinical trial identification number. NCT02284139 IMPLICATIONS FOR PRACTICE: Patients with non-small cell lung cancer, pancreatic cancer, or colorectal cancer who are treated with epidermal growth factor (EGF) receptor (EGFR) inhibitors may experience dermatologic reactions to their treatment. This study investigated the benefit of an EGF ointment in the treatment of these adverse events and observed the ointment to be effective in managing EGFR inhibitor-related skin adverse events.


Asunto(s)
Pomadas/uso terapéutico , Enfermedades de la Piel/tratamiento farmacológico , Adulto , Anciano , Anciano de 80 o más Años , Método Doble Ciego , Receptores ErbB/genética , Femenino , Humanos , Masculino , Persona de Mediana Edad , Proyectos Piloto , Enfermedades de la Piel/inducido químicamente
10.
MMWR Morb Mortal Wkly Rep ; 69(37): 1310-1312, 2020 Sep 18.
Artículo en Inglés | MEDLINE | ID: mdl-32941408

RESUMEN

The use of any tobacco product by youths is unsafe, including electronic cigarettes (e-cigarettes) (1). Most e-cigarettes contain nicotine, which is highly addictive, can harm the developing adolescent brain, and can increase risk for future addiction to other drugs (1). E-cigarette use has increased considerably among U.S. youths since 2011 (1,2). Multiple factors have contributed to this increase, including youth-appealing flavors and product innovations (1-3). Amid the widespread use of e-cigarettes and popularity of certain products among youths, on February 6, 2020, the Food and Drug Administration (FDA) implemented a policy prioritizing enforcement against the manufacture, distribution, and sale of certain unauthorized flavored prefilled pod or cartridge-based e-cigarettes (excluding tobacco or menthol).


Asunto(s)
Estudiantes/psicología , Vapeo/epidemiología , Adolescente , Niño , Estudios Transversales , Humanos , Instituciones Académicas/estadística & datos numéricos , Estudiantes/estadística & datos numéricos , Estados Unidos/epidemiología
11.
MMWR Morb Mortal Wkly Rep ; 69(50): 1881-1888, 2020 Dec 18.
Artículo en Inglés | MEDLINE | ID: mdl-33332300

RESUMEN

Tobacco use is the leading cause of preventable disease and death in the United States; nearly all tobacco product use begins during youth and young adulthood (1,2). CDC and the Food and Drug Administration (FDA) analyzed data from the 2019 and 2020 National Youth Tobacco Surveys (NYTS) to determine changes in the current (past 30-day) use of seven tobacco products among U.S. middle (grades 6-8) and high (grades 9-12) school students. In 2020, current use of any tobacco product was reported by 16.2% (4.47 million) of all students, including 23.6% (3.65 million) of high school and 6.7% (800,000) of middle school students. Electronic cigarettes (e-cigarettes) were the most commonly used tobacco product among high school (19.6%; 3.02 million) and middle school (4.7%; 550,000) students. From 2019 to 2020, decreases in current use of any tobacco product, any combustible tobacco product, multiple tobacco products, e-cigarettes, cigars, and smokeless tobacco occurred among high school and middle school students; these declines resulted in an estimated 1.73 million fewer current youth tobacco product users in 2020 than in 2019 (6.20 million) (3). From 2019 to 2020, no significant change occurred in the use of cigarettes, hookahs, pipe tobacco, or heated tobacco products. The comprehensive and sustained implementation of evidence-based tobacco control strategies at the national, state, and local levels, combined with tobacco product regulation by FDA, is warranted to help sustain this progress and to prevent and reduce all forms of tobacco product use among U.S. youths (1,2).


Asunto(s)
Estudiantes/psicología , Productos de Tabaco/estadística & datos numéricos , Uso de Tabaco/epidemiología , Adolescente , Niño , Estudios Transversales , Femenino , Encuestas Epidemiológicas , Humanos , Masculino , Instituciones Académicas/estadística & datos numéricos , Estudiantes/estadística & datos numéricos , Estados Unidos/epidemiología
12.
Int J Cancer ; 145(9): 2459-2467, 2019 11 01.
Artículo en Inglés | MEDLINE | ID: mdl-30973963

RESUMEN

Erythropoiesis-stimulating agents (ESAs), such as erythropoietin (EPO) and darbepoetin, may alleviate anemia in diffuse large B-cell lymphoma (DLBCL) patients. However, many cancer cells express EPO receptors (EPOR), through which exogenously administered ESAs potentially promote cancer cell growth. We conducted preclinical/phase II studies to investigate the safety and efficacy of ESAs for managing chemotherapy-related anemia in DLBCL patients. We examined EPOR expression in germinal center B-cell (GCB)- and activated B-cell (ABC)-DLBCL cell lines, and investigated the effects of ESAs on cell proliferation, and rituximab-mediated complement-dependent cytotoxicity (CDC). The clinical study enrolled 50 histologically confirmed DLBCL patients receiving rituximab/cyclophosphamide/doxorubicin/vincristine/prednisolone (R-CHOP) who had hemoglobin levels <10.0 g/dl after a maximum of three R-CHOP cycles and received ≥4 doses of fixed-dose darbepoetin (360 µg) once every 3 weeks. EPOR mRNA was detected in all GCB-DLBCL cell lines, but little/none was detected in ABC-DLBCL cell lines. GCB-DLBCL and ABC-DLBCL cell proliferation was unaffected by EPO or darbepoetin. Rituximab-mediated CDC of DLBCL cell lines with/without EPOR expression was not affected adversely by EPO. In the clinical study, baseline mean hemoglobin was 9.19 g/dl; the overall mean change in hemoglobin was 1.59 ± 1.3 g/dl (16 weeks). Forty-eight percent of enrolled patients achieved a hematopoietic response. Our study shows that ESAs do not affect the growth of DLBCL cells or rituximab-mediated CDC under the experimental conditions that we used, and the appropriate use of ESAs may be effective and safe for DLBCL patients with anemia after R-CHOP.


Asunto(s)
Anemia/inducido químicamente , Anemia/tratamiento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Proliferación Celular/efectos de los fármacos , Hematínicos/farmacología , Linfoma de Células B Grandes Difuso/tratamiento farmacológico , Adulto , Anciano , Linfocitos B/efectos de los fármacos , Linfocitos B/metabolismo , Línea Celular Tumoral , Ciclofosfamida/efectos adversos , Ciclofosfamida/uso terapéutico , Supervivencia sin Enfermedad , Doxorrubicina/efectos adversos , Doxorrubicina/uso terapéutico , Femenino , Centro Germinal/efectos de los fármacos , Centro Germinal/metabolismo , Hemoglobinas/metabolismo , Humanos , Linfoma de Células B Grandes Difuso/metabolismo , Masculino , Persona de Mediana Edad , Prednisolona/efectos adversos , Prednisolona/uso terapéutico , Estudios Prospectivos , Rituximab/uso terapéutico , Vincristina/efectos adversos , Vincristina/uso terapéutico
14.
BMC Cancer ; 19(1): 748, 2019 Jul 30.
Artículo en Inglés | MEDLINE | ID: mdl-31362708

RESUMEN

BACKGROUND: Primary retroperitoneal serous adenocarcinoma (PRSA) is an extremely uncommon malignancy exclusively reported in females. Due to the rarity of the disease, it is difficult to establish a standardized treatment. CASE PRESENTATION: We describe a unique case of PRSA in a 71-year-old male who presented with right-sided lower back pain and numbness. Magnetic resonance imaging identified a mass invading the adjacent psoas muscle and twelfth rib. Tissue biopsy confirmed poorly differentiated PRSA. Patient was initially treated with neoadjuvant carboplatin and paclitaxel chemotherapy regimen. This resulted in complete radiological resolution of the tumor. However, 12 weeks later, rapid recurrence was noted on follow-up CT scan. The patient was then treated with external radiotherapy with concurrent nivolumab, an anti-PD-1 antibody. The patient displayed a positive response to treatment with reduction in primary tumor and metastases and had a sustained disease control. CONCLUSION: Treatment with radiotherapy in combination with anti-PD-1 antibody could be an effective modality of management for PRSA.


Asunto(s)
Antineoplásicos Inmunológicos/uso terapéutico , Cistadenocarcinoma Seroso/radioterapia , Cistadenocarcinoma Seroso/terapia , Inmunoterapia/métodos , Nivolumab/uso terapéutico , Neoplasias Retroperitoneales/radioterapia , Neoplasias Retroperitoneales/terapia , Anciano , Antineoplásicos Inmunológicos/farmacología , Antineoplásicos Fitogénicos/efectos adversos , Antineoplásicos Fitogénicos/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Carboplatino/efectos adversos , Carboplatino/uso terapéutico , Cistadenocarcinoma Seroso/diagnóstico por imagen , Estudios de Seguimiento , Humanos , Factores Inmunológicos/uso terapéutico , Imagen por Resonancia Magnética , Masculino , Terapia Neoadyuvante , Recurrencia Local de Neoplasia , Nivolumab/farmacología , Paclitaxel/efectos adversos , Paclitaxel/uso terapéutico , Receptor de Muerte Celular Programada 1/antagonistas & inhibidores , Receptor de Muerte Celular Programada 1/inmunología , Neoplasias Retroperitoneales/diagnóstico por imagen , Resultado del Tratamiento
15.
Oncologist ; 22(11): 1354-1361, 2017 11.
Artículo en Inglés | MEDLINE | ID: mdl-28687626

RESUMEN

BACKGROUND: To assess whether the rotation of dexamethasone to methylprednisolone decreases the intensity of dexamethasone-induced hiccup (DIH) in cancer patients treated with chemotherapy. MATERIALS AND METHODS: Adult patients who experienced DIH within 3 days after the administration of dexamethasone as an antiemetic were screened. Eligible patients were randomly assigned to receive dexamethasone (n = 33) or methylprednisolone (n = 32) as an antiemetic (randomization phase). In the next cycle of chemotherapy, the dexamethasone group received methylprednisolone and vice versa in the methylprednisolone group (crossover phase). The primary endpoint was the difference in hiccup intensity as measured using the numeric rating scale (NRS) between two groups. RESULTS: No female patients were enrolled, although the study did not exclude them. At the randomization phase, hiccup frequency was 28/33 (84.8%) in the dexamethasone group versus 20/32 (62.5%) in the methylprednisolone group (p = .04). Intensity of hiccup was significantly higher in the dexamethasone group than that in the methylprednisolone group (mean NRS, 3.5 vs. 1.4, p < .001). At the crossover phase, hiccup intensity was further decreased after the rotation of dexamethasone to methylprednisolone in the dexamethasone group (mean NRS, 3.5 to 0.9, p < .001), while it was increased by rotating methylprednisolone to dexamethasone in the methylprednisolone group (mean NRS, 1.4 to 3.3, p = .025). There were no differences in emesis intensity between the two groups at either the randomization or crossover phases. Clinicaltrials.gov identifier: NCT01974024. CONCLUSION: Dexamethasone-induced hiccup is a male-predominant phenomenon that can be ameliorated by rotating dexamethasone to methylprednisolone without compromising the antiemetic efficacy. IMPLICATIONS FOR PRACTICE: In this randomized, multicenter, phase III trial, hiccup intensity was significantly lower when the antiemetic corticosteroid was rotated from dexamethasone to methylprednisolone without a change in emesis intensity than that when dexamethasone was maintained. At the crossover phase, hiccup intensity was increased again if dexamethasone was readministered instead of methylprednisolone. The present study demonstrated that dexamethasone-induced hiccup can be improved by rotating from dexamethasone to methylprednisolone without compromising its antiemetic efficacy.


Asunto(s)
Corticoesteroides/administración & dosificación , Dexametasona/administración & dosificación , Metilprednisolona/administración & dosificación , Neoplasias/tratamiento farmacológico , Corticoesteroides/efectos adversos , Adulto , Anciano , Anciano de 80 o más Años , Antieméticos/administración & dosificación , Antieméticos/efectos adversos , Dexametasona/efectos adversos , Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos/clasificación , Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos/tratamiento farmacológico , Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos/patología , Hipo/inducido químicamente , Hipo/prevención & control , Humanos , Masculino , Metilprednisolona/efectos adversos , Persona de Mediana Edad , Neoplasias/complicaciones , Vómitos/tratamiento farmacológico , Vómitos/patología
19.
BMC Health Serv Res ; 14: 40, 2014 Jan 27.
Artículo en Inglés | MEDLINE | ID: mdl-24467793

RESUMEN

BACKGROUND: As of October 1, 2012, hospitals in the United States with excess readmissions based on the Centers for Medicare and Medicaid Services (CMS) risk-adjusted ratio began being penalized. Given the impact of high readmission rates to hospitals nationally, it is important for individual hospitals to identify which patients may be at highest risk of readmission. The objective of this study was to assess the association of institution specific factors with 30-day readmission. METHODS: The study is a retrospective observational study using administrative data from January 1, 2009 through December 31, 2010 conducted at a 257 bed community hospital in Massachusetts. The patients included inpatient medical discharges from the hospitalist service with the primary diagnoses of congestive heart failure, pneumonia or chronic obstructive pulmonary disease. The outcome was 30-day readmission rates. After adjusting for known factors that impact readmission, provider associated factors (i.e. hours worked and census on the day of discharge) and hospital associated factors (i.e. floor of discharge, season) were compared. RESULTS: Over the study time period, there were 3774 discharges by hospitalists, with 637 30-day readmissions (17% readmission rate). By condition, readmission rates were 19.6% (448/2284) for congestive heart failure, 13.0% (141/1083) for pneumonia, and 14.7% (200/1358) for chronic obstructive lung disease. After adjusting for known risk factors (gender, age, length of stay, Elixhauser sum score, admission in the previous year, insurance, disposition, primary diagnosis), we found that patients discharged in the winter remained significantly more likely to be readmitted compared to the summer (OR 1.54, p = 0.0008). Patients discharged from the cardiac floor had a trend toward decreased readmission compared a medical/oncology floor (OR 0.85, p = 0.08). Hospitalist work flow factors (census and hours on the day of discharge) were not associated with readmission. CONCLUSIONS: We found that 30 day hospital readmissions may be associated with institution specific risk factors, even after adjustment for patient factors. These institution specific risk factors may be targets for interventions to prevent readmissions.


Asunto(s)
Hospitales Comunitarios/estadística & datos numéricos , Readmisión del Paciente/estadística & datos numéricos , Anciano , Humanos , Masculino , Massachusetts/epidemiología , Alta del Paciente/estadística & datos numéricos , Estudios Retrospectivos , Ajuste de Riesgo , Factores de Riesgo
20.
J Am Med Inform Assoc ; 31(7): 1583-1587, 2024 Jun 20.
Artículo en Inglés | MEDLINE | ID: mdl-38741288

RESUMEN

INTRODUCTION: The transition to digital tools prompted by the pandemic made evident digital disparities. To address digital literacy gaps, we implemented a system-wide digital navigation program. METHODS: The Digital Access Coordinator (DAC) program consists of 12 multilingual navigators who support patients in enrolling and using the patient portal and digital tools. We implemented the program in our primary care network which consists of 1.25 million patients across 1211 clinicians. RESULTS: From May 2021 to November 2022, the DACs completed outreach to 16 045 patients. Of the 13 413 patients they reached, they successfully enrolled 8193 (61%) patients in the patient portal. Of those patients they enrolled, most patients were of Other race, Hispanic ethnicity, and were English-speaking (44%) and Spanish-speaking patients (44%). Using our embedded model, we increased enrollment across 7 clinics (mean increase: 21.3%, standard deviation: 9.2%). Additionally, we identified key approaches for implementing a digital navigation program. CONCLUSION: Organizations can support patient portal enrollment, a key part of digital health equity, by creating and prioritizing digital navigation programs.


Asunto(s)
Portales del Paciente , Atención Primaria de Salud , Humanos , Atención Primaria de Salud/organización & administración , Equidad en Salud , COVID-19 , Navegación de Pacientes/organización & administración , Brecha Digital
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