Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 48
Filtrar
Mais filtros

Bases de dados
País/Região como assunto
Tipo de documento
Intervalo de ano de publicação
1.
Gastroenterology ; 161(1): 66-80.e8, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-33722583

RESUMO

BACKGROUND & AIMS: In celiac disease (CeD), gluten induces immune activation, leading to enteropathy. TAK-101, gluten protein (gliadin) encapsulated in negatively charged poly(dl-lactide-co-glycolic acid) nanoparticles, is designed to induce gluten-specific tolerance. METHODS: TAK-101 was evaluated in phase 1 dose escalation safety and phase 2a double-blind, randomized, placebo-controlled studies. Primary endpoints included pharmacokinetics, safety, and tolerability of TAK-101 (phase 1) and change from baseline in circulating gliadin-specific interferon-γ-producing cells at day 6 of gluten challenge, in patients with CeD (phase 2a). Secondary endpoints in the phase 2a study included changes from baseline in enteropathy (villus height to crypt depth ratio [Vh:Cd]), and frequency of intestinal intraepithelial lymphocytes and peripheral gut-homing T cells. RESULTS: In phase 2a, 33 randomized patients completed the 14-day gluten challenge. TAK-101 induced an 88% reduction in change from baseline in interferon-γ spot-forming units vs placebo (2.01 vs 17.58, P = .006). Vh:Cd deteriorated in the placebo group (-0.63, P = .002), but not in the TAK-101 group (-0.18, P = .110), although the intergroup change from baseline was not significant (P = .08). Intraepithelial lymphocyte numbers remained equal. TAK-101 reduced changes in circulating α4ß7+CD4+ (0.26 vs 1.05, P = .032), αEß7+CD8+ (0.69 vs 3.64, P = .003), and γδ (0.15 vs 1.59, P = .010) effector memory T cells. TAK-101 (up to 8 mg/kg) induced no clinically meaningful changes in vital signs or routine clinical laboratory evaluations. No serious adverse events occurred. CONCLUSIONS: TAK-101 was well tolerated and prevented gluten-induced immune activation in CeD. The findings from the present clinical trial suggest that antigen-specific tolerance was induced and represent a novel approach translatable to other immune-mediated diseases. ClinicalTrials.gov identifiers: NCT03486990 and NCT03738475.


Assuntos
Doença Celíaca/imunologia , Gliadina/imunologia , Tolerância Imunológica/imunologia , Nanopartículas/administração & dosagem , Doença Celíaca/patologia , Método Duplo-Cego , Gliadina/administração & dosagem , Glicolatos/administração & dosagem , Humanos , Infusões Intravenosas
2.
Echocardiography ; 39(2): 240-247, 2022 02.
Artigo em Inglês | MEDLINE | ID: mdl-35034372

RESUMO

INTRODUCTION: Cardiac point-of-care ultrasound (c-POCUS) is an increasingly implemented diagnostic tool with the potential to guide clinical management. We sought to characterize and analyze the existing c-POCUS literature with a focus on the temporal trends and differences across specialties. METHODS: A literature search for c-POCUS and related terms was conducted using Ovid (MEDLINE and Embase) and Web of Science databases through 2020. Eligible publications were classified by publication type and topic, author specialty, geographical region of senior author, and journal specialty. RESULTS: The initial search produced 1761 potential publications. A strict definition of c-POCUS yielded a final total of 574 cardiac POCUS manuscripts. A yearly increase in c-POCUS publications was observed. Nearly half of publications were original research (48.8%) followed by case report or series (22.8%). Most publications had an emergency medicine senior author (38.5%), followed by cardiology (20.8%), anesthesiology (12.5%), and critical care (12.5%). The proportion authored by emergency medicine and cardiologists has decreased over time while those by anesthesiology and critical care has generally increased, particularly over the last decade. First authorship demonstrated a similar trend. Articles were published in emergency medicine (24.4%) and cardiology journals (20.5%) with comparable frequency. CONCLUSION: The annual number of c-POCUS publications has steadily increased over time, reflecting the increased recognition and utilization of c-POCUS. This study can help inform clinicians of the current state of c-POCUS and augment the discussion surrounding barriers to continued adoption across all specialties.


Assuntos
Sistemas Automatizados de Assistência Junto ao Leito , Testes Imediatos , Cuidados Críticos , Coração , Humanos , Ultrassonografia
3.
J Oncol Pharm Pract ; 26(3): 680-687, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31500517

RESUMO

BACKGROUND: Acute myeloid leukemia patients receive anthracycline-containing induction chemotherapy. Anthracyclines cause cardiotoxicity; however, there is a paucity of data reflecting the risk of cardiotoxicity in the acute myeloid leukemia population, and risk factors for development of reduced left ventricular ejection fraction are not well established in this population. METHODS: A retrospective cohort study of adult acute myeloid leukemia patients receiving anthracycline-containing induction chemotherapy between March 2011 and August 2017 was performed. Baseline and all additional cardiac monitoring within one year of induction were collected. Home medications and new medication initiation were determined via the electronic health record and new outpatient prescriptions. RESULTS: Of 97 evaluable patients, 25 (25.8%) developed reduced left ventricular ejection fraction and 18 (18.6%) experienced clinical heart failure within one year of induction. The median difference from baseline to lowest left ventricular ejection fraction was -5.0 percentage points, with a range of +10.0 to -52.5. The median time to onset of reduced left ventricular ejection fraction was 27 days, at a median cumulative anthracycline dose of 270 mg/m2. No patient-specific or medication-specific factors were significantly associated with the risk of developing reduced left ventricular ejection fraction. Of 14 patients started on medical management for reduced left ventricular ejection fraction, 10 (71%) responded to therapy. CONCLUSIONS: In this retrospective analysis, we observed that acute myeloid leukemia patients experienced reduced left ventricular ejection fraction more quickly and at lower doses than previously reported in the solid tumor population. Reduced left ventricular ejection fraction was at least partially reversible in most patients started on medical management. Although no factors were significantly associated with decreased cardiomyopathy risk, future assessment of cardioprotective medications may be warranted.


Assuntos
Antraciclinas/efeitos adversos , Antibióticos Antineoplásicos/efeitos adversos , Cardiomiopatias/induzido quimicamente , Leucemia Mieloide Aguda/tratamento farmacológico , Adulto , Idoso , Cardiotoxicidade/etiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos
5.
J Infect Dis ; 218(12): 1890-1899, 2018 11 05.
Artigo em Inglês | MEDLINE | ID: mdl-29982727

RESUMO

Background: GEN-003 is a candidate therapeutic vaccine for genital herpes simplex virus type 2 (HSV-2). We compared virologic and clinical impact of varying GEN-003 doses. Methods: Adults with symptomatic HSV-2 received placebo or GEN-003 (30 or 60 µg antigen with 25, 50, or 75 µg adjuvant). Viral shedding and lesion rates before vaccination were compared with those measured immediately after vaccination, then at weeks 29-33 and 53-57 after last dose. Results: Compared with baseline shedding rates, the rate ratios for viral shedding immediately after treatment were as follows: 0.82 (95% confidence interval [CI], 0.49-1.36), 30 µg antigen/25 µg adjuvant (30/25) dose; 0.64 (95% CI, 0.45-0.92), 30/50 dose; 0.63 (95% CI, 0.37-1.10), 30/75 dose; 0.56 (95% CI, 0.36-0.88), 60/25 dose; 0.58 (95% CI, 0.38-0.89), 60/50 dose; 0.45 (95% CI, 0.16-0.79), 60/75 dose; and 0.98 (95% CI, 0.76-1.26), placebo. Lesion rate reductions by GEN-003 ranged from 31% to 69%, but lesion rates also decreased among placebo recipients (62%). Reductions in shedding and lesion rate were durable for 12 months for the 60 µg antigen plus 50 or 75 µg adjuvant groups. No serious adverse events occurred with vaccination. Conclusions: The most efficacious vaccine combinations for GEN-003 were the 60 µg/50 µg and 60 µg/75 µg doses.


Assuntos
Herpes Genital/terapia , Herpesvirus Humano 2/imunologia , Imunoterapia , Vacinas Virais/uso terapêutico , Adjuvantes Imunológicos , Adolescente , Adulto , Feminino , Herpes Genital/virologia , Humanos , Masculino , Pessoa de Meia-Idade , Vacinação , Vacinas Virais/administração & dosagem , Eliminação de Partículas Virais , Adulto Jovem
6.
Support Care Cancer ; 26(12): 4105-4113, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-29869294

RESUMO

PURPOSE: The aims of this study were to compare the application of three geriatric medication screening tools to the Beers Criteria alone for potentially inappropriate medication quantification and to determine feasibility of a pharmacist-led polypharmacy assessment in a geriatric oncology clinic. METHODS: Adult patients with cancer aged 65 and older underwent a comprehensive geriatric assessment. A polypharmacy assessment was completed by a pharmacist and included a review of all drug therapies. Potentially inappropriate medications were screened using the Beers Criteria, Screening Tool to Alert doctors to Right Treatment/Screening Tool of Older Persons' Prescriptions, and the Medication Appropriateness Index. Deprescribing occurred after discussion with the pharmacist, geriatric oncologist, patient, and caregiver. RESULTS: Data were collected for 26 patients. The mean number of medications was 12. The Beers Criteria alone identified 38 potentially inappropriate medications compared to 119 potentially inappropriate medications with the three-tool assessment; a mean of 5 potentially inappropriate medications were identified per patient. After the application of the three-tool assessment, 73% of potentially inappropriate medications identified were deprescribed, resulting in a mean of 3 medications deprescribed per patient. Approximately two thirds of patients reported a reduction in symptoms after the deprescribing intervention. Healthcare expenditures of $4282.27 per patient were potentially avoided as a result of deprescribing. CONCLUSIONS: Our three-tool assessment identified three times more potentially inappropriate medications than the Beers Criteria alone. Pharmacist-led deprescribing interventions are feasible and may lead to improved patient outcomes and cost savings. This three-tool assessment process should be incorporated into interdisciplinary assessments of older patients with cancer and validated in future studies.


Assuntos
Prescrição Inadequada/tendências , Neoplasias/tratamento farmacológico , Farmacêuticos/normas , Polimedicação , Lista de Medicamentos Potencialmente Inapropriados/tendências , Idoso , Idoso de 80 Anos ou mais , Desprescrições , Feminino , Avaliação Geriátrica , Humanos , Masculino , Projetos Piloto
7.
J Infect Dis ; 215(6): 856-864, 2017 03 15.
Artigo em Inglês | MEDLINE | ID: mdl-28329211

RESUMO

Background: Genital herpes simplex virus type 2 (HSV-2) infection causes recurrent lesions and frequent viral shedding. GEN-003 is a candidate therapeutic vaccine containing HSV-2 gD2∆TMR and ICP4.2, and Matrix-M2 adjuvant. Methods: Persons with genital herpes were randomized into 3 dose cohorts to receive 3 intramuscular doses 21 days apart of 10 µg, 30 µg, or 100 µg of GEN-003, antigens without adjuvant, or placebo. Participants obtained genital swab specimens twice daily for HSV-2 detection and monitored genital lesions for 28-day periods at baseline and at intervals after the last dose. Results: One hundred and thirty-four persons received all 3 doses. Reactogenicity was associated with adjuvant but not with antigen dose or dose number. No serious adverse events were attributed to GEN-003. Compared with baseline, genital HSV-2 shedding rates immediately after dosing were reduced with GEN-003 (from 13.4% to 6.4% for 30 µg [P < .001] and from 15.0% to 10.3% for 100 µg [P < .001]). Lesion rates were also significantly (P < .01) reduced immediately following immunization with 30 µg or 100 µg of GEN-003. GEN-003 elicited increases in antigen binding, virus neutralizing antibody, and T-cell responses. Conclusions: GEN-003 had an acceptable safety profile and stimulated humoral and cellular immune responses. GEN-003 at doses of 30 µg and 100 µg reduced genital HSV shedding and lesion rates. Clinical Trials Registration: NCT01667341 (funded by Genocea).


Assuntos
Herpes Genital/tratamento farmacológico , Herpes Genital/imunologia , Herpesvirus Humano 2/imunologia , Vacinas Virais/imunologia , Vacinas Virais/uso terapêutico , Adolescente , Adulto , Anticorpos Antivirais/sangue , Feminino , Herpes Genital/prevenção & controle , Herpes Genital/virologia , Humanos , Imunoglobulina G/sangue , Imunoterapia , Masculino , Pessoa de Meia-Idade , Vacinas Virais/efeitos adversos , Eliminação de Partículas Virais , Adulto Jovem
8.
J Pediatr Gastroenterol Nutr ; 64(3): 425-430, 2017 03.
Artigo em Inglês | MEDLINE | ID: mdl-28045770

RESUMO

OBJECTIVES: Familial intrahepatic cholestasis 1 (FIC1) deficiency is caused by a mutation in the ATP8B1 gene. Partial external biliary diversion (PEBD) is pursued to improve pruritus and arrest disease progression. Our aim is to describe clinical variability after PEBD in FIC1 disease. METHODS: We performed a single-center, retrospective review of genetically confirmed FIC1 deficient patients who received PEBD. Clinical outcomes after PEBD were cholestasis, pruritus, fat-soluble vitamin supplementation, growth, and markers of disease progression that included splenomegaly and aspartate aminotransferase-to-platelet ratio index. RESULTS: Eight patients with FIC1 disease and PEBD were included. Mean follow-up was 32 months (range 15-65 months). After PEBD, total bilirubin was <2 mg/dL in all patients at 8 months after surgery, but 7 of 8 subsequently experienced a total of 15 recurrent cholestatic events. Subjective assessments of pruritus demonstrated improvement, but itching exacerbation occurred during cholestatic episodes. High-dose fat-soluble vitamin supplementation persisted, with increases needed during cholestatic episodes. Weight z scores improved (-3.4 to -1.65, P < 0.01). Splenomegaly did not worsen or develop and 1 patient developed an aminotransferase-to-platelet ratio index score of >0.7 suggesting development of fibrosis 24 months after PEBD. CONCLUSIONS: Clinical variability is evident among genetically defined FIC1 deficient patients after PEBD, even among those with identical mutations. Recurrent, self-limited episodes of cholestasis and pruritus are reminiscent of the benign recurrent intrahepatic cholestasis phenotype. Despite diversion of bile from the intestinal lumen, weight gain improved while fat-soluble vitamin requirements persisted. Significant progression of liver disease was not evident during follow-up.


Assuntos
Procedimentos Cirúrgicos do Sistema Biliar/métodos , Colestase Intra-Hepática/cirurgia , Pré-Escolar , Colestase Intra-Hepática/complicações , Colestase Intra-Hepática/diagnóstico , Progressão da Doença , Feminino , Seguimentos , Humanos , Lactente , Masculino , Prurido/etiologia , Prurido/cirurgia , Estudos Retrospectivos , Resultado do Tratamento
9.
Oncologist ; 21(6): 723-30, 2016 06.
Artigo em Inglês | MEDLINE | ID: mdl-27151653

RESUMO

UNLABELLED: : Inappropriate medication use and polypharmacy are extremely common among older adults. Numerous studies have discussed the importance of a comprehensive medication assessment in the general geriatric population. However, only a handful of studies have evaluated inappropriate medication use in the geriatric oncology patient. Almost a dozen medication screening tools exist for the older adult. Each available tool has the potential to improve aspects of the care of older cancer patients, but no single tool has been developed for this population. We extensively reviewed the literature (MEDLINE, PubMed) to evaluate and summarize the most relevant medication screening tools for older patients with cancer. Findings of this review support the use of several screening tools concurrently for the elderly patient with cancer. A deprescribing tool should be developed and included in a comprehensive geriatric oncology assessment. Finally, prospective studies are needed to evaluate such a tool to determine its feasibility and impact in older patients with cancer. IMPLICATIONS FOR PRACTICE: The prevalence of polypharmacy increases with advancing age. Older adults are more susceptible to adverse effects of medications. "Prescribing cascades" are common, whereas "deprescribing" remains uncommon; thus, older patients tend to accumulate medications over time. Older patients with cancer are at high risk for adverse drug events, in part because of the complexity and intensity of cancer treatment. Additionally, a cancer diagnosis often alters assessments of life expectancy, clinical status, and competing risk. Screening for polypharmacy and potentially inappropriate medications could reduce the risk for adverse drug events, enhance quality of life, and reduce health care spending for older cancer patients.


Assuntos
Avaliação Geriátrica , Neoplasias/tratamento farmacológico , Polimedicação , Lista de Medicamentos Potencialmente Inapropriados , Idoso , Humanos
10.
J Pediatr Gastroenterol Nutr ; 62(3): 424-8, 2016 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-26756876

RESUMO

In vitro studies have suggested that 4-phenylbutyrate (PBA) may rescue missense mutated proteins that underlie some forms of progressive familial intrahepatic cholestasis. Encouraging preliminary responses to 4-PBA have been reported in liver disease secondary to mutations in ABCB11 and ATP8B1. A 4-year-old boy with Byler disease was treated with 4-PBA in the forms of sodium PBA (5 months) and then glycerol PBA (7 months) as part of expanded access single patient protocols. During this therapy serum total bilirubin fell and his general well-being was reported to be improved, although total serum bile acids were not reduced. Discontinuation of rifampin therapy, which had been used to treat pruritus, resulted in reversible severe acute liver injury that was potentially the result of phenylacetate toxicity. Interactions between 4-PBA and cytochrome P450 enzymes should be considered in the use of this agent with special attention to potential phenylacetate toxicity.


Assuntos
Antineoplásicos/uso terapêutico , Doença Hepática Induzida por Substâncias e Drogas/diagnóstico , Doença Hepática Induzida por Substâncias e Drogas/etiologia , Colestase Intra-Hepática/tratamento farmacológico , Fígado/efeitos dos fármacos , Fenilacetatos/toxicidade , Fenilbutiratos/uso terapêutico , Rifampina/efeitos adversos , Bilirrubina/sangue , Pré-Escolar , Colestase Intra-Hepática/fisiopatologia , Humanos , Lactente , Testes de Função Hepática , Masculino , Prurido/tratamento farmacológico
11.
J Pediatr Gastroenterol Nutr ; 60(4): 460-6, 2015 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-25825852

RESUMO

OBJECTIVES: Byler disease, originally described in Amish kindred, results from mutations in ATPase Class I Type 8b Member 1 (ATP8b1). Specific clinical reports of Amish Byler disease were last published 40 years ago. These investigations were directed at the present detailed clinical understanding of the early course of hepatic manifestations of Byler disease. METHODS: This study analyzed routine clinical practice and outcomes of children with Byler disease (defined by homozygous c.923G>T mutation in ATP8b1), who initially presented to Children's Hospital of Pittsburgh of UPMC between January 2007 and October 2014. Data were analyzed to the earlier of 24 months of age or partial external biliary diversion. RESULTS: Six children presented between 1 and 135 days of life: 2 presented with newborn direct hyperbilirubinemia, 2 had complications of coagulopathy, 1 had failure to thrive and rickets, and 1 sibling was identified by newborn genetic testing. Intensive fat-soluble vitamin supplementation was required to prevent insufficiencies in vitamins D, E, and K. Hyperbilirubinemia was variable both over time and between children. Serum bile acid levels were elevated, whereas γ-glutamyltranspeptidase levels were low normal. Scratching behavior (pruritus) was intractable in 4 of 6 children with onset between 6 and 12 months of age. Features of portal hypertension were not observed. Partial external biliary diversion was used during the second year of life in 4 children. CONCLUSIONS: Detailed analysis of Byler disease revealed varied disease presentation and course. Nutritional issues and pruritus dominated the clinical picture in the first 2 years of life.


Assuntos
Adenosina Trifosfatases/genética , Ductos Biliares/patologia , Colestase Intra-Hepática/patologia , Fígado/patologia , Mutação , Deficiência de Vitaminas/etiologia , Ácidos e Sais Biliares/sangue , Ductos Biliares/cirurgia , Colestase Intra-Hepática/epidemiologia , Colestase Intra-Hepática/terapia , Insuficiência de Crescimento/epidemiologia , Insuficiência de Crescimento/etiologia , Testes Genéticos , Hospitais , Humanos , Hiperbilirrubinemia/epidemiologia , Hiperbilirrubinemia/etiologia , Incidência , Lactente , Recém-Nascido , Pennsylvania/epidemiologia , Prevalência , Prurido/etiologia , Raquitismo/epidemiologia , Raquitismo/etiologia , gama-Glutamiltransferase/sangue
12.
J Med Imaging Radiat Sci ; 55(2): 212-220, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38403520

RESUMO

BACKGROUND: 18F-FDG-PET/CT is a valuable tool in the staging and surveillance of cutaneous melanoma; however, recent studies prompt debate on the clinical significance of imaging patients below the lesser trochanter. This study explored two research questions. In patients with a known primary cutaneous melanoma within the standard field of view (SFOV, between the orbits and lesser trochanter), what is the prevalence of metastasis to sites solely within the lower extremities? and, In patients with a known primary cutaneous melanoma within the SFOV what demographic and clinical factors are associated with sole metastasis to the lower extremities? METHODS: A retrospective, multi-centered, observational study of consecutive case reports was conducted. Subjects included 619 patients who underwent extended field of view (EFOV) 18F-FDG-PET/CT (from vertex to toes) for staging and/or follow-up of cutaneous melanoma. Data was collected at three primary healthcare centers in Canada (Nova Scotia, Alberta, and British Columbia). Inclusion criteria were patients >18 years of age, confirmed primary cutaneous melanoma, and a known location of the primary within the SFOV. Patients with primary cutaneous melanoma lesions in lower extremities and previous other cancers were excluded. To determine the prevalence of lesions located below the lesser trochanter, the proportion of such lesions were computed, and 95% confidence intervals ensured a precise estimation of the proportion. RESULTS: 2512 patient charts were reviewed with 619 meeting the inclusion criteria, 298 of these were females. Six percent had metastases in both the lower extremities and sites within the SFOV. The number of subjects who had no metastasis within their SFOV was 361 (58.3%). The number of subjects who presented with confirmed metastasis in the lower extremities without concurrent metastasis in the SFOV region was one (0.58%). Despite a large initial study sample, the number of patients with metastasis in the lower extremities was insufficient to allow correlation of factors associated with risk of spread to the lower extremities. CONCLUSION: Lower extremity 18F-FDG-PET/CT provided additional, relevant clinical data in a sole patient. This finding supports prior research suggesting the prevalence is rare. Future studies should seek to define demographic and clinical factors that predict such rare occurrences, where follow up would be warranted. This study highlights feasibility challenges associated with such investigation.


Assuntos
Fluordesoxiglucose F18 , Melanoma , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Compostos Radiofarmacêuticos , Neoplasias Cutâneas , Humanos , Melanoma/diagnóstico por imagem , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada/métodos , Neoplasias Cutâneas/diagnóstico por imagem , Neoplasias Cutâneas/patologia , Feminino , Masculino , Estudos Retrospectivos , Pessoa de Meia-Idade , Idoso , Imagem Corporal Total/métodos , Adulto , Melanoma Maligno Cutâneo , Idoso de 80 Anos ou mais , Extremidade Inferior/diagnóstico por imagem , Estadiamento de Neoplasias
14.
Onco Targets Ther ; 16: 1-16, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36685611

RESUMO

Allogeneic hematopoietic cell transplantation (allo-HCT) represents an important and potentially curative treatment option for adult patients with acute lymphoblastic leukemia. Relapse continues to remain the most important factor influencing overall survival post allo-HCT. We discuss early identification, clinical manifestations, and management of relapsed disease. Routine evaluation of measurable residual disease (MRD) and change in donor chimerism play a crucial role in early detection. Pivotal clinical trials have led to FDA approval of multiple novel agents like blinatumomab and inotuzumab. Combining targeted therapy with cellular immunotherapy serves as the backbone for prolonging overall survival in these patients. Donor lymphocyte infusions have traditionally been used in relapsed disease with suboptimal outcomes. This review provides insight into use of cellular therapy in MRD positivity and decreasing donor chimerism. It also discusses various modalities of combining cellular therapy with novel agents and discussing the impact of chimeric antigen receptor T-cell therapy in the setting of post allo-HCT relapse both as consolidative therapy and as a bridge to second transplant.

15.
Int J Neonatal Screen ; 9(1)2022 Dec 22.
Artigo em Inglês | MEDLINE | ID: mdl-36648768

RESUMO

Judith "Judi" Tuerck, RN, MS, one of the true pioneers in the development of newborn screening (NBS), passed away on Saturday, 18 June 2022 (Figure 1) [...].

16.
PLoS One ; 17(6): e0268885, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35704562

RESUMO

Over 1 million dogs are imported into the United States and roughly 340,000 dogs into the United Kingdom yearly. Although the official number of dogs arriving to Canada is currently unknown, local animal professionals estimate that thousands of dogs are imported into Canada each year. Dog importation may be increasing globally while regulation and surveillance are still limited, resulting in concerns for the health and welfare of imported dogs. To date, few studies have investigated how the source location of dogs influences the owner-dog relationship. The current report presents two independent studies that were conducted to assess whether owners of imported dogs reported a poorer owner-dog relationships compared to owners of Canadian-born dogs. In both studies, an online survey was distributed to dog owners (Study 1: n = 803; Study 2: n = 878) in British Columbia, Canada, containing questions on various aspects of the owner-dog relationship. The first study included questions from the Lexington Attachment to Pets Scale, Canine Behavioral Assessment and Research Questionnaire, Human-Animal Bond questionnaire, Monash Dog Owner Relationship Scale, and constructed questions about training methods, expectations, and health. The second study was comprised of original questions assessing difficult behaviour, training practices, health, attachment, and perceived level of burden of owning a dog. Both studies found no evidence of a poorer owner-dog relationship in non-Canadian-sourced dogs. In fact, owners of Canadian-sourced dogs used harsh training methods more frequently and had higher expectations for their dog. While no signs of poorer owner-dog relationship in non-Canadian-sourced dogs were found, future research should continue the investigation of age, health, and backgrounds of incoming dogs.


Assuntos
Escala de Avaliação Comportamental , Vínculo Humano-Animal , Animais , Colúmbia Britânica , Cães , Inquéritos e Questionários , Reino Unido
17.
Curr Hematol Malig Rep ; 17(4): 69-81, 2022 08.
Artigo em Inglês | MEDLINE | ID: mdl-35616771

RESUMO

PURPOSE OF REVIEW: Measurable residual disease (MRD) is an important monitoring parameter that can help predict survival outcomes in acute lymphoblastic leukemia (ALL). Identifying patients with MRD has the potential to decrease the risk of relapse with the initiation of early salvage therapy and to help guide decision making regarding allogeneic hematopoietic cell transplantation. In this review, we discuss MRD in ALL, focusing on advantages and limitations between MRD testing techniques and how to monitor MRD in specific patient populations. RECENT FINDINGS: MRD has traditionally been measured through bone marrow samples, but more data for evaluation of MRD via peripheral blood is emerging. Current and developmental testing strategies for MRD include multiparametric flow cytometry (MFC), next-generation sequencing (NGS), quantitative polymerase chain reaction (qPCR), and ClonoSeq. Novel therapies are incorporating MRD as an outcome measure to demonstrate efficacy, including blinatumomab, inotuzumab ozogamicin, and chimeric antigen receptor T (CAR-T) cell therapy. Understanding how to incorporate MRD testing into the management of ALL could improve patient outcomes and predict efficacy of new therapy options.


Assuntos
Transplante de Células-Tronco Hematopoéticas , Leucemia-Linfoma Linfoblástico de Células Precursoras , Transplante de Células-Tronco Hematopoéticas/métodos , Humanos , Imunoterapia Adotiva , Inotuzumab Ozogamicina , Neoplasia Residual/diagnóstico , Leucemia-Linfoma Linfoblástico de Células Precursoras/diagnóstico , Leucemia-Linfoma Linfoblástico de Células Precursoras/genética , Leucemia-Linfoma Linfoblástico de Células Precursoras/terapia
18.
Clin Pharmacol Drug Dev ; 11(8): 966-975, 2022 08.
Artigo em Inglês | MEDLINE | ID: mdl-35316579

RESUMO

Most stimulants used to treat attention-deficit/hyperactivity disorder are administered in the morning and absorbed in the upper gastrointestinal tract. DR/ER-MPH (formerly HLD200), an evening-dosed delayed-release and extended-release methylphenidate, is predicted to be absorbed in the proximal colon. The pharmacokinetic (PK) profile of DR/ER-MPH is characterized by an 8- to 10-hour delay in initial methylphenidate absorption and a subsequent gradual increase in plasma concentration, followed by a slow decline. To examine the relationship of absorption site to pharmacokinetics, the DR/ER-MPH formulation was altered to release methylphenidate in the small intestine and distal colon. The 3 formulations were administered in an open-label, 3-way, crossover study in healthy adults (N = 18). Compared with the small intestine formulation, the PK profile of the proximal colon (DR/ER-MPH) formulation exhibited a longer delay before initial methylphenidate absorption, decreased peak methylphenidate concentration, increased time to peak concentration, and decreased bioavailability; these characteristics were amplified in the distal colon formulation. Safety profiles fell within the expectations for methylphenidate products. Modeled PK profiles were similar between the small intestine formulation and a morning-dosed extended-release methylphenidate (both predicted to release methylphenidate in the upper gastrointestinal tract), providing additional evidence that the PK profile of DR/ER-MPH is shaped by colonic absorption.


Assuntos
Estimulantes do Sistema Nervoso Central , Metilfenidato , Adulto , Estimulantes do Sistema Nervoso Central/farmacocinética , Colo , Estudos Cross-Over , Preparações de Ação Retardada , Humanos , Metilfenidato/farmacocinética
19.
MedEdPORTAL ; 18: 11213, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35087932

RESUMO

Introduction: In-hospital cardiac arrest in patients with COVID-19 presents significant challenges to health care teams. Airborne precautions can delay patient care, place providers at high risk of virus exposure, and exacerbate an already stressful environment. Within the constraints of an ongoing pandemic, an efficient educational program is required to prepare health care teams for airborne isolation code blue. Methods: This simulation was conducted in a room on the target unit using a CPR manikin to represent the patient. A "talk-through walk-through" scripted simulation directed learners (internal medicine residents, unit nurses, and other code blue responders) through a resuscitation using an airborne isolation code blue protocol. Key scripted events prompted role identification, communication, and item transfer. Learners self-assessed their airborne isolation code blue knowledge and skills and their confidence in providing quality care while maintaining safety using a pre-/posttraining 5-point Likert-scale survey. Results: We trained 100 participants over a 5-month period, with 65 participants surveyed (43 respondents; 16 residents, 22 nurses). Following training, participants had a statistically significant (p < .001) increase in percentage selecting agree/strongly agree for all statements related to knowledge and skills specific to airborne isolation code blue protocol, as well as confidence in providing care while keeping themselves and their colleagues safe. Discussion: Our simulation program allowed a small number of educators to feasibly train a large number of learners, let learners practice required skills, and improved learners' self-assessed knowledge, skills, and confidence regarding quality and safety of care.


Assuntos
COVID-19 , Reanimação Cardiopulmonar , Parada Cardíaca , Equipe de Respostas Rápidas de Hospitais , Competência Clínica , Parada Cardíaca/terapia , Humanos , SARS-CoV-2
20.
J Voice ; 2022 Mar 09.
Artigo em Inglês | MEDLINE | ID: mdl-35279346

RESUMO

INTRODUCTION: Chronic cough is a persistent cough lasting greater than eight weeks. The prevalence rate is estimated to be 9% to 33% in the United States. There are several treatment modalities described in current literature including medical, surgical, and behavioral interventions. Behavioral intervention with a speech-language pathologist (SLP) includes education on laryngeal hygiene and the voluntary control of cough as well as respiratory retraining to suppress or reduce the duration of cough. Cough suppression therapy, like other behavioral therapies, requires patient motivation and commitment to participation and completion in therapy. METHODS: This study was a prospective cross-sectional survey at a single academic institution. Adult patients evaluated by a laryngologist for chronic cough regardless of their primary etiology were included. Patients who were tracheostomy dependent, on oxygen therapy, had vocal fold paralysis/immobility, or had undergone previous laryngeal surgery were excluded. Patients were surveyed at the end of the initial clinic visit or at the beginning of the first cough suppression therapy session. Subjects reported their motivational factors for undergoing cough suppression therapy. RESULTS: The majority of patients, 21 (58.33%), identified as female, 15 patients (41.20%) identified as male, and no patients identified as transgender, nonbinary, and/or other gender. The patients in this study had a mean age of 57.75 (12.12) years. 35 patients (97.22%) were interested in cough suppression therapy. The mean presenting cough severity index (CSI) was 19.39 (10.28) with the mean cough duration of 8.69 (12.10) years. CONCLUSIONS: Patients primarily sought cough suppression therapy due to intrinsic factors rather than extrinsic influence. By understanding the relationship between symptomatology and patient motivation, clinicians can better counsel their patients and improve methods to assess candidacy for behavioral treatment.

SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA