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1.
Oncologist ; 29(4): e431-e446, 2024 Apr 04.
Artigo em Inglês | MEDLINE | ID: mdl-38243853

RESUMO

BACKGROUND: Rural residents have a higher prevalence of colorectal cancer (CRC) mortality compared to urban individuals. Policies have been aimed at improving access to CRC screening to reduce these outcomes. However, little attention has been paid to other determinants of CRC-related outcomes, such as stage at diagnosis, treatment, or survivorship care. The main objective of this analysis was to evaluate literature describing differences in CRC screening, stage at diagnosis, treatment, and survivorship care between rural and urban individuals. MATERIALS AND METHODS: We conducted a systematic review of electronic databases using a combination of MeSH and free-text search terms related to CRC screening, stage at diagnosis, treatment, survivorship care, and rurality. We identified 921 studies, of which 39 were included. We assessed methodological quality using the ROBINS-E tool and summarized findings descriptively. A meta-analysis was performed of studies evaluating CRC screening using a random-effects model. RESULTS: Seventeen studies reported disparities between urban and rural populations in CRC screening, 12 on treatment disparities, and 8 on staging disparities. We found that rural individuals were significantly less likely to report any type of screening at any time period (pooled odds ratio = 0.81, 95% CI, 0.76-0.86). Results were inconclusive for disparities in staging at diagnosis and treatment. One study reported a lower likelihood of use of CRC survivorship care for rural individuals compared to urban individuals. CONCLUSION: There remains an urgent need to evaluate and address CRC disparities in rural areas. Investigators should focus future work on assessing the quality of staging at diagnosis, treatment, and survivorship care in rural areas.


Assuntos
Neoplasias Colorretais , Sobrevivência , Humanos , População Rural , Detecção Precoce de Câncer , Neoplasias Colorretais/diagnóstico , Neoplasias Colorretais/epidemiologia , Neoplasias Colorretais/terapia , Programas de Rastreamento
2.
J Oncol Pharm Pract ; 30(1): 15-18, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36945881

RESUMO

Current guidelines for vaccination in allogeneic hematopoietic stem cell transplant (HCT) recipients recommend initiation of pneumococcal vaccination series three to six months post-HCT, with most data supporting initiation at six months due to a more robust immune response. This single-center, retrospective, observational chart review aimed to evaluate the impact of initiating the pneumococcal vaccine series at three months post-HCT compared to six months post-HCT. The primary endpoints were defined as a percentage of patients with a serologic response of >1 and >1.3 µg/mL for over 50% of the defined serotypes. Outcomes showed no difference in immunologic response between the two groups.


Assuntos
Transplante de Células-Tronco Hematopoéticas , Infecções Pneumocócicas , Humanos , Infecções Pneumocócicas/prevenção & controle , Vacinas Pneumocócicas , Estudos Retrospectivos , Vacinação
3.
J Thromb Thrombolysis ; 57(2): 293-301, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-37932590

RESUMO

Direct oral anticoagulants (DOACs) for venous thromboembolism (VTE) treatment are of interest in oncology due to ease of administration and lack of need for therapeutic monitoring compared to other anticoagulants. Data supporting their use in patients with hematologic malignancies post-hematopoietic stem cell transplant (HCT) are limited. The purpose of the study is to characterize DOAC use in HCT patients. This multicenter, retrospective cohort analysis included allogeneic and autologous HCT recipients. The primary outcome was major bleeding. Secondary outcomes included clinically relevant non-major bleeding (CRNMB)/minor bleeding and VTE recurrence. Of 126 patients, 91 (72.2%) patients received an autologous HCT, and 35 (27.8%) patients received an allo-HCT. No major bleeding occurred in either transplant recipient groups. In autologous HCT recipients, CRNMB/minor bleeding occurred in four (4.4%) patients and VTE recurrence occurred in one (1.1%) patient. For allogeneic HCT recipients, CRNMB/minor bleeding occurred in five (14.3%) patients and VTE recurrence occurred in two (5.7%) patients. For patients that experienced a CRNMB, five (100%) of the allogeneic HCT and two (50%) of the autologous HCT recipients were thrombocytopenic at the time of bleeding. Only 38.5% of patients who experienced a drug-drug interaction requiring DOAC dose adjustment received the appropriate dose adjustment. DOACs were associated with low rates of recurrent VTE and no major bleeding events, similar to published data on DOAC use in the general cancer patient population. This suggests that DOACs may be safe therapeutic options with proactive management of drug interactions and careful monitoring for bleeding events, especially in the allogeneic HCT population where minor bleeding rates were slightly higher.


Assuntos
Transplante de Células-Tronco Hematopoéticas , Tromboembolia Venosa , Adulto , Humanos , Tromboembolia Venosa/etiologia , Tromboembolia Venosa/induzido quimicamente , Estudos Retrospectivos , Transplantados , Anticoagulantes/efeitos adversos , Hemorragia/induzido quimicamente , Hemorragia/tratamento farmacológico , Administração Oral , Transplante de Células-Tronco Hematopoéticas/efeitos adversos
4.
Am J Pharm Educ ; 87(10): 100041, 2023 10.
Artigo em Inglês | MEDLINE | ID: mdl-37852680

RESUMO

OBJECTIVE: The primary objective of this study was to compare grit, subjective happiness, satisfaction with life, and academic resilience among pharmacy and occupational therapy/physical therapy (OT/PT) students at 2 distinct universities using the short grit scale, subjective happiness scale (SHS), satisfaction with life scale (SWLS), and the academic resilience scale (ARS-30). METHODS: In January 2019, investigators administered an online survey to students at 2 universities using a cross-sectional, voluntary, anonymous survey design using grit scale, SHS, SWLS, and ARS-30. Descriptive statistics, t tests, a 2-way analysis of variance, Pearson correlation, and regression analyses were used to examine the relationship between these scores. RESULTS: There were 227 respondents who consented to participate in the study and completed all 4 surveys. The overall response rate for pharmacy students was 44% and 43% for OT/PT students, with most pharmacy and OT/PT students in the 19-25-year range. Grit scores did not differ between pharmacy students and OT/PT students, while SHS scores were significantly higher in OT/PT students. Subjective happiness was higher in the private university, with young, female students at the private university reporting higher SHS scores. Although the grit score was not correlated with SWLS, SHS, or ARS-30 scores, the SWLS was correlated with SHS. The SHS was a strong predictor of academic resilience in both OT/PT and pharmacy students. CONCLUSION: Subjective happiness and satisfaction with life were found to be strong predictors of academic resilience among pharmacy students. Colleges of pharmacy may consider administering the SHS and/or SWLS at baseline and annually to measure well-being.


Assuntos
Educação em Farmácia , Farmácia , Estudantes de Farmácia , Humanos , Feminino , Universidades , Felicidade , Estudos Transversais , Inquéritos e Questionários , Satisfação Pessoal
5.
J Thromb Thrombolysis ; 56(3): 439-446, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37421494

RESUMO

BACKGROUND: Direct oral anticoagulant (DOAC) use in cancer-associated venous thromboembolism (CA-VTE) has increased due to updates in recent guidelines and literature. However, select guidelines caution against DOAC use in patients with gastrointestinal (GI) malignancies due to reported increased bleeding events. The objective of this study was to compare the safety and effectiveness of DOACs versus low-molecular-weight heparins (LMWHs) for CA-VTE treatment in patients with GI malignancies. PATIENTS AND METHODS: This multicenter, retrospective cohort study included patients with primary GI malignancies who received therapeutic anticoagulation with a DOAC or LMWH for CA-VTE between January 1, 2018, and December 31, 2019. The primary outcome was the incidence rate of bleeding events (major, clinically relevant non-major, or minor bleeding events) within a 12-month period following the initiation of therapeutic anticoagulation. The secondary endpoint was the incidence rate of recurrent VTE events within a 12-month period following the start of therapeutic anticoagulation. RESULTS: After screening, 141 patients met inclusion criteria. The incidence rate of all bleeding events significantly differed between DOAC (4.98 events/100 person-months) and LWMH (10.2 events/100 person-months) recipients. The corresponding incidence rate ratio (IRR) with the DOAC group serving as the reference was 2.05 (p = 0.01), with the majority of bleeds in both groups presenting as minor bleeds. No difference was found between the incidence rate of recurrent VTE within a 12-month period of starting therapeutic anticoagulation between groups (IRR 3.08, p = 0.06). CONCLUSION: Our results suggest that DOACs do not pose an additional bleeding risk compared to LMWH in patients with certain GI malignancies. Careful selection of DOAC therapy with respect to bleeding risk is still warranted.


Assuntos
Neoplasias Gastrointestinais , Neoplasias , Tromboembolia Venosa , Humanos , Heparina de Baixo Peso Molecular/efeitos adversos , Tromboembolia Venosa/prevenção & controle , Anticoagulantes/efeitos adversos , Estudos Retrospectivos , Administração Oral , Neoplasias Gastrointestinais/complicações , Neoplasias Gastrointestinais/tratamento farmacológico , Neoplasias/complicações , Hemorragia/tratamento farmacológico
6.
Am J Pharm Educ ; 87(6): 100080, 2023 06.
Artigo em Inglês | MEDLINE | ID: mdl-37316141

RESUMO

Until now, the term "advocacy" in pharmacy education and practice has focused on advocating for the advancement of the pharmacy profession or patient advocacy. With the 2022 Curricular Outcomes and Entrustable Professional Activities publication, the focus of advocacy has broadened to include advocacy for other causes that impact the health of patients. This commentary will highlight 3 pharmacy-focused organizations advocating for social issues impacting the health of patients as well as encourage members of the Academy to continue to expand personal social advocacy efforts.


Assuntos
Educação em Farmácia , Assistência Farmacêutica , Farmácias , Humanos , Academias e Institutos , Defesa do Paciente
7.
J Am Pharm Assoc (2003) ; 63(4): 1138-1149, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37207713

RESUMO

OBJECTIVE(S): Letermovir (LET), a novel antiviral, has largely supplanted more traditional preemptive therapy (PET) for cytomegalovirus (CMV) prophylaxis in allogeneic hematopoietic stem cell transplant (allo-HCT) patients. Use of LET demonstrated efficacy against placebo in phase III randomized controlled trials, but is considerably more expensive than PET. This review aimed to evaluate the real-world effectiveness of LET in preventing clinically significant CMV infection (csCMVi) for allo-HCT recipients and related outcomes. DESIGN: A systematic literature review was performed using an a priori protocol using PubMed, Scopus, and ClinicalTrials.gov from January 2010 to October 2021. SETTING AND PARTICIPANTS: Studies were included if they met the following criteria: LET compared with PET, CMV-related outcomes, patients aged 18 years or older, and English language-only articles. Descriptive statistics were used to summarize study characteristics and outcomes. OUTCOME MEASURES: CMV viremia, csCMVi, CMV end-organ disease, graft-versus-host-disease, all-cause mortality. RESULTS: A total of 233 abstracts were screened, with 30 included in this review. Randomized trials demonstrated efficacy of LET prophylaxis in preventing csCMVi. Observational studies demonstrated varying degrees of effectiveness of LET prophylaxis compared with use of PET alone. All studies with a comparator group resulted in lower rates of csCMVi for patients using LET. Included studies varied widely by CMV viral load threshold cutoff and CMV test units, limiting synthesis of results owing to high heterogeneity. CONCLUSION: LET reduces risk of csCMVi, but lack of standardized clinical definitions on how to evaluate csCMVi and related outcomes largely prevent synthesis of results. Clinicians must consider this limitation in the context of evaluating the effectiveness of LET to other antiviral therapies, especially for patients at risk of late-onset CMV. Future studies should focus on prospective data collection through registries and concordance of diagnostic definitions to mitigate study heterogeneity.


Assuntos
Infecções por Citomegalovirus , Transplante de Células-Tronco Hematopoéticas , Humanos , Citomegalovirus , Antivirais/uso terapêutico , Infecções por Citomegalovirus/prevenção & controle , Infecções por Citomegalovirus/etiologia , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Transplantados
8.
J Oncol Pharm Pract ; 29(7): 1715-1724, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-36731514

RESUMO

BACKGROUND: For patients with multiple myeloma (MM) who have undergone autologous stem cell transplant (auto-SCT), the immunomodulatory agent lenalidomide is a first-line option for maintenance therapy. Because longer durations of lenalidomide maintenance are associated with improved survival, identifying strategies to avoid premature cessation of maintenance is an important priority in the post-transplant setting. OBJECTIVES: The primary objective of this analysis was to identify specific clinical predictors of lenalidomide treatment duration that could guide optimal medication management. Key secondary objectives included predictors of intolerable toxicity, rationale for lenalidomide dose reduction/discontinuation, and characterization of dose adjustments. STUDY DESIGN: This retrospective, multi-center cohort study included adults with MM who underwent auto-SCT and initiated maintenance lenalidomide between 01/01/2012 and 02/28/2021. Variables assessed as potential predictors of maintenance duration or intolerable toxicity included age, body mass index (BMI), Eastern Cooperative Oncology Group (ECOG) performance status at time of auto-SCT, renal function, initial lenalidomide dose, use of combination maintenance therapy, and cytogenetic risk category. RESULTS: Among 299 patients included, the median age at time of auto-SCT was 62 years (range 30-77). The majority of patients had standard-risk cytogenetics (64%) and an ECOG performance status of 0 or 1 (72%). In the overall population, the median duration of maintenance was 1.3 years (range 0.3-8.6 years). The median initial dose of lenalidomide was 10 mg daily (range 2.5-25 mg). During the study period, 35% of patients had a dose reduction due to toxicity, 21% stopped lenalidomide due to disease progression, and 19% stopped due to toxicity. Multivariate linear regression analyses did not identify any significant predictors of lenalidomide duration or discontinuation due to intolerable toxicity. The most frequently reported toxicities leading to discontinuation were cytopenias, rash, and fatigue. CONCLUSION: This analysis did not identify any significant risk factors to predict the duration of lenalidomide maintenance or discontinuation for toxicity following auto-SCT in patients with MM. While limited by the retrospective design and relatively small sample size, our findings suggest that a priori lenalidomide dose reductions based on patient co-morbidities or performance status may not substantially affect the duration of lenalidomide maintenance.


Assuntos
Transplante de Células-Tronco Hematopoéticas , Mieloma Múltiplo , Adulto , Humanos , Pessoa de Meia-Idade , Idoso , Mieloma Múltiplo/tratamento farmacológico , Lenalidomida/uso terapêutico , Estudos Retrospectivos , Estudos de Coortes , Intervalo Livre de Doença , Transplante Autólogo , Transplante de Células-Tronco , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico
9.
Pharmacoecon Open ; 7(3): 393-404, 2023 May.
Artigo em Inglês | MEDLINE | ID: mdl-36840894

RESUMO

PURPOSE: The aim of this study was to assess the cost effectiveness of letermovir prophylaxis with the option for subsequent pre-emptive therapy (PET) for the prevention of cytomegalovirus (CMV) infection compared with a PET-only scenario in adult allogeneic hematopoietic stem cell transplant (allo-HCT) recipients in the United States over a 10-year time horizon. MATERIALS AND METHODS: A publicly available decision tree model was constructed using a commercial third-party payer perspective to simulate an allo-HCT recipient's clinical trajectory in the first-year post-transplant, followed by entry to a Markov model to simulate years 2 through 10. Clinical inputs and utility estimates were derived from published literature. Costs were derived from published literature and US Department of Veterans Affairs Federal Supply Schedule drug pricing. Outcomes assessed included life expectancy, quality-adjusted life-years (QALYs), direct medical costs, and the incremental cost-effectiveness ratio (ICER). One-way and probabilistic sensitivity analyses (PSA) were performed to test the robustness of the findings. RESULTS: Compared with PET alone, letermovir prophylaxis was projected to increase life-years per person (4.99 vs. 4.70 life-years), and increase QALYs (3.29 vs. 3.08) and costs (US$83.411 vs. US$70,698), yielding an ICER of US$59,356 per QALY gained. One-way sensitivity analyses indicated our model was sensitive to mortality (ICER: $164,771/QALY) and utility (letermovir ICER: $117,447/QALY; PET ICER: $107,290/QALY) in the first-year post-transplant. In 57.1% of the PSA simulations, letermovir was a cost-effective option using a willingness-to-pay threshold of US$100,000 per QALY. CONCLUSIONS: Letermovir prophylaxis is cost effective compared with PET alone with a willingness-to-pay threshold of US$100,000 per QALY gained. Sensitivity analysis results indicate future research is required to understand the impact of mortality and quality of life in the first-year post-transplant to arrive at a conclusive decision on letermovir adoption.

10.
Ann Pharmacother ; 57(1): 29-35, 2023 01.
Artigo em Inglês | MEDLINE | ID: mdl-35511200

RESUMO

BACKGROUND: Lenalidomide is an immunomodulatory drug used to treat multiple myeloma that requires renal dosing adjustment based on Cockcroft-Gault (CG). Various equations to estimate kidney function exist and pose a potential issue with lenalidomide dosing. OBJECTIVE: The objective of this analysis was to evaluate the impact of estimating kidney function in newly diagnosed multiple myeloma patients with CG, Modification of Diet in Renal Disease (MDRD), and Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) and their potential impact on lenalidomide dosing. METHODS: Data from 1121 multiple myeloma patients at the time of diagnosis acquired from the Mayo Clinic were used to calculate creatinine clearance (CrCl) using Cockcroft-Gault with actual body weight (CGABW), ideal body weight (CGIBW), or adjusted body weight (CGAdjBW); MDRD; and CKD-EPI for each subject. Discordances in dosing were then analyzed, and lenalidomide exposure was calculated for each subject to assess impact on pharmacokinetics of lenalidomide for patients who received discordant doses. RESULTS: Overall, approximately 16% of patients received a discordant dose when using MDRD or CKD-EPI instead of CGABW. The most common dose discordance was the decrease of a full dose of lenalidomide 25 mg when using CGABW down to 10 mg and when using MDRD or CKD-EPI with 53.8% to 55.6% of all discordances in this category. When assessing different body weights, the most common discordance was a decrease from 25 to 10 mg when using CGIBW instead of CGABW; the same trend was observed when using CGAdjBW instead as well. Patients were also at risk of over- or underexposure based on area under the concentration versus time curve (AUC) for discordant dosing. CONCLUSION AND RELEVANCE: A significant proportion of patients are at risk of under- or overdose of lenalidomide if CKD-EPI or MDRD are used instead of CGABW. Physicians should use CGABW when estimating renal function to dose lenalidomide.


Assuntos
Mieloma Múltiplo , Insuficiência Renal Crônica , Humanos , Taxa de Filtração Glomerular , Lenalidomida/uso terapêutico , Creatinina , Mieloma Múltiplo/tratamento farmacológico , Insuficiência Renal Crônica/diagnóstico , Rim , Peso Corporal
11.
J Am Pharm Assoc (2003) ; 63(1): 424-429, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36470731

RESUMO

In the United States, coronavirus disease 2019 (COVID-19) has resulted in more than 95 million infections and 1 million deaths (as of September 2022), with individuals of racially/ethnically minoritized groups being disproportionately represented among these numbers. Despite the apparent pandemic fatigue in many communities, systemic and structural racism continue to place racially/ethnically minoritized groups at a disadvantage for overcoming the virus, especially as it relates to receiving vaccinations and COVID-19 targeted therapeutics. Test to Treat programs have the potential to mitigate these disparities by rapidly identifying the presence of a COVID-19 infection and readily offering treatment options. Nonetheless, Test to Treat programs must be optimized to adequately address the limitations to care within racially/ethnically minoritized communities.


Assuntos
COVID-19 , Humanos , Estados Unidos/epidemiologia , Grupo Social , Pandemias , Vacinação
12.
Explor Res Clin Soc Pharm ; 6: 100136, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-35909716

RESUMO

Background: In the US, medical costs for cancer patients have grown from $27 billion in 1990 to $174 billion in 2020. The increased financial strain that cancer patients and survivors endure is referred to as financial toxicity. Objective: To quantify the relationship between indicators of financial toxicity and health utilization and quality of life in patients ever diagnosed with cancer. Methods: Adult cancer patients and survivors in 2017 were identified using the Medical Expenditure Panel Survey. Multiple logistic regression models were used to quantify the relationship between three financial toxicity exposures (concern for keeping an income, paying large medical bills, and going into debt or borrowing money) and two discrete outcomes of being able to purchase prescriptions and often worrying that cancer would worsen or come back. Results: This study assessed 609 respondents. After survey weighting was applied, that represented 16,215,673 individuals. Patients who reported concern for keeping an income were at 2.91 (95% Confidence Interval [CI], 1.16 to 7.31) and 2.97 (95% CI, 2.01 to 2.67) times increased odds to report avoiding purchase of prescriptions and worry of cancer status, respectively, versus those who did not. Patients who reported worry about paying large medical bills were at 4.46 (95% CI, 2.15 to 9.24) and 2.80 (95% CI, 1.98 to 3.96) times increased odds to report avoiding purchase of prescriptions and worry of cancer status, respectively, versus those who did not. Patients who reported borrowing money or going into debt were at 3.04 (95% CI, 1.19 to 7.76) and 2.42 (95% CI, 1.54 to 3.18) times increased odds to report avoiding purchase of prescriptions and worry of cancer status, respectively, versus those who did not. Conclusions: Financial toxicity is associated with decreased prescription utilization and quality of life in the form of excessive worry among cancer patients including cancer survivors.

14.
J Am Pharm Assoc (2003) ; 62(3): 701-705, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35367143

RESUMO

Due to the effects of structural racism, disproportionately lower numbers of Black, Hispanic or LatinX, American Indian, and Alaska Native students pursue a career in pharmacy and successfully matriculate into the profession. Despite these disparities being present for many years, little progress has been achieved in diversifying the pharmacy profession, resulting in a persistent lack of diversity within pharmacy leadership across employers and pharmacy organizations. Consistent with recent recommendations for improving diversity in pharmacy, the PharmGradWishlist (PGWL) initiative was created as a way for practicing pharmacists and organizations to provide direct financial sponsorship to racially and ethnically minoritized trainees to offset costs incurred during training and during the transition from student to practicing pharmacist. Many of these costs, such as residency and fellowship application fees, job interview travel costs, board exam and licensing fees, and moving expenses, are not typically subsidized by federal student funding. Offsetting these costs is an important way to reduce barriers to entering the profession and postgraduate training, the latter of which may be particularly important in trainees' pursuit of academic and leadership positions in pharmacy. The initial development and advertisement of the initiative occurred through social media and the grassroots efforts of the PGWL team, a group of 10 volunteer pharmacists from across the country, and resulted in generous donations from a small proportion of practicing pharmacists nationwide. It is now time for the profession as a whole to embrace the role of direct sponsorship in improving diversity in the profession. We call upon pharmacists and pharmacy organizations to advocate for and participate in financial sponsorship of racially and ethnically minoritized trainees and pharmacists as a way to increase diversity and promote health equity.


Assuntos
Educação em Farmácia , Farmácia , Estudantes de Farmácia , Promoção da Saúde , Humanos , Farmacêuticos
15.
Br J Haematol ; 197(1): 63-70, 2022 04.
Artigo em Inglês | MEDLINE | ID: mdl-35174480

RESUMO

We investigated the incidence of invasive fungal infections (IFIs) and other infectious complications in patients receiving venetoclax and hypomethylating agent therapy for acute myeloid leukaemia (AML). This retrospective, multicentre cohort study included adult patients with AML who received at least one cycle of venetoclax and either azacitidine or decitabine between January 2016 and August 2020. The primary outcome was the incidence of probable or confirmed IFI. Secondary outcomes included antifungal prophylaxis prescribing patterns, incidence of bacterial infections, and incidence of neutropenic fever hospital admissions. Among 235 patients, the incidence of probable or confirmed IFI was 5.1%. IFI incidence did not differ significantly according to age, antifungal prophylaxis use, or disease status. In the subgroup of patients with probable or confirmed IFIs, six (50%) were receiving antifungal prophylaxis at the time of infection. The overall incidence of developing at least one bacterial infection was 33.6% and 127 (54%) patients had at least one hospital admission for febrile neutropenia. This study demonstrated an overall low risk of developing probable or confirmed IFI as well as a notable percentage of documented bacterial infections and hospital admissions due to neutropenic fever.


Assuntos
Infecções Fúngicas Invasivas , Leucemia Mieloide Aguda , Adulto , Antifúngicos/uso terapêutico , Compostos Bicíclicos Heterocíclicos com Pontes , Estudos de Coortes , Humanos , Infecções Fúngicas Invasivas/epidemiologia , Leucemia Mieloide Aguda/complicações , Estudos Retrospectivos , Sulfonamidas
16.
Clin Lymphoma Myeloma Leuk ; 22(3): e161-e184, 2022 03.
Artigo em Inglês | MEDLINE | ID: mdl-34649791

RESUMO

Acute myeloid leukemia (AML) is the most common acute leukemia of adults, with a five-year survival that remains poor (approximately 25%). Knowledge and understanding of AML genomics have expanded tremendously over the past decade and are now included in AML prognostication and treatment decisions. FMS-like tyrosine kinase 3 (FLT3) is a Class III receptor tyrosine kinase (RTK) expressed primarily in the cell membranes of early hematopoietic progenitor cells, found in 28% of all patients with AML. FLT3 is the second most frequent mutation in adult AML following Nuclear-cytoplasmic shuttling phosphoprotein (NPM1), which is found in 50% of cases.1 FLT3 inhibitors are promising new molecular therapeutics increasingly becoming standard of care for both newly diagnosed and relapsed/refractory FLT3 positive AML. This review will focus on the clinical trials/evidence, similarities, differences, clinical toxicities, and drug interactions relevant to treating clinicians as pertains to 5 FLT3-inhibitors: midostaurin, sorafenib, gilteritinib, crenolanib, and quizartinib.


Assuntos
Antineoplásicos , Leucemia Mieloide Aguda , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Humanos , Leucemia Mieloide Aguda/terapia , Mutação , Inibidores de Proteínas Quinases/efeitos adversos , Sorafenibe/uso terapêutico , Tirosina Quinase 3 Semelhante a fms/genética
17.
Thromb Res ; 208: 148-155, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34798446

RESUMO

INTRODUCTION: Patients with central nervous system malignancies have limited representation in studies evaluating DOACs for VTE treatment. This study evaluated the safety and efficacy of DOACs in comparison with LMWH for cancer-associated VTE in patients with primary brain tumors or secondary brain metastases. MATERIALS & METHODS: In this multicenter, retrospective cohort study, adult patients with a diagnosis of primary brain tumor or secondary brain metastases who received either a DOAC or LMWH for treatment of cancer-associated VTE were evaluated. The primary outcome was the cumulative incidence of any intracranial hemorrhage within a 6-month period following the initiation of anticoagulation. Secondary outcomes included the cumulative incidence of any bleeding event, and recurrent VTE events. RESULTS: Between January 1, 2012 and October 9, 2019, one-hundred eleven patients met inclusion criteria. The 6-month cumulative incidence of intracranial hemorrhage was 4.3% (95% CI, 0.74-13.2%) in the DOAC group, compared to 5.9% (95% CI, 1.5-14.9%) in the LMWH group (p = 0.61). The 6-month cumulative incidence of bleeding events was 14.3% (95% CI, 6.2-25.8%) in the DOAC group, compared to 27.8% (95% CI, 15.5-41.6%) in the LMWH group (p = 0.10). The 6-month cumulative incidence of recurrent VTE events was 5.6% in the DOAC group (95% CI, 1.5-14.2%), compared to 6.6% in the LMWH group (95% CI, 1.7-16.5%) (p = 0.96). No differences were found with respect to other secondary outcomes. CONCLUSION: There were no significant differences in bleeding or recurrent VTE events between DOACs and LMWH. These findings suggest DOACs may be safe and effective for VTE treatment in this patient population.


Assuntos
Neoplasias Encefálicas , Tromboembolia Venosa , Anticoagulantes/efeitos adversos , Neoplasias Encefálicas/complicações , Heparina de Baixo Peso Molecular/efeitos adversos , Humanos , Estudos Retrospectivos , Tromboembolia Venosa/tratamento farmacológico
18.
Sci Rep ; 11(1): 17324, 2021 08 30.
Artigo em Inglês | MEDLINE | ID: mdl-34462476

RESUMO

Antibodies targeting the PD-1, PD-L1, and CTLA-4 immune checkpoint axis have been used in a variety of tumor types. They achieve anti-tumor activity through activating the patient's own immune system to target immune response evading cancer cells. However, this unique mechanism of action may cause immune-related adverse events, irAEs. One of these irAEs is myocarditis which is associated with an alarming mortality rate. In this study we presented clinical cases of myocarditis from safety trial datasets submitted to the U.S. Food and Drug Administration, FDA. Additionally, we analyzed over fourteen million FDA Adverse Event Reporting System, FAERS, submissions. The statistical analysis of the FAERS data provided evidence of significantly increased reporting of myocarditis in patients administered immune checkpoint inhibitors alone, in combination with another immune checkpoint inhibitor, the kinase inhibitor axitinib, or chemotherapy, for all cancer types, when compared to patients administered chemotherapy. All combination therapies led to further increased reporting odds ratios of myocarditis. We further analyzed the occurrence of myocarditis by stratifying the reports into sub-cohorts based on specific cancer types and treatment/control groups in major cancer immunotherapy efficacy trials and confirmed the observed trend for each cohort.


Assuntos
Antineoplásicos Imunológicos/efeitos adversos , Imunoterapia/efeitos adversos , Miocardite/etiologia , Neoplasias/terapia , Sistemas de Notificação de Reações Adversas a Medicamentos , Antineoplásicos Imunológicos/uso terapêutico , Coleta de Dados , Humanos , Inibidores de Checkpoint Imunológico , Miocardite/complicações , Neoplasias/complicações , Razão de Chances , Estudos Retrospectivos , Estados Unidos , United States Food and Drug Administration
19.
J Oncol Pharm Pract ; 27(4): 821-826, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32605497

RESUMO

INTRODUCTION: Blinatumomab is a CD19/CD3 bispecific T-cell engager (BiTE) antibody that simultaneously binds CD19 on the surface of B-cells and CD3 on the surface of T-cells, resulting in tumor cell lysis. It is approved for the treatment of patients with relapsed/refractory B-cell acute lymphoblastic leukemia (B-ALL) and in patients with minimal residual disease after intensive induction chemotherapy. Relapse patterns after treatment with blinatumomab have not been well characterized. METHODS: We reviewed patients treated with blinatumomab with relapsed, refractory or minimal residual disease-positive B-ALL from 1 December 2014 to 31 December 2018 at a single academic medical center. Patient demographics, blast percentage prior to blinatumomab initiation, prior lines of therapy, blinatumomab treatment duration, sites of relapse, progression free survival, and overall survival were collected. RESULTS: A total of 20 patients were identified. Four (20%) patients developed extramedullary relapse following blinatumomab. The median time from treatment initiation to extramedullary relapse was 179 days (range 47-241). Sites of extramedullary relapse included the pancreas, adrenal gland, kidneys, liver, parotid gland, and brain. CONCLUSION: Extramedullary relapse occurs frequently following treatment of B-ALL with blinatumomab. Further studies aimed at preventing extramedullary relapse following blinatumomab treatment are warranted.


Assuntos
Anticorpos Biespecíficos/uso terapêutico , Antineoplásicos/uso terapêutico , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamento farmacológico , Adulto , Resistencia a Medicamentos Antineoplásicos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Metástase Neoplásica , Estadiamento de Neoplasias , Leucemia-Linfoma Linfoblástico de Células Precursoras/patologia , Intervalo Livre de Progressão , Recidiva , Fatores Socioeconômicos , Análise de Sobrevida
20.
Pharmacotherapy ; 40(8): 808-841, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32652612

RESUMO

Annually, ~50,000 patients undergo hematopoietic stem cell transplantation (HCT) worldwide with almost 22,000 of these patients receiving HCT in the United States. HCT is a curative option for a wide range of hematologic malignancies, and advances in transplantation medicine have resulted in an increase in HCT survivors. It is anticipated that the number of HCT survivors will more than double from 242,000 in 2020 to ~500,000 in 2030. Survivors of HCT are at an increased risk of developing late complications due to exposure to chemotherapy and/or radiation in the pre-, peri-, and post-HCT phases and these cumulative exposures have the potential to damage normal tissue. This tissue damage leads to the early onset of chronic health conditions resulting in premature mortality in HCT survivors, who have a 15-year cumulative incidence of severe or life-threatening chronic health conditions exceeding 40%. Due to the significant burden of morbidity in HCT survivors and the delay in the development of long-term complications, this delicate patient population requires life-long monitoring due to the risk for neuropsychological, cardiac, pulmonary, renal, hepatic, ocular, skeletal, cardiac, endocrine, fertility, and sexual health complications, as well as secondary neoplasms. This review will focus on recent advances in screening, monitoring, and therapeutics for late-occurring or long-term complications in HCT survivors.


Assuntos
Neoplasias Hematológicas/terapia , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Sobreviventes , Antineoplásicos/administração & dosagem , Antineoplásicos/efeitos adversos , Doença Crônica , Terapia Combinada , Transplante de Células-Tronco Hematopoéticas/métodos , Humanos , Programas de Rastreamento/métodos , Lesões por Radiação/epidemiologia , Fatores de Tempo
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