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1.
NEJM Evid ; 3(4): EVIDoa2300213, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38776868

RESUMO

BACKGROUND: Administration of anti-CD19 chimeric antigen receptor T-cell (CART19) immunotherapy for large B-cell lymphomas (LBCLs), a subset of non-Hodgkin lymphoma (NHL), involves high costs and access to specialized tertiary care centers. We investigated whether minority health populations (MHPs) have equal access to CART19 and whether their outcomes are similar to those of non-MHPs. METHODS: We analyzed the prevalence and clinical outcomes of patients treated with commercial CART19 at two geographically and socioeconomically different institutions: the Abramson Cancer Center (ACC, Philadelphia, Pennsylvania) and the Knight Cancer Institute (KCI, Portland, Oregon). RESULTS: In the ACC catchment area, 8956 patients were diagnosed with NHL between 2015 and 2019 (latest available data from the state registry), including 17.9% MHPs. In the ACC, between 2018 and 2022 (CART became available in 2018), 1492 patients with LBCL were treated, and 194 received CART19. The proportion of MHPs was 15.7% for the entire LBCL cohort but only 6.7% for the CART19 cohort. During the same time, in the KCI catchment area, 4568 patients were diagnosed with NHL, including 4.2% MHPs. In the KCI, 396 patients with LBCL were treated, and 47 received CART19. The proportion of MHPs was 6.6% for the entire LBCL cohort and 4.2% for the CART19 cohort. The 3-month response, survival, and toxicities after CART19 infusion showed similar results, although the number of patients who were treated was limited. CONCLUSIONS: This study shows that the access of MHPs to tertiary centers for LBCL care was preserved but appeared reduced for commercial CART19 immunotherapy. Although clinical outcomes of MHPs seemed similar to those of non-MHPs, the small sample size precludes drawing firm conclusions. Further studies are needed. (Funded by the Laffey McHugh Foundation and others.).


Assuntos
Imunoterapia Adotiva , Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Imunoterapia Adotiva/efeitos adversos , Idoso , Adulto , Grupos Minoritários/estatística & dados numéricos , Receptores de Antígenos Quiméricos/imunologia , Antígenos CD19/imunologia , Antígenos CD19/uso terapêutico
2.
J Hematol Oncol ; 17(1): 19, 2024 Apr 22.
Artigo em Inglês | MEDLINE | ID: mdl-38644469

RESUMO

Bendamustine has been retrospectively shown to be an effective and safe lymphodepletion regimen prior to the anti-CD19 chimeric antigen receptor T cell (CART) products tisagenlecleucel and axicabtagene ciloleucel, as well as the anti-BCMA CART products idecabtagene vicleucel and ciltacabtagene autoleucel. However, bendamustine as lymphodepletion prior to lisocabtagene maraleucel (liso-cel), a 4-1BB co-stimulated, fixed CD4:CD8 ratio anti-CD19 CART product, has not been described yet. Thus, we studied a cohort of sequentially-treated patients with large B-cell lymphomas who received bendamustine lymphodepletion before liso-cel at the University of Pennsylvania between 5/2021 and 12/2023 (n = 31). Patients were evaluated for toxicities and responses. Of note, 7 patients (22.6%) would have dnot met the inclusion criteria for the registrational liso-cel clinical trials, mostly due to older age. Overall and complete response rates were 76.9% and 73.1%, respectively. At a median follow-up of 6.3 months, the 6-month progression-free and overall survival were 59.9% and 91.1%, respectively. Rates of cytokine-release syndrome (CRS) and neurotoxicity (ICANS) of any grade were 9.7% and 9.7%, respectively, with no grade ≥ 3 events. No infections were reported during the first 30 days following liso-cel infusion. Neutropenia ≥ grade 3 was observed in 29.0% of patients; thrombocytopenia ≥ grade 3 occurred in 9.7%. In conclusion, bendamustine lymphodepletion before liso-cel appears to be a strategy that can drive tumor responses while ensuring a mild toxicity profile.


Assuntos
Cloridrato de Bendamustina , Imunoterapia Adotiva , Humanos , Cloridrato de Bendamustina/uso terapêutico , Pessoa de Meia-Idade , Masculino , Feminino , Idoso , Imunoterapia Adotiva/métodos , Imunoterapia Adotiva/efeitos adversos , Estudos Retrospectivos , Adulto , Linfoma Difuso de Grandes Células B/tratamento farmacológico , Antineoplásicos Alquilantes/uso terapêutico , Antineoplásicos Alquilantes/efeitos adversos , Produtos Biológicos/uso terapêutico , Produtos Biológicos/efeitos adversos , Idoso de 80 Anos ou mais , Resultado do Tratamento
3.
Transplant Cell Ther ; 2024 Mar 16.
Artigo em Inglês | MEDLINE | ID: mdl-38494076

RESUMO

Brexucabtagene autoleucel (brexu-cel) is an autologous CD19-directed chimeric antigen receptor (CAR) T-cell therapy approved for treatment of relapsed/refractory mantle cell lymphoma (MCL). During a fludarabine shortage, we used bendamustine as an alternative to standard cyclophosphamide/fludarabine (cy/flu) lymphodepletion (LD) prior to brexu-cel. We assessed MCL patient outcomes as well as CAR T-cell expansion and persistence after brexu-cel following bendamustine or cy/flu LD at our center. This was a retrospective single institution study that utilized prospectively banked blood and tissue samples. Clinical efficacy was assessed by 2014 Lugano guidelines. CAR T-cell expansion and persistence in peripheral blood were assessed on day 7 and at ≥month 6 for patients with available samples. Seventeen patients received bendamustine and 5 received cy/flu. For the bendamustine cohort, 14 (82%) received bridging therapy and 4 (24%) had CNS involvement. Fifteen patients (88%) developed CRS with 4 (24%) ≥grade 3 events. Six (35%) patients developed ICANS with 4 (24%) events ≥grade 3. No patient had ≥grade 3 cytopenias at day 90. Best objective (BOR) and complete response (CRR) rates were 82% and 65%, respectively. At 24.5 months median follow-up, 12-month progression-free survival (PFS) was 45%, 24-month PFS was 25%, and median duration of response was 19 months. Median OS was not reached. BOR was 25% (1/4) for patients with CNS involvement. CAR transgene expansion after bendamustine LD was observed on day 7 in all (4/4) patients tested and persisted at ≥6 months (2/2), regardless of response. Bendamustine LD before brexu-cel for MCL is feasible and safe with a lower frequency and shorter duration of cytopenias than reported for cy/flu. Both CAR T-cell expansion and persistence were observed after bendamustine LD. Outcomes appear comparable to the real world outcomes reported with cy/flu LD.

4.
Blood Adv ; 8(3): 653-666, 2024 02 13.
Artigo em Inglês | MEDLINE | ID: mdl-38113468

RESUMO

ABSTRACT: Lymphodepletion (LD) is an integral component of chimeric antigen receptor T-cell (CART) immunotherapies. In this study, we compared the safety and efficacy of bendamustine (Benda) to standard fludarabine/cyclophosphamide (Flu/Cy) LD before CD19-directed, CD28-costimulated CART axicabtagene ciloleucel (axi-cel) for patients with large B-cell lymphoma (LBCL) and follicular lymphoma (FL). We analyzed 59 patients diagnosed with LBCL (n = 48) and FL (n = 11) consecutively treated with axi-cel at the University of Pennsylvania. We also analyzed serum samples for cytokine levels and metabolomic changes before and after LD. Flu/Cy and Benda demonstrated similar efficacy, with complete remission rates of 51.4% and 50.0% (P = .981), respectively, and similar progression-free and overall survivals. Any-grade cytokine-release syndrome occurred in 91.9% of patients receiving Flu/Cy vs 72.7% of patients receiving Benda (P = .048); any-grade neurotoxicity after Flu/Cy occurred in 45.9% of patients and after Benda in 18.2% of patients (P = .031). In addition, Flu/Cy was associated with a higher incidence of grade ≥3 neutropenia (100% vs 54.5%; P < .001), infections (78.4% vs 27.3%; P < .001), and neutropenic fever (78.4% vs 13.6%; P < .001). These results were confirmed both in patients with LBCL and those with FL. Mechanistically, patients with Flu/Cy had a greater increase in inflammatory cytokines associated with neurotoxicity and reduced levels of metabolites critical for redox balance and biosynthesis. This study suggests that Benda LD may be a safe alternative to Flu/Cy for CD28-based CART CD19-directed immunotherapy with similar efficacy and reduced toxicities. Benda is associated with reduced levels of inflammatory cytokines and increased anabolic metabolites.


Assuntos
Produtos Biológicos , Citocinas , Linfoma Folicular , Humanos , Cloridrato de Bendamustina/efeitos adversos , Antígenos CD28 , Imunoterapia Adotiva/efeitos adversos , Imunoterapia Adotiva/métodos , Ciclofosfamida
5.
Transplant Cell Ther ; 29(8): 495-503, 2023 08.
Artigo em Inglês | MEDLINE | ID: mdl-37211154

RESUMO

Patients diagnosed with relapsed/refractory (R/R) diffuse large B cell lymphoma (DLBCL) or high-grade B cell lymphoma (HGBL) may achieve prolonged survival following receipt of high-dose chemotherapy/autologous stem cell transplantation (HDC/ASCT) or CD19-directed chimeric antigen receptor modified T cell therapy (CART19). Although early results from randomized clinical trials suggest that assignment to CART19 versus salvage immunochemotherapy as second-line therapy results in improved survival, analysis of a large series of patients who actually received HDC/ASCT or CART19 has yet to be performed. Such an analysis may inform future research efforts to optimize the risk stratification of R/R DLBCL/HGBL patients who are candidates for either therapy. The aim of this study was to evaluate clinicopathologic factors predictive of freedom from treatment failure (FFTF) for R/R DLBCL/HGBL patients following receipt of HDC/ASCT or CART19, and to compare patterns of treatment failure (TF) in R/R DLBCL/HGBL patients receiving HDC/ASCT and those receiving CART19. THE STUDY GROUP COMPRISED: patients age ≤75 years with R/R DLBCL/HGBL who received HDC/ASCT demonstrating partial or complete metabolic response to salvage immunochemotherapy and/or CART19 in the standard of care setting at the University of Pennsylvania between 2013 and 2021. Survival analyses were performed from the time of infusion of either HDC/ASCT or CART19, as well as at landmark time points postinfusion for patients who achieved FFTF. For 100 HDC/ASCT patients with a median follow-up of 62.7 months, the estimated 36-month FFTF and overall survival (OS) rates were 59% and 81%, respectively. For 109 CART19 patients with a median follow-up of 37.6 months, the estimated 36-month FFTF and OS rates were 24% and 48%, respectively. HDC/ASCT patients had significantly higher rates of estimated 36-month FFTF when they achieved actual FFTF at 3, 6, 12 and 24 months. Additionally, the rates of baseline characteristics predictive of TF at 36 months for either HDC/ASCT or CART19 patients were either similar to or significantly lower for CART19 patients compared to HDC/ASCT patients who achieved actual FFTF at 3, 6, 12, and 24 months. Patients with R/R DLBCL/HGBL achieving response to salvage immunochemotherapy who received HDC/ASCT had a high rate of estimated FFTF regardless of whether they harbored features predictive of resistance to salvage immunochemotherapy, which may be more durable than that of R/R DLBCL/HGBL patients receiving CART19. These findings support further investigation of disease characteristics, such as molecular features, that may predict response to salvage immunochemotherapy in patients fit for HDC/ASCT.


Assuntos
Transplante de Células-Tronco Hematopoéticas , Linfoma Difuso de Grandes Células B , Receptores de Antígenos Quiméricos , Humanos , Idoso , Receptores de Antígenos Quiméricos/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Transplante Autólogo/métodos , Linfoma Difuso de Grandes Células B/terapia , Linfócitos T
6.
Future Oncol ; 18(19): 2415-2431, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-35583358

RESUMO

Background: Chimeric antigen receptor T-cell (CAR-T) therapy represents a new frontier in multiple myeloma. It is important to understand critical success factors (CSFs) that may optimize its use in this therapeutic area. Methods: We estimated the CAR-T process using time-driven activity-based costing. Information was obtained through interviews at four US oncology centers and with payer representatives, and through publicly available data. Results: The CAR-T process comprises 13 steps which take 177 days; it was estimated to include 46 professionals and ten care settings. CSFs included proactive collaboration, streamlined reimbursement and CAR-T administration in alternative settings when possible. Implementing CSFs may reduce episode time and costs by 14.4 and 13.2%, respectively. Conclusion: Our research provides a blueprint for improving efficiencies in CAR-T therapy, thereby increasing its sustainability for multiple myeloma.


Patients with multiple myeloma can now be treated with chimeric antigen receptor T-cell (CAR-T) therapy. We studied how CAR-T therapy is used for multiple myeloma. We also studied things that could help make this therapy easier for doctors to use. The CAR-T process takes 13 steps and 177 days. It begins with the choice to use the therapy and ends about 100 days after it is used. The process uses 46 different healthcare professionals and ten different locations. We found several possible changes that can improve this process. Of these changes, three stand out. First, improved teamwork between members of the care team can help them prepare for and resolve possible problems. Second, reducing insurance red tape will make it easier to provide CAR-T therapy to patients. Third, allowing use of CAR-T therapy in places other than hospitals can help more patients receive this therapy. If applied, these three things may lower the time needed to treat patients by 14.4% and may reduce costs by 13.2%.


Assuntos
Mieloma Múltiplo , Receptores de Antígenos Quiméricos , Terapia Baseada em Transplante de Células e Tecidos , Humanos , Imunoterapia Adotiva , Mieloma Múltiplo/terapia , Receptores de Antígenos de Linfócitos T/genética , Receptores de Antígenos Quiméricos/genética , Linfócitos T
7.
Clin Lymphoma Myeloma Leuk ; 22(8): e730-e737, 2022 08.
Artigo em Inglês | MEDLINE | ID: mdl-35595619

RESUMO

INTRODUCTION: Chimeric antigen receptor T-cell therapy (CAR T) is a revolutionary adoptive immunotherapy approach in lymphoma; however, substantial resources are necessary for administration and care of these patients. Our institution has administered tisagenlecleucel primarily in an outpatient setting, and here we report our clinical outcomes. PATIENTS AND METHODS: We conducted a single institution, retrospective study investigating outcomes of adult lymphoma patients treated with commercial tisagenlecleucel between 10/2017 and 12/2020. We analyzed patient characteristics and outcomes of efficacy and safety including overall response rate, progression-free survival, overall survival and cytokine-release syndrome, neurotoxicity, and hospitalizations. RESULTS: Seventy-two patients with relapsed or refractory non-Hodgkin lymphoma (NHL) who received commercial tisagenlecleucel were identified; 68 (94.4%) patients received outpatient tisagenlecleucel. The overall response rate was 43% with a complete response observed in 25 patients (34.7%). At a median follow-up of 9.1 months, the median progression-free survival was 3.3 months. Grade 3-4 cytokine release syndrome was not observed in the study group and two patients had grade 3-4 neurotoxicity. Twenty-six patients (36.1%) were admitted within 30 days after infusion with a median length of stay of 5 days. Fourteen patients (19.4%) were admitted within 72 hours of infusion. No patient died of CAR T cell-related toxicity. CONCLUSION: Our experience affirms treatment with tisagenlecleucel in the outpatient setting is safe and feasible with close supervision and adequate institutional experience. After infusion, adverse events were manageable and the majority of patients did not require hospitalization.


Assuntos
Linfoma Folicular , Receptores de Antígenos de Linfócitos T , Adulto , Antígenos CD19 , Citocinas , Humanos , Imunoterapia Adotiva , Linfoma Folicular/tratamento farmacológico , Estudos Retrospectivos
8.
Semin Oncol Nurs ; 37(4): 151178, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-34340892

RESUMO

OBJECTIVE: Tisagenlecleucel is a CD19-directed, genetically modified, autologous T-cell immunotherapy indicated for pediatric and young adult patients with relapsed/refractory B-cell precursor acute lymphoblastic leukemia and for adult patients with relapsed/refractory diffuse large B-cell lymphoma. Treatment with any chimeric antigen receptor (CAR)-T cell therapy is a multistep process in which nurses and nurse practitioners are key to managing patient safety. Managing patients receiving CAR-T cell therapy in the outpatient setting (as Penn does with tisagenlecleucel and lisocabtagene maraleucel) requires an even more complex process. The objective of this manuscript is to provide guidance on the role of nurses in the outpatient administration of tisagenlecleucel therapy and postinfusion care in adult patients with diffuse large B-cell lymphoma. Oncology and apheresis nurses discuss institutional processes and perspectives related to the patient experience with tisagenlecleucel therapy at the Hospital of the University of Pennsylvania. DATA SOURCES: Author experience. CONCLUSION: Nurses are vital for the success of the patient management processes involved with tisagenlecleucel therapy. Nurses must be thoroughly educated in tisagenlecleucel therapy and adverse event management and be able to effectively communicate all aspects of therapy among the multidisciplinary team of the hospital, the product manufacturer, and patients and families. Establishment of the nurse cellular therapy coordinator at the Hospital of the University of Pennsylvania was advantageous in facilitating effective communication in all these situations. IMPLICATIONS FOR NURSING: This encompassing approach to patient management is particularly necessary during administration of tisagenlecleucel therapy and other CAR-T cell therapies that are managed in the outpatient setting.


Assuntos
Pacientes Ambulatoriais , Receptores de Antígenos de Linfócitos T , Antígenos CD19 , Criança , Humanos , Imunoterapia Adotiva
9.
J Bone Joint Surg Am ; 102(23): 2077-2086, 2020 Dec 02.
Artigo em Inglês | MEDLINE | ID: mdl-33093298

RESUMO

BACKGROUND: Congenital pseudarthrosis of the tibia is a rare and challenging pediatric condition. The pre-fracture state, called congenital tibial dysplasia or anterolateral bowing of the tibia, presents a high fracture risk due to underlying bowing and dysplasia. After fracture, there is a substantial risk of nonunion. Any union achieved may be complicated by refracture, deformity, leg-length discrepancy, stiffness, pain, and dysfunction. We present the results of using distal tibial growth modulation to improve tibial alignment and to decrease fracture risk in this condition. To our knowledge, this is the first report of isolated distal tibial growth modulation as the primary surgical treatment for this condition. METHODS: This is a retrospective study of 10 patients with congenital tibial dysplasia who presented prior to pseudarthrosis and underwent distal tibial growth modulation as a primary treatment. The medical records and radiographs were reviewed for age at the times of diagnosis and treatment, fracture, secondary procedures, complications, residual deformity, cystic changes, and leg-length discrepancy. RESULTS: Ten patients had a mean follow-up (and standard deviation) of 5.1 ± 1.9 years. No patient sustained a tibial fracture, and no patient developed a tibial pseudarthrosis after guided growth was initiated. The mean age at the initiation of growth modulation was 2.6 ± 1.3 years. Six patients required a plate exchange. The mean residual tibial diaphyseal angular deformity at the most recent follow-up was 4.3° ± 3.2° of varus and 8.4° ± 5.8° in the sagittal plane. Only 1 patient had a clinically important leg-length discrepancy, with the affected leg being longer. CONCLUSIONS: In this series of 10 patients with congenital tibial dysplasia, distal tibial growth modulation delayed or possibly prevented fracture, decreased tibial malalignment, improved radiographic appearance of bone quality, and preserved leg length. No patient developed tibial fracture or pseudarthrosis after the initiation of guided growth treatment. Although early results are promising, follow-up to maturity is required to define the exact role of this simple outpatient procedure in congenital tibial dysplasia. LEVEL OF EVIDENCE: Therapeutic Level IV. See Instructions for Authors for a complete description of levels of evidence.


Assuntos
Pseudoartrose/congênito , Fraturas da Tíbia/prevenção & controle , Placas Ósseas , Parafusos Ósseos , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Masculino , Pseudoartrose/cirurgia , Estudos Retrospectivos , Tíbia/anormalidades , Tíbia/crescimento & desenvolvimento , Tíbia/cirurgia
11.
Anesth Analg ; 127(3): 642-649, 2018 09.
Artigo em Inglês | MEDLINE | ID: mdl-29757781

RESUMO

Administration of preoperative antimicrobial prophylaxis, often with a cephalosporin, is the mainstay of surgical site infection prevention guidelines. Unfortunately, due to prevalent misconceptions, patients labeled as having a penicillin allergy often receive alternate and less-effective antibiotics, placing them at risk of a variety of adverse effects including increased morbidity and higher risk of surgical site infection. The perioperative physician should ascertain the nature of previous reactions to aid in determining the probability of the prevalence of a true allergy. Penicillin allergy testing may be performed but may not be feasible in the perioperative setting. Current evidence on the structural determinants of penicillin and cephalosporin allergies refutes the misconception of cross-reactivity between penicillins and cefazolin, and there is no clear evidence of an increased risk of anaphylaxis in cefazolin-naive, penicillin-allergic patients. A clinical practice algorithm for the perioperative evaluation and management of patients reporting a history of penicillin allergy is presented, concluding that cephalosporins can be safely administered to a majority of such patients.


Assuntos
Anestesiologistas/normas , Antibacterianos/efeitos adversos , Hipersensibilidade a Drogas/diagnóstico , Penicilinas/efeitos adversos , Mal-Entendido Terapêutico , Anestesiologistas/tendências , Antibacterianos/imunologia , Cefazolina/efeitos adversos , Cefazolina/imunologia , Cefalosporinas/efeitos adversos , Cefalosporinas/imunologia , Reações Cruzadas/efeitos dos fármacos , Reações Cruzadas/imunologia , Hipersensibilidade a Drogas/epidemiologia , Hipersensibilidade a Drogas/imunologia , Humanos , Penicilinas/imunologia , Papel do Médico , Infecção da Ferida Cirúrgica/etiologia , Infecção da Ferida Cirúrgica/imunologia , Infecção da Ferida Cirúrgica/prevenção & controle
12.
Clin Infect Dis ; 65(7): 1059-1065, 2017 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-28575226

RESUMO

Background: ß-lactam allergy skin testing (BLAST) is recommended by antimicrobial stewardship program (ASP) guidelines, yet few studies have systematically evaluated its impact when delivered at point of care. Methods: We conducted a pragmatic multicenter prospective evaluation of the use of point-of-care BLAST by ASPs. In staggered 3-month intervals, ASP teams at 3 hospitals received training by allergists to offer BLAST for eligible patients with infectious diseases receiving nonpreferred therapy due to severity of their reported allergy. The primary outcome was the proportion of patients receiving the preferred ß-lactam therapy. Results: Of 827 patients with reported ß-lactam allergy over 15 months, ß-lactam therapy was preferred among 632 (76%). During baseline periods, 50% (124/246) received preferred ß-lactam therapy based on history, compared with 60% (232/386) during the intervention periods (P = .02), which improved further to 81% (313/386) upon provision of BLAST (P < .001) without any increase in incidence of adverse drug reactions (4% vs 3%; P = .4). After adjusting for patient variables and the correlation between hospitals, the intervention period was associated with a 4.5-fold greater odds of receiving preferred ß-lactam therapy (95% confidence interval, 2.4-8.2; P < .0001). Conclusions: The use of BLAST at the point of care across 3 hospital ASPs resulted in greater use of preferred ß-lactam therapy without increasing the risk of adverse drug reactions. Longer-term studies are needed to better assess the safety and clinical impact of this ASP intervention.


Assuntos
Antibacterianos/efeitos adversos , Antibacterianos/imunologia , Hipersensibilidade a Drogas/imunologia , beta-Lactamas/efeitos adversos , beta-Lactamas/imunologia , Idoso , Idoso de 80 Anos ou mais , Gestão de Antimicrobianos/métodos , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/imunologia , Feminino , Hospitais , Humanos , Masculino , Pessoa de Meia-Idade , Testes Imediatos , Estudos Prospectivos , Testes Cutâneos/métodos
13.
Clin Infect Dis ; 63(7): 904-910, 2016 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-27402820

RESUMO

BACKGROUND: Reported allergy to beta-lactam antibiotics is common and often leads to unnecessary avoidance in patients who could tolerate these antibiotics. We prospectively evaluated the impact of these reported allergies on clinical outcomes. METHODS: We conducted a trainee-led prospective cohort study to determine the burden and clinical impact of reported beta-lactam allergy on patients seen by infectious diseases consultation services at 3 academic hospitals. The primary outcome was a composite measure of readmission for the same infection, acute kidney injury, Clostridium difficile infection, or drug-related adverse reactions requiring discontinuation. Predictors of interest were history of beta-lactam allergy and receipt of preferred beta-lactam therapy. RESULTS: Among 507 patients, 95 (19%) reported beta-lactam allergy; preferred therapy was a beta-lactam in 72 (76%). When beta-lactam therapy was preferred, 25 (35%) did not receive preferred therapy due to their report of allergy even though 13 (52%) reported non-severe prior reactions. After adjustment for confounders, patients who did not receive preferred beta-lactam therapy were at greater risk of adverse events (adjusted odds ratio [aOR], 3.1; 95% confidence interval [CI], 1.28-7.89) compared with those without reported allergy. In contrast, patients who received preferred beta-lactam therapy had a similar risk of adverse events compared with patients not reporting allergy (aOR, 1.33; 95% CI, .62-2.87). CONCLUSIONS: Avoidance of preferred beta-lactam therapy in patients who report allergy is associated with an increased risk of adverse events. Development of inpatient programs aimed at accurately identifying beta-lactam allergies to safely promote beta-lactam administration among these patients is warranted.


Assuntos
Gestão de Antimicrobianos , Hipersensibilidade a Drogas , Hospitalização/estatística & dados numéricos , beta-Lactamas/efeitos adversos , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Resultado do Tratamento
14.
Dermatitis ; 27(2): 68-71, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-26983093

RESUMO

BACKGROUND: Adverse reactions from lidocaine are commonly reported. When allergy is suspected, patients may be referred for specific skin testing to confirm the association of their clinical findings. OBJECTIVE: We aimed to investigate 13 cases of suspected lidocaine allergy to analyze if positive patch results restricted future use as an injectable local anesthetic. METHODS: A prospective study was conducted from March 2013 to September 2014 at 2 academic hospital-based patch test clinics in Toronto. Patients were tested to the North American Contact Dermatitis Group standard series (Smart Practice, Phoenix, AZ) and, if suspicion for lidocaine allergy was high, a local anesthetic series (Chemotechnique Diagnostics, Malmö, Sweden) was added. Intradermal skin testing to local anesthetics below irritant concentrations was subsequently conducted in lidocaine-positive patients. If negative, a subcutaneous challenge with 1% lidocaine was done. RESULTS: Thirteen of 756 patients patch tested were positive to lidocaine. Seven patients had relevant reactions to over-the-counter products containing lidocaine, 2 reacted to subcutaneous lidocaine, and 4 had incidental findings. There were no patients with positive results to intradermal testing. Three patients had delayed reactions to the subcutaneous challenge. CONCLUSIONS: Patients with positive patch tests to lidocaine and negative results to intradermal testing and subcutaneous challenge may be safe to use lidocaine as an injectable local anesthetic in the future.


Assuntos
Anestésicos Locais/efeitos adversos , Hipersensibilidade a Drogas/diagnóstico , Lidocaína/efeitos adversos , Hipersensibilidade a Drogas/etiologia , Humanos , Testes Intradérmicos , Testes do Emplastro , Estudos Prospectivos
15.
Cardiovasc Revasc Med ; 16(5): 266-71, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26242981

RESUMO

BACKGROUND: Adenosine is the gold standard for augmenting coronary flow during fractional flow reserve (FFR) testing of intermediate coronary stenoses. However, intravenous infusion is time-consuming and intracoronary injection is subject to variability. Regadenoson is a newer adenosine alternative administered as a single intravenous bolus during nuclear stress testing, but its efficacy and safety during FFR testing have been evaluated only in small, single-center studies. METHODS: We pooled data from 5 academic hospitals, in which patients undergoing clinically-indicated FFR prospectively underwent comparison of intravenous adenosine infusion (140-175mcg/kg/min) versus regadenoson bolus (400mcg). Hemodynamics and symptoms with adenosine were recorded until maximal hyperemia occurred, and after returning to baseline hemodynamics, regadenoson was administered and monitoring was repeated. In a subset of patients with coronary flow data, average peak velocity (APV) at the distal flow sensor was recorded. RESULTS: Of 149 patients enrolled, mean age was 59±9years, 76% were male, and 54% underwent testing of the left anterior descending artery. Mean adenosine-FFR and regadenoson-FFR were identical (0.82±0.10) with excellent correlation of individual values (r=0.96, p<0.001) and no difference in patient-reported symptoms. Four patients (2.6%) had discrepancies between the 2 drugs for the clinical decision-making cutoff of FFR≤0.80. Coronary flow responses to adenosine and regadenoson were similar (APV at maximal hyperemia 36cm/s for both, p=0.81). CONCLUSIONS: Regadenoson single-bolus administration has comparable FFR, symptoms, and coronary flow augmentation when compared with standard intravenous adenosine infusion. With its greater ease of administration, regadenoson may be a more "user-friendly" option for invasive ischemic testing.


Assuntos
Adenosina/uso terapêutico , Cateterismo , Circulação Coronária/efeitos dos fármacos , Reserva Fracionada de Fluxo Miocárdico/efeitos dos fármacos , Purinas/uso terapêutico , Pirazóis/uso terapêutico , Vasodilatadores/uso terapêutico , Adenosina/administração & dosagem , Idoso , Cateterismo/métodos , Estenose Coronária/diagnóstico , Vasos Coronários/efeitos dos fármacos , Feminino , Humanos , Hiperemia/tratamento farmacológico , Infusões Intravenosas/métodos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Purinas/administração & dosagem , Pirazóis/administração & dosagem , Vasodilatadores/administração & dosagem
16.
Prof Psychol Res Pr ; 45(4): 221-230, 2014 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-25177080

RESUMO

Little research has examined the transition to parenthood among couples who adopt through the child welfare system. The current qualitative study of 84 individuals within 42 couples (17 lesbian, 13 gay, and 12 heterosexual), who were placed with a child via foster care three months earlier, examined perceived changes in their intimate relationship. Findings indicated that, like heterosexual biological-parent couples, some adoptive parents perceived the loss of their partner's undivided attention as stressful to the relationship. Adoption-specific stressors were also identified, including the need to find state-approved child care to facilitate "couple time" and the legal insecurity of foster-to-adopt placements. Although our findings were similar for heterosexual, lesbian, and gay adoptive parents, same-sex couples cited some additional stressors related to their sexual minority status. Findings have implications for individual, couple, and family practitioners who work with lesbian, gay, and heterosexual adoptive parents, particularly during their transition to parenthood.

18.
J Hand Surg Am ; 37(2): 316-21, 2012 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-22119603

RESUMO

The Food and Drug Administration (FDA) indicates that bone morphogenetic protein (BMP) products are contraindicated in pediatric patients. However, it acknowledges the off-label use of BMP in difficult cases. Although the relative safety of BMP in children has been reported for lower extremity and spine procedures, little information exists for the safety of BMP used in the pediatric upper extremity. We present a case of a massive inflammatory reaction after use of recombinant human BMP-2 for repair of a symptomatic ulnar nonunion in a child. The case illustrates the potential difficulties of using the dose-dependent properties of BMP in the treatment of pediatric upper extremity nonunions when the dose calculations of BMP for children have not yet been defined.


Assuntos
Proteína Morfogenética Óssea 2/efeitos adversos , Reabsorção Óssea/induzido quimicamente , Fraturas não Consolidadas/terapia , Osteíte/induzido quimicamente , Deiscência da Ferida Operatória/induzido quimicamente , Fator de Crescimento Transformador beta/efeitos adversos , Fraturas da Ulna/terapia , Criança , Fraturas não Consolidadas/patologia , Humanos , Masculino , Uso Off-Label , Proteínas Recombinantes/efeitos adversos , Fraturas da Ulna/patologia
19.
Ann Pharmacother ; 44(4): 740-5, 2010 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-20233910

RESUMO

OBJECTIVE: To report 3 cases of immediate hypersensitivity reactions to moxifloxacin in patients who tolerated ciprofloxacin. CASE SUMMARIES: A 71-year-old man, a 44-year-old woman, and a 70-year-old woman with a history of a moxifloxacin reaction developed an immediate hypersensitivity reaction upon oral challenge with moxifloxacin in our Drug Safety Clinic. The reaction was mainly characterized by pruritus and urticaria, although dyspnea and hypotension were noted in the first and second patient, respectively. Two of the patients had negative oral challenge tests with ciprofloxacin and all 3 patients tolerated full treatment courses of oral ciprofloxacin. In all 3 cases, use of the Naranjo probability scale indicated a highly probable adverse drug reaction. DISCUSSION: Moxifloxacin, similar to other fluoroquinolones, can cause immediate hypersensitivity reactions. Previous publications have reported both cross-reactivity and a lack of cross-reactivity among various fluoroquinolones. The 3 patients discussed demonstrated a lack of cross-reactivity between moxifloxacin and ciprofloxacin since they tolerated oral challenge tests and full treatment courses of ciprofloxacin. Moxifloxacin has unique side chains at positions 7 and 8 on its bicyclic ring structure. Antigenic specificity to particular side chains at positions 7 and 8 on the bicyclic ring structure of moxifloxacin may explain this lack of cross-reactivity. Higher reporting rates of anaphylaxis to moxifloxacin compared to other fluoroquinolones may also be related to side chain specificity, although definitive evidence for this is lacking. CONCLUSIONS: Based on our experience, patients who develop immediate hypersensitivity reactions to moxifloxacin may receive ciprofloxacin therapy in an appropriately monitored setting if they have previously tolerated full treatment courses of ciprofloxacin. Research into whether there is a specific side chain reaction unique to moxifloxacin is warranted.


Assuntos
Antibacterianos/efeitos adversos , Compostos Aza/efeitos adversos , Ciprofloxacina/efeitos adversos , Toxidermias/patologia , Hipersensibilidade a Drogas/patologia , Hipersensibilidade Imediata/patologia , Quinolinas/efeitos adversos , Adulto , Antibacterianos/uso terapêutico , Compostos Aza/uso terapêutico , Bronquiectasia/tratamento farmacológico , Ciprofloxacina/uso terapêutico , Toxidermias/diagnóstico , Hipersensibilidade a Drogas/diagnóstico , Feminino , Fluoroquinolonas , Humanos , Hipersensibilidade Imediata/diagnóstico , Masculino , Pessoa de Meia-Idade , Moxifloxacina , Quinolinas/uso terapêutico , Testes Cutâneos , Urticária/etiologia
20.
J Bone Joint Surg Am ; 91(8): 1973-84, 2009 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-19651957

RESUMO

BACKGROUND: Distraction osteogenesis creates a challenging bone-healing environment with protracted demand for cells of the osteoblast lineage. Platelet-derived growth factor-BB (PDGF-BB) is an osteoblast mitogen and chemotaxin that has been shown to accelerate and/or enhance bone-healing in several preclinical studies. The purpose of the present study was to determine whether recombinant human platelet-derived growth factor-BB (rhPDGF-BB) would have a similar effect on regenerate healing after distraction osteogenesis. METHODS: Unilateral 7-mm mid-diaphyseal femoral lengthening procedures were performed in eighty-three male Sprague-Dawley rats that were separated into five experimental groups. During the distraction period (Days 7 to 28), each animal received a weekly 50-microL injection of either sodium acetate buffer, bovine collagen dissolved in sodium acetate buffer, or one of three concentrations of rhPDGF-BB (100, 300, or 1000 microg/mL) into the distraction site. Animals from each group were killed on Days 35, 42, 49, 56, and 63. Healing was assessed with biweekly serial radiographs, micro-computed tomography of the explanted bones, and histologic analysis. RESULTS: rhPDGF-BB treatment significantly increased new-bone formation at the midconsolidation time points (Days 42, 49, and 56) as well as the union rate. On Day 49 regenerate bone volume was significantly greater in each of the three rhPDGF-BB-treated groups than in the controls (p < 0.05, p = 0.0002, and p < 0.05 for the 100, 300, and 1000 microg/mL rhPDGF-BB groups, respectively), whereas on Day 42 regenerate bone volume was significantly greater in the 300 and 1000 microg/mL rhPDGF-BB groups than in the controls (p = 0.0002 and p < 0.05, respectively) and on Day 56 regenerate bone volume was significantly greater in the 100 and 300 microg/mL rhPDGF-BB groups than in the controls (p < 0.05 and p < 0.0001, respectively). The overall union rate was 40.4% (nineteen of forty-seven) in the rhPDGF-BB-treated animals, compared with 4.5% (one of twenty-two) in the controls (p = 0.01). The radiographic and histologic results were consistent with new-bone formation as quantified by micro-computed tomography, although they were less definitive. CONCLUSIONS: The administration of exogenous rhPDGF-BB into the distraction site during diaphyseal distraction enhanced bone-healing in a rat model of distraction osteogenesis as evidenced by both increased regenerate new-bone formation and a higher union rate.


Assuntos
Indutores da Angiogênese/farmacologia , Regeneração Óssea/efeitos dos fármacos , Consolidação da Fratura/efeitos dos fármacos , Osteogênese por Distração , Fator de Crescimento Derivado de Plaquetas/farmacologia , Animais , Becaplermina , Modelos Animais de Doenças , Masculino , Proteínas Proto-Oncogênicas c-sis , Ratos , Ratos Sprague-Dawley
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