RESUMO
BACKGROUND: No approved treatment for peanut allergy exists for children younger than 4 years of age, and the efficacy and safety of epicutaneous immunotherapy with a peanut patch in toddlers with peanut allergy are unknown. METHODS: We conducted this phase 3, multicenter, double-blind, randomized, placebo-controlled trial involving children 1 to 3 years of age with peanut allergy confirmed by a double-blind, placebo-controlled food challenge. Patients who had an eliciting dose (the dose necessary to elicit an allergic reaction) of 300 mg or less of peanut protein were assigned in a 2:1 ratio to receive epicutaneous immunotherapy delivered by means of a peanut patch (intervention group) or to receive placebo administered daily for 12 months. The primary end point was a treatment response as measured by the eliciting dose of peanut protein at 12 months. Safety was assessed according to the occurrence of adverse events during the use of the peanut patch or placebo. RESULTS: Of the 362 patients who underwent randomization, 84.8% completed the trial. The primary efficacy end point result was observed in 67.0% of children in the intervention group as compared with 33.5% of those in the placebo group (risk difference, 33.4 percentage points; 95% confidence interval, 22.4 to 44.5; P<0.001). Adverse events that occurred during the use of the intervention or placebo, irrespective of relatedness, were observed in 100% of the patients in the intervention group and 99.2% in the placebo group. Serious adverse events occurred in 8.6% of the patients in the intervention group and 2.5% of those in the placebo group; anaphylaxis occurred in 7.8% and 3.4%, respectively. Serious treatment-related adverse events occurred in 0.4% of patients in the intervention group and none in the placebo group. Treatment-related anaphylaxis occurred in 1.6% in the intervention group and none in the placebo group. CONCLUSIONS: In this trial involving children 1 to 3 years of age with peanut allergy, epicutaneous immunotherapy for 12 months was superior to placebo in desensitizing children to peanuts and increasing the peanut dose that triggered allergic symptoms. (Funded by DBV Technologies; EPITOPE ClinicalTrials.gov number, NCT03211247.).
Assuntos
Anafilaxia , Dessensibilização Imunológica , Hipersensibilidade a Amendoim , Pré-Escolar , Humanos , Lactente , Alérgenos/efeitos adversos , Anafilaxia/etiologia , Arachis/efeitos adversos , Dessensibilização Imunológica/efeitos adversos , Dessensibilização Imunológica/métodos , Hipersensibilidade a Amendoim/complicações , Hipersensibilidade a Amendoim/terapia , Administração CutâneaRESUMO
OBJECTIVE: To characterize the awareness of, adherence to, and barriers to the 2017 National Institute of Allergy and Infectious Diseases (NIAID) peanut allergy prevention guidelines among the pediatrics health care workforce STUDY DESIGN: Pediatricians, family physicians, advanced practice providers (APPs), and dermatologists who provide care for infants were solicited for a population-based online survey, administered from June 6, 2022, through July 3, 2022. The survey collected information about NIAID guideline awareness, implementation, and barriers as well as concerns related to the guidelines. RESULTS: A total of 250 pediatricians, 250 family physicians, 504 advanced practice practitioners (APPs), and 253 dermatologists met inclusion criteria. Self-reported guideline awareness was significantly higher for pediatricians (76%) compared with dermatologists (58%), family physicians (52%), and APPs (45%) (P < .05). Among participants who were aware of the guidelines, most reported using part or all of the guidelines in their clinical practices. Reported practice patterns for peanut introduction in 6-month-old infants were variable and did not always align with guidelines, particularly for infants with mild-to-moderate atopic dermatitis. CONCLUSIONS: Although pediatricians have the highest self-reported level of NIAID guideline awareness, awareness was suboptimal irrespective of provider type. Education for all pediatric clinicians is urgently needed to promote evidence-based peanut allergy prevention practices.
RESUMO
This practice parameter update focuses on 7 areas in which there are new evidence and new recommendations. Diagnostic criteria for anaphylaxis have been revised, and patterns of anaphylaxis are defined. Measurement of serum tryptase is important for diagnosis of anaphylaxis and to identify underlying mast cell disorders. In infants and toddlers, age-specific symptoms may differ from older children and adults, patient age is not correlated with reaction severity, and anaphylaxis is unlikely to be the initial reaction to an allergen on first exposure. Different community settings for anaphylaxis require specific measures for prevention and treatment of anaphylaxis. Optimal prescribing and use of epinephrine autoinjector devices require specific counseling and training of patients and caregivers, including when and how to administer the epinephrine autoinjector and whether and when to call 911. If epinephrine is used promptly, immediate activation of emergency medical services may not be required if the patient experiences a prompt, complete, and durable response. For most medical indications, the risk of stopping or changing beta-blocker or angiotensin-converting enzyme inhibitor medication may exceed the risk of more severe anaphylaxis if the medication is continued, especially in patients with insect sting anaphylaxis. Evaluation for mastocytosis, including a bone marrow biopsy, should be considered for adult patients with severe insect sting anaphylaxis or recurrent idiopathic anaphylaxis. After perioperative anaphylaxis, repeat anesthesia may proceed in the context of shared decision-making and based on the history and results of diagnostic evaluation with skin tests or in vitro tests when available, and supervised challenge when necessary.
Assuntos
Anafilaxia , Mordeduras e Picadas de Insetos , Mastocitose , Adulto , Humanos , Criança , Adolescente , Anafilaxia/diagnóstico , Anafilaxia/tratamento farmacológico , Anafilaxia/prevenção & controle , Mordeduras e Picadas de Insetos/tratamento farmacológico , Epinefrina/uso terapêutico , Mastocitose/diagnóstico , AlérgenosRESUMO
BACKGROUND: Dupilumab is a monoclonal antibody that targets the interleukin (IL)-4 receptor alpha subunit, thus blocking the effects of IL-4 and IL-13, and has shown efficacy in treating various conditions including asthma, atopic dermatitis, eosinophilic esophagitis, and others. Because of its immune modulatory effects, clinical trials that studied dupilumab did not allow patients to receive live vaccines during the clinical trials because of an abundance of caution, and thus package inserts recommend that patients who are being treated with dupilumab should avoid live vaccines. Because dupilumab is now approved for use in patients from 6 months of age for the treatment of atopic dermatitis, this reported contraindication is now posing a clinical dilemma for patients and clinicians. OBJECTIVE: To perform a systematic review of literature on the safety and efficacy of vaccinations in patients who are receiving dupilumab and to provide expert guidance on the use of vaccines in patients who are receiving dupilumab. METHODS: A systematic review of the literature was performed, and an expert Delphi Panel was assembled. RESULTS: The available literature on patients who received vaccinations while using dupilumab overall suggests that live vaccines are safe and that the vaccine efficacy, in general, is not affected by dupilumab. The expert Delphi panel agreed that the use of vaccines in patients receiving dupilumab was likely safe and effective. CONCLUSION: Vaccines (including live vaccines) can be administered to patients receiving dupilumab in a shared decision-making capacity.
RESUMO
BACKGROUND: Guidance addressing atopic dermatitis (AD) management, last issued in 2012 by the American Academy of Allergy, Asthma and Immunology/American College of Allergy, Asthma and Immunology Joint Task Force, requires updating as a result of new treatments and improved guideline and evidence synthesis methodology. OBJECTIVE: To produce evidence-based guidelines that support patients, clinicians, and other decision-makers in the optimal treatment of AD. METHODS: A multidisciplinary guideline panel consisting of patients and caregivers, AD experts (dermatology and allergy/immunology), primary care practitioners (family medicine, pediatrics, internal medicine), and allied health professionals (psychology, pharmacy, nursing) convened, prioritized equity, diversity, and inclusiveness, and implemented management strategies to minimize influence of conflicts of interest. The Evidence in Allergy Group supported guideline development by performing systematic evidence reviews, facilitating guideline processes, and holding focus groups with patient and family partners. The Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach informed rating the certainty of evidence and strength of recommendations. Evidence-to-decision frameworks, subjected to public comment, translated evidence to recommendations using trustworthy guideline principles. RESULTS: The panel agreed on 25 recommendations to gain and maintain control of AD for patients with mild, moderate, and severe AD. The eAppendix provides practical information and implementation considerations in 1-2 page patient-friendly handouts. CONCLUSION: These evidence-based recommendations address optimal use of (1) topical treatments (barrier moisturization devices, corticosteroids, calcineurin inhibitors, PDE4 inhibitors [crisaborole], topical JAK inhibitors, occlusive [wet wrap] therapy, adjunctive antimicrobials, application frequency, maintenance therapy), (2) dilute bleach baths, (3) dietary avoidance/elimination, (4) allergen immunotherapy, and (5) systemic treatments (biologics/monoclonal antibodies, small molecule immunosuppressants [cyclosporine, methotrexate, azathioprine, mycophenolate, JAK inhibitors], and systemic corticosteroids) and UV phototherapy (light therapy).
Assuntos
Asma , Dermatite Atópica , Eczema , Hipersensibilidade , Inibidores de Janus Quinases , Criança , Humanos , Estados Unidos , Dermatite Atópica/tratamento farmacológico , National Academies of Science, Engineering, and Medicine, U.S., Health and Medicine Division , Corticosteroides , ImunossupressoresRESUMO
BACKGROUND: Up to 10% of children are reported to be allergic to penicillin, but many allergy labels are unverified and may require formal testing. Inaccurate drug allergy labels are associated with a range of adverse clinical outcomes. Patients with hematological disorders may experience frequent and severe infections; those who have been incorrectly labeled penicillin allergic may benefit from allergy de-labeling (ADL) efforts to facilitate access to beta-lactam antibiotics. We developed a multidisciplinary, pharmacist-driven process that enabled non-allergist trained providers to assess and de-label penicillin allergies in a pediatric hematology center. METHODS: Volunteers, including physicians, advanced practice providers, nurses, and pharmacists, were trained in skin testing and oral challenge procedures. Patients were identified by review of electronic medical records for penicillin or penicillin-derivative allergy. Patient and family interviews were conducted in cases where a true penicillin allergy was deemed uncertain based on chart review. If allergy could not be de-labeled by chart review or interview alone, patients were offered skin and/or oral challenge testing. RESULTS: Fifty-nine patients were initially labeled as penicillin allergic. Allergy labels of 11 (19%) were removed by chart review only, and 15 (25%) after conducting interviews. A total of two (3%) patients were ineligible due to contraindications, and five (9%) declined participation. Twenty-six patients (44%) underwent allergy testing (50% skin testing, 50% oral challenge) of which 23 (88%) were negative. CONCLUSIONS: ADL was possible in most patients previously identified as penicillin allergic. Testing was well tolerated with no serious adverse effects.
Assuntos
Hipersensibilidade a Drogas , Penicilinas , Humanos , Hipersensibilidade a Drogas/diagnóstico , Hipersensibilidade a Drogas/etiologia , Penicilinas/efeitos adversos , Criança , Feminino , Masculino , Pré-Escolar , Adolescente , Testes Cutâneos , Lactente , Antibacterianos/efeitos adversosRESUMO
BACKGROUND: The perioperative use of dexamethasone in diabetic patients remains controversial due to concerns related to infection and adverse events. This study aimed to determine whether clinical evidence supports withholding dexamethasone in diabetic patients due to concern for infection risk. We hypothesized that there is no difference in infectious outcomes between dexamethasone-treated patients and controls. METHODS: A literature search was performed on November 22, 2022 to identify randomized, placebo-controlled trials investigating short-course (<72 hours), perioperative dexamethasone that explicitly included diabetic patients and measured at least 1 clinical outcome. Pertinent studies were independently searched in PubMed, Embase, and Cochrane. Authors for all identified studies were contacted with the aim of performing quantitative subgroup analyses of diabetic patients. The primary end point was surgical site infection and the secondary end point was a composite of adverse events. Qualitative remarks were reported based on the total available data and a quality assessment tool. Meta-analyses were performed using inverse variance with random effects. Heterogeneity was assessed via standard χ2 and I2 tests. RESULTS: Sixteen unique studies were included, 5 of which were analyzed quantitatively. Of the 2592 diabetic patients, 2344 (1184 randomized to dexamethasone and 1160 to placebo) were analyzed in at least 1 quantitative outcome. Quantitative analysis showed that the use of perioperative dexamethasone had no effect on the risk of surgical site infections (log odds ratio [LOR], -0.10, 95%; 95% confidence interval [CI], -0.64 to 0.44) while significantly reducing the risk of composite adverse events (LOR, -0.33; 95% CI, -0.62 to -0.05). Qualitative analysis reinforced these findings, demonstrating noninferior to superior results across all clinical outcomes. There was high heterogeneity between the included studies. CONCLUSIONS: Current evidence suggests perioperative dexamethasone may be given to diabetic patients without increasing the risk of infectious complications. Prospective investigations aimed at optimizing dose, frequency, and timing are needed, as well as studies aimed explicitly at exploring the use of dexamethasone in patients with poorly controlled diabetes.
Assuntos
Dexametasona , Diabetes Mellitus , Assistência Perioperatória , Ensaios Clínicos Controlados Aleatórios como Assunto , Infecção da Ferida Cirúrgica , Dexametasona/administração & dosagem , Dexametasona/uso terapêutico , Dexametasona/efeitos adversos , Humanos , Assistência Perioperatória/métodos , Diabetes Mellitus/tratamento farmacológico , Infecção da Ferida Cirúrgica/prevenção & controle , Resultado do Tratamento , Fatores de RiscoRESUMO
BACKGROUND: A survey was conducted at the 2023 Annual Meeting of the American Association of Hip and Knee Surgeons (AAHKS) to assess practice management strategies among current AAHKS members. METHODS: Members of AAHKS used an app to answer both multiple-choice and "yes or no" questions related to a variety of issues related to their practices. RESULTS: The number of AAHKS members in private practice (37%) continues to decline, and 4% are now in private equity-employed practices. Fee for service (30%) and relative value units (30%) are the major forms of compensation. The number of AAHKS members that perform total joint arthroplasties at ambulatory surgery centers continues to increase, and supply chain issues (91%) remain a problem. There has been a decrease in surgeon participation in bundled payment programs and gainsharing arrangements with hospitals. CONCLUSIONS: This member's survey provides valuable information regarding practice patterns. The shift to outpatient surgery has continued. Future surveys will be performed to monitor changes in practice patterns over time.
RESUMO
The obesity epidemic in the United States continues to grow with more than 40% of individuals now classified as obese (body mass index >30). Obesity has been readily demonstrated to increase the risk of developing hip and knee osteoarthritis and is known to increase the risk of complications following joint arthroplasty. Weight loss prior to arthroplasty may mitigate this risk of complications; however, the existing evidence remains mixed with no clear consensus on the optimal method of weight loss and timing prior to arthroplasty. Treatment options for weight loss have included nonsurgical lifestyle modifications consisting of structured diet, physical activity, and behavioral modification, as well as bariatric and metabolic surgery (ie, sleeve gastrectomy, Roux-en-Y gastric bypass, and the adjustable gastric band). Recently, glucagon-like peptide-1 receptor agonists have gained notable popularity within the scientific literature and media for their efficacy in weight loss. The aim of this review is to provide a foundational primer for joint arthroplasty surgeons regarding the current and emerging options for weight loss to aid surgeons in shared decision-making with patients prior to arthroplasty.
Assuntos
Cirurgia Bariátrica , Laparoscopia , Obesidade Mórbida , Osteoartrite do Quadril , Osteoartrite do Joelho , Cirurgiões , Humanos , Estados Unidos , Obesidade Mórbida/complicações , Osteoartrite do Quadril/cirurgia , Osteoartrite do Joelho/cirurgia , Osteoartrite do Joelho/complicações , Obesidade/complicações , Obesidade/cirurgia , Cirurgia Bariátrica/efeitos adversos , Redução de Peso , Resultado do TratamentoRESUMO
BACKGROUND: Academic accomplishments and demographics for presidents of hip and knee arthroplasty societies are poorly understood. This study compares the characteristics of presidents nominated to serve the Hip Society, Knee Society, and American Association of Hip and Knee Surgeons. METHODS: This was a cross-sectional study of arthroplasty presidents in the United States (1990 to 2022). Curriculum vitae and academic websites were analyzed for demographic, training, bibliometric, and National Institutes of Health (NIH) funding data. Comparisons were made between organizations and time periods (1990 to 2005 versus 2006 to 2022). RESULTS: There were 97 appointments of 78 unique arthroplasty presidents (80%). Most presidents were male (99%) and Caucasian (95%). There was 1 woman (1%) and 5 non-Caucasian presidents (2% Asian, 3% Hispanic). There were no differences in demographics between the 3 arthroplasty organizations and the 2 time periods (P > .05). Presidents were appointed at 55 ± 10 years old, which was on average 24 years after completion of residency training. Most presidents had arthroplasty fellowship training (68%), and the most common were the Hospital for Special Surgery (21%) and Massachusetts General Hospital (8%). The median h-index was 53 resulting from 191 peer-reviewed publications, which was similar between the 3 organizations (P > .05). There were 2 presidents who had NIH funding (2%), and there were no differences in NIH funding between the 3 organizations (P > .05). CONCLUSIONS: Arthroplasty society presidents have diverse training pedigrees, high levels of scholarly output, and similar demographics. There may be future opportunities to promote diversity and inclusion among the highest levels of leadership in total joint arthroplasty.
Assuntos
Artroplastia de Quadril , Artroplastia do Joelho , Sociedades Médicas , Humanos , Estados Unidos , Feminino , Masculino , Artroplastia de Quadril/estatística & dados numéricos , Estudos Transversais , Pessoa de Meia-Idade , LiderançaRESUMO
BACKGROUND: Same-day total hip arthroplasty (THA) and total knee arthroplasty (TKA) continue to gain popularity in the United States. The present study sought to quantify recent same-day outpatient trends taking into consideration the COVID-19 pandemic as well as the removal of these procedures from the Medicare inpatient only (IPO) list. METHODS: Patients undergoing primary elective TKA and THA were identified using the Nationwide Ambulatory Surgery Sample and the National Inpatient Sample from January 1, 2016, to December 31, 2020. The same-day cohort included Nationwide Ambulatory Surgery Sample and National Inpatient Sample patients with a length of stay = 0 days. The inpatient cohort included patients with length of stay ≥1 day. National estimates were extrapolated using weight functions. RESULTS: From January 2016 to December 2020, the proportion of same-day TKA increased from 1.2 (719) to 62.4% (31,293) and the proportion of same-day THA increased from 2.0 (599) to 54.5% (18,252). Following removal from the Medicare IPO list, same-day TKAs increased from 3.2% (1,895) in December 2017 to 13.8% (9,269) in January 2018, and same-day THAs increased from 10.7% (4,295) in December 2019 to 22.5% (8,708) in January 2020. Between February and March 2020, same-day TKAs increased from 42.4 (26,148) to 44.4% (16,972) and same-day THAs increased from 28.5 (10,729) to 30.2% (7,409). CONCLUSIONS: The proportion of same-day TKA and THA dramatically increased following removal from the Medicare IPO list and in response to the COVID-19 pandemic. By December 2020, same-day TKA and THA accounted for >50% of all cases performed in the United States.
Assuntos
Artroplastia de Quadril , Artroplastia do Joelho , COVID-19 , Humanos , Idoso , Estados Unidos/epidemiologia , Medicare , Pacientes Internados , Pandemias , Tempo de Internação , Fatores de Risco , COVID-19/epidemiologia , Estudos RetrospectivosRESUMO
BACKGROUND: Postoperative infection is a devastating complication of total joint arthroplasty (TJA). Perioperative use of dexamethasone in patients who have diabetes mellitus (DM) remains controversial due to concern for increased infection risk. This study aimed to evaluate the association between dexamethasone and infection risk among patients who have DM undergoing TJA. METHODS: This was a retrospective cohort study conducted on adult patients who underwent primary, elective total knee arthroplasty (TKA) or total hip arthroplasty (THA) between January 2016 and December 2021 using a large national database. We identified 110,568 TJA patients (TKA: 66.6%; THA: 33.4%), 31.0% (34,298) of which had DM. Patients who received perioperative dexamethasone were compared to those who did not. The primary end points were the 90-day risk of postoperative periprosthetic joint infection, surgical site infection (SSI), and other non-SSI (urinary tract infection, pneumonia, sepsis). RESULTS: When modeling the association between dexamethasone exposure and study outcomes while accounting for the interaction between dexamethasone and morning blood glucose levels, dexamethasone administration conferred no increased odds of postoperative periprosthetic joint infection nor SSI in diabetics. However, dexamethasone significantly lowered the adjusted odds of other postoperative infections in diabetic patients (TKA: adjusted odds ratio = 09, 95% confidence interval = 0.8 to 1.0, P = .030; THA: adjusted odds ratio = 0.7, 95% confidence interval = 0.6 to 0.9, P = .001); specifically in patients with morning blood glucose levels between 110 to 248 mg/dL in TKA and ≤ 172 mg/dL in THA. CONCLUSIONS: This study provides strong evidence against withholding dexamethasone in diabetic patients undergoing TJA based on concern for infection. Instead, short-course perioperative dexamethasone reduced infection risk in select patients. The narrative surrounding dexamethasone should shift away from questions about whether dexamethasone is appropriate for diabetic patients, and instead focus on how best to optimize its use.
Assuntos
Artroplastia de Quadril , Artroplastia do Joelho , Dexametasona , Hiperglicemia , Infecção da Ferida Cirúrgica , Humanos , Dexametasona/administração & dosagem , Dexametasona/efeitos adversos , Masculino , Feminino , Estudos Retrospectivos , Artroplastia de Quadril/efeitos adversos , Pessoa de Meia-Idade , Idoso , Artroplastia do Joelho/efeitos adversos , Hiperglicemia/etiologia , Infecção da Ferida Cirúrgica/prevenção & controle , Infecção da Ferida Cirúrgica/epidemiologia , Infecção da Ferida Cirúrgica/etiologia , Diabetes Mellitus , Infecções Relacionadas à Prótese/etiologiaRESUMO
BACKGROUND: Obesity, defined as a body mass index (BMI) ≥ 30, is an ever-growing epidemic, with > 35% of adults in the United States currently classified as obese. Super-obese individuals, defined as those who have a BMI ≥ 50, are the fastest-growing portion of this group. This study sought to quantify the infection risk as well as the incidence of surgical, medical, and thromboembolic complications among super-obese patients undergoing total knee arthroplasty (TKA). METHODS: An all-payer claims database was used to identify patients who underwent elective, primary TKA between 2016 and 2021. Patients who had a BMI ≥ 50 were compared to those who had a normal BMI of 18 to 25. Demographics and the incidence of 90-days postoperative complications were compared between the 2 groups. Univariate analysis and multivariable regression were used to assess differences between groups. RESULTS: In total, 3,376 super-obese TKA patients were identified and compared to 17,659 patients who had a normal BMI. Multivariable analysis indicated that the super-obese cohort was at an increased postoperative risk of periprosthetic joint infection (adjusted odds ratio [aOR] 3.7, 95% confidence interval [CI]: 2.1 to 6.4, P < .001), pulmonary embolism (aOR 2.2, 95%-CI: 1.0 to 5.0, P = .047), acute respiratory failure (aOR 4.1, 95%-CI: 2.7 to 6.1, P < .001), myocardial infarction (aOR 2.5, 95%-CI: 1.1 to 5.8, P = .026), wound dehiscence (aOR 2.3, 95%-CI: 1.4 to 3.8, P = .001), and acute renal failure (aOR 3.2, 95%-CI: 2.4 to 4.2, P < .001) relative to patients who have normal BMI. CONCLUSIONS: Super-obese TKA patients are at an elevated risk of postoperative infectious, surgical, medical, and thromboembolic complications. As such, risk stratification, as well as appropriate medical management and optimization, is of utmost importance for this high-risk group.
RESUMO
BACKGROUND: Dexamethasone (DEX) has demonstrated promise with respect to decreasing postoperative thromboembolic complications following total joint arthroplasty (TJA). Therefore, the aim of this study was to investigate the effects of perioperative intravenous DEX on rates of pulmonary embolism (PE) and deep vein thrombosis (DVT) after primary TJA in patients who have a history of venous thromboembolism (VTE). METHODS: Patients who have a history of VTE who underwent primary elective TJA from 2015 to 2021 were identified using a commercial health care database. Patients were divided based on receipt of perioperative intravenous DEX [DEX(+) versus DEX(-)] on the day of index TJA. Patient demographics and hospital factors were collected. The 90-day risk of postoperative complications, readmission, and in-hospital mortality were compared. RESULTS: Overall, 70,147 patients who had a history of VTE underwent TJA, of which 40,607 (57.89%) received DEX and 29,540 (42.11%) did not. The DEX(+) patients were younger (67 ± 9.8 versus 68 ± 9.9 years, P < .001) and had a significantly shorter length of stay compared to the DEX(-) patients (1.8 ± 1.6 versus 2.2 ± 1.8 days, P < .001). The DEX(+) patients demonstrated lower rates of PE (1.37 versus 1.75%, P < .001) and DVT (2.37 versus 3.01%, P < .001) compared to DEX(-) patients. The DEX(+) patients experienced a lower risk of PE (adjusted odds ratio: 0.78, 95% confidence interval: 0.66 to 0.93, P = .006) and DVT (adjusted odds ratio: 0.84, 95% confidence interval: 0.74 to 0.95, P = .006) compared to DEX(-) patients. The DEX(+) patients demonstrated no differences in the odds of surgical site infection, periprosthetic joint infection, or sepsis compared to the DEX(-) patients (P > .05). CONCLUSIONS: The administration of DEX was associated with a decreased risk of PE and DVT in patients who have a history of VTE who underwent TJA. These data warrant further study investigating the postoperative benefits of perioperative DEX administration for high-risk patients undergoing TJA. LEVEL OF EVIDENCE: Level III.
RESUMO
These evidence-based guidelines support patients, clinicians, and other stakeholders in decisions about the use of intranasal corticosteroids (INCS), biologics, and aspirin therapy after desensitization (ATAD) for the management of chronic rhinosinusitis with nasal polyposis (CRSwNP). It is important to note that the current evidence on surgery for CRSwNP was not assessed for this guideline nor were management options other than INCS, biologics, and ATAD. The Allergy-Immunology Joint Task Force on Practice Parameters formed a multidisciplinary guideline panel balanced to include the views of multiple stakeholders and to minimize potential biases. Systematic reviews for each management option informed the guideline. The guideline panel used the Grading of Recommendations Assessment, Development and Evaluation approach to inform and develop recommendations. The guideline panel reached consensus on the following statements: (1) In people with CRSwNP, the guideline panel suggests INCS rather than no INCS (conditional recommendation, low certainty of evidence). (2) In people with CRSwNP, the guideline panel suggests biologics rather than no biologics (conditional recommendation, moderate certainty of evidence). (3) In people with aspirin (nonsteroidal anti-inflammatory drug)-exacerbated respiratory disease, the guideline panel suggests ATAD rather than no ATAD (conditional recommendation, moderate certainty of evidence). The conditions for each recommendation are discussed in the guideline.
Assuntos
Produtos Biológicos , Pólipos Nasais , Rinite , Sinusite , Humanos , Sinusite/tratamento farmacológico , Corticosteroides/uso terapêutico , Administração Intranasal , Pólipos Nasais/tratamento farmacológico , Doença Crônica , Produtos Biológicos/uso terapêutico , Aspirina/uso terapêutico , Rinite/tratamento farmacológicoRESUMO
Immunoglobulin E (IgE)-mediated food allergy is an immune response, typically to a food protein. Accurate diagnosis reduces unnecessary dietary restrictions and economic and psychological burden on patients and caregivers but relies on a rigorous clinical history, specific IgE diagnostic tests and, where needed, oral food challenge. Increased awareness is needed around which patients to test for IgE-mediated food allergy, as well as terms commonly associated with IgE-mediated food allergy testing, in order to optimise patient diagnosis and management. Herein, we describe approaches to diagnosis of IgE-mediated food allergy, appropriate interpretation of results and risks of overtesting.
RESUMO
Human adipose-derived mesenchymal stem cells (ASCs) transduced with a lentiviral vector system to express bone morphogenetic protein 2 (LV-BMP-2) have been shown to reliably heal bone defects in animal models. However, the influence of donor characteristics such as age, sex, race, and medical co-morbidities on ASC yield, growth and bone regenerative capacity, while critical to the successful clinical translation of stem cell-based therapies, are not well understood. Human ASCs isolated from the infrapatellar fat pads in 122 ASC donors were evaluated for cell growth characteristics; 44 underwent additional analyses to evaluate in vitro osteogenic potential, with and without LV-BMP-2 transduction. We found that while female donors demonstrated significantly higher cell yield and ASC growth rates, age, race, and the presence of co-morbid conditions were not associated with differences in proliferation. Donor demographics or the presence of comorbidities were not associated with differences in in vitro osteogenic potential or stem cell differentiation, except that transduced ASCs from healthy donors produced more BMP-2 at day 2. Overall, donor age, sex, race, and the presence of co-morbid conditions had a limited influence on cell yield, proliferation, self-renewal capacity, and osteogenic potential for non-transduced and transduced (LV-BMP-2) ASCs. These results suggest that ASCs are a promising resource for both autologous and allogeneic cell-based gene therapy applications.
Assuntos
Tecido Adiposo , Células-Tronco Mesenquimais , Animais , Humanos , Feminino , Tecido Adiposo/metabolismo , Osteogênese , Diferenciação Celular/genética , Células-Tronco Mesenquimais/metabolismo , Regeneração ÓsseaRESUMO
Ex-vivo gene therapy has been shown to be an effective method for treating bone defects in pre-clinical models. As gene therapy is explored as a potential treatment option in humans, an assessment of the safety profile becomes an important next step. The purpose of this study was to evaluate the biodistribution of viral particles at the defect site and various internal organs in a rat femoral defect model after implantation of human ASCs transduced with lentivirus (LV) with two-step transcriptional activation (TSTA) of bone morphogenetic protein-2 (LV-TSTA-BMP-2). Animals were sacrificed at 4-, 14-, 56-, and 84-days post implantation. The defects were treated with either a standard dose (SD) of 5 million cells or a high dose (HD) of 15 million cells to simulate a supratherapeutic dose. Treatment groups included (1) SD LV-TSTA-BMP-2 (2) HD LV-TSTA-BMP-2, (3) SD LV-TSTA-GFP (4) HD LV-TSTA-GFP and (5) SD nontransduced cells. The viral load at the defect site and ten organs was assessed at each timepoint. Histology of all organs, ipsilateral tibia, and femur were evaluated at each timepoint. There were nearly undetectable levels of LV-TSTA-BMP-2 transduced cells at the defect site at 84-days and no pathologic changes in any organ at all timepoints. In conclusion, human ASCs transduced with a lentiviral vector were both safe and effective in treating critical size bone defects in a pre-clinical model. These results suggest that regional gene therapy using lentiviral vector to treat bone defects has the potential to be a safe and effective treatment in humans.
Assuntos
Proteína Morfogenética Óssea 2 , Lentivirus , Ratos , Humanos , Animais , Distribuição Tecidual , Lentivirus/genética , Lentivirus/metabolismo , Proteína Morfogenética Óssea 2/genética , Proteína Morfogenética Óssea 2/metabolismo , Terapia Genética/métodos , Células-Tronco/metabolismoRESUMO
PURPOSE: To assess the efficacy, pharmacokinetics, and safety of a new, highly purified 10% IVIg (BT595, Yimmugo®) administered in children with PID. METHODS: This was an open-label, prospective, uncontrolled, multicenter Phase III pivotal trial. Among the 67 subjects in the trial were 18 pediatric patients aged 2 to 17 years with diagnosis of PID included in this analysis. They received doses between 0.2 and 0.8 g/kg body weight for approximately 12 months at intervals of either 3 or 4 weeks. Dosage and dosing interval were based on each patient's pre-trial infusion schedule. The rates of acute serious bacterial infections (SBI), secondary efficacy, safety, and pharmacokinetic outcomes were evaluated. RESULTS: No SBI occurred in the pediatric population. Two hundred sixty infusions were administered to the 18 pediatric patients. The mean (SD) IgG trough level was 8.55 (1.67) g/L at baseline and 8.84 (2.17) g/L at the follow-up visit after the last BT595 infusion. At the single infusions respectively, the average mean IgG trough levels ranged between 8.52 and 10.58 g/L. More than 85% of all infusions administered were not associated with any infusional AE (start during or within 72 h post-infusion). None of the severe or serious AEs were related to the investigational medicinal product (IMP). No premedication was used. Thirteen children reached a maximum infusion rate between > 2.0 and 8 mL/kg/h; no AE with an onset during the infusion occurred at these infusion rates. CONCLUSION: BT595 is effective, convenient, well tolerated, and safe for the treatment of children with PID. TRIAL REGISTRATION: EudraCT: 2015-003652-52; NCT02810444, registered June 23, 2016.
Assuntos
Infecções Bacterianas , Síndromes de Imunodeficiência , Doenças da Imunodeficiência Primária , Humanos , Criança , Estudos Prospectivos , Síndromes de Imunodeficiência/diagnóstico , Imunoglobulina G/uso terapêutico , Imunoglobulinas Intravenosas/uso terapêutico , Infecções Bacterianas/tratamento farmacológico , Doenças da Imunodeficiência Primária/tratamento farmacológicoRESUMO
The field of food allergy has seen tremendous change over the past 5-10 years with seminal studies redefining our approach to prevention and management and novel testing modalities in the horizon. Early introduction of allergenic foods is now recommended, challenging the previous paradigm of restrictive avoidance. The management of food allergy has shifted from a passive avoidance approach to active interventions that aim to provide protection from accidental exposures, decrease allergic reaction severity and improve the quality of life of food-allergic patients and their families. Additionally, novel diagnostic tools are making their way into clinical practice with the goal to reduce the need for food challenges and assist physicians in the-often complex-diagnostic process. With all the new developments and available choices for diagnosis, prevention and therapy, shared decision-making has become a key part of medical consultation, enabling patients to make the right choice for them, based on their values and preferences. Communication with patients has also become more complex over time, as patients are seeking advice online and through social media, but the information found online may be outdated, incorrect, or lacking in context. The role of the allergist has evolved to embrace all the above exciting developments and provide patients with the optimal care that fits their needs. In this review, we discuss recent developments as well as the evolution of the field of food allergy in the next decade.