Choice Of Initial Therapy Research Articles

Respiratory tract and bloodstream infections: microbiological profile in an intensive care unit for COVID-19

This is a retrospective cross-sectional study aimed at identifying the profile of lower respiratory tract (RTI) and bloodstream infections (BSI) in patients in the Intensive Care Unit (ICU) of a Reference Hospital for COVID-19 in Recife, Pernambuco. Data were collected on the age and sex of patients, material used in cultures, microorganisms detected, and resistance and sensitivity to the antimicrobials used. The most frequent species was Acinetobacter baumannii in RTI and Staphylococcus haemolyticus in BSI, being more resistant to levofloxacin and more sensitive to linezolid. Knowing the pathogens and their respective susceptibility patterns facilitates the choice of initial therapy, as well as the establishment of action protocols for health professionals and hospital infection control committees.

Antibiotic therapy for skin and soft tissue infections. current algorithms

Antibiotic therapy for infectious lesions of the skin and soft tissues requires a careful approach to ensure the effectiveness of treatment and prevent the development of resistance. The article discusses the basic principles and algorithms of antibacterial treatment for skin and soft tissue infections, taking into account modern clinical recommendations and standards of pharmaco - therapy. The initial choice of antibiotic is of ten based on the t ypical pathogens associated with the infection (most commonly Staphylococcus aureus and Streptococcus pyogenes). If MRSA (methicillin-resistant Staphylococcus aureus) or other resistant microorganisms are suspected, they must be taken into account in the choice of initial therapy. A fter receiving the results of culture studies and determining the sensitivit y of microorganisms, therapy should be adjusted. It is essential to maintain the antibiotic concentration at a level sufficient to eliminate the infection and prevent recurrence. The choice of antibiotic should take into account the side effects and possible interactions with other drugs.

Intravenous levetiracetam versus intravenous phenytoin as second Line treatment in pediatric convulsive status epilepticus- open label randomized controlled trial.

Benzodiazepines (BZDs) are recommended as the initial therapy of choice in status epilepticus (SE). The age-old second-line treatment for BZD refractory convulsive SE is intravenous phenytoin (PHT) based predominantly on nonrandomized clinical trial data. We did this study to compare the efficacy and safety of intravenous levetiracetam (LEV) and PHT as second-line antiseizure medication (ASM) for children with SE. A prospective, randomized controlled, open-label study was conducted in children 3 months to 15 years of age with SE in Pediatric Emergency. A total of 41 children were randomly allocated to either group 1 (Levetiracetam) or group 2 (Phenytoin) on the basis of computer-generated randomization. Children who were already on antiseizure medications, either LEV or PHT, or receiving these drugs outside for SE were excluded. Data analysis was done by SPSS V25. The most common age group presenting with SE was 12 months to 5 years. Clinical cessation of seizure 5 minutes after the completion of drugs was 85% (17/20) in Levetiracetam group and 90.5% (19/21) in Phenytoin group. Recurrence of seizure within 24 hours was noted in 35% (7/20) in Levetiracetam group and 38.1% (8/21) in Phenytoin group. There was no statistically significant difference noted in both the groups in terms of seizure cessation, adverse events, and recurrence. The efficacy and safety of LEV were found to be comparable to those of PHT in controlling seizure as second-line ASM in SE.

Determinant factors for first-line treatment choice and effectiveness in pediatric eosinophilic esophagitis: an analysis of the EUREOS EoE CONNECT registry

This study compared short-term effectiveness of proton pump inhibitors (PPI), swallowed topical corticosteroids (STC), and dietary therapies in reversing clinical and histological features in pediatric patients with eosinophilic esophagitits (EoE). Determinants for treatment choice and PPI therapy effectiveness were also assessed. A cross-sectional study analysis of patients under 18 years old recruited onto the multicenter EoE CONNECT registry was performed. Clinico-histological response was defined as symptomatic improvement plus a peak eosinophil count below 15 per high-power field after treatment. Effectiveness of first-line options used in monotherapy was compared. Overall, 393 patients (64% adolescents) receiving PPI, STC, or dietary monotherapy to induce EoE remission were identified. PPI was the preferred option (71.5%), despite STC providing the highest clinico-histological response rates (66%) compared to PPI (44%) and diet (42%). Logistic regression identified fibrotic features and recruitment at Italian sites independently associated to first-line STC treatment; age under 12 associated to dietary therapy over other options. Analysis of 262 patients in whom PPI effectiveness was evaluated after median (IQR) 96 (70–145) days showed that this effectiveness was significantly associated with management at pediatric facilities and use of high PPI doses. Among PPI responders, decrease in rings and structures in endoscopy from baseline was documented, with EREFS fibrotic subscore for rings also decreasing among responders (0.27 ± 0.63 vs. 0.05 ± 0.22, p < 0.001). Conclusion: Initial therapy choice for EoE depends on endoscopic phenotype, patient’s age, and patients’ origin. High PPI doses and treatment in pediatric facilities significantly determined effectiveness, and reversed fibrotic endoscopic features among responders.What is Known:• Proton pump inhibitors are widely used to induce and maintain remission in EoE in real practice, despite other first-line alternative therapies possibly providing higher effectiveness.What is New:• Proton pump inhibitors represent up to two-thirds of first-line monotherapies used to induce EoE remission in pediatric and adolescent patients with EoE. The choice of STC as first-line treatment for EoE was significantly associated with fibrotic features at baseline endoscopy and recruitment in Italian centers; age less than 12 years was associated with dietary therapy.• PPI effectiveness was found to be determined by use of high doses, attendance at pediatric facilities, presenting inflammatory instead of fibrotic or mixed phenotypes, and younger age. Among responders, PPI therapy reversed both inflammatory and fibrotic features of EoE after short-term treatment.

ADMIRE Study: Dapagliflozin and Metformin Fixed-dose Combination as Initial Choice of Therapy in Type 2 Diabetes Mellitus: A Real-world Study

Abstract Introduction: The use of sodium-glucose cotransporter 2 inhibitors with metformin has become one of the preferred therapies for the management of Type 2 diabetes mellitus (T2DM). In this study, we assessed prescribing patterns in T2DM patients who were initiated dapagliflozin and metformin (Dapa-Met) as initial choice fixed dose combination (FDC). We assessed the indications for choosing Dapa-Met FDC and changes in cardiometabolic parameters. Methods: In this retrospective analysis, we included T2DM patients with hemoglobin A1C (HbA1C) &gt;7% who were initiated with Dapa-Met FDC as initial treatment. Data HbA1C, fasting plasma glucose (FPG), postprandial plasma glucose (PPG), weight, systolic blood pressure (BP), and diastolic BP were recorded after 6 months of Dapa-Met FDC. Results: In total, data from 485 T2DM patients (mean age: 59.7 ± 9.8 years) were included. The mean duration of diabetes was 6.9 ± 4.7 years. For Dapa-Met FDC, 10 mg and 500 mg were the most preferred strengths. Nearly, 78% of patients required additional antidiabetic drug. Sulphonylureas (50.7%) and dipeptidyl peptidase 4-inhibitors (36.7%) were the most common co-prescribed drugs. Besides glycemia control, Dapa-Met FDC was preferred for weight loss (77.1%) and reducing cardiovascular events and related hospitalizations (46.8%). After 6 months, changes in HbA1C (D - 2.19%, P &lt; 0.0001), FPG (D - 21.4 mg/dL, P &lt; 0.0001), and PPG (D - 37.1 mg/dL, P &lt; 0.0001) were significant. Hypoglycemic events (16.7%) and genitourinary infections (8.9%) were the common adverse events. Conclusion: Dapa-Met (10/500 mg) as FDC is effective and safe in Indian patients with T2DM when used as an initial choice treatment for T2DM. Additional antidiabetic therapies may be necessary to achieve glycemic targets.

Initiation, response assessment, and switch of antibody therapies in patients with severe asthma – A survey among German specialists

BackgroundFor therapy of severe asthma 5 monoclonal antibodies have been available in Germany up to November 2022, but no clear rules exist on choice of initial therapy, assessment of response, and switch. ObjectiveTo assess current practice on all aspects of biologic therapy by specialists in Germany. MethodsA questionnaire was created by specialists for severe asthma, which was tested and modified by further experts. We invited 119 pulmonologists of the German Asthma Net (GAN) to complete the survey and used SoSci Survey and SPSS for data collection and analysis. ResultsForty-seven pulmonologists took part in the survey with a median annual number of patients treated with biologics of 35, 55% worked in an outpatient practice, and 40% in a hospital. Exacerbations and oral steroid use were the most important factors for the decision to start a biologic therapy. Accordingly, these parameters were also the most relevant for assessment of response. Most participants considered type-2 inflammation biomarkers and comorbidities (foremost CRSwNP and AD) for choosing initial biologic. Asthma Control Test (ACT) was the most common instrument for assessing status of disease control. There was no consensus on thresholds for response of pulmonary function tests including FEV1, FVC, and RV. Eighty-five percent of participants distinguished between “responders”, “partial responders” and “non-responders”. Comorbidities played an important role for the decision to switch to another biologic, eg, when initial therapy had insufficient effectiveness on CRSwNP. ConclusionThis study provides a detailed insight into current opinions and practice of biologic use in severe asthma in Germany.

SAT184 Improving Access To Osteoporosis Specialists Using Electronic Consultations

Abstract Disclosure: C. Sethuram: None. W. Brown: None. G. Gill: None. C. Liddy: None. A. Afkham: None. E. Keely: None. Background: Timely access to osteoporosis specialists remains a challenge in Canada, where patients face long wait times for specialist care. Electronic consultations (eConsults) help address this issue by allowing primary care providers (PCPs) to pose clinical questions to specialists using a secure online platform. This study identifies the types of osteoporosis-related questions being asked by PCPs and describes the impact of the advice provided by osteoporosis specialists using eConsult. Methods: We performed a cross-sectional study of osteoporosis-related eConsults submitted to endocrinologists between January 2018 and December 2020 on the Champlain BASE™ eConsult Service in Ontario, Canada. Each eConsult was coded according to clinical question and answer type through consensus between two authors, based on pre-determined taxonomies established by the reviewers. We analyzed eConsult utilization data, including response times, PCP satisfaction, and referral outcomes, which were collected via PCP surveys following completion of the eConsult. Results: Of the 2534 eConsults sent to endocrinologists during the study period, 408 (16%) were specific to osteoporosis. The most common questions asked by PCPs were regarding whether or not to start treatment (18%), the initial therapy choice (13%), and how often to complete bone mineral density scans (8%). The most common responses from specialists included recommendations for bone mineral density scanning (13%), recommendation to start therapy (9%), and recommendation to treat using a bisphosphonate without the dose specified (9%). The median response interval was 3.1 days, and the median time spent by endocrinologists responding to the eConsult was 10.0 minutes. Eighty-four percent of cases were resolved without requiring an in-person referral. A course of action that PCPs already had in mind was confirmed in 42% of cases. Clear advice for a new course of action for PCPs to implement was provided in 54% of cases. Conclusion: Osteoporosis eConsults provide timely access to valuable specialist advice while avoiding unnecessary face-to-face clinic visits. Further, we identified commonly recurring osteoporosis questions asked by PCPs, which can be used to inform planning of future continuing professional development events. Presentation: Saturday, June 17, 2023

Improving Access to Osteoporosis Specialists Using Electronic Consultations

ObjectiveTo identify the types of osteoporosis-related questions being asked by primary care providers (PCPs) and describe the impact of the advice provided by osteoporosis specialists using eConsult. MethodsWe performed a cross-sectional study of osteoporosis-related eConsults submitted to endocrinologists between January 2018 and December 2020 on the Champlain eConsult BASE™ Service in Ontario, Canada. Each eConsult was coded according to clinical question and answer type through consensus between 2 authors, based on predetermined taxonomies. We analyzed eConsult utilization data, including response times, PCP satisfaction, and referral outcomes (collected via PCP surveys). ResultsOf the 2,528 eConsults sent to endocrinologists during the study period, 408 (16%) were specific to osteoporosis. The most common questions asked by PCPs were regarding whether or not to start treatment (35%), the initial therapy choice (25%), and how often to complete bone mineral density scans (15%). The most common responses from specialists included recommendations for bone mineral density scanning (34%), recommendation to start therapy (24%), and recommendation to treat using a bisphosphonate without the dose specified (23%). The median response interval was 3.1 days. Most cases (84%) were resolved without requiring an in-person referral. Clear advice for a new course of action for PCPs to implement was provided in 54% of cases. ConclusionOsteoporosis eConsults provide timely access to valuable specialist advice while avoiding unnecessary face-to-face clinic visits. We identified commonly recurring osteoporosis questions asked by PCPs, which can be used to inform planning of future continuing professional development events.

Diagnosis and therapy of membranous nephropathy-2023

Membranous nephropathy (MN) is an immune-complex glomerulonephritis and is one of the most common causes of nephrotic syndrome in adults and is also one of the autoimmune kidney diseases with the highest rate of spontaneous remission. The most common autoantigen (> 70% of cases) is directed against the phospholipase A2 receptor (PLA2-R) and, with its detection and clinical course, allows for excellent diagnostics as well as optimal therapy monitoring. Other autoantigens are constantly being published and will enable an autoantigen-based diagnostic and therapeutic algorithm for MN in the future. In the absence of spontaneous remission, aspecific B‑cell-directed therapy, especially with rituximab, is the initial therapy of choice. Calcineurininhibitors or cyclophosphamide should only be used if they are carefully indicated in the respective clinical context and if there are serious clinical consequences both from the nephrotic syndrome and from loss of kidney function. Since immune complexes within the kidney often require along time to be degraded, proteinuria response can follow the immunological remission after many months. The therapy of MN represents the favorable case of aprecision medicine-based therapy in nephrology, whereby new therapeutic B‑cell antibodies for the rare but difficult forms of MN will find their way into clinical routine in the not-too-distant future.

Age-specific differences in hypertension combination management and associated factors influencing treatment choice.

The current hypertension guideline emphasizes combination therapy, especially single-pill combination therapy (SPC). However, few studies compared the prevalence and factors associated with initial therapy choice across heterogeneous age groups in a current population. First, the authors consecutively identified 964 treatment naïve hypertensive patients in a large academic hospital from 01/31/2019 to 01/31/2020. All patients were grouped into (1) young aged, age<55; (2) middle-aged, 55≤age<65; and (3) older aged, age ≥65. The multivariable regression model examined the factors associated with the combination therapy by age group. Overall, 80 (8.3%) were young, 191 (19.8%) were middle, and 693 (71.9%) were older aged. Compared with older age, younger patients were more likely to be male, highly educated, regularly exercised, have metabolic syndrome, and less likely to have cardiovascular-related comorbidities, with a lower systolic but higher diastolic pressure. Only one in five patients used SPC, and the prevalence decreased with age. Besides hypertension grade, young patients without catheterization or echo test were less likely to receive multiple therapies, while older patients who were male with lower weight and lower risk levels were less likely to receive multiple therapies. In conclusion, combination therapy, especially SPC, was underused in the targeted hypertensive population. Our contemporary population study showed that young patients (<55) without a history of catheterization or echo examination and male older-aged (≥65) patients with low-risk classification were the population most likely to be neglected. Such information can help triage medical care resources in improving SPC use.

Considerations for shared decision-making in treatment of chronic rhinosinusitis with nasal polyps.

Shared decision-making is an approach where physicians and patients work together to determine a personalized treatment course. Such an approach is integral to patient-centered care in chronic rhinosinusitis with nasal polyps (CRSwNP). CRSwNP is a chronic inflammatory condition of the sinonasal cavity that can severely impact physical health, smell, and quality of life (QOL). Traditional standard-of-care treatment options include topical (i.e. sprays) and oral corticosteroids and endoscopic sinus surgery, but more recently, novel corticosteroid delivery methods (i.e. high volume irrigations, recently-approved exhalation breath-powered delivering devices, and drug-eluting steroid implants) and 3 new FDA approved biologics directed against type II immunomodulators have become available. The availability of these therapeutics offers exciting new opportunities in CRSwNP management but requires personalized and shared-decision making as each modality has variable impacts on CRSwNP and related comorbid conditions. Studies have published treatment algorithms, but the practical use of these lean guidelines is heavily influenced by the lens of the treating physician, the most common being otolaryngologists and allergy immunologists. Clinical equipoise occurs when there is no basis for one intervention to be regarded as "better" than another. While most guidelines, in general, support the use of topical corticosteroids with or without oral corticosteroids followed by ESS for the majority of unoperated CRSwNP patients, there are situations of clinical equipoise that arise particularly in CRSwNP who have failed surgery or those with severe comorbid conditions. In the shared decision-making process, clinicians and patients must consider symptomatology, goals, comfort, compliance, treatment efficacy, and treatment cost when determining the initial choice of therapy and escalation of therapy with the potential use of multiple modalities for recalcitrant CRSwNP. A summary of salient considerations that might constitute shared decision-making is presented in this summary.

USE OF PROBIOTICS FOR THE MANAGEMENT OF ACUTE GASTROENTERITIS IN CHILLDREN : A SYSTEMATIC REVIEW

One of the illnesses that affect children the most frequently is acute gastroenteritis. There are around 500 million children throughout the world who are affected by this illness each year. The acute infectious diarrhea that occurs in affluent nations often has a moderate clinical course, and symptoms typically disappear on their own within a few days. The assessment of dehydration is the most essential part of both diagnostic and therapeutic care since it establishes the degree of AGE and is one of the criteria that is considered when deciding whether or not a patient should be admitted to the hospital. Outpatient care is appropriate for the vast majority of patients; hospitalization should only be considered for individuals who require rehydration by enteral or parenteral routes. Oral rehydration with fluids of a hypoosmolar concentration is the initial therapy of choice. Antidiarrheals such as racecadotril and diosmectite, probiotics such as Lactobacillus GG and Saccharomyces boulardii, and ondansetron, which lessens the severity of nausea and vomiting, are also beneficial. Antibiotherapy is something that should only be explored in the most dire of circumstances. Acute diarrhea is a well-known medical condition that is straightforward to cure if the patient adheres to a few basic guidelines that have been clearly outlined. There is an insufficient amount of data to support the use of probiotics in either a therapeutic or preventative capacity for the treatment of acute gastroenteritis in children.

НОВІ ПІДХОДИ ДО ВЕДЕННЯ ХВОРИХ НА САРКОЇДОЗ ЛЕГЕНЬ (методичний посібник)

Sarcoidosis is an inflammatory multi-systemic disease of unknown origin with wide spectrum of clinical manifestations. Sarcoidosis may affect practically any organ — predominantly lungs, lymphatic system, skin, eyes alone or in combination. The disease is characterized by formation of non-caseous granuloma. In 1999 American Thoracic society (ATS), European Respiratory society (ERS) and World Association of Sarcoidosis and Other Granulomatous diseases (WASOG) adopted an international consensus statement on diagnosis and treatment of sarcoidosis «Statement on Sarcoidosis». Based on ATS, ERS and WASOG 1999 Statement the national documents such as “Evidence-based adapted clinical guideline on sarcoidosis” and “Unified clinical protocol of primary, secondary (specialized) and tertiary (highly-specialized) medical care for sarcoidosis” approved by MOH of Ukraine (decree # 634 dated 08 Sep 2014) were developed by current authors in Ukraine. For a more detailed description of the principles of diagnosis and treatment of pulmonary sarcoidosis, we have developed and published methodological guidelines "Diagnosis of respiratory tract sarcoidosis" (2014) and "Treatment of pulmonary sarcoidosis" (2018). In 2020 ATS experts published an updated «Diagnosis and Detection of Sarcoidosis. An Official American Thoracic Society Clinical Practice Guideline», according to which the diagnosis of sarcoidosis was based on 3 criteria: compatible clinical symptoms, presence of non-necrotizing granulomatous inflammation in one or more tissue samples (not always required) and exclusion of alternative causes of granulomatous disorder. Finally, in 2021 ERS task force report was published “ERS clinical practice guidelines on treatment of sarcoidosis”, which outlined completely new approaches to management of sarcoidosis patients. According to this document, a decision about treatment of patient depends on 2 major factors: risk of death or organ failure and deterioration of quality of life of a patient. In addition, main principle of management of sarcoidosis patients is a balance between: a) minimization of risk of disability or death due to lung injury and decrease of quality of life, and b) risk of comorbidity and reduction of quality of life due to corticosteroid or other therapies. Methodical guideline focuses on analysis of major statements of these documents, disputable questions of initial therapy choice in patients with pulmonary sarcoidosis.

Differential responses to taxanes and PARP inhibitors in ATM-versus BRCA2-mutated metastatic castrate-resistant prostate cancer.

PARP(poly(ADP-ribose) polymerase) inhibitors (PARPi) are now standard of care in metastatic castrate-resistant prostate cancer (mCRPC) patients with select mutations in DNA damage repair (DDR) pathways, but patients with ATM- and BRCA2 mutations may respond differently to PARPi. We hypothesized that differences may also exist in response to taxanes, which may inform treatment sequencing decisions. mCRPC patients (N = 158) with deleterious ATM or BRCA2 mutations who received taxanes, PARPi, or both were retrospectively identified from 11 US academic centers. Demographic, treatment, and survival data were collected. Kaplan-Meier analyses were performed and Cox hazard ratios (HR) were calculated for progression-free survival (PFS) as well as overall survival (OS), from time of first taxane or PARPi therapy. Fifty-eight patients with ATM mutations and 100 with BRCA2 mutations were identified. Fourty-four(76%) patients with ATM mutations received taxane only or taxane before PARPi, while 14 (24%) received PARPi only or PARPi before taxane. Patients with ATM mutations had longer PFS when taxane was given first versus PARPi given first (HR: 0.74 [95% confidence interval[CI]: 0.37-1.50]; p = 0.40). Similarly, OS was longer in patients with ATM mutations who received taxane first (HR: 0.56 [CI: 0.20-1.54]; p = 0.26). Among patients with BRCA2 mutations, 51 (51%) received taxane first and 49 (49%) received PARPi first. In contrast, patients with BRCA2 mutations had longer PFS when PARPi was given first versus taxane given first (HR: 0.85 [CI: 0.54-1.35]; p = 0.49). Similarly, OS was longer in patients with BRCA2 mutations who received PARPi first (HR: 0.75 [CI: 0.41-1.37]; p = 0.35). Our retrospective data suggest differential response between ATM and BRCA2 mutated prostate cancers in terms of response to PARPi and to taxane chemotherapy. When considering the sequence of PARPi versus taxane chemotherapy for mCRPC with DDR mutations, ATM, and BRCA2 mutation status may be helpful in guiding choice of initial therapy.

Epstein-Barr virus seroprevalence and viral load at disease onset in children with inflammatory bowel disease.

Background and AimPatients with inflammatory bowel disease (IBD) are at increased risk for life‐threatening complications of Epstein–Barr virus (EBV), including lymphoproliferative diseases. These complications are likely related to inherent immune dysfunction and immunomodulating therapies often used. We aimed to determine the seroprevalence of EBV at diagnosis in our population, its impact on disease at onset, and the risk of active EBV infection.MethodsWe included patients newly diagnosed with IBD for whom an EBV serology was performed over a 2‐year period. Demographic information and data on disease characteristics were collected retrospectively. Stored serum from the time of diagnosis was retrieved when available for the patients with positive EBV serology, and quantitative polymerase chain reaction testing was performed to assess the pre‐treatment viral load of EBV.ResultsOne hundred twenty patients were included in the study. Fifty‐three patients (44.2%) had positive EBV serology at diagnosis. Stratified by age group, the prevalence of seropositive patients was for 0 to <10 years 35%, 10 to <17 years 46%, and ≥17 years 50%. Overall, therapies started within 6 months of diagnosis were similar in both the seropositive and seronegative groups. Within the seropositive group, 66% received systemic corticosteroids, 32.1% infliximab, 5.7% adalimumab, and 5.7% azathioprine.ConclusionEBV seroprevalence is high in pediatric patients with IBD. EBV seropositivity did not seem to influence the severity of disease at onset or initial choice of therapy.

How Genetics Can Drive Initial Therapy Choices for Older Patients with Acute Myeloid Leukemia.

Treatment of older adults with acute myeloid leukemia (AML) is challenging. Therapy decisions must be guided by multiple factors including aging-related conditions (e.g., comorbidities, functional impairment), therapy benefits and risks, patient preferences, and disease characteristics. Balancing these factors requires understanding the unique, and frequently higher-risk cytogenetic and molecular characteristics of AML in older adult populations, which should caution providers not to reduce therapy intensity on the basis of age alone. Instead, geriatric assessments should be employed to determine fitness for therapy. Treatment options in AML are increasingly targeted to specific mutations or recognized to have differential benefits on the basis of genomics, and representation of older adults and geriatric outcome reporting in clinical trials is improving. Additionally, newer studies have begun to explore personalized therapy strategies on the basis of initial genetic testing. Review and refinement of practice guidelines for older patients on the basis of these advances is needed and is anticipated to remain an important topic in ongoing hematology/oncology clinical education.

Early quality of life (QOL) and symptom analysis from the DREAMseq phase III randomized control trial of combination immunotherapy versus targeted therapy in patients (pts) with BRAF-mutant metastatic melanoma (MM) (ECOG-ACRIN EA6134).

9559 Background: Combinations of either immune checkpoint inhibitors (anti-PD-1/anti-CTLA-4) or BRAF/MEK-targeted therapies have shown significant clinical benefit in pts with BRAFV600 mutant MM. Until recently, little prospective data existed to guide the choice of initial therapy or sequence. Results of the DREAMseq Trial showed that the treatment sequence beginning with nivolumab/ipilimumab (Nivo/Ipi) immunotherapy produced a clinically meaningful 20% improvement in 2-year overall survival (OS) compared to the sequence beginning with dabrafenib/trametinib (Dab/Tram) targeted therapy. The OS and progression-free survival (PFS) curves were biphasic crossing at 10 and 6 months, respectively. Our aim is to characterize QOL trends within and between the initial therapies through 24 weeks (wks). Methods: 265 pts were randomly assigned to Nivo/Ipi for up to 12 wks then Nivo alone (Arm A) or Dab/Tram continuously (Arm B) and at disease progression (PD) received the alternate therapy. QOL was assessed by the PROMIS Profile 29 at baseline, wk 12 (end of cycle (C) 2), and wk 24 (end of C4). Wilcoxon Signed Rank test was used to examine changes over time within treatment arms. OS was estimated by Kaplan-Meier method to compare between pts who stopped treatment for toxicity on Arm A by C2 and who continued on Arm A therapy to C4. A complete case analysis compared QOL domain means for (C2) vs. (C4). Pt-reported adverse events were also collected. Results: Baseline completion rates for the PROMIS-29 for Arm A (n = 108, 81.2%) and Arm B (n = 117, 88.6%) and decreased to 28.6% and 53.8%, respectively at C4. Through C4, the principal reasons for dropout were toxicity (35.2% for Arm A and 11.9% for Arm B) and PD (26.1% for Arm A and 18.6% for Arm B). From Baseline to C2: Arm B reported statistically significant improvements in Pain Interference (-3.45, P = 0.007), Sleep (-2.11, P = 0.014), and Anxiety (-3.74, P &lt; 0.001). By C4, these early differences had dissipated (mean diff. = 0.73 – 1.73, all p = NS). For pts remaining on treatment to C4 (n = 157), a complete case analysis indicates no significant QOL differences between C2 vs C4. Pts stopping for toxicity on Arm A after C2 had similar 2-yr OS to pts who continued on Arm A to C4. QOL at C2 (Arm A: stopping for toxicity vs. on treatment) were meaningful, but underpowered (Physical Health (PH) mean difference = -3.5, p = 0.18). Conclusions: Over the first 12 wks, Dab/Tram is associated with significant improvement in overall function and less disturbance in in sleep, pain, physical function, and PH than Nivo/Ipi as expected by PFS curves and toxicity profiles. These differences dissipate by 24 wks when Arm A therapy has switched to Nivo alone and PFS curves cross. Early QOL and treatment cessation due to Nivo/Ipi toxicity was not associated with differences in 2-yr OS. Clinical trial information: NCT02224781.

Optimizing Treatment of Patients With Relapsed or Refractory Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma

Tremendous progress has been made in the treatment of relapsed/refractory (R/R) chronic lymphocytic leukemia (CLL) and small lymphocytic lymphoma (SLL) over the past few decades, starting with the development of glucocorticoids and alkylating agents, moving to combination chemotherapy, and then to chemoimmunotherapy. More recently, the advent of targeted agents has led to significant improvements in overall survival, progression-free survival, and quality of life. Most patients with R/R CLL and SLL are now treated with 1 of 5 approved targeted therapies rather than chemoimmunotherapy as standard of care. There are 2 main chemotherapy-free approaches in the R/R setting: Bruton’s tyrosine kinase inhibition and venetoclax-based therapy. Treatment after disease progression on first-line therapy depends on the initial choice of therapy, reason for discontinuation of prior lines of therapy, and available options.

A128 PATIENT CHARACTERIZATION AND ASSESSMENT OF REMISSION RATES IN CHILDREN WITH EOSINOPHILIC ESOPHAGITIS AFTER INITIAL TREATMENT AND 1-YEAR POST-DIAGNOSIS

BackgroundEosinophilic esophagitis (EoE) is a chronic immune- or antigen-mediated esophageal disorder characterized by symptoms of esophageal dysfunction and eosinophil-predominant inflammation. With incidence rates rapidly increasing, EoE is the leading cause of food bolus impaction and the second leading cause of chronic esophagitis. The treatment of EoE includes both induction and maintenance therapy to prevent complications including esophageal fibrosis and strictures. Despite significant advances in the diagnosis and treatment of EoE, the natural history and long-term management of the disease remains poorly understood.AimsTo describe the clinical characterization of children with EoE, and to assess remission rates after initial treatment and 1-year post-diagnosis.MethodsIn this ongoing, single-center retrospective study, the electronic medical charts of children newly diagnosed with EoE between January 2017-March 2021 participating in the EoE-AHEAD Registry study were reviewed. Children aged 6 months-18 years with a confirmed diagnosis of EoE based on consensus guidelines and receiving outpatient care at the SickKids EoE clinic were included.ResultsA total of 37 children with a median age of 11 years (IQR: 4.5, 12.5) were included, the majority of which were male (86.5%). Demographic and clinical characteristics are shown in Table 1. On initial treatment, 2.7% of children were on an elemental diet, 18.9% on a food elimination diet, 40.5% on proton-pump inhibitor (PPI) therapy, 16.2% on topical steroids, 8.1% on systemic steroids, and 13.5% on a combination therapy. Of the 30 children with a second endoscopy (mean interval since diagnosis of 6.1 months (3.9)), 30% achieved histological remission after the initial treatment (see Figure 1). Of the 14 children with a one-year follow-up endoscopy, 14.2% were in remission, 3 of which had relapsed. No significant differences in treatment modality were found between those who achieved remission and those who did not.ConclusionsThis is the first Canadian registry study to examine the longitudinal outcomes of EoE in a pediatric setting. Our preliminary results show that only 30% of children achieved histological remission following first-line treatment. The choice of initial therapy varied, although the majority of patients (62.2%) were prescribed a PPI and/or a topical steroid. Our findings highlight the importance of identifying different disease phenotypes to develop personalized therapeutic approaches for the management of EoE.Demographic and clinical characterization (n=37)Age, year (median, IQR)11 (4.5, 12.5)Sex (% Male)86.5%Ethnicity (% Caucasian)40.9%Personal history of atopy91.9%Family history of atopy73.0% Funding AgenciesSickKids start-up funds (JM Hulst) and the Comprehensive Research Experience for Medical Students (CREMS) Program

A Systematic Review of Multi-decade Antibiotic Resistance Data for Ocular Bacterial Pathogens in the United States.

IntroductionSince 2009, the Antibiotic Resistance Monitoring in Ocular Microorganisms (ARMOR) surveillance study has been assessing in vitro antibiotic resistance for bacterial isolates sourced from ocular infections in the US. The main goal of this systematic review was to compare in vitro resistance data for ocular pathogens from published US studies with the most recently published data from the ARMOR study (2009–2018) and, where possible, to evaluate trends in bacterial resistance over time over all studies.MethodsA literature search was conducted using MEDLINE®, BIOSIS Previews®, and EMBASE® databases (1/1/1995–6/30/2021). Data were extracted from relevant studies and antibiotic susceptibility rates for common ocular pathogens (Staphylococcus aureus, coagulase-negative staphylococci [CoNS], Streptococcus pneumoniae, Pseudomonas aeruginosa, and Haemophilus influenzae), longitudinal changes in susceptibility, and multidrug resistance (MDR) were compared descriptively.ResultsThirty-two relevant studies were identified. High in vitro resistance was found among S. aureus and CoNS to fluoroquinolones, macrolides, and methicillin/oxacillin across studies, with high rates of MDR noted, specifically among methicillin-resistant staphylococci. Data from studies pre-dating or overlapping the early years of ARMOR reflected increasing rates of S. aureus resistance to fluoroquinolones, macrolides, methicillin/oxacillin, and aminoglycosides, while the ARMOR data suggested slight decreases in resistance to these classes between 2009 and 2018. Overall, methicillin-resistant S. aureus (MRSA) prevalence peaked from 2005 to 2015 with a possible decreasing trend in more recent years.Discussion and ConclusionsData from local and regional US datasets were generally consistent with data from the national ARMOR surveillance study. Continued surveillance of ocular bacterial pathogens is needed to track trends such as methicillin resistance and MDR prevalence and any new emerging antibiotic resistance phenotypes. Susceptibility data from ARMOR can inform initial choice of therapy, especially in practice areas where local antibiograms are unavailable.Supplementary InformationThe online version contains supplementary material available at 10.1007/s40123-021-00449-9.