Multiple Courses Of Treatment Research Articles

P018 A review of the use of anakinra in hyperinflammatory conditions at a large central London teaching hospital

Abstract Background/Aims The interleukin-1 receptor antagonist, anakinra, is increasingly used to treat inflammatory disorders. We recognized a need to provide patients with accurate information regarding the trajectory of their treatment. In this service evaluation project, we collected data on patients prescribed anakinra at a London teaching hospital over a 4-year period. Methods Patients included were started on anakinra to manage an inflammatory disorder between April 2019 and Feb 2023. Patients were identified by searching a high-cost drugs system. Data on indication for the drug, start and stop date(s) of treatment and any adverse effects were then collected using electronic patient records. Results 74 patients met inclusion criteria, 43 females and 31 males. Median age 38.5 years. 56 patients were treated for haemophagocytic lymphohisticytosis (HLH), 5 for Juvenile Idiopathic Arthritis (JIA) and 13 for Adult Onset Still’s Disease (AOSD). Median time on anakinra was 140.5 days (IQR 563.5), 1487.5 days (IQR 861) and 673 days (IQR 1017) for HLH, JIA and AOSD respectively. Of those treated for HLH, drivers and median duration of anakinra treatment for each respective driver were: infection (seven patients, 31 days), rheumatological (six patients, 785 days), haematological (26 patients, 36.5 days), iatrogenic (1 patient, 89 days), primary HLH (2 patients, 89 days), underlying rheumatological condition with infective/drug trigger (3 patients, 345 days), unknown (11 patients, 191 days). 9/56 patients with HLH remained on treatment at data collection - 4 with an unknown driver, two with AOSD, one with underlying Sjogren’s and a drug trigger, one with a haematological driver and one with primary HLH. 12/56 patients with HLH had died. Of those who died, eight had a haematological malignancy driving their condition, three had an infective driver and one an unknown driver. Five patients in our study had HLH driven by AOSD. Of these, 2/5 successfully stopped anakinra during the study period. Five patients (8.9%) with HLH required multiple courses of treatment with anakinra; three had lymphoma associated HLH, one primary HLH and one idiopathic HLH. Three patients were unable to continue with therapy due to side effects: neutropenia(1), rash (1), problems self-injecting (1). Conclusion From this data set we can begin to formulate answers to many commonly encountered questions regarding anakinra therapy. The length of time someone can expect to receive treatment with anakinra is significantly impacted by the indication for prescribing. Those with a haematological malignancy driving their HLH receive anakinra for the shortest time of all groups, usually while awaiting definitive treatment for their cancer, or before transition to palliative management. Some patients with AOSD driven HLH can safely stop treatment. Some patients may require multiple courses of treatment with anakinra for disease relapse. Adverse effects requiring treatment cessation are low in all groups. Disclosure I. Munro: None. R. Allen: None. A. Jones: None. J. Manson: None.

Tecovirimat Resistance in Mpox Patients, United States, 2022-2023.

During the 2022 multinational outbreak of monkeypox virus (MPXV) infection, the antiviral drug tecovirimat (TPOXX; SIGA Technologies, Inc., https://www.siga.com) was deployed in the United States on a large scale for the first time. The MPXV F13L gene homologue encodes the target of tecovirimat, and single amino acid changes in F13 are known to cause resistance to tecovirimat. Genomic sequencing identified 11 mutations previously reported to cause resistance, along with 13 novel mutations. Resistant phenotype was determined using a viral cytopathic effect assay. We tested 124 isolates from 68 patients; 96 isolates from 46 patients were found to have a resistant phenotype. Most resistant isolates were associated with severely immunocompromised mpox patients on multiple courses of tecovirimat treatment, whereas most isolates identified by routine surveillance of patients not treated with tecovirimat remained sensitive. The frequency of resistant viruses remains relatively low (<1%) compared with the total number of patients treated with tecovirimat.

Integration of prison health care into national disease surveillance and health informatic systems: opportunities and challenges for Europe and beyond

Abstract Approximately six million people are incarcerated annually in the WHO EURO region. The majority of these people spend only a minority of their lives in prison. Many people living in prison (PLP) experience significant health &amp; social care inequalities/inequities and have higher levels of health &amp; care needs than their peers in the community. Imprisonment can represent a public health opportunity to identify and address such needs. Programmes delivered in prisons targeting infectious diseases like HBV, HCV, HIV and tuberculosis (TB) can improve active case finding specifically in prison settings but can also impact on elimination and control targets for whole populations by addressing high risk transmission networks centred in and around prison associated populations. But too often prisons represent a ‘black hole’ for health &amp; care data flows, neither receiving health information from community-based health systems nor providing, in an accessible way, details of health interventions delivered in prisons. The result is discontinuity of care and inefficiencies (economic&amp;clinical) in treatment and care programmes. For example, people being screened multiple times for an infection (e.g. HCV) but not receiving treatment, or starting and stopping multiple courses of treatment in a chaotic way which could add to public health risks, e.g. multi-drug resistant TB. National disease surveillance systems missing data on prison populations also risk health security given the ability of prisons to amplify infectious diseases which could pose health threats to wider communities. Significant efforts are required to ensure that national disease surveillance and health information systems routinely include PLP to improve health intelligence, health security and continuity of care. This can support delivery of screening, diagnostic and therapeutic services. But can also enable health service evaluation, health &amp; care needs assessment, and quality improvement programmes.

Predicting Dosimetry of Stereotactic Ablative Radiotherapy for the Treatment of Multiple Lung Lesions

Stereotactic ablative radiotherapy (SABR) has recently been used to treat increasing numbers of lung metastases, either synchronously or over multiple courses of treatment. Selecting the optimal dose and fractionation to balance risk of local failure and treatment toxicity is challenging. This project uses machine learning to provide rapid dosimetry predictions of SABR to multiple lung lesions, allowing exploration of different dose prescription options prior to the radiation (RT) planning process. A generative adversarial network (GAN) was trained to predict the dosimetry of multi-lesion thoracic SABR treatment from the planning CT scan, target and organ at risk contours, and the prescribed dose-fractionation without the need to carry out treatment planning. RT plans of patients who received at least one SABR treatment for ≥2 lung lesions between 2014-2020 at a single tertiary center were included in the analysis. All prescriptions were converted to their equivalent doses in two Gray fractions (EQD2). SABR treatments received at different timepoints were registered, and EQD2 doses were accumulated with no repair. Model performance was assessed using 5-fold cross validation. Plans were randomly divided into 5 folds, stratified by the number of lesions (no patients crossed folds). Each fold served as the testing set once, with the model trained on the other 4 folds. The model was evaluated on the difference in the volume of lung receiving above 20 Gray (V20) of the predicted dosimetry compared to the true dosimetry. Treatment plans (n = 103) were included from 81 patients with 280 lesions (62, 23, 8, and 10 plans had 2, 3, 4, and ≥5 lesions respectively). Fifty-five, 18, and 4 patients had a single, 2 and 3 courses of RT respectively. Fifty-two patients were treated for primary lung cancer, 28 patients treated for metastases from other sites, and 1 patient for both. Seven patients (8.6%) developed ≥ Grade 2 pneumonitis. Doses prescribed were 60/8 (n = 136), 55/5 (n = 49), 54/3 (n = 27), 24/1 (n = 21), 35/5 (n = 13), 30/5 (n = 9), and other (n = 25). The mean lung V20 for all patients was 11.3% [1.5%-29.6%]; the mean lung V20 was 9.3%, 12.2%, 13.5% and 20.4% for plans with 2, 3, 4, ≥ 5 lesions respectively. The mean absolute difference (MAD) in lung V20 between the predicted dosimetry and true dosimetry over all 5-folds was 1.9% [0.0%-13.4%]; the MAD in lung V20 between the predicted and actual dosimetry was 1.6%, 2.1%, 2.9% and 2.6% for plans with 2, 3, 4, ≥ 5 lesions respectively. The GAN-based model created in this study can predict the dosimetry of any number of lesions in the thorax treated with SABR. The model can be used to quickly determine the feasibility of SABR treatment for multiple synchronous lesions, or in the retreatment setting. The ability to explore the dosimetry of different prescription options for a given patient prior to RT planning may allow for personalized risk-adapted treatment if combined with local control and toxicity modelling.

B-245 Applicability of metagenomic Next-Generation Sequencing (mNGS) in challenging infectious diseases in a tertiary hospital

Abstract Background Infectious diseases caused by rare pathogens or with unusual presentations pose a diagnostic challenge. Traditional microbiologic tests can be time-consuming, labor-intensive and have limited sensitivity for some organisms. Plasma metagenomic Next-Generation Sequencing (mNGS) detects whole microbial genetic material and detects even unsuspected organisms. We present three cases of challenging infectious diseases and discuss the applicability of mNGS in different scenarios. Methods Plasma NGS was performed at Karius, Inc. (Redwood City, CA, USA). Patient data was collected from hospital and laboratory electronic records. Results Case 1: An 8-year-old female with sickle-cell anemia developed a persistent daily fever two weeks after recovery from sepsis due to Streptococcus pyogenes. Clinical exam was normal and investigation was negative (blood cultures, echocardiogram, thoracic and abdominal CT scans and bone scintigraphy). Two weeks later mNGS was performed, which came out positive for Cytomegalovirus. As patient became afebrile in 48 h and the viral burden was low, she could be safely discharged. Case 2: A 43-year-old male with prosthetic aortic valve and an intraluminal aortic ring had a year-long history of fatigue, weight loss and hypoalbuminemia. CT scans showed ground-glass infiltrates and enlarged mediastinal lymph nodes. Empirical treatment for tuberculosis was ineffective. A year later, he developed hepatosplenomegaly, fever and pancytopenia. Blood cultures, bone marrow biopsy and serologies (HIV, hepatitis B/C, syphilis, brucellosis, bartonellosis, leishmaniasis) were negative. Cardiac surgery found no apparent signs of endocarditis and the prosthetic aortic valve biopsy revealed only an inflammatory infiltrate. A new CT scan showed thickened intraluminal aortic ring with aortic pseudoaneurysms and splenomegaly with splenic infarction. A blood sample was then collected for mNGS and liver biopsy and splenectomy were performed. However, surgery complicated with hemodynamic instability, renal and liver failure and the patient died in less than 24 h. Two days later, mNGS came out positive for Coxiella burnetti. Case 3: A 45-year-old female with relapsed AML treating a chronic disseminated candidiasis with micafungin for 3 months had persistent liver and splenic nodules and new pulmonary nodules on the CT scan. In the following three months after chemotherapy (Gilteritinib), she developed multiple episodes of febrile neutropenia, some without microbiological documentation, leading to multiple courses of antibiotic treatment and a shift to liposomal amphotericin B. After clinical improvement and bone marrow recovery, liposomal amphotericin B was replaced by isavuconazole. A negative mNGS result allowed antifungal treatment to be safely discontinued, avoiding six months of unnecessary antifungal treatment. Conclusion We summarize three different scenarios of mNGS applications. In common, patients were submitted to multiple laboratory and image testing and received large doses of empirical antimicrobials due to lack of a precise diagnosis. In two cases, mNGS was diagnostic, shortened hospital stay and reduced overall costs. In case 2, the patient’s death might have been prevented if mNGS had been performed earlier. Vulnerable hospitalized patients with a broad spectrum of diagnostic possibilities, in whom sequential diagnostic tests could delay adequate therapy and cause significant adverse effects, could greatly benefit from mNGS when performed in a timely manner.

Impact of Targeted Neonatal Echocardiography on Patent Ductus Arteriosus Management in a Canadian Tertiary Care Neonatal Unit: A Retrospective Cohort Study.

Comprehensive assessment of hemodynamic significance of a patent ductus arteriosus (PDA) is a common indication to perform targeted neonatal echocardiography (TNE). Impact of implementation of such an assessment on PDA management decisions remains to be reported. The objective of this study is to compare PDA-related hemodynamic information and PDA treatment decisions before and after introduction of TNE service. This was a retrospective cohort study at a tertiary level neonatal intensive care unit in Southwestern Ontario. We investigated two time periods: Epoch-1 (non-TNE 2013-2016) versus Epoch-2 (TNE 2018-2021). We included neonates < 32 weeks with PDA. Data on baseline clinical characteristics, PDA-related echocardiographic parameters, PDA treatment details, and relevant long-term outcomes were collected. Primary outcome was defined as PDA treatment rates and need for multiple courses. Secondary outcomes included availability of PDA hemodynamic data and neonatal mortality/morbidity (PDA-related) RESULTS: A total of 275 neonates were included. A total of 162 were assessed by conventional echocardiography in Epoch-1, whereas 113 were assessed by TNE in Epoch-2. Baseline clinical characteristics were similar. Epoch-2 had more echocardiographic assessments per patient of 2.7 (±1.8) versus 1.9 (± 1.3), p < 0.001 in Epoch1. The mean postnatal age at first echocardiographic assessment was higher in Epoch-2 (12.7 days [ ± 14.6]) than in Epoch-1 (7.9 days [ ± 10.4]), p < 0.001. Comprehensive hemodynamic assessment of PDA-related echocardiographic parameters such as PDA size, shunt pattern, effect on systemic circulation, and pulmonary circulation were higher in Epoch-2. Overall, PDA treatment rates were comparable in the two time periods. The use of multiple courses of treatment was higher in Epoch-1 than in Epoch-2 (47.8 vs. 31.7%, p = 0.047). In Epoch-1, neonates received PDA treatment earlier than in Epoch-2. With the implementation of the TNE service, increased echocardiographic evaluations per patient were completed with availability of more comprehensive hemodynamic information about PDA. PDA treatment rates were similar in the two epochs, but need for multiple courses were less in TNE era. · TNE allows comprehensive hemodynamic assessment of PDA.. · Implementation of dedicated TNE service led to increased use of echocardiography to assess PDA.. · Standardized hemodynamic assessment of PDA may allow improved individualization of treatment need..

Impact of Prenatal Acetaminophen Exposure for Hippocampal Development Disorder on Mice.

Non-steroidal anti-inflammatory drugs (NSAIDs) are widely used as analgesic agents. They have been detected in various environmental matrices. The degradation of environmental contaminants and the long-term adverse effects have become a major public concern. Prenatal exposure to acetaminophen can cause damage to the developing hippocampus. However, the molecular mechanisms behind hippocampal damage following prenatal acetaminophen exposure (PAcE) remain unclear. The present study shows an increased risk of adverse neurodevelopmental outcomes in offspring following exposure to acetaminophen during pregnancy on mice. The results revealed that different doses, timings, and duration of exposure to acetaminophen during pregnancy were associated with dose-dependent changes in the hippocampus of the offspring. Furthermore, exposure to high doses, multiple-treatment courses, and late pregnancy induced pathological changes, such as wrinkling and vacuolation, inhibited hippocampal proliferation and increased apoptosis. In addition, PAcE significantly decreased the expression of genes related to synaptic development in fetal hippocampal neurons and hippocampal astrocyte and microglia were also damaged to varying degrees. The significant reduction either in SOX2, an essential gene in regulating neural progenitor cell proliferation, and reduction of genes related to the SOX2/Notch pathway may suggest that the role of SOX2/Notch pathway in impaired hippocampal development in the offspring due to PAcE. In general, PAcE at high doses, multiple-treatment courses, and mid- and late gestation were associated with neurodevelopmental toxicity to the offspring.

The Prevalence and Incidence of Hemolytic Uremic Syndrome: A Systematic Review.

A hemolytic uremic syndrome is an uncommon but severe condition brought on by an overactive alternative complement system, typically involving a hereditary component. It will be crucial to comprehend the epidemiology of hemolytic uremic syndrome as research advances toward bettering its diagnosis and treatment. A systematic review was conducted to evaluate the incidence and prevalence estimates of hemolytic uremic syndrome (HUS) internationally. A thorough literature search was conducted using PubMed, Springer, Cochrane Library for Systematic Reviews, and Embase databases between 2012 and 2023 in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 recommendations. A further source of data was the PubMed Central search engine. To make sure that the evaluation included just the studies that were the most pertinent, a population, interventions, comparators, and outcomes (PICO) eligibility criterion was also used. Eight articles were included in this review. HUS had an annual crude incidence of 0.66 per 100,000 people and a standard annual incidence of 0.57 per 100,000 people. Females were more likely than males to develop HUS, but only marginally more frequently. Patients under 20 years old were the age group where HUS was most common. HUS had an average cost of $21,500 per patient, which was more expensive than the country's overall inpatient average cost for the same period. This is due to patients requiring supportive care, antibiotics, plasma exchange, plasma infusion, and renal replacement therapy, and it could take multiple courses of treatment before they improve. It was concluded that several variables, including the region, the age group affected, and the frequency of the underlying bacterial infection, determine the prevalence and incidence of HUS. HUS is often more common in children than adults and is more common in some nations. Overall, HUS is an uncommon disorder that can have significant repercussions for people who have it. For better results and fewer consequences, HUS must be diagnosed and treated as soon as possible.

The effect of antimalarials on the safety and persistence of treatment with biologic agents or Janus kinase inhibitors in rheumatoid arthritis.

To test the association of use of antimalarials with the overall safety of treatment in RA patients receiving one or multiple courses of biologic (b)DMARDs or a Janus kinase inhibitor (JAKi). BiobadaBrasil is a multicentric registry-based cohort study of Brazilian patients with rheumatic diseases starting their first bDMARD or JAKi. The present analysis includes RA patients recruited from January 2009 to October 2019, followed up over one or multiple (up to six) courses of treatment (latest date, 19 November 2019). The primary outcome was the incidence of serious adverse events (SAEs). Total and system-specific adverse events (AEs) and treatment interruption served as secondary outcomes. Negative binomial regression with generalized estimating equations (to estimate multivariate incidence rate ratios, mIRR) and frailty Cox proportional hazards models were used for statistical analyses. The number of patients enrolled was 1316 (2335 treatment courses, 6711 patient-years [PY]; 1254.5 PY on antimalarials). The overall incidence of SAEs was 9.2/100 PY. Antimalarials were associated with reduced risk of SAEs (mIRR: 0.49; 95% CI: 0.36, 0.68; P < 0.001), total AEs (0.68; 95% CI: 0.56, 0.81; P < 0.001), serious infections (0.53; 95% CI: 0.34, 0.84; P = 0.007) and total hepatic AEs (0.21; 95% CI: 0.05, 0.85; P = 0.028). Antimalarials were also related to better survival of treatment course (P = 0.003). There was no significant increase in the risk of cardiovascular AEs. Among RA patients on treatment with bDMARDs or JAKi, concomitant use of antimalarials was associated with reduced the incidence of serious and total AEs and with longer treatment course survival.

Effects of amoxicillin exposure at different stages, doses and courses of pregnancy on adrenal development in fetal mice.

Pregnant women are usually treated with amoxicillin before cesarean section to prevent infection. This study aimed to investigate the effects of amoxicillin exposure on fetal adrenal development at different stages, doses and courses of pregnancy. We found prenatal amoxicillin exposure (PAmE) could cause adrenal developmental toxicity in both male and female fetal mice in a stage, dose and course-dependent manner, among which the third trimester, high dose and multiple courses of PAmE could significantly reduce the maximum cross-sectional area and diameter. Besides, the proliferation was inhibited, the apoptosis was enhanced, and the serum corticosterone level and expression of steroidogenic enzymes were decreased in the PAmE group. Further, the insulin-like growth factor 1 (IGF1) signaling pathway were inhibited in the male and female fetal mice at the third trimester, high dose and multiple courses of treatment, and adrenal IGF1 expression was positively correlated with the indicators of adrenal development. In conclusion, PAmE could induce adrenal dysplasia in fetal mice in the stage, dose and course-dependent manner, which was related to the inhibition of IGF1 signaling pathway. This study provides guidance for evaluating the toxicity and risk of fetal adrenal development and the rational use of amoxicillin during pregnancy.

Dynamics of the structure of renal tuberculosis over 20 years

Tuberculosis is a serious medical and social problem that does not lose its importance, despite all the advances in pharmacology and surgery. Diagnosis of urogenital tuberculosis (UGTB), as a rule, is delayed due to low index of suspicion to tuberculosis and the absence of pathognomonic symptoms. Determining the change in the ratio of clinical forms of renal tuberculosis from 1999 to 2020. A retrospective cohort comparative non-interventional study on the spectrum of the incidence of extrapulmonary tuberculosis (EPTB) was carried out. Among all 13852 extrapulmonary tuberculosis patients which were diagnosed from 1999 to 2020, patients with renal tuberculosis were selected, and the spectrum of their clinical forms in three periods was analyzed: 1st period 1999-2004 (1155 patients), second period 2005-2014 (2657 patients), and the third period 2015-2020 (671 patients). The clinical features of nephrotuberculosis in 88 patients was also estimated. Over the 20 years of the analyzed period, the number of patients with UGTB decreased by 80.6%; for the year of the COVID-19 pandemic, this figure fell by another third. In the first period, destructive complicated forms of nephrotuberculosis prevailed (922 patients - 79.8%), while the so-called "minor forms" were diagnosed in 233 patients (20.2%). In the second period, the situation was statistically significantly more favorable: the proportion of destructive and complicated forms of renal tuberculosis decreased to 43.8% (1124 patients), "small forms" were diagnosed in 1443 patients (56.2%). In the third period, destructive and complicated forms of nephrotuberculosis were diagnosed in 531 patients (77.6%), and the proportion of "small forms" in comparison with the previous period decreased by half, to 22.4%. Analysis of the clinical features of renal tuberculosis, depending on the prevalence of the destruction, showed that an asymptomatic course is possible, and pain, dysuria, intoxication and renal colic are present with different frequencies, and the clinical picture of tuberculosis of the renal parenchyma differs significantly from the clinical picture of tuberculous papillitis, cavernous nephrotuberculosis and symptoms of renal tuberculosis as whole. Currently, there is no screening on urogenital tuberculosis at all. Patients are diagnosed by referral, with a long history, after receiving multiple courses of antibacterial treatment; mainly through the pathomorphological examination of the operating material. Thus, a sharp decrease in the proportion of UGTB patients does not mean the disappearance of tuberculosis of this localization, but only states the tragic defects in timely diagnosis and low index of suspicion of medical doctors in relation to UGTB.

Real-World Utilization Patterns of Intravenous Immunoglobulin in Adults With Generalized Myasthenia Gravis in the United States

Objective To evaluate real-world utilization patterns of intravenous immunoglobulin (IVIg) among patients with generalized myasthenia gravis (gMG) over 3 years post-IVIg initiation. Background gMG is a rare autoimmune neuromuscular disorder with no known cure. Although IVIg is the most commonly used add-on therapy after standard of care treatments in gMG, it is currently unclear whether it is more commonly used as a “one-off” treatment to manage exacerbations, or as maintenance therapy aimed at reducing or replacing steroid use. Design/Methods Patients with gMG who initiated IVIg treatment were identified from a US claims database (Symphony Health, an ICON plc Company, Integrated Dataverse [IDV]®, January 1, 2014-December 31, 2019). The frequency of subsequent IVIg treatment and associated cost during the first 12 months post-IVIg initiation were analyzed. Usage patterns of concomitant gMG treatments during the year preceding and 3 years post-IVIg initiation were compared. Results Among 1225 patients with gMG who initiated IVIg treatment, 706 patients (57.6%) received 1 to 5 IVIg treatment courses (intermittent IVIg users), and 519 patients (42.4%) received = 6 IVIg treatment courses (chronic IVIg users) within the subsequent year. Mean annual medical cost per patient was nearly 2.5-fold higher for chronic vs intermittent IVIg users ($161,478 vs $64,888, p &lt; 0.001). Usage frequency of other immunotherapy treatments did not decrease over the follow-up period, even for patients who continued annual chronic IVIg for 3 consecutive years post-initiation. Conclusions Nearly half of patients with gMG received chronic and multiple IVIg treatment courses within the first year once initiating IVIg treatment, indicating higher usage than expected. For all IVIg initiators, usage frequency of other immunotherapy treatments did not decrease over 3 years despite IVIg initiation.

Real-world utilization patterns of intravenous immunoglobulin in adults with generalized myasthenia gravis in the United States

ObjectiveTo evaluate real-world utilization patterns of intravenous immunoglobulin (IVIg) among patients with generalized myasthenia gravis (gMG) over 3 years post-IVIg initiation. MethodsPatients with gMG who initiated IVIg treatment were identified from a United States claims database (Symphony Health's Integrated Dataverse [IDV]®, January 1, 2014 − December 31, 2019). The frequency of subsequent IVIg treatment and associated cost during the year post-IVIg initiation were analyzed. Usage patterns of IVIg and concomitant gMG treatments during the year preceding and 3 years post-IVIg initiation were compared. ResultsAmong 1225 patients with gMG who initiated IVIg treatment, 706 patients (57.6%) received 1 to 5 IVIg treatment courses (intermittent IVIg users), and 519 patients (42.4%) received ≥6 IVIg treatment courses (chronic IVIg users) within the subsequent year. Mean annual medical cost per patient was nearly 2.5-fold higher for chronic vs. intermittent IVIg users ($161,478 vs. $64,888, p < 0.001). The proportion of patients using corticosteroids and nonsteroidal immunosuppressive treatments (NSISTs) was not reduced over the 3-year follow-up period following IVIg initiation, even for patients who continued annual chronic IVIg for 3 consecutive years post-initiation. ConclusionsNearly half of patients with gMG received chronic and multiple IVIg treatment courses within the first year once initiating IVIg treatment, indicating higher usage than expected. For all IVIg initiators, the proportion of patients using corticosteroids and NSISTs did not decrease over 3 years despite IVIg initiation.

Rapid Standardized CT-Based Method to Determine Lean Body Mass SUV for PET-A Significant Improvement Over Prediction Equations.

In 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography (PET) studies, maximum standardized uptake value (SUVmax) is the parameter commonly used to provide a measurement of the metabolic activity of a tumor. SUV normalized by body mass is affected by the proportions of body fat and lean tissue, which present high variability in patients with cancer. SUV corrected by lean body mass (LBM), denoted as SUL, is recommended to provide more accurate, consistent, and reproducible SUV results; however, LBM is frequently estimated rather than measured. Given the increasing importance of a quantitative PET parameter, especially when comparing PET studies over time to evaluate disease response clinically, and its use in oncological clinical trials, we set out to evaluate the commonly used equations originally derived by James (1976) and Janmahasatian et al. (2005) against computerized tomography (CT)-derived measures of LBM.MethodsWhole-body 18F-FDG PET images of 195 adult patients with cancer were analyzed retrospectively. Representative liver SUVmean was normalized by total body mass. SUL was calculated using a quantitative determination of LBM based on the CT component of the PET/CT study (LBMCT) and compared against the equation-estimated SUL. Bland and Altman plots were generated for SUV-SUL differences.ResultsThis consecutive sample of patients undergoing usual care (men, n = 96; women, n = 99) varied in body mass (38–127 kg) and in Body Mass Index (BMI) (14.7–47.2 kg/m2). LBMCT weakly correlated with body mass (men, r2 = 0.32; women, r2 = 0.22), and thus SUV and SULCT were also weakly correlated (men, r2 = 0.24; women, r2 = 0.11). Equations proved inadequate for the assessment of LBM. LBM estimated by James’ equation showed a mean bias (overestimation of LBM compared with LBMCT) in men (+6.13 kg; 95% CI 4.61–7.65) and in women (+6.32 kg; 95% CI 5.26–7.39). Janmahasatian’s equation provided similarly poor performance.ConclusionsCT-based LBM determinations incorporate the patient’s current body composition at the time of a PET/CT study, and the information garnered can provide care teams with information with which to more accurately determine FDG uptake values, allowing comparability over multiple scans and treatment courses and will provide a robust basis for the use of PET Response Criteria in Solid Tumors (PERCIST) in clinical trials.

A rare case of recurrent group A streptococcal vulvovaginitis in a premenopausal woman.

A rare case of recurrent group A streptococcal vulvovaginitis in a premenopausal woman.

Evaluation of treatment patterns, healthcare resource utilization, and costs among patients receiving treatment for cytomegalovirus following allogeneic hematopoietic cell or solid organ transplantation

Aim Management of cytomegalovirus (CMV) infection/disease in transplant recipients may be complicated by toxicities and resistance to conventional antivirals, adding to the overall healthcare burden. We characterized treatment patterns, healthcare resource utilization (HCRU), and costs to elucidate the healthcare burden associated with CMV therapies post-transplant. Materials and methods A retrospective, longitudinal cohort study of transplant recipients using data from a US commercial insurance claims database (2013–2017) was conducted. Patients with a claim for post-transplant CMV diagnosis and anti-CMV treatment (ganciclovir, valganciclovir, foscarnet, or cidofovir) were identified (Treated CMV cohort) and compared with patients with neither a claim for CMV diagnosis nor anti-CMV treatment (No CMV cohort) for outcomes including HCRU and associated costs. Allogeneic hematopoietic cell transplantation (HCT) or solid organ transplantation (SOT) recipients were analyzed separately. Anti-CMV treatment patterns were assessed in the Treated CMV cohort. Costs were evaluated among subgroups with myelosuppression or nephrotoxicity. Results Overall, 412 allogeneic HCT and 899 SOT patients were included in the Treated CMV cohorts, of which 41.7% and 52.5%, respectively, received multiple antiviral courses. Treated CMV cohorts compared with No CMV cohorts had higher mean monthly healthcare visits per patient (allogeneic HCT: 8.83 vs 6.61, SOT: 5.61 vs 4.45) and had an incremental adjusted mean monthly cost per patient differences of $8,157 (allogeneic HCT, p < .004) and $2,182 (SOT, p < .004). Among Treated CMV cohorts, HCRU and costs increased with additional CMV antiviral treatment courses. Mean monthly costs were higher for patients with than without myelosuppression or nephrotoxicity. Limitations Results may not be generalizable to patients covered by government insurance or outside the USA. Conclusions CMV post-transplant managed with conventional treatment is associated with substantial HCRU and costs. The burden remains particularly high for patients requiring multiple treatment courses for post-transplant CMV or for transplant recipients who develop myelosuppression or nephrotoxicity.

Effectiveness and safety of artesunate\u2013amodiaquine versus artemether\u2013lumefantrine for home-based treatment of uncomplicated Plasmodium falciparum malaria among children 6\u2013120\xa0months in Yaound\xe9, Cameroon: a randomized trial

BackgroundMany studies have reported high efficacy and safety of artesunate-amodiaquine (AS-AQ) and artemether-lumefantrine (AL) when administered under direct observation in Cameroon. There is paucity of data to support their continuous use in home-based treatment of uncomplicated Plasmodium falciparum malaria in Cameroon. Hence, this study aimed to assess the effectiveness and safety of AS-AQ versus AL for home-based treatment of uncomplicated P. falciparum malaria among children 6–120 months in Yaoundé, Cameroon.MethodsA two-arm, open-label, randomized, controlled trial comparing the equivalence of AS-AQ (experimental group) and AL (control group) was carried out from May 2019 to April 2020 at two secondary hospitals in Yaoundé. Participants were randomized to receive either AS-AQ or AL. After the first dose, antimalarial drugs were given at home, rather than under direct observation by a study staff. The conventional on-treatment and post-treatment laboratory and clinical evaluations were not done until day 3 of the full antimalarial treatment course. The evaluation of effectiveness was mainly based on per protocol polymerase chain reaction adjusted adequate clinical and parasitological response (PP PCR adjusted ACPR) on day 28 post-treatment. Safety was based on assessment of adverse events (AEs) and severe adverse events (SAEs) from day 1 to day 28.ResultsA total of 242 children were randomized to receive AS-AQ (n = 114) and AL (n = 128). The PP PCR adjusted day 28 cure rates were [AS-AQ = 96.9% (95% CI, 91.2–99.4) versus AL = 95.5% (95% CI, 89.9–98.5), P = 0.797]. Expected mild to moderate adverse events were reported in both arms [AS-AQ = 83 (84.7%) versus AL = 99 (86.1%), P = 0.774]. The most common adverse events included: transient changes of hematologic indices and fever.ConclusionsThis study demonstrated that AS-AQ and AL are effective and safe for home management of malaria in Yaoundé. The evidence from this study supports the parallel use of the two drugs in routine practice. However, the findings from this study do not describe the likely duration of antimalarial effectiveness in holoendemic areas where multiple courses of treatment might be required.Trial registration: This study is a randomized controlled trial and it was retrospectively registered on 23/09/2020 at ClinicalTrials.gov with registration number NCT04565184.

Follicular Lymphoma: a Focus on Current and Emerging Therapies

Follicular lymphoma (FL) is the most common indolent lymphoma and is characterized by a relapsing and remitting course. In addition to significant biologic heterogeneity, the clinical trajectory for patients is variable, with some being observed for many years, and others having aggressive disease requiring multiple treatment courses. Unfortunately, FL remains incurable, and continues to cause early mortality. Improved understanding of the genetic and immune biology of FL has led to several FDA-approved therapies in the relapsed and refractory setting, including PI3K inhibitors; immunomodulatory agents; the EZH2 inhibitor, tazemetostat; and anti-CD19 chimeric antigen receptor (CAR) T-cell therapy, axicabtagene ciloleucel. This review outlines the current approach to the diagnosis and treatment of FL with a focus on emerging investigational therapies, including targeted protein inhibitors, antibody-drug conjugates, monoclonal antibodies, bispecific antibodies, and novel combination strategies.

The impact of anti-CD20-based therapy on hypogammaglobulinemia in patients with follicular lymphoma

Although treatment with anti-CD20 monoclonal antibodies (mAb) has improved outcomes in B-cell malignancies, it’s associated with increased risk of hypogammaglobulinemia (HG). Our study aimed to determine the effects of anti-CD20 mAb on serum immunoglobulins (Ig) in follicular lymphoma (FL). Ig concentrations, infectious complications, and need for intravenous Ig were evaluated by level of exposure to anti-CD20 mAb in 380 patients. Prevalence of HG significantly differed by level of treatment exposure (p < 0.001). Single course anti-CD20 mAb was associated with rising IgG (+10.3 mg/dL/year), whereas the addition of maintenance therapy (−7.4 mg/dL/year) or multiple courses of treatment (−10.3 mg/dL/year) was associated with declining IgG. Among patients treated with anti-CD20 mAb, 45.2% developed IgG-HG and 10.3% developed symptomatic IgG-HG. Pretreatment IgG levels gradually declined in all patients, suggesting tumor burden may contribute to HG. Baseline and periodic monitoring of serum Ig is appropriate in patients with FL, including those managed with active surveillance.

Follicular Lymphoma: a Focus on Current and Emerging Therapies

Follicular lymphoma (FL) is the most common indolent lymphoma and is characterized by a relapsing and remitting course. In addition to significant biologic heterogeneity, the clinical trajectory for patients is variable, with some being observed for many years, and others having aggressive disease requiring multiple treatment courses. Unfortunately, FL remains incurable, and continues to cause early mortality. Improved understanding of the genetic and immune biology of FL has led to several FDA-approved therapies in the relapsed and refractory setting, including PI3K inhibitors; immunomodulatory agents; the EZH2 inhibitor, tazemetostat; and anti-CD19 chimeric antigen receptor (CAR) T-cell therapy, axicabtagene ciloleucel. This review outlines the current approach to the diagnosis and treatment of FL with a focus on emerging investigational therapies, including targeted protein inhibitors, antibody-drug conjugates, monoclonal antibodies, bispecific antibodies, and novel combination strategies.