Difference In Treatment Failure Research Articles

Low Anti-Tumor Necrosis Factor Levels During Maintenance Phase Are Associated With Treatment Failure in Children With Crohn's Disease.

Higher drug levels and combination therapy with low-dose oral methotrexate (LD-MTX) may reduce anti-tumor necrosis factor (TNF) treatment failure in pediatric Crohn's disease. We sought to (1) evaluate whether combination therapy with LD-MTX was associated with higher anti-TNF levels, (2) evaluate associations between anti-TNF levels and subsequent treatment failure, and (3) explore the effect of combination therapy on maintenance of remission among patients with therapeutic drug levels (>5 µg/mL for infliximab and >7.5 µg/mL for adalimumab). We conducted a post hoc analysis of the COMBINE trial, which compared anti-TNF monotherapy to combination therapy with LD-MTX. We included participants who entered maintenance therapy and provided a serum sample approximately 4 months from randomization. Among 112 infliximab and 41 adalimumab initiators, median drug levels were similar between combination therapy and monotherapy (infliximab: 8.8 vs 7.5 μg/mL [P = .49]; adalimumab: 11.1 vs 10.5 μg/mL [P = .11]). Median drug levels were lower in patients experiencing treatment failure (infliximab: 4.2 vs 9.6 μg/mL [P < .01]; adalimumab: 9.1 vs 12.3 μg/mL [P < .01]). Among patients treated with infliximab with therapeutic drug levels, we observed no difference in treatment failure between participants assigned monotherapy or combination therapy. Among patients treated with adalimumab, a trend towards reduced treatment failure in the combination therapy arm was not statistically significant (P = .14). LD-MTX combination was not associated with higher drug levels, but higher drug levels were associated with reduced risk of treatment failure. Among patients with therapeutic drug levels, we observed no benefit of LD-MTX for patients treated with infliximab. A nonsignificant trend towards reduced treatment failure with the addition of LD-MTX patients treated with adalimumab warrants further investigation.

Drug-resistant tuberculosis treatments, the case for a phase III platform trial.

Most phase III trials in drug-resistant tuberculosis have either been underpowered to quantify differences in microbiological endpoints or have taken up to a decade to complete. Composite primary endpoints, dominated by differences in treatment discontinuation and regimen changes, may mask important differences in treatment failure and relapse. Although new regimens for drug-resistant tuberculosis appear very effective, resistance to new drugs is emerging rapidly. There is a need for shorter, safer and more tolerable regimens, including those active against bedaquiline-resistant tuberculosis. Transitioning from multiple regimen A versus regimen B trials to a single large phase III platform trial would accelerate the acquisition of robust estimates of relative efficacy and safety. Further efficiencies could be achieved by adopting modern adaptive platform designs. Collaboration among trialists, affected community representatives, funders and regulators is essential for developing such a phase III platform trial for drug-resistant tuberculosis treatment regimens.

Efficacy of Antibiotic Regimens for Pneumonia in Young Infants Aged 0-59 Days: A Systematic Review.

Pneumonia is a leading cause of death in young infants. To evaluate the efficacy of different antibiotic regimens to treat young infant pneumonia on critical clinical outcomes. MEDLINE, Embase, CINAHL, World Health Organization (WHO) Global Index Medicus, Cochrane Central Registry of Trials. We included randomized controlled trials of young infants aged 0 to 59 days with pneumonia (population) comparing the efficacy of antibiotic regimens (intervention) with alternate regimens or management (control) on clinical outcomes. We extracted data and assessed risk of bias in duplicate. We used Grading of Recommendations, Assessment, Development, and Evaluation to assess certainty of evidence. Trials were heterogeneous, which precluded data pooling. Of 2601 publications screened, 10 randomized controlled trials were included. Seven trials were hospital-based (n = 869) and 3 were nonhospital-based (n = 4329). No hospital-based trials evaluated WHO-recommended first-choice regimens. One trial found the WHO-recommended second-choice antibiotic, cefotaxime, to have similar rates of treatment success as non-WHO-recommended regimens of either amoxicillin-clavulanate (RR 0.99, 95% confidence interval 0.82-1.10) or amoxicillin-clavulanate/cefotaxime (RR 1.02, 95% confidence interval 0.86-1.12). Among 3 nonhospital-based trials comparing oral amoxicillin to alternate regimens to treat isolated tachypnea among infants aged 7-59 days, there were no differences in treatment failure between amoxicillin and alternate regimens. Certainty of evidence was low or very low for all primary outcomes. We found limited evidence to support the superiority of any single antibiotic regimen over alternate regimens to treat young infant pneumonia.

Antibiotic Eluting Bone Void Filler Versus Systemic Antibiotics For Pedal Osteomyelitis

Osteomyelitis complicates 20% of patients with infected diabetic foot ulcers. In this study, two strategies for treating pedal osteomyelitis were compared in a pilot study.This was a retrospective, non-randomized, single center 2 arm cohort study, conducted between 2020-2022 involving 53 patients at a tertiary limb salvage unit. All patients were managed with debridement and proximal bone biopsy. Group A was treated with systemic antibiotics for up to 6 weeks. Group B had vancomycin or gentamycin eluting bone void filler implanted into the diseased bone medullary cavity(s) and 1 week of oral antibiotics. Patients were followed independently for the primary endpoint of osteomyelitis treatment failure and secondary endpoints of amputation free survival, wound healing, minor amputation, and treatment-limiting side-effects.Survival analysis demonstrated no significant difference in treatment failure (p=0.35) or amputation free survival (p=0.46). Limb salvage rates were 88% in Group A and 89% in Group B. Wounds healed in 85% in Group A and 89% in Group B. Minor amputations occurred in 21% in Group A and 11% in Group B. Treatment limiting side effects occurred in 6% in Group A and were absent in Group B.In conclusion, the use of antibiotic eluting bone void filler appeared safe without extended systemic antibiotics in this study. Group B had fewer intravenous lines, requirement for home nursing, and treatment limiting side effects. A larger randomized controlled trial examining longer term clinical and radiological efficacy, treatment costs and side effects is warranted. Level of Clinical EvidenceThis is a retrospective cohort study, therefore the level of clinical evidence is 2.

The impact of the COVID-19 pandemic on tuberculosis treatment outcomes in 49 high burden countries

BackgroundThe COVID-19 pandemic disrupted tuberculosis (TB) health services, including treatment support and access to drugs, as patients were not able to access health facilities. While the effect of this disruption on treatment outcomes has been studied in isolated treatment centres, cities and provinces, the impact of the pandemic on TB treatment outcomes at a country and regional level has not been evaluated.MethodsWe used treatment outcomes for new and relapse TB cases reported to the World Health Organization (WHO) from 49 high TB, TB/HIV and drug-resistant TB burden countries from 2012 to 2019. We developed multinomial logistic regression models for trends in TB treatment success, failure, death and loss to follow up. We predicted TB treatment outcomes for 2020 and 2021, comparing these to observations, by computing ratios between observed and predicted probabilities. We aggregated these risk ratios (RR) for six WHO-defined regions using random-effects meta-analysis.ResultsAcross 49 countries and four TB treatment outcomes, 17 (out of 196) country-outcome pairs in 2020 and 21 in 2021 had evidence of systematic differences between observed and predicted TB treatment outcome probabilities. Regionally, only four (out of 24) region-outcome pairs had evidence of systematic differences in 2020 and four in 2021, where the European region accounted for four of these in total. Globally, there was evidence of systematic differences in treatment failure in both 2020 (RR: 1.14, 95%CI: 1.01–1.28, p = 0.0381) and 2021 (RR: 1.36, 95%CI: 1.03–1.78, p = 0.0277), deaths in 2020 (RR: 1.08, 95%CI: 1.03–1.13, p = 0.0010) and losses to follow up in 2020 (RR: 0.91, 95%CI: 0.86–0.97, p = 0.0059).ConclusionsWhile for some countries and regions there were significant differences between observed and predicted treatment outcomes probabilities, there was insufficient evidence globally to identify systematic differences between observed and expected TB treatment outcome probabilities because of COVID-19-associated disruptions in general. However, larger numbers of treatment failures and deaths on treatment than expected were observed globally, suggesting a need for further investigation.

Dental treatment outcomes in Thai children treated for severe early-childhood caries under general anaesthesia and non-pharmacological behaviour management: a retrospective study

PurposeThe aim of this study was to compare dental-treatment outcomes, oral-hygiene improvement, and patient co-operation during follow-up visits between children treated under general anaesthesia (GA) and non-pharmacological behaviour management (NP).MethodsThis retrospective study reviewed the dental chart records of healthy patients less than 71-month-old with severe early childhood caries (S-ECC) from 2008 to 2020 with at least a 6-month follow-up. The demographical data, dental-treatment outcomes, oral-hygiene status, and patient behaviour at the follow-up visits were analysed by the Mann–Whitney U test, Pearson’s Chi-square, Fisher’s exact test, Friedman test, and Wilcoxon test with a significance level of 0.05.ResultsThis study included 210 GA cases and 210 age-matched control NP cases. The GA group had a significantly higher caries experience, lower patient co-operation, poorer oral hygiene, and higher number of complex dental treatment than the NP group at baseline (p < 0.001). The number of children who had incomplete dental treatment under non-pharmacological behaviour management was higher than the GA group. After treatment, the number of new carious teeth in the NP group was significantly higher than in the GA group only at the 6-month follow-up. However, there was no significant difference in treatment failure, oral-hygiene improvement, and patient behaviour between groups.ConclusionAlthough patients in the GA group had higher dental and behaviour problems than the NP group, the overall dental-treatment outcomes, including oral hygiene and behaviour improvement, were not significantly different between groups Therefore, regular follow-up and preventive treatment in the maintenance phase are essential for children with severe early-childhood caries.

Comparative Effectiveness of Partial Gland Cryoablation Versus Robotic Radical Prostatectomy for Cancer Control

Background and objectiveThere is an absence of high-level evidence comparing oncologic endpoints for partial gland ablation, and most series used prostate-specific antigen (PSA) rather than biopsy endpoints. Our aim was to compare oncologic outcomes between partial gland cryoablation (PGC) and radical prostatectomy (RP) for prostate cancer. MethodsThis was a retrospective, single-center analysis of subjects treated with PGC (n = 98) or RP (n = 536) between January 2017 and December 2022 as primary treatment for intermediate-risk (Gleason grade group [GG] 2–3) prostate cancer. Oncologic endpoints included protocol surveillance biopsies after PGC in comparison to serial PSA testing after RP. The primary outcome was treatment failure, defined as a need for any salvage treatment or development of metastatic disease. Treatment failure and survival analyses were conducted using Cox proportional-hazard regression and Kaplan Meier survival curves. Key findings and limitationsAfter applying the inclusion/exclusion criteria, the PGC (n = 75) and RP (n = 298) groups were compared. PGC patients were significantly older (71 vs 64 yr; p < 0.001) but there were no differences in PSA, biopsy GG, or treatment year between the groups. The PGC group had higher rates of treatment failures at 24 mo (33% vs 11%; p < 0.001) and 48 mo (43% vs 14%; p < 0.001). One PGC patient (2.1%) and one RP patient (0.7%) had developed metastases by 48-mo follow-up (p = 0.4). On adjusted analysis, PGC was associated with a higher risk of treatment failure (hazard ratio 4.6, 95% confidence interval 2.7–7.9; p < 0.001). Limitations include observational biases associated with the retrospective study design. ConclusionsThis is the first comparative effectiveness study of cancer control outcomes for PGC versus RP. The results demonstrate an almost fivefold higher risk of treatment failure with PGC during short-term follow-up. Patient summaryWe compared cancer control outcomes for patients with intermediate-risk prostate cancer treated with partial prostate gland cryoablation versus radical prostatectomy. We found that partial gland cryoablation had an almost fivefold higher risk of treatment failure. Men with prostate cancer should be counseled regarding this difference in treatment failure.

Shorter versus longer duration of antimicrobial therapy for early Lyme disease: A systematic review and meta-analysis

BackgroundAntibiotic therapy for patients with early Lyme disease is necessary to prevent later-stage Lyme disease complications. This systematic review and meta-analysis compares shorter versus longer antibiotic regimens in treating early Lyme disease. MethodsA systematic search of PubMed, Embase, and Cochrane Central Register of Controlled Trials was conducted up to November 2023. We examined treatment failure, complete response, and photosensitivity. Short vs. long therapy was defined as ≤10 days vs. >10 days. Subgroup analyses included antibiotic type and varying treatment durations. Analysis utilized RStudio 4.1.2. PROSPERO registration: CRD42023423876. ResultsSeven studies, encompassing 1,462 patients, were analyzed. No significant differences in treatment failure, 12-month complete response, final visit complete response were found between short and long durations of antibiotic therapy. Subgroup and sensitivity analyses corroborated these findings. ConclusionShorter and longer antibiotic regimens for early Lyme disease show similar efficacy, highlighting the potential of ≤10-day courses, as effective treatment options.

Cefdinir vs cephalexin for the treatment of urinary tract infections: A retrospective evaluation.

Cefdinir and cephalexin are cephalosporin antibiotics commonly used in the treatment of urinary tract infections (UTIs). Their efficacy depends on achieving sufficient time with concentrations exceeding the minimum inhibitory concentration (MIC). Despite being frequently prescribed for UTIs, cefdinir has markedly lower urine penetration compared to cephalexin. It is possible that differences in pharmacokinetics could result in dissimilar efficacy between these agents; however, comparative studies of cephalosporins in UTIs are lacking. This was a retrospective comparative study of patients discharged from emergency departments within a community health system with a diagnosis of acute cystitis who were prescribed cefdinir or cephalexin. Treatment failure rates at 7 and 14 days were compared between the 2 agents using a χ2 or Fisher's exact test, as appropriate. There were no differences in overall treatment failure between the cefdinir and cephalexin groups. Treatment failure at 7 days occurred in 11.6% (n = 14) of patients in the cefdinir group and 8.3% (n = 10) of patients in the cephalexin group (P = 0.389). Treatment failure at 14 days was higher for cefdinir at 20.7% (n = 25) than for cephalexin at 11.8% (n = 14), but this difference was not statistically significant (P = 0.053). There were no differences in the rate of treatment failure in subgroup analyses of uncomplicated or complicated UTIs. The results of this study suggest that cefdinir and cephalexin have comparable efficacy for the treatment of lower UTIs. While there was a numerically higher rate of treatment failure with cefdinir, there were no significant differences in treatment failure between the agents.

The effects of flow settings during high-flow nasal cannula oxygen therapy for neonates and young children.

During neonatal and paediatric high-flow nasal cannula therapy, optimising the flow setting is crucial for favourable physiological and clinical outcomes. However, considerable variability exists in clinical practice regarding initial flows and subsequent adjustments for these patients. Our review aimed to summarise the impact of various flows during high-flow nasal cannula treatment in neonates and children. Two investigators independently searched PubMed, Embase, Web of Science, Scopus and Cochrane for in vitro and in vivo studies published in English before 30 April 2023. Studies enrolling adults (≥18 years) or those using a single flow setting were excluded. Data extraction and risk of bias assessments were performed independently by two investigators. The study protocol was prospectively registered with PROSPERO (CRD42022345419). 38 406 studies were identified, with 44 included. In vitro studies explored flow settings' effects on airway pressures, humidity and carbon dioxide clearance; all were flow-dependent. Observational clinical studies consistently reported that higher flows led to increased pharyngeal pressure and potentially increased intrathoracic airway pressure (especially among neonates), improved oxygenation, and reduced respiratory rate and work of breathing up to a certain threshold. Three randomised controlled trials found no significant differences in treatment failure among different flow settings. Flow impacts exhibited significant heterogeneity among different patients. Individualising flow settings in neonates and young children requires consideration of the patient's peak inspiratory flow, respiratory rate, heart rate, tolerance, work of breathing and lung aeration for optimal care.

The Pyogenic Hepatic Abscess: To Drain or not to Drain, that is the Question. Clinical Presentation and Outcome Evaluation after Conservative and Invasive Treatment

Background: Pyogenic hepatic abscess (PHA) is an uncommon infectious disease of the liver that should represents a life-threatening condition if not correctly diagnosed and managed. Nowadays there are not precise indications and clear evidences on the best therapeutic approach and on the superiority of a treatment. Methods: Patients with diagnosis of PHA admitted at the Policlinico “Paolo Giaccone” at Palermo University Hospital between January 2010 and December 2022 were identified in a prospective database. Among the demographic, epidemiological and clinical data collected we included the therapeutic choices – antibiotic treatment, image guided percutaneous drainage and surgical operation – and their effect in terms of healing time, treatment failure and time of hospitalization. Results: Patients with single abscesses treated with antibiotics have significant high healing time (p=0.0001) and in-hospital time (p=0.0001) and no differences in treatment failure than patients treated with invasive techniques. Patients that underwent surgical operation have significant higher healing time than percutaneous group (p=0.002) such as higher mean hospital stay (p=0.03 for abscesses &lt;5 cm and p=0.02 for abscesses larger than 5 cm). The last, the percutaneous approach shows a failure rate significantly higher than the surgical procedure (p=0.009 for abscesses &lt;5 cm and p=0.001 for abscesses larger than 5 cm). Conclusions: The study proposed showed the antibiotic therapy is the first line treatment and should first empirically and then directly modified on specimen culture results. Image guided percutaneous drainage should be considered when the antibiotic therapy alone is not sufficient or as bridge to surgery if surgical indications are proven.

A Randomized Controlled Trial Comparing Ultrasonography-Guided Needle Aspiration and Surgical Drainage for the Management of Breast Abscess.

Background A breast abscess is a localized collection of inflammatory exudate in breast tissue. It is more common in lactating women. Treatment of the breast abscess is usually by incision and drainage, which is accompanied by extensive trauma, lengthy surgical incisions, psychological distress, surgical scar, and discomfort during dressing changes. Recent research has shown that ultrasonography-guided needle aspiration is an alternative to incision and drainage for breast abscess treatment, has superior cosmetic outcomes, and has fewer costs. However, there are no clear guidelines for the same. The primary objective of this study was to assess and contrast the outcomes and efficacy of two approaches in the treatment of breast abscesses: ultrasonography-guided needle aspiration and conventional incision and drainage. Methods This was a single-center, prospective, randomized, controlled, non-inferiority trial. Patients with breast abscesses were randomized either to receive needle aspiration or incision drainage. Patients with lactational breast abscesses were encouraged to breastfeed from either breast. The antibiotic was given for 10 days to all the patients. The study's main focus was on the primary outcome, which was the failure rate. Additionally, several secondary outcomes were examined, including postoperative pain, time required for healing, presence of residual abscess or recurrence, formation of fistulas, and the assessment of scar appearance. Results A total of 44 patients were randomized to 23 and 21 in each arm. There was no statistical difference in treatment failure (p-value=0.862), fistula formation (p-value=1.00), and recurrence (p-value=1.00). There was a significant statistical difference in healing period (p-value <0.001), scar formation (p-value <0.0001), continuation of breastfeeding (p-value=0.005), and clinical resolution (p-value=0.002). There was a significant reduction in post-intervention pain in the needle aspiration group than in the other group (p-value <0.001). Conclusion This study showed a significant difference in postoperative pain, healing time, the continuation of breastfeeding, and scar formation in the needle aspiration group, favouring minimally invasive treatment for breast abscess. However, due to the small sample size, we could not conclude that ultrasonography-guided needle aspiration of the breast abscess is non-inferior to the conventional incision and drainage.

Methicillin-Resistant Staphylococcus aureus Bacteremia Treated With Vancomycin Calculated by Area-Under-the-Curve in Patients With Elevated Vancomycin Minimum Inhibitory Concentrations.

Purpose: Vancomycin is recommended as first-line treatment of methicillin-resistant Staphylococcus aureus (MRSA) bacteremia, dosed by area-under-the-curve (AUC) with an assumed minimum inhibitory concentration (MIC) of 1 mcg/mL via broth microdilution. The purpose of this study was to compare effectiveness of AUC-based and trough-based dosing in MRSA bacteremia with an MIC > 1 mcg/mL via Etest. Methods: This was a retrospective, observational cohort that compared vancomycin dosed by AUC or trough between January 1, 2017 and September 1, 2022. The primary outcome was a composite of treatment failure defined as peristent bacteremia ≥ 7 days, inpatient mortality within 90 days, or microbiologic relapse or readmission within 30 days. Secondary outcomes compared nephrotoxicity, hospital and ICU length of stay, MIC differences, and difference in exposure measured by AUC. Results: Twenty-four patients in each group met inclusion criteria. For the primary outcome, there was no statistical difference in treatment failure between trough and AUC groups, respectively [10 (41.7%) vs 10 (41.7%), P = 1.000]. There was no statistical difference in secondary outcomes, with incidence of nephrotoxicity [3 (12.5%) trough vs 2 (8.33%) AUC, P = 1.000] and median AUC exposure over treatment course [502.9 mcg.h/mL (454.1-599.9) vs 474 mcg.h/mL (435.3-533), P = .312] similar between groups. Conclusion: There was no statistically significant difference in treatment failure for vancomycin by AUC or trough with an Etest MIC > 1 mcg/mL. Overall exposure to vancomycin and incidence of nephrotoxicty were numerically higher in the trough group, suggesting that dosing by AUC may limit exposure without impact on treatment failure.

Impact of a discharge prescription for dexamethasone on outcomes of children treated in the emergency department for acute asthma exacerbations

Objective To evaluate dexamethasone prescribing practices, patient adherence, and outcomes by dosing regimen in children with acute asthma discharged from the emergency department (ED). Study design Prospective study of children 2–18 years treated with dexamethasone for acute asthma prior to discharge from an urban, tertiary care ED between 2018 and 2022. Demographics, clinical characteristics, ED treatment, and discharge prescriptions were collected via chart review. The exposure was discharge prescription (additional dose) versus no discharge prescription for dexamethasone. The primary outcome was treatment failure, defined as return ED visit, unplanned primary care visit, and/or ongoing bronchodilator use. Secondary outcomes included medication adherence, symptom persistence, quality-of-life, and school/work absenteeism. Outcomes were assessed by telephone 7–10 days after discharge. Results 564 subjects were enrolled; 338 caregivers (60%) completed follow-up. Children were a median age 7 years, 30% Black or African American, 49% Hispanic, and 79% had public insurance. A discharge prescription for dexamethasone was written for 482 (86%) children and was significantly associated with exacerbation severity, number of combined albuterol/ipratropium treatments, and longer length of stay. There was no difference in treatment failure between the discharge prescription and no discharge prescription groups (RR 0.87; 0.67, 1.12), including after adjusting for potential confounders; there was no difference between groups in secondary outcomes. Conclusions Prescription for an additional dexamethasone dose was not associated with reduced treatment failure or improved outcomes for children with acute asthma discharged from the ED. Single, ED-dose of dexamethasone prior to discharge may be sufficient for children with mild to moderate asthma exacerbations.

Comparison of Characteristics of Chronic Myeloid Leukemia Combined with Different Degrees of Myelofibrosis : A Real-World Multicenter Retrospective Study from China

Chronic myeloid leukemia (CML) is a hematological malignancy characterized by excessive proliferation of myeloid cells, which belongs to the group of myeloproliferative neoplasms (MPNs). Myelofibrosis (MF) is a significant prognostic indicator of CML, and its discovery at the time of diagnosis aids in decisions regarding the patient's course of treatment, according to a descriptive cross-sectional study. Nevertheless, the influence of MF is not clear. Our study is to investigate clinical characteristics and prognosis of CML pantients with different degrees of myelofibrosis, exploring the influence of MF. We retrospectively analyzed 1757 CML patients with bone marrow biopsy results and compared the characteristics of CML combined with different degrees of MF in 44 Chinese institutions from January 2010 to October 2022(ChiCTR2200061208). A total of 1757 CML patients with MF, including 1090 males (62.0%) and 667 females (38.0%) with a median age of 49 (6-92) years. 1757 CML patients were treated with TKIs, as shown in the picture ( Figure A).The median WBC count was 119.8×10 9/L (0.1-910.8×10 9/L) in peripheral blood at diagnosis, the median HB level was 111.5 g/L (12.6-181 g/L), the median PLT count was 512.1×10 9/L (5-4384×10 9/L), the median EOS% was 3.3% (0.0-31.1%), the median BAS% was 4.3% (0.0-19.0%), the median spleen size was 4.10 cm (0.0-26.0 cm). Patients with MF were older (p&amp;lt;0.001); had higher leukocyte counts (p&amp;lt;0.001) and platelet counts (p&amp;lt;0.001); were more prone to anemia (p&amp;lt;0.001), acidophilia (p&amp;lt;0.001), alkalophilia (p&amp;lt;0.001), and splenomegaly (p&amp;lt;0.001); and a higher proportion of peripheral blood blast cells (p&amp;lt;0.001). There was no significant difference between the two groups in the male to female ratio. Patients without MF were more likely to reach 3-month EMR (p&amp;lt;0.001), 6-month BCR::ABL IS ≤ 1% (p&amp;lt;0.001), and 12-month MMR (p&amp;lt;0.001). The proportion of medium / high-risk patients with MF according to the Sokal score (p&amp;lt;0.001), Hasford score (p&amp;lt;0.001), ELTS score (p&amp;lt;0.001) and EUTOS score (p=0.002) was significantly increased ( Figure B). CML patients with MF had lower OS and PFS than patients without MF (p=0.007, p=0.006, Figure D, E). CML patients with MF were more prone to treatment failure with imatinib as the first-line treatment (p&amp;lt;0.001, Figure F). There was no statistically significant difference in treatment failure between first-generation TKI (1G-TKI) and second-generation TKI (2G-TKI) (p=0.222, Figure G).With increasing degree of MF, CML patients had higher leukocyte counts were more susceptible to anemia and splenomegaly, and had more peripheral blood blast cells. However, there was no significant difference in sex ratio, age, platelets, eosinophils, and basophils. CML patients without MF were more likely to achieve 3-month EMR, 6-month BCR::ABL IS ≤ 1%, and 12-month MMR. As the degree of MF increased, the proportion of intermediate / high risk patients according to Sokal score, Hasford score, and ELTS score increased significantly ( Figure C), OS and PFS of CML patients decreased (p&amp;lt;0.001, p&amp;lt;0.001, Figure H, I) and the failure rate of first-line treatment increased (p&amp;lt;0.001, p&amp;lt;0.001, Figure J, K). In conclusion, we performed 1757 CML patients with MF and compared the characteristics of CML combined with different degrees of MF. As the degree of MF increased, the proportion of intermediate / high risk patients according to Sokal score, Hasford score, and ELTS score increased, the efficacy of TKIs was lower, the prognosis of patients was worse. So MF is an independent risk factor affecting the prognosis of patients with CML. Acknowledgement: This research was funded by the Key R&amp;D Program of Zhejiang, No. 2022C03137; Public Technology Application Research Program of Zhejiang, China, No. LGF21H080003; Zhejiang Medical Association Clinical Medical Research special fund project, No. 2022ZYC-D09. *Correspondence to: Dr Jian Huang, Department of Hematology, The First Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou 310003,Zhejiang, Peoples R China.E-mail: househuang@zju.edu.cn

Trimethoprim-Sulfamethoxazole for Pediatric Osteoarticular Infections.

Trimethoprim-sulfamethoxazole (TMP-SMX) is active against most Staphylococcus aureus isolates but is not widely used for treatment of pediatric osteoarticular infections. This was a comparative effectiveness study of hospitalized patients ≤18 years treated with TMP-SMX versus other antibiotic regimens for acute osteoarticular infections between 2016 and 2021 at three hospitals using inverse probability of treatment weighted propensity score analysis. The primary outcome was treatment failure, a composite of unanticipated emergency department (ED) or outpatient visits, hospital readmissions, extension or change of antibiotic therapy due to inadequate clinical response, or death, all within 6 months after completing antibiotics. The secondary outcome was antibiotic-associated adverse events (AEs) within 6 months. The exposed group for the treatment failure analysis included children who received ≥7 days of TMP-SMX and did not experience treatment failure while on another antibiotic. Children receiving at least one dose of TMP-SMX were the exposed group for the AE analysis. 116 patients met eligibility criteria; 26 (22.4%) patients were classified into the TMP-SMX cohort and 90 (77.6%) into the other antibiotics cohort (most commonly clindamycin, vancomycin, and cefazolin). There was no significant difference in treatment failure between TMP-SMX and other antibiotics (43% vs 19%; 95% CI 0.9-10.4). More patients in the TMP-SMX cohort experienced an unplanned ED or outpatient visit (OR 4.8, 95% CI 1.3-17.8). There was no difference in hospital readmission, antibiotic change, or duration extension. Exposure to TMP-SMX was associated with more AEs (41% vs 19%, p=0.012). Treatment with TMP-SMX was not associated with greater clinical failure but was associated with more AEs compared to alternative agents for the treatment of pediatric acute osteoarticular infections.

Anal Cancers in Previously Screened Versus Unscreened Patients: Tumor Stage and Treatment Outcomes.

Targeted screening programs for patients at high risk for anal squamous cell carcinoma have been proposed; however, the evidence in support of screening remains unclear. This study aimed to determine whether screening high-risk patients (predominantly those living with HIV) detected squamous cell carcinoma at an earlier stage compared to the routine practice of not screening. This is a cohort study. This study was conducted at a quaternary care center in Canada. Included patients were at least 18 years old with a pathologic diagnosis of invasive anal squamous cell carcinoma between 2002 and 2022. Patients diagnosed through a high-risk screening program were compared to those who did not undergo screening. The primary outcome was clinical stage at presentation, categorized as T1N0M0 vs. other. Secondary outcomes included treatments received, treatment failure, and overall survival. A total of 612 anal squamous cell carcinoma patients were included, with 26 of those patients diagnosed through a screening program. Patients with screen-detected cancers had greater odds of presenting with T1N0M0 tumors compared to unscreened patients (18 [69.2%] vs. 84 [14.3%]; adjusted odds ratio 9.95; 95% confidence interval 3.95-25.08). A propensity score matched sensitivity analysis found similar results (odds ratio 11.13; 95% confidence interval 4.67-26.52; p < 0.001). Screened patients had greater odds of treatment with wide local excision alone, as opposed to any combination of chemotherapy, radiation, and surgery (3 [12.5%] vs. 18 [3.2%]; odds ratio 4.38; 95% confidence interval 1.20-16.04). There were no statistically significant differences in treatment failure or overall survival between groups. The small number of screened patients limits the power of the analysis. Screening for anal squamous cell carcinoma amongst high-risk populations detects cancers at an earlier stage. Patients with screen-detected cancers also had a greater likelihood of being candidates for wide local excision alone, which may have spared them the morbidity associated with chemoradiotherapy or abdominoperineal resection.

Two Times Versus Four Times Daily Cephalexin Dosing for the Treatment of Uncomplicated Urinary Tract Infections in Females.

The current treatment guidelines of the Infectious Diseases Society of America recommend β-lactam antibiotics as alternative rather than first-line agents for the treatment of uncomplicated urinary tract infection (uUTI). Cephalexin is a commonly prescribed first-generation cephalosporin with excellent bioavailability and urinary penetration; however, little data exist to support optimal dosing for uUTI. This retrospective multicenter cohort study included adult female patients who received 5 to 7 days of cephalexin for symptomatic uUTI with a cefazolin-susceptible urine culture. The primary objective was to compare uUTI treatment failure (eg, continued or recurrent symptoms within 30 days) between patients treated with cephalexin 500 mg twice daily (BID group) and 500 mg 4 times daily (QID group) in the outpatient setting. Secondary outcomes included time to treatment failure, reported adverse events within 7 days of treatment, and occurrence of Clostridioides difficile within 30 days of treatment. A total of 261 patients were included (BID, n = 173; QID, n = 88). Baseline characteristics were similar between the groups. Escherichia coli was the most commonly isolated pathogen (85.4%). There was no difference in treatment failure observed between the groups (BID 12.7% vs QID 17%, P = .343), including failure while undergoing therapy (BID 2.3% vs QID 5.7%, P = .438) or recurrence within 30 days (BID 10.4% vs QID 11.3%, P = .438). No differences in reported adverse events (BID 4.6% vs QID 5.6%, P = .103) were observed between groups. Twice-daily cephalexin is as effective as 4-times-daily dosing for uUTI. A twice-daily dosing strategy may improve patient adherence.

High flow nasal cannula for respiratory support in term infants.

High flow nasal cannula for respiratory support in term infants.

17th International Conference on Malignant Lymphoma, Palazzo dei Congressi, Lugano, Switzerland, 13 - 17 June, 2023.

Introduction: High dose chemotherapy/autologous stem cell transplantation (ASCT) and CD19-directed chimeric antigen receptor-modified T cells (CART19) are potentially-curative treatment options for patients (pt) diagnosed with relapsed/refractory (R/R) diffuse large B cell lymphoma (DLBCL) and high grade B cell lymphoma (HGBL). Analysis of a large series of pt receiving ASCT and/or CART19 has not been performed and may reveal differences in treatment failure (TF) which could inform efforts to optimize pt selection for these therapies. Methods: Included pt were age ≤75 years who received ASCT and/or CART19 for R/R DLBCL/HGBL at the University of Pennsylvania between 3/1/13 and 3/1/21. All ASCT pt demonstrated either partial or complete metabolic response to salvage immunochemotherapy (IC). Freedom from TF (FFTF) was defined as the interval between receipt of cell infusion and proven/suspected relapse of lymphoma (DLBCL/HGBL for ASCT pt or any lymphoma for CART19 pt) or last follow-up (f/u) in remission. Data were censored on 3/1/23. Results: Characteristics at the time of relapse preceding ASCT or CART19 are listed in the Table. Minimum prior LOT was 1 for ASCT and 2 for CART19 pt. With a median length of f/u of 62.7 months (mo) for ASCT pt and 37.6 mo for CART19 pt, the estimated (est) rate of FFTF at 36 mo were 59% and 24%, respectively. Cox regression analysis of characteristics predictive of TF at 36 mo revealed history of tIL (hazard ratio [HR] 0.23, P = 0.016) for ASCT pt, and history of tIL (HR 0.48, P = 0.004) as well as IPI score ≥3 (HR 2.7, P < 0.001) for CART19 pt. As depicted in the Figure, ASCT pt experienced significantly higher est rates of FFTF at 36 mo if achieving actual FFTF at 3 mo (64% vs. 38%, P = 0.002), 6 mo (76% vs. 52%, P = 0.02), 12 mo (84% vs. 62%, P = 0.03) and 24 mo (95% vs. 78%, P = 0.03) post-infusion as compared to CART19 pt. For characteristics which predict for TF at 36 mo (no history of tIL and IPI score ≥3), the incidence was either similar or significantly lower for CART19 versus ASCT pt who achieved actual FFTF at 3, 6, 12 and 24 mo. Keyword: Aggressive B-cell non-Hodgkin lymphoma Conflicts of interests pertinent to the abstract. D. J. Landsburg Consultant or advisory role: Morphosys, Epizyme, Calithera, ADC Therapeutics, Karyopharm Research funding: Curis, Calithera, Epizyme Educational grants: Novartis S. D. Nasta Research funding: Pharmacyclics, Roche, Rafael, FortySeven J. Svoboda Consultant or advisory role: SEAGEN, Pharmacyclics, Incyte, Genmab, BMS, Atara, Astra Zeneca, Adaptive, ADCT Research funding: TG, SEAGEN, Pharmacyclics, Merck, Incyte, BMS, Astra Zeneca J. N. Gerson Consultant or advisory role: Genentech, Abbvie Research funding: Loxo S. J. Schuster Consultant or advisory role: Novartis, Regeneron, Nordic, Morphosys, MustangBio, Incyte, Genentech/Roche, Janssen, Legend Biotech, Loxo, Acerta, BiGene, Celgene, Nanovecter Research funding: Novartis, Pharmacyclics, Merck, DTRM, Juno Therapeutics, Abbvie, Adaptive Biotechnologies, Incyte, Genentech/Roche, Celgene, TG Therapeutics S. K. Barta Consultant or advisory role: Daiichi Sankyo, Kyowa Kirin, Janssen, Affimed Honoraria: Acrotech, Seagen, Kyowa Kirin E. A. Chong Honoraria: Juno/BMS, Novartis, Beigene, KITE, Tessa A. L. Garfall Consultant or advisory role: Jannsen, GlaxoSmithKline, Bristol-Myers Squibb Research funding: Novartis, Tmunity Therapeutics, Janssen, Crispr Therapeutics E. A. Stadtmauer Research funding: BMS, Celgene, Abbvie, Sorrento N. V. Frey Consultant or advisory role: Sana Biotechnology, Kite Pharma, Syndax Pharmaceuticals Research funding: Research Funding D. L. Porter Consultant or advisory role: Novartis, Kite/Gilead, Incyte, Janssen, Jazz, DeCart, BMS, Bluebird Bio, Angiocrine, Mirror Biologics, Capstan Therapeutics, Instill Bio Research funding: Novartis