Quality of life (QoL) in head and neck cancer (HNC) is influenced by complex biopsychosocial factors, yet few longitudinal studies have examined these relationships immediately post-treatment. In this prospective study, 232 patients newly diagnosed with primary HNC completed psychometric assessments, clinical interviews, and medical chart reviews at baseline, 3, 6, and 12 months. QoL was measured using the Functional Assessment of Cancer Therapy-HNC module. A two-step cluster analysis identified distinct biopsychosocial subgroups, and mixed ANOVA tested QoL trajectories across time. Three clusters emerged: (1) early-stage disease with low treatment intensity; (2) high psychological burden and (3) advanced disease with high treatment intensity. These were associated with highest QoL, persistently lowest QoL (p < 0.001), and intermediate QoL that improved over time respectively. Psychological distress exerted a stronger influence on QoL than medical burden. Early identification and intervention for psychosocial risk factors may optimize recovery in HNC patients.

Treatment-resistant depression (TRD), affecting approximately 20% to 30% of individuals with major depressive disorder, is associated with significant disability, reduced quality of life, and an increased risk of hospitalization and suicide. Repetitive transcranial magnetic stimulation (rTMS), a noninvasive neuromodulation therapy, has demonstrated strong efficacy for TRD but is typically limited to research contexts or private clinics. Existing research on patient perspectives on rTMS is limited and largely retrospective, focusing on individuals who have already undergone treatment. As a result, little is known about the factors that influence patients' decisions to accept or decline rTMS at the time of referral, particularly within real-world clinical settings. This study aims to address the gap in the literature by prospectively examining decision-making processes surrounding rTMS in a community hospital outpatient clinic. This prospective mixed methods cohort study will recruit 30 adults with TRD referred to a public rTMS clinic. Participants will be stratified based on their decision to opt in or out of treatment. Data collection will include hybrid card sorting interviews, self-report questionnaires (assessing depression, well-being, cognitive flexibility, decisional conflict, and health literacy), and medical chart reviews. Each participant will complete a baseline and 6-month follow-up interview and survey. Qualitative data will be analyzed using constant comparative analysis, informed by bounded rationality and prospect theory. Quantitative data will be analyzed using bivariate statistics and hierarchical cluster analysis to identify patterns in decision-making factors. This study is being funded by a charitable donation from Jack and Pat Kay to Humber River Health, which is also supporting the establishment of the rTMS clinic, committed to in April 2024. Recruitment commenced in December 2025 and is expected to conclude in December 2026; no participants have been enrolled as of February 2026. To the best of our knowledge, this is the first study to prospectively examine decision-making regarding rTMS in a real-world, publicly funded clinic including both individuals who initiate and those who decline treatment. The findings may inform the development of patient educational and engagement materials and highlight gaps in patient-physician communication during the rTMS decision-making process.

Human Papillomavirus (HPV) is the most common sexually transmitted infection globally, with millions of new cases reported each year. Human Papillomavirus is associated with cervical, anal, vulva, penile, and esophageal cancer. Cervical cancer is a significant threat to women because of its insidious nature; thus, cervical cancer screening remains crucial for early detection and intervention.The most effective method to protect against HPV-related cancers is through vaccination with the HPV vaccine. The Human Papillomavirus vaccine targets the most common high-risk HPV strains. Vaccination is recommended for both males and females between the ages of 9-26. Vaccination reduces the risk of infection and contributes to the prevention of HPV-related cancers, representing a crucial public health initiative in battling HPV. The active duty military population has low HPV vaccination rates. A visit for a pap smear, the screening for cervical cancer, is an optimal time for providers to discuss the HPV vaccine. This research aims to understand the low HPV vaccination rate among active duty women and whether providers are maximizing opportunities to promote vaccination against HPV. A retrospective medical chart review was performed at a single military treatment facility (MTF) of active duty women between the ages of 21-26, who had an abnormal pap smear, and no record of receiving the HPV vaccine. A chart review was conducted for the visit in which the pap smear was performed, as well as the follow-up visit/phone call to discuss the abnormal pap smear results. Seven hundred fifty-one charts were reviewed from 2005 to 2021 of unvaccinated active duty women with an abnormal pap smear. 46.3% of the abnormal pap smears were low-grade squamous intraepithelial cells (LGSIL), whereas 3.3% were high-grade squamous intraepithelial cells (HGSIL). Of the charts reviewed, 8.3% of the patients noted they had been vaccinated; 13.8% of the charts had documented recommendations for the HPV vaccination; and 77.9% had no documentation regarding the patient's HPV status or recommendation for vaccination. Although the HPV vaccine is effective in reducing the risk of HPV-related cancers, our results indicate the need for increased awareness and education practices amongst providers in promoting the HPV vaccine.A limitation of the study was that it was conducted at a single MTF. The study was not able to distinguish between provider types or clinic settings. Possible proposals for future studies include evaluating why the HPV vaccination rates amongst the active duty population are low. Pap smears are a prime opportunity for providers to engage in discussion of the importance of the HPV vaccine and encourage adherence.

Background/Objectives: Chronic limb-threatening ischemia (CLTI) is a severe form of peripheral artery disease characterized by ischemic rest pain or ulcer necrosis. In Europe, spinal cord stimulation (SCS) can be offered to CLTI patients with chronic pain to improve mobility and prolong limb preservation. We evaluated the long-term, real-world outcomes of SCS therapy in patients with CLTI. Methods: In this observational study, medical chart review data from consecutive CLTI patients treated with SCS were analyzed. Results: Fifty-three patients (56.6% Fontaine Stage III, 39.6% Fontaine Stage IV, 3.8% Fontaine Stage IIb) had a single-stage SCS implant procedure between 2013 and 2022. Two years after SCS therapy activation, claudication pain intensity had significantly improved; the overall numerical rating scale pain score decreased from 9.4 ± 0.9 at baseline to 3.7 ± 3.2 (p < 0.0001). In addition, walking distance increased by more than 350 m (from 70 ± 87 to 429 ± 320 m, p < 0.0001), and pre-existing skin lesions stabilized in ten patients (63%). The probability of limb survival in Fontaine's stage IIb/III and Fontaine's stage IV patients at 12 months was 90% and 70%, respectively (log-rank p-value = 0.04). Finally, significant associations were found between the occurrence of an amputation after SCS and Fontaine Stage (p = 0.01), active smoking (p = 0.02), hypertension (p = 0.04), and prior minor amputation (p = 0.02). No major complications were reported. Conclusions: Our real-world experience suggests that SCS for CLTI patients provides significant and durable improvements in ischemic pain and functional outcomes. SCS may also help reduce the natural risk of major amputation, especially when implemented at early CLTI stages.

Comparative data on vedolizumab versus ustekinumab in biologic-naive patients with moderate-to-severe Crohn's disease (CD) are lacking. To compare the effectiveness and safety of vedolizumab versus ustekinumab as first-line biologic treatments in patients with CD. EVOLVE expansion (ClinicalTrials.gov, NCT05056441) was a 36-month retrospective medical chart review study in biologic-naive patients who initiated vedolizumab or ustekinumab treatment in Australia, Belgium, and Switzerland. Outcomes included clinical remission, clinical response, mucosal healing, treatment persistence, serious adverse events (SAEs), serious infections (SIs), and health care resource utilization (HCRU). Inverse probability of treatment weighting was used to account for differences in baseline characteristics between treatment groups. The study included 623 patients (vedolizumab, 347; ustekinumab, 276). During 36 treatment months, cumulative rates of clinical remission (vedolizumab, 89.8%; ustekinumab, 89.1%; P=0.829) and clinical response (vedolizumab, 82.6%; ustekinumab, 83.8%; P=0.909) were similar between groups; mucosal healing was significantly higher with vedolizumab (vedolizumab, 91.1%; ustekinumab, 88.5%; P=0.036); treatment persistence was significantly higher with ustekinumab (vedolizumab, 69.9%; ustekinumab, 80.2%; P=0.035). SIs were higher in the vedolizumab group (vedolizumab, 14 events in 9 patients, 2.8/100 patient-years; ustekinumab, 6 events in 2 patients, 0.8/100 patient-years; P=0.026). No significant differences in SAEs, CD exacerbations, CD-related surgeries, or CD-related hospitalizations were observed. In a real-world setting, clinical response, clinical remission, SAEs, and HCRU were similar in patients treated with vedolizumab and ustekinumab during 36 treatment months. Treatment persistence was higher with ustekinumab. Mucosal healing was higher with vedolizumab (see Supplemental Digital Content 1 for visual summary, http://links.lww.com/JCG/B336).

Chronic inflammation as seen in patients with primary sclerosing cholangitis (PSC) is linked to accelerated development and progression of atherosclerosis. This study aimed to assess atherosclerotic cardiovascular disease (ASCVD) risk and cardiovascular health (CVH) profiles in patients with PSC. This cross-sectional study included PSC patients with and without concomitant inflammatory bowel disease (IBD), assessing cardiovascular risk with anthropometric measurements, serum samples, self-reported questionnaires, and medical chart review. The ideal CVH score was calculated according to the American Heart Association guidelines. Comparisons across groups were analyzed using χ2 and Mann-Whitney U-test. Ninety-eight patients with PSC were included [72% male; median age 49 years, interquartile range: 34-61 years], with 65% having concomitant IBD. PSC-IBD patients exhibited higher prevalence of obesity (15% vs 0%; P= 0.016), hypertension (35% vs 21%; P= 0.069), diabetes (9% vs 3%; P= 0.525), active smokers (10% vs 3%; P= 0.253) and metabolic syndrome (8% vs 3%; P= 0.363), and lower prevalence of hypercholesterolemia (30% vs 50%; P= 0.020). Nonideal CVH was more common among PSC-IBD (46% vs 22%; P = 0.045). Ten patients had a history of 16 ASCVD events. At time of these events, at 13/16 events patients had one or more traditional ASCVD risk factors of which 77% were modifiable. One-third of PSC patients exhibit nonideal CVH, particularly PSC-IBD patients. In this cohort, 10% had prior ASCVD with mostly modifiable risk factors at time of the event. These findings suggest that PSC patients might benefit from proactive ASCVD surveillance and risk management.

Despite the rising burden of hypertension (HTN) across Africa, the rate of blood pressure (BP) control among hypertensive patients remains unacceptably low. One of the key contributors to this treatment gap is therapeutic inertia (TI) the failure to initiate or intensify therapy when clinically indicated. However, evidence on the magnitude and determinants of TI in Ethiopia remains scarce. Objective: To assess the prevalence of therapeutic inertia and identify associated factors among hypertensive patients attending the outpatient department of Wolaita Sodo University Comprehensive Specialized Hospital. A hospital-based cross-sectional study was conducted among 189 hypertensive patients from August to November 2023. Participants were selected through consecutive sampling. Data were collected via interviews with patients and physicians, along with a review of medical charts. Descriptive statistics (frequencies, percentages, means ± SD, and medians with interquartile ranges) were used to summarize patient characteristics. Bivariate and multivariable logistic regression analyses were performed to identify factors associated with TI. Adjusted odds ratios (AORs) with 95% confidence intervals (CIs) were reported. Of the 189 patients, 50.8% were male, with a mean age of 53.8years. The prevalence of therapeutic inertia was 58.7% (95% CI: 52.3%-65.4%). Factors significantly associated with lower odds of TI included treatment with amlodipine (AOR = 0.137; 95% CI: 0.019-0.975), use of NPH insulin (AOR = 0.174; 95% CI: 0.036-0.833), and higher diastolic BP readings (AOR = 0.910; 95% CI: 0.839-0.986). In contrast, physician-reported reasons for not intensifying treatment such as "BP being close to the target value" (AOR = 6.074; 95% CI: 1.315-28.060) and "concerns about patient adherence" (AOR = 5.487; 95% CI: 1.061-28.362) were positively associated with TI. Therapeutic inertia was observed in nearly 6 out of 10 cases of uncontrolled hypertension in this setting, highlighting a significant gap in clinical decision-making. Addressing therapeutic inertia through improved adherence to hypertension treatment guidelines and strengthened physician education may help improve blood pressure control in similar settings. Stakeholders should implement systems that support timely treatment intensification and encourage adherence to evidence-based management strategies.

To report on the Italian validation of the Child Epilepsy Quality of Life Questionnaire (CHEQOL-25), including both the child self-report and parent-proxy versions. The validation procedure was conducted at a single Italian centre between July 2024 and July 2025, involving 252 children with epilepsy and their parents. A forward-backward translation process was carried out in line with established best-practice guidelines. Data collection included family interviews and medical chart reviews. Psychometric evaluation covered reliability and validity. All items exceeded the accepted thresholds (≥ 0.78) for both content validity and comprehensibility. The factor structure closely replicated the original five-factor model, with certain items showing stronger loadings than the original study within the Interpersonal/Social and Intrapersonal/Emotional domains in both related versions. The Secrecy factor showed greater variability (h2=0.06-.83), possibly reflecting differences in parental interpretation or their sensitivity to the epilepsy concealment. Children who engaged in playful activities scored higher across most subscales, particularly in the Interpersonal/Social and the Quest for Normality domains of the self-report version. Importantly, children not receiving school support reported higher scores across several subscales, suggesting fewer perceived psychosocial challenges. Agreement between child self-reports and parent proxy-reports ranged from moderate to strong (ICC = 0.53-.71). The Italian version of the CHEQOL-25 measure demonstrates strong psychometric properties (consistent with the original version) and reinforces the value of assessing quality of life in children with epilepsy across diverse cultural contexts.

Active vaccine safety monitoring system using health insurance claims data in Japan: The Vaccine Effectiveness, Networking, and Universal Safety (VENUS) study.

Antiretroviral therapy (ART) has been associated with components of metabolic syndrome (MetS), including glucose intolerance, weight gain, and dyslipidemia. However, with the advent of newer agents such as dolutegravir (DTG), evidence on the burden of MetS remains limited. Therefore, this study aimed to assess the prevalence of MetS and its determinants among people living with HIV (PLWH) receiving DTG-based ART at Debre Markos Comprehensive Specialized Hospital (DMCSH), Northwest Ethiopia. An institution-based cross-sectional study was conducted from December 1, 2021, to February 28, 2022, among 422 randomly selected participants using face-to-face interviews, anthropometric assessments, medical chart reviews, and biochemical measurements. MetS was defined based on the 2009 harmonized criteria. Epi-Data version 4.6 and SPSS version 26 were used for data entry and statistical analysis, respectively. Bivariable and multivariable logistic regression analyses were employed to identify factors associated with MetS. A statistical significance was decided at P ≤ 0.05. The prevalence of MetS was 27.7% (95% CI: 23.7-32.2), with reduced high-density lipoprotein cholesterol (60.9%) was the most prevalent component. In adjusted analysis, alcohol use (AOR: 1.92; 95% CI: 1.02-3.6), inadequate physical activity (AOR: 1.7; 95% CI: 1.08-2.67), body mass index (BMI) ≥ 25 kg/m2 (AOR: 1.75; 95% CI: 1.1-2.76), and CD4+ T-cell count ≥500 cell/mm3 (AOR: 1.73; 95% CI: 1.1-2.73) were significantly associated with MetS. Overall, our study showed that MetS (27.7%) was relatively common among PLWH receiving DTG-based ART. Alcohol use, inadequate physical activity, BMI ≥25 kg/m2, and CD4 T-cell count ≥500 cell/mm3 were significantly associated with MetS. Routine clinical monitoring and assessment of all MetS components are recommended for PLWH receiving DTG-based ART, with particular attention to those who consume alcohol, have inadequate physical activity, elevated BMI, or higher CD4+ T-cell count.

Timely, accurate reporting is essential for population-based surveillance of birth defects. Searching specific diagnosis codes in hospital discharge data is standard practice for identifying potential cases; however, it lacks the confidence obtained through chart review for case confirmation. While inarguably valuable, case confirmation is time-consuming. This study aimed to assess the value of diagnosis and procedure codes for case confirmation using various combinations of ICD-10-CM/PCS codes (henceforth termed ICD-10). For birth years 2021 and 2022, Arizona used two databases for case-finding and case confirmation analysis. The authors used the Arizona Hospital Discharge Database to identify potential gastroschisis cases, querying ICD-10 codes Q793, 0WQF0ZZ, and 0WUF0JZ. Arizona's Birth Defect Registry (BDR) database represents our gold standard for true cases, as they are all confirmed via medical chart review. Arizona used standard epidemiology practices for comparing the data, focusing on positive predictive value (PPV) to compare two cohorts: Diagnosis Only and Diagnosis + Procedure. The traditional query of diagnosis code only yielded a PPV of 68.8%, whereas the new query using both diagnosis code and 1 or 2 procedure codes produced a PPV of 100.0%. The combination of codes produced results with more confidence than just the typical case-finding process, and could feasibly be used to confirm cases without chart reviews. Using the diagnosis code and procedure code simultaneously enables a more efficient gastroschisis case-confirmation process and potentially improves overall surveillance.

Acute aortic dissection (AD) and pulmonary thromboembolism (PE) are life-threatening conditions requiring timely diagnosis. In Japan, large-scale validation studies of administrative data for these diagnoses are limited. It is required to validate the accuracy of International Classification of Diseases, 10th Revision (ICD-10) codes for acute AD and PE in the Diagnosis Procedure Combination (DPC) database using medical chart review as the reference standard.We reviewed DPC data from the University of Tokyo Hospital (April 2018-March 2024). Patients with I710 (AD) or I260/I269 (PE) listed in key diagnosis fields were identified. Chart reviews confirmed diagnoses, and 199 randomly selected patients without AD/PE codes served as negative controls. Sensitivity, specificity, and positive predictive value (PPV) were calculated.Among 10,483 records, 54 had DPC-coded AD and 71 had PE. Chart review confirmed 47 cases of acute AD and 48 of acute PE. No false negatives were found among controls. For acute AD, sensitivity was 100.0% (95% CI: 92.5-100.0), specificity 96.6% (93.1-98.6), and PPV 87.0% (75.1-94.6). For acute PE, sensitivity was 100.0% (92.6-100.0), specificity 89.6% (84.9-93.3), and PPV 67.6% (55.5-78.2).ICD-10 codes in the DPC database accurately identify acute AD and PE, with particularly high sensitivity. While PPV for acute PE is lower, likely due to inclusion of chronic conditions, DPC data can be cautiously used for research and surveillance in academic hospital settings. Multicenter validation is needed to ensure broader generalizability.

Purpose: To explore the impact of age, race/ethnicity, and mental health history on the prevalence of postpartum depression (PPD) among individuals who are pregnant and using substances. Background: Associations exist between substance use during pregnancy and PPD, however it remains unclear how this varies among different age groups, racial/ethnic groups, or how mental health history influences these outcomes. PPD is one of the most prevalent morbidities related to pregnancy, affecting 13% to 19% of women who give birth. There is significant research highlighting the risks associated with PPD emphasizing the prevalence and negative outcomes for both the mother and child Methods: This study involved a retrospective review of electronic medical charts from two academic pediatric practices in the Midwestern U.S. The study included a racially, culturally, and geographically diverse sample of patients, designed to oversample those who used tobacco, marijuana, and/or opioids during pregnancy. Participants were limited to maternal-child dyads involving children born since July 2016 with pediatric medical records available through age 3, and with linked maternal prenatal and delivery records also available. All data collection for this study was performed via manual review of medical records for an extensive set of study variables for the parent study including maternal medical and background factors, and child outcomes. Patient dyads were included in the parent study if prenatal records were available for the mother, delivery records were available for both the mother and the child, and fewer than three well check appointments were missing up to one year of life for the child. For the current study, only women who used substances during pregnancy were included. The primary outcome was the development of postpartum depression in the mother. Postpartum depression was determined by maternal responses on the Edinburgh Postpartum Depression Scale (EPDS), which was administered to mothers at all pediatric well child checks up to 12 months of age at our participating practices, as well as maternal report of an outside diagnosis or treatment for PPD. A mother was considered positive for PPD if at least one EPDS score was 10 or greater, or if she reported she had been diagnosed or treated for PPD elsewhere. Primary predictors were maternal race/ethnicity, age, and mental health history, all of which were extracted from the medical records. Additional demographic and medical information were extracted for the purposes of describing the study sample and exploring additional predictors of PPD. Descriptive analyses were utilized to describe the sample, and chi-square and t-test analysis was used to examine bivariate relationships between PPD and the other study variables. To determine which variables were most predictive of PPD, logistic regression analyses was used with dichotomous PPD as the outcome, and simultaneous entry of potential predictors including maternal age, race/ethnicity, marital status, medical insurance status (income dependent vs private, a marker of SES), adequacy of prenatal care utilization, self-report and biochemically confirmed pregnancy substance use (tobacco, marijuana, and opioids), and having been diagnosed with a mental health condition prior to pregnancy. Results: The study sample contained all cases that were part of the larger Maternal-Child EMR project that involved substance use during pregnancy. Of those 185 cases, 173 had complete data on the primary predictor and outcome variables and were retained for the current report. One quarter of this sample (25.2%) was positive for PPD. In bivariate analyses, compared to those who did not experience PPD, those who did were significantly more likely to have private insurance. Overall, logistic regression analysis showed the predictors explained nearly a third of the variance in the experience of PPD (R2 = .30, p= .036). Two factors specifically were significant independent predictors of PPD, with those who had private medical insurance more than four times more likely than those with income dependent insurance to develop PPD, and those who used marijuana in pregnancy nearly three times more likely to develop PPD than those who did. After accounting for marijuana use and type of insurance and the other factors in the model, while having a prior mental health issue more than doubled the likelihood of developing PPD, this relationship was not statistically significant. Conclusions: This study underscores the multifaceted nature of postpartum depression (PPD) among pregnant individuals who use substances, revealing that marijuana use and private insurance status are significant independent predictors of PPD risk. In contrast, while age, race/ethnicity, and preexisting mental health conditions were associated with higher PPD rates, these factors did not reach statistical significance in the final model, reflecting complex interrelationships among income, mental health history, and substance use. The unexpectedly higher PPD incidence among women with private insurance may highlight potential barriers to diagnosis or treatment for low-income women in underserved areas, warranting further investigation.

Abstract Background In vitro datiderocol and newly developed β-lactam–β-lactamase inhibitors (BL–BLIs). The PROVE study enrolled patients with serious Gram-negative bacterial infections treated with cefiderocol. We compared patient characteristics, pathogens, and clinical outcomes by susceptibility status to BL–BLIs. Methods PROVE was an observational medical chart review study (November 2020–July 2024). Data from hospitalized patients with confirmed Gram-negative bacterial infections and known BL–BLI susceptibility who received cefiderocol for ≥72 hours were included. Susceptible bacteria were susceptible to all BL–BLIs tested (S); non-susceptible bacteria were resistant or intermediate to at least one BL–BLIs tested (NS): ceftazidime-avibactam, ceftolozane-tazobactam, and imipenem-relebactam. Baseline demographics, clinical characteristics, and clinical outcomes were assessed. Results Among 504 patients, those infected by NS (N=382) vs S (N=122) bacteria were older (median age 62.0 vs 56.0 years, respectively; Table 1). Proportionally, fewer patients with NS vs S bacteria had indicators of more severe disease at cefiderocol initiation (intensive care unit stay: 52.6% vs 67.2%; organ support: 39.8% vs 51.6%). Patients with S vs NS pathogens more frequently had respiratory tract infections (71.3% vs 49.2%; Table 1) and were more likely to have ≥2 risk factors for acquired CR Gram-negative bacteria (66.4% vs 58.9%; Table 2). Polymicrobial infections were more common in patients with S vs NS bacteria (45.1% vs 25.1%, respectively). Nearly all NS bacteria were carbapenem resistant. Clinical cure rates were similar in patients with NS and S bacteria (70.2% vs 70.5%, respectively). 30-day all-cause mortality was numerically lower for patients with S vs NS bacteria (18.9% vs 23.6%, respectively) (Table 2). Conclusion Clinical cure rates were similar in patients with BL–BLI-S and NS pathogens, but differences in baseline severity limit comparability. Further analyses are needed to clarify the role of cefiderocol in infections caused by NS pathogens. Disclosures Mathias W. Pletz, MD, GSK: Advisor/Consultant|GSK: Honoraria|MSD: Advisor/Consultant|MSD: Honoraria|Pfizer: Advisor/Consultant|Pfizer: Grant/Research Support|Pfizer: Honoraria|Shionogi: Advisor/Consultant|Shionogi: Honoraria Maria Cruz Soriano Cuesta, MD, Gilead: Advisor/Consultant|Gilead: Honoraria|MSD: Advisor/Consultant|MSD: Honoraria|Mundipharma: Advisor/Consultant|Mundipharma: Honoraria|Pfizer: Advisor/Consultant|Pfizer: Honoraria|Shionogi: Advisor/Consultant|Shionogi: Honoraria|Viatris: Advisor/Consultant|Viatris: Honoraria Stefano Verardi, MD, Shionogi BV: Employee Karan Gill, Master of Science, Shionogi BV: Employee Anne Santerre Henriksen, PHD, Shionogi BV: Advisor/Consultant Sean T. Nguyen, PharmD, Shionogi Inc: Employee

BackgroundThe PROVE study enrolled 508 patients in the USA with serious Gram-negative bacterial infections treated with cefiderocol in routine clinical practice. The clinical outcomes of this subset of patients were assessed.MethodsPROVE was an international, retrospective, observational medical chart review study (November 2020–July 2024). Data were analyzed from hospitalized US patients with confirmed Gram-negative bacterial infections, who received cefiderocol for the first time for ≥72 hours. Baseline demographics, clinical characteristics, cefiderocol use, clinical response, clinical cure, and all-cause mortality (ACM) were assessed.ResultsMedian (interquartile range [IQR]) age of patients was 58 (44–67) years and 61.2% were men (Table 1). The three most frequent concomitant conditions were diabetes mellitus (36.0%), chronic pulmonary disease (25.0%), and sepsis/septic shock (23.2%). Cefiderocol was given for a median (IQR) of 10 (7–16) days and as combination therapy in 33.1% of patients. At cefiderocol initiation, 57.3% of patients were in the intensive care unit and 47.6% were receiving organ support. Most patients (93.3%) had ≥1 risk factor for acquiring carbapenem-resistant (CR) Gram-negative bacteria. Respiratory tract infection (RTI) was the most common infection (n=272; 53.5%), followed by skin and skin structure infection (n=74; 14.6%) (Table 2). Overall rates of clinical cure, clinical response, and 30-day ACM were 70.1%, 77.8%, and 20.7%, respectively. Among patients with RTIs, clinical cure and 30-day ACM rates were 64.7% and 25.7%, respectively. Clinical cure rates were 73.7% (95% CI: 62.3–85.1%) when cefiderocol was used empirically and 72.3% (95% CI: 67.7–76.8%) when used for documented infections, whereas clinical cure rate was 54.3% (95% CI: 42.6–66.0%) when used as salvage therapy. Clinical cure rates for patients with Enterobacterales and Pseudomonas aeruginosa infections were 79.3% and 70.4%, with respective 30-day ACM rates of 17.2% and 20.4%.ConclusionUS patients at risk for acquiring CR infections receiving cefiderocol as salvage therapy had a lower clinical cure rate than those treated empirically or for documented infections; thus, earlier cefiderocol treatment prior to clinical decline may be beneficial for such patients.DisclosuresCornelius J. Clancy, MD, Merck: Grant/Research Support|Shionogi: Advisor/Consultant Anne Lachiewicz, MD, MPH, Basilea: Grant/Research Support|Pfizer: Grant/Research Support|Shionogi: Grant/Research Support Stefano Verardi, MD, Shionogi BV: Employee Karan Gill, Master of Science, Shionogi BV: Employee Anne Santerre Henriksen, PHD, Shionogi BV: Advisor/Consultant Sean T. Nguyen, PharmD, Shionogi Inc: Employee

Abstract Background Cytomegalovirus (CMV) infection is a risk factor for mortality in hematopoietic cell transplant (HCT) recipients. This real-world analysis describes the impact of viremia clearance on outcomes in HCT recipients with refractory/resistant (RR) CMV infection or intolerance (I) to anti-CMV agents. Methods This multicenter, retrospective, medical chart review included data from adult HCT recipients with RRI CMV in 10 transplant centers in Austria, Belgium, Greece, Poland, Serbia, Canada and Israel. Patient follow-up was ≥ 12 months from the index episode or until death. Patients with vs without viremia clearance during the first RRI CMV episode after transplant (index episode) were compared using Chi-Square or Fisher's Exact tests for categorical variables, independent t-test or Mann-Whitney U tests for quantitative variables, and Cox regression analysis for mortality. All tests were two-sided (significance level, 5%). Results Among 79 patients with a first RRI CMV episode, 60 (76%) achieved viremia clearance and 19 (24%) did not. Patient characteristics and outcomes are shown in the Table. Patients with no viremia clearance tended to have higher comorbidity index scores and receive less intensive conditioning regimens than those with viremia clearance. Intermediate/high viral load levels (≥9100 IU/mL) were detected before/at treatment start in 49% vs 31% of patients with vs without viremia clearance. In patients with vs without viremia clearance, the index CMV episode was classified as RR in 68% vs 89% and I in 32% vs 11% of patients. Graft failure occurred in 10% vs 0% and CMV-related hospitalizations in 45% vs 37% of patients with or without viremia clearance, respectively (Table). All patients without viremia clearance died vs 63% with viremia clearance, and survival time from CMV index date was significantly longer with viremia clearance (Table and Figure). Conclusion These results highlight the poor prognosis of HCT recipients with RRI CMV infection. In this difficult-to-treat population, the mortality rate was higher in patients without viremia clearance than in patients with viremia clearance, reinforcing the vital role of viremia clearance. The data should be interpreted with caution due to low patient numbers under consideration. Disclosures Johan A. Maertens, MD PhD, Amgen: Consulting fees and non-financial support|Astellas Pharma: Honoraria|Astellas Pharma: Consulting fees and non-financial support|Basilea: Consulting fees and non-financial support|Bio-Rad: Grant/Research Support|Bio-Rad: Consulting fees and non-financial support|Cidara: Consulting fees and non-financial support|F2G: Honoraria|F2G: Consulting fees and non-financial support|Gilead Sciences: Grant/Research Support|Gilead Sciences: Honoraria|Gilead Sciences: Consulting fees and non-financial support|Merck: Grant/Research Support|Merck: Consulting fees and non-financial support|Merck Sharpe &amp; Dohme: Honoraria|Mundipharma: Honoraria|Pfizer: Grant/Research Support|Pfizer: Honoraria|Pfizer: Consulting fees and non-financial support|Schering-Plough: Consulting fees and non-financial support|Scynexis: Consulting fees and non-financial support|Shire/Takeda: Consulting fees Shariq Haider, MD, FRCPC, FACP, CCST, Merck: Advisor/Consultant|Takeda: Advisor/Consultant|Takeda: Clinical Trials Matthew Cheng, MD, Amplyx Pharmaceuticals: Grant/Research Support|AstraZeneca: Honoraria|Canadian Institutes of Health Research: Grant/Research Support|Cidara Therapeutics: Grant/Research Support|Fonds de Recherche du Québec – Santé: Grant/Research Support|GEn1E Lifesciences: Advisor/Consultant|GEn1E Lifesciences: Personal fees|Kanvas Biosciences: Ownership Interest|Merck: Honoraria|Nomic Bio: Advisor/Consultant|Nomic Bio: Personal fees|Pfizer: Honoraria|Scynexis: Grant/Research Support|Takeda: Honoraria Ilaria Albieri, PhD, Takeda: Employee|Takeda: Stocks/Bonds (Public Company) François Gavini, MSc, Takeda: Employee|Takeda: Stocks/Bonds (Public Company) Tien Bo, PharmD, Takeda: Employee|Takeda: Stocks/Bonds (Public Company) Irmgard Andresen, MD, Takeda: Employee|Takeda: Stocks/Bonds (Public Company)

BackgroundCabotegravir + rilpivirine long acting (CAB +RPV LA) has demonstrated superior efficacy when compared to oral therapy in a randomized controlled trial of people with HIV (PWH) with adherence challenges (LATITUDE). Real-world adherence and clinical outcomes from PREFER-LA (Perspectives on Treatment with CAB+RPV LA Injectable Therapy from PWH in the US with Prior Adherence Challenges to Oral ART) are presented.Table 1.PWH characteristics and demographics (eCRF, n=159)Figure 1.HCP reported type adherence challenge PWH experienced when receiving their previous oral ART (eCRF, n = 159)MethodsPREFER-LA was an observational real-world US study of PWH receiving CAB+RPV LA for ≥6 months to ≤18 months with documented adherence challenges on prior oral ART. The study consisted of: (1) cross-sectional survey of PWH to evaluate experiences of historical oral ART use and perspectives of treatment with CAB+RPV LA, (2) corresponding retrospective medical chart review (eCRF) to establish treatment history and clinical outcomes, and (3) cross-sectional survey of healthcare providers (HCP) from each site.Figure 2.PWH prior ART history (eCRF)Figure 3.Viral suppression status before and after switch to CAB+RPV LA (eCRF, n = 159)ResultsMedian age of the 159 participants was 39 years and median time since HIV diagnosis was 11.7 years (Table 1). HCPs identified the type of sub-optimal adherence for each PWH for study eligibility (Figure 1). HCPs reported forgetfulness (64%) as the most common factor impacting daily oral ART adherence. From the PWH perspective, remembering to take oral ART was the most common adherence challenge (84%). For nearly 70% of PWH, CAB+RPV LA was at least their third ART regimen (Figure 2). Over 90% of PWH switched from a single tablet oral ART; bictegravir/tenofovir alafenamide/emtricitabine (59%) was the most common prior single tablet oral ART. No resistance data were available at time of switch for 38% of PWH. Nearly one quarter of PWH had a viral load >50 copies/mL at time of switch (Figure 3). At the time of evaluation, median follow-up time on CAB+RPV LA was 1 year, and viral load < 200 copies/mL was achieved/maintained in over 98% of PWH (Figure 3). Missed/skipped/delayed CAB+RPV LA injections were uncommon (13%).ConclusionIn this cohort of PWH with documented adherence challenges to oral ART, virological control was achieved/maintained by most after switching to CAB+RPV LA. These real-world findings complement existing clinical trial and real-world evidence regarding use of CAB+RPV LA in PWH with identified adherence challenges on prior oral ART.DisclosuresAll Authors: No reported disclosures

BackgroundBroad spectrum antibiotic (BSA) use within the Yale New Haven Health System (YNHHS) is evaluated daily as part of pharmacist workflow. To prompt evaluation of these antibiotics, the electronic medical record (EMR) alerts pharmacists and providers based on use greater than 48 hours and all expiring/expired BSA orders placed. Pharmacists are expected to document according to these alerts using a template designed to determine therapy appropriateness and encourage antibiotic stewardship interventions. The objective of this research was to assess overall compliance with and quality of documentation to better understand antibiotic stewardship challenges and identify opportunities for improvement.MethodsThis was a quality improvement assessment with same-day, concurrent medical chart review at all five hospitals within YNHHS. Patients admitted from October 1, 2024, through November 15, 2024 who had orders for BSA (ceftriaxone, ceftazidime, cefepime, or piperacillin-tazobactam) greater than 48 hours and/or had expiring/expired antibiotic orders were included. To monitor overall compliance, evaluation of the total number of alerts per day and number of alerts documented were assessed three times per week. To assess the quality of documentation, 10 random patient charts were reviewed each week at each site for appropriate utilization of the prespecified template. Data collection obtained from the EMR included patient demographics, current antibiotics, indication, day of therapy, culture results, pharmacist assessment, intervention, and follow-up.ResultsTwo hundred patient charts were reviewed. Overall compliance with the specific note template was 31%. When the template was used, ten interventions (16%) were made to de-escalate antibiotics, and five interventions (8%) were made to discontinue antibiotics. Forty-seven recommendations (76%) were made to continue antibiotics as they were deemed appropriate or additional information was needed prior to intervening.ConclusionCompliance with the pharmacist BSA note template was low. The combined effort of providers and pharmacists is needed to promote optimal antimicrobial stewardship efforts. Meeting with frontline pharmacists to adjust the note may increase compliance and therefore number of interventions.DisclosuresAll Authors: No reported disclosures

Hypofractionated short course radiation therapy for recurrent ovarian cancer

sObjectiveTo assess prevalence and associated factors of adverse childhood experiences (ACEs) among patients with severe mood disorders (SMDs).DesignAn institution-based cross-sectional study.SettingGedeo Zone Public Hospitals, Southern Ethiopia.Participants374 patients with SMDs were recruited using a systematic sampling technique.Primary and secondary outcome measuresThe data were collected using an interview-administered questionnaire and medical chart review. The outcome variable was assessed using the ACEs questionnaire. Data were coded and entered into Epi Data 3.1 and analysed using SPSS V.26. Bivariate and multivariable logistic regression analyses were performed to identify factors associated with ACEs. The presence of an association was examined using an adjusted OR (AOR) with a 95% CI. Variables with P-values less than 0.05 were considered a statistically significant association.ResultsThe overall prevalence of ACEs among patients with SMDs was 51.6% (95% CI 49.2 to 53.9), and the prevalence of ACEs among patients with severe bipolar disorders and depressive disorders was 14.7% with (95% CI 46.8 to 52.4) and 36.9% with (95% CI 46.7 to 55.8), respectively. Having low socioeconomic status (SES) (AOR=2.04 (95% CI 1.40 to 3.45), poor social support (AOR=2.43 (95% CI 1.74 to 4.17)), low resilient coping strategies (AOR=1.48 (95% CI 1.21 to 2.83)) and severity of depressive symptoms (AOR=3.82 (95% CI 2.89 to 6.00)) were significantly associated with ACEs.ConclusionThis study reveals a high prevalence of ACEs among patients with SMDs, with more than half of the participants reporting at least one ACE. Low SES, low resilient coping strategies and poor social support were factors significantly associated with ACEs, and severe depressive symptoms were significantly associated with ACEs. Therefore, these findings underscore the importance of early screening and appropriate intervention for SMDs and ACEs, and providing more holistic mental healthcare for SMDs and ACEs, improving access to education and economic support, strengthening social support networks, enhancing resilience-building programmes and integrating routine ACEs assessments into mental health evaluations could potentially contribute to improved clinical outcomes and support long-term recovery.Trial registrationNot applicable