Eligible Patients Research Articles

Medication for Opioid Use Disorder for Hospitalized Patients at Six New York City Public Hospitals with an Addiction Consult Service

Objectives We explored medications for opioid use disorder treatment (MOUD) utilization in six New York City public hospitals that implemented the “Consultation for Addiction Care and Treatment in Hospitals (CATCH)” program. Methods CATCH rolled out between October 2018 and February 2020. Data from the electronic health record were analyzed for the first year post-implementation. Eligible cases included adults with an opioid-related diagnosis admitted to inpatient departments served by CATCH, with a stay of ≥1 night. Patients were classified as receiving an MOUD order if there was at least 1 order of buprenorphine, methadone, or naltrexone. Logistic regression modeled the impact of CATCH consults on MOUD orders, controlling for demographic and clinical characteristics with hospital as a random effect. Result Among 2117 eligible patients, 71.4% were male, with a mean age of 51.2 years, and 27.2% identified as Black, 21.2% as White, and 34.5% as Hispanic. MOUD was ordered in 60.9% of admissions, and 41.5% had a completed CATCH consult. Patients identified as Black had lower odds of receiving a MOUD order than those identified as White (OR: 0.52, 95% CI: 0.38–0.71; P < 0.001). Patients with a CATCH consult had higher odds of receiving a MOUD order (OR: 3.22, 95% CI: 2.54–4.07; P < 0.001). Conclusion Majority of patients in our sample received a MOUD order, with higher odds among those with a CATCH consult. Further research is needed on the drivers of racial disparities in MOUD, and other contextual, organizational, and population-specific barriers and facilitators contributing to receipt of hospital-based addiction consult services and MOUD.

Treatment of Covid-19 Ambulatory Patients with A Medicinal Preparation of Echinacea Purpurea: The Ecco-2 Investigator-Initiated, Randomised, Double Blind, Controlled Trial

Background: The COVID-19 pandemic has affected millions throughout the entire world, causing an unprecedented disruption of the daily lives of many more millions. While vaccines have proven to be a powerful prophylactic tool co contain the spread of the disease, treatment options are very limited. Echinacea phytotherapy is known to be efficacious in the treatment of mild respiratory viral infections, therefore we and others hypothesized that it might be helpful in the treatment of ambulatory COVID-19. Purpose: To evaluate the clinical efficacy and safety of a medicinal preparation of cryo-milled root of Echinacea purpurea added to the standard-of-care (SOC) treatment in ambulatory COVID-19 patients with mild clinical symptoms, with a respiratory profile. Methods: We designed and conducted a prospective, double-blind, multicentre, randomized, controlled clinical trial involving four hospitals in Spain, from July 2021 to June 2022. Participants were ambulatory adults with COVID-19 infection, assessed by a positive PCR or antigen test, with mild symptoms of a respiratory profile. Patients were given Echinacea Arkopharma, hard caplets containing 250 mg of Echinacea purpurea (L.) Moench, 1.5 g/day (2 caplets every 8 hours, i.e., 6 g/day, 7 days) added to standard care (vide infra). Participants were followed for 28 additional days. The primary outcome of effectiveness (OE) was OE1: number of days with fever (body temperature ≥ 37ºC at any moment of the day). The secondary outcomes were OE2: days with subjective dyspnea, OE3: days with unsaturation (≤ 96%), OE4: days with disease, OE5: percentage of hospitalizations, OE6: length of hospitalization (days), OE7: days of sick leave, OE8: percentage to visits to emergency room, OE9: percentage of admissions to intensive care units, OE10: percentage of deaths, OE11: subjective perception by the recruiting physician of the treatment usefulness to improve the evolution of the disease, OE12: subjective perception by the patient of the treatment usefulness to improve the evolution of the disease. The secondary outcomes of safety (OS) were OS1: incidence of respiratory adverse effects, OS2: incidence of palpitations (> 110x'), OS3: incidence of transaminase elevations (AST level ≥ 3x the normal range limit), OS4: incidence of headaches, OS5: incidence of digestive adverse effects, OS6: incidence of insomnia and nervousness. For all cases, OS1 to OS6, percentage of dropouts for that specific reason. Results: The target recruitment number, 230, was not achieved. Rather, 99 eligible patients could be recruited (age 35.50 ± 11.9 years; 51.5 % female). They were randomised to SOC + treatment (n=50) and SOC + placebo group (n=49). There were no statistically significant differences between the treatment and placebo groups in the main variables studied, however, it should be noted that an important limitation of the study is the fact that we could not reach our recruitment target by far. Incidence of serious AEs was nil. Mild AE consisting of diarrhea were seen in 2 cases, and 1 effort- induced tachycardization, although there is no statistical evidence supporting that they were caused by the treatment. Conclusion: Echinacea, added to the SOC treatment for mild COVID-19, was safe and well tolerated but had no major impact on clinical outcomes. Some effectiveness trends suggest that further studies with full recruitment are warranted to definitively assess its efficacy in moderately affected COVID-19 patients.

Multi-institutional Analysis of Immune-Oncology Combination Therapy for Metastatic MiT Family Translocation Renal Cell Carcinoma.

Metastatic translocation renal cell carcinomas (mtRCCs) are rare and aggressive tumors with limited treatment options. Recent studies demonstrated promising activity of immune-oncology (IO) combinations in mtRCC. However, the effectiveness of dual IO combinations versus IO plus VEGF-TKI combinations remains unclear. We conducted a retrospective analysis of IO combinations in mtRCC patients at 4 institutions. Eligible patients had confirmed mtRCC by genitourinary pathologist and received IO combination therapy (IO+IO or IO+VEGF-TKI). Clinical data and treatment outcomes were recorded from the start of systemic therapy. Objective response rate (ORR) was retrospectively evaluated, and time to treatment failure (TTF), and overall survival (OS) were compared for IO+IO and IO+VEGF-TKI groups. We identified 22 mtRCC patients who received IO combinations, all confirmed to have TFE3 rearrangement by FISH. Most patients were female (68%) with a median age of 41 years (16-79). Treatment breakdown included: IO+IO (n=8, 36%) and IO+VEGF-TKI (n=14, 64%). In the evaluable patients for the efficacy analysis, ORR was 14% (1/7) for the IO+IO group and 54% (6/11) for the IO+VEGF-TKI group. With a median follow-up of 32.4 months, the median TTF was 1.2 months and 6.2 months in the IO+IO and IO+VEGF-TKI groups, respectively (P=0.12). There was no statistically significant difference in median OS between both groups, 36.7 months in the IO+IO group and 15.6 months in IO+VEGF-TKI (P=0.9). Our findings demonstrate that IO+VEGF-TKI resulted in higher ORR and TTF point estimates without statistically detectable differences, compared with IO+IO therapy. Larger studies are needed to validate these findings and optimize treatment selection.

Comparative efficacy of cetuximab combined with FOLFOX or CAPEOX in first-line treatment of RAS/BRAF wild-type metastatic colorectal cancer: a multicenter case-control study.

FOLFOX combined with cetuximab is a recommended first-line treatment regimen for RAS/BRAF wild-type metastatic colorectal cancer (mCRC). CAPEOX combined with cetuximab differs from the FOLFOX regimen by using oral capecitabine instead of continuous infusion of fluorouracil, offering greater convenience and cost-effectiveness with higher patient acceptance. However, the comparative efficacy of these two regimens remains debatable, necessitating further evidence to explore any differences in their efficacy. This study collected medical records of mCRC patients who were treated with CAPEOX or FOLFOX combined with cetuximab from 1 October 2021 to 16 October 2023 at Harbin Medical University Cancer Hospital and the First Hospital of Shanxi Medical University. Eligible patients were selected based on inclusion criteria and followed up through the hospital's follow-up system and telephone interviews. Kaplan-Meier survival analysis and Cox proportional hazards regression analysis were used to assess patients' progression-free survival (PFS) and overall survival (OS). A total of 71 eligible patients were enrolled in this study; 43 patients received CAPEOX combined with cetuximab (Group A, n = 43), and 28 patients received FOLFOX combined with cetuximab (Group B, n = 28). The two groups achieved similar median PFS (mPFS) and median OS (mOS), with mPFS of 18 months and 12 months, respectively (P = 0.23), and mOS of 33 months and 20 months, respectively (P = 0.21), with no statistically significant differences. The results of this study demonstrated that CAPEOX combined with cetuximab is an equally viable option for first-line treatment of RAS/BRAF wild-type mCRC as FOLFOX combined with cetuximab.

Upadacitinib in active non-radiographic axial spondyloarthritis: 2-year data from the phase 3 SELECT-AXIS 2 study.

In SELECT-AXIS 2, upadacitinib improved the signs and symptoms of active non-radiographic axial spondyloarthritis (nr-axSpA) through 52 weeks versus placebo and was well tolerated. Here, we evaluated the efficacy and safety of upadacitinib through 2 years. The study enrolled eligible adult patients with a clinical diagnosis of nr-axSpA who met the 2009 Assessment of SpondyloArthritis international Society (ASAS) classification criteria and had objective signs of active inflammation on magnetic resonance imaging (MRI) of sacroiliac joints and/or high-sensitivity C-reactive protein. Patients were randomized 1:1 to receive double-blinded treatment with upadacitinib 15mg once daily (QD) or placebo for 52 weeks, after which all patients received open-label treatment with upadacitinib 15mg QD. Efficacy results over 104 weeks were reported as observed (AO) and either AO with non-responder imputation (AO-NRI; binary endpoints) or AO with mixed-effect model for repeated measures (continuous endpoints). Treatment-emergent adverse events (TEAEs) were summarized through week 104. Of 313 patients randomized and treated, 224 (continuous upadacitinib n = 117; placebo/upadacitinib n = 107) completed 104 weeks of treatment. In patients who received continuous upadacitinib, sustained improvement was observed through 2 years of treatment across efficacy endpoints including disease activity, pain, function, enthesitis, quality of life, and MRI measures of inflammation. At week 104, 57.1%, 59.0%, and 31.4% of patients achieved ASAS40 response, and low disease activity and inactive disease (as defined by Axial Spondyloarthritis Disease Activity Score), respectively (AO-NRI); week 104 outcomes were generally similar in patients who initially received placebo and were switched to upadacitinib at week 52. In total, 286 patients were exposed to ≥ 1 dose of upadacitinib, comprising 378.3 patient-years (PY) of exposure. Upadacitinib was generally well tolerated, with exposure-adjusted event rates (EAERs) for TEAEs, serious adverse events (AEs), and AEs leading to study drug discontinuation of 207.5, 8.7, and 5.3 events/100 PY, respectively. EAERs of TEAEs of special interest were broadly consistent with those reported through week 52. Treatment with upadacitinib demonstrated consistent improvement and maintenance of treatment effect across efficacy endpoints through 2 years; no new safety signals were identified with additional exposure. NCT04169373.

Effects of the disconnection technique and preemptive one-lung ventilation on lung collapse during one-lung ventilation in thoracoscopic surgery.

During thoracoscopic surgery with one-lung ventilation (OLV), achieving lung collapse is critical for providing surgeons with a good visibility of the surgical field and to minimise tissue compression. The aim of this study was to evaluate the efficacy of both the disconnection technique and preemptive one-lung ventilation in facilitating lung collapse during thoracoscopic surgery using a double-lumen tube (DLT). Ninety-seven eligible patients were included and randomly divided into three groups. OLV was initiated when the surgeon started the skin incision and exposed the operative side. Disconnection group: OLV was started two minutes after the DLT was disconnected, this procedure started when the surgeon performed the skin incision. Preemptive group: OLV was initiated promptly after the patient was turned to the lateral position, and the bronchial tube port was clamped on the operative side at the lateral position for no less than 6min until the pleura was opened. The primary outcome was the time to achieve satisfactory lung collapse, defined as the time required to reach a lung collapse score of eight points. The secondary outcomes included the lung collapse scores at different time points, Pleural opening times, OLV times, blood gas analysis results and the incidence of hypoxemia and pulmonary complications. The hypothesis formulated before data collection was that both the disconnection technique and preemptive OLV decrease the time to satisfactory lung collapse. Compared to the control group, both the disconnection and the preemptive group had a shorter time to satisfactory lung collapse (P < 0.001), lung collapse in the preemptive group was superior to that in the disconnection group at one minute (P = 0.045), no significant differences were found among the three groups in terms of other outcomes. Both the disconnection technique and preemptive OLV decrease the time to satisfactory lung collapse. However, preemptive OLV results in superior early lung collapse and is therefore may more suitable for clinical application than the disconnection technique. The protocol of this study was registered at www. chictr. org. cn (29/07/2022, ChiCTR2200062199).

Effectiveness of Electronic Quality Improvement Activities to Reduce Cardiovascular Disease Risk in People With Chronic Kidney Disease in General Practice: Cluster Randomized Trial With Active Control.

Future Health Today (FHT) is a program integrated with electronic medical record (EMR) systems in general practice and comprises (1) a practice dashboard to identify people at risk of, or with, chronic disease who may benefit from intervention; (2) active clinical decision support (CDS) at the point of care; and (3) quality improvement activities. One module within FHT aims to facilitate cardiovascular disease (CVD) risk reduction in people with chronic kidney disease (CKD) through the recommendation of angiotensin-converting enzyme inhibitor inhibitors (ACEI), angiotensin receptor blockers (ARB), or statins according to Australian guidelines (defined as appropriate pharmacological therapy). This study aimed to determine if the FHT program increases the proportion of general practice patients with CKD receiving appropriate pharmacological therapy (statins alone, ACEI or ARB alone, or both) to reduce CVD risk at 12 months postrandomization compared with active control (primary outcome). General practices recruited through practice-based research networks in Victoria and Tasmania were randomly allocated 1:1 to the FHT CKD module or active control. The intervention was delivered to practices between October 4, 2021, and September 30, 2022. Data extracted from EMRs for eligible patients identified at baseline were used to evaluate the trial outcomes at the completion of the intervention period. The primary analysis used an intention-to-treat approach. The intervention effect for the primary outcome was estimated with a marginal logistic model using generalized estimating equations with robust SE. Overall, of the 734 eligible patients from 19 intervention practices and 715 from 21 control practices, 82 (11.2%) and 70 (9.8%), respectively, had received appropriate pharmacological therapy (statins alone, ACEI or ARB alone, or both) at 12 months postintervention to reduce CVD risk, with an estimated between-trial group difference (Diff) of 2.0% (95% CI -1.6% to 5.7%) and odds ratio of 1.24 (95% CI 0.85 to 1.81; P=.26). Of the 470 intervention patients and 425 control patients that received a recommendation for statins, 61 (13%) and 38 (9%) were prescribed statins at follow-up (Diff 4.3%, 95% CI 0 to 8.6%; odds ratio 1.55, 95% CI 1.02 to 2.35; P=.04). There was no statistical evidence to support between-group differences in other secondary outcomes and general practice health care use. FHT harnesses the data stored within EMRs to translate guidelines into practice through quality improvement activities and active clinical decision support. In this instance, it did not result in a difference in prescribing or clinical outcomes except for small changes in statin prescribing. This may relate to COVID-19-related disruptions, technical implementation challenges, and recruiting higher performing practices to the trial. A separate process evaluation will further explore factors impacting implementation and engagement with FHT. ACTRN12620000993998; https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=380119.

Treatment Patterns of Pancreatic Neuroendocrine Tumor (pNET) Patients at Two Canadian Cancer Centres

Pancreatic neuroendocrine tumors (pNETs) are rare but increasingly prevalent malignancies with varied prognoses and a diverse range of treatment options, including surgery, somatostatin analogues (SSAs), chemotherapy, targeted therapy, and peptide receptor radionuclide therapy (PRRT). This retrospective cohort study analyzed treatment patterns among 189 pNET patients treated between January 2010 and June 2021 at two Canadian cancer centres: the Verspeeten Family Cancer Centre (VFCC), which offers PRRT, and the Ottawa Hospital Cancer Centre (TOHCC), which does not at the time of the study. Data on demographics, tumor characteristics, and treatment modalities were collected, and statistical analyses were conducted using chi-square, Fisher’s exact test, and the Kruskal–Wallis test. Among eligible patients, 53% presented with stage IV disease. Surgical resection was the most common treatment, followed by SSAs, chemotherapy, PRRT, and targeted therapy. Stage IV patients at VFCC were significantly more likely to receive PRRT (60%) compared to TOHCC (6%) and underwent more PRRT cycles, with a higher prevalence of well-differentiated tumors observed at VFCC. With these differences it was clear that the non-PRRT centre was unable to provide patients with the same level of PRRT access during the study period compared to patients seen at the PRRT site. The findings underscore the critical role of PRRT availability in influencing treatment patterns and highlight the need for equitable access to specialized therapies across Canada to optimize outcomes for pNET patients.

Screening and treatment of iron deficiency among heart failure patients with impaired ejection fraction: The impact of a pharmacist‐led protocol

AbstractBackgroundDespite guideline‐recommended routine screening and iron deficiency (ID) treatment among heart failure (HF) patients, these practices are often underutilized. Currently, limited data are available on the outcomes of pharmacists' programs to enhance ID screening and management. Accordingly, we sought to describe the frequency and yield of screening for ID and intravenous (IV) iron replacement rates among our cohort of HF patients and examined the impact of implementing a pharmacist‐led protocol (PLP) aimed at enhancing these rates.MethodsWe conducted a retrospective study involving HF patients with left ventricular ejection fraction (LVEF) &lt;45% at a quaternary care hospital in the Middle East/Gulf region. The PLP was introduced in August 2022. Data on demographics, comorbidities, echocardiographic parameters, laboratory findings (including ID screening and its findings), and rates of treatment with IV iron replacement were analyzed and compared between the pre‐implementation group (n = 432, October 2015–February 2020) and the post‐implementation group (n = 154, August 2022–January 2023).ResultsBefore the PLP, 63.2% (n = 273) of eligible patients underwent ID screening, with 80.6% (n = 220) found to have ID. Following the implementation of the PLP, screening rates significantly increased to 86.4% (n = 133) (p = 0.03), with 53.4% (n = 71) diagnosed with ID. The rate of IV iron replacement in ID patients improved from 30.4% (n = 67) in the pre‐PLP group to 73% (n = 52) in the post‐PLP group (p &lt; 0.001). Multivariable logistic regression identified baseline glomerular filtration rate (GFR) and hemoglobin levels as significant predictors of IV iron replacement in the pre‐PLP cohort.ConclusionsImplementing a pharmacist‐led protocol was significantly associated with enhancing the screening and treatment of ID in patients with HF and LVEF &lt;45%. This study demonstrates the crucial role of pharmacists in optimizing guideline‐directed therapies, which can be replicated in various healthcare settings.

Survival and risk factors for metastatic colorectal cancer patients with a history of prior malignancy

Given concerns about treatment, there is uncertainty surrounding the effect of prior malignancy on the survival of individuals with metastatic colorectal cancer. This study sought to evaluate how prior malignancy impacts the survival of patients with metastatic colorectal cancer (mCRC). Patients diagnosed with stage IV mCRC (per the American Joint Committee on Cancer [AJCC] 6th edition) between 2004 and 2015 were identified from the Surveillance, Epidemiology, and End Results (SEER) database. Those without a prior history of malignancy were assigned to the control group, whereas those with a prior history of malignancy were assigned to the research group. Propensity score matching (PSM) was utilized to ensure that the baseline characteristics were balanced. The Kaplan‒Meier method was used for survival analysis, as were the multivariate Cox proportional hazard model and multivariate competing risk model. The PSM analysis included 54365 eligible patients with mCRC. Among them, 4,845 (8.9%) had a history of prior malignancy. A history of prior malignancy was associated with a greater cancer-specific survival rate (adjusted hazard ratio (AHR) ) = 0.49; 95% CI [0.47–0.51]). Subgroup analyses revealed that a prior diagnosis of a skin tumour (AHR = 1.37; 95% CI [1.11–1.69]) and a history of prior malignancy of more than five years (AHR = 1.39; 95% CI [1.23–1.57]) had adverse effects on the clinical outcomes of patients with mCRC. Our findings suggest that patients with a prior malignancy diagnosis may experience prolonged survival. Subgroup analysis indicated that a malignancy diagnosed more than 5 years ago may adversely impact the clinical outcomes of patients with mCRC. Therefore, we advocate for active standardized treatment for these patients and propose expanding the range of prior malignancies included in clinical trials based on publication timelines, primary tumour locations, and genetic testing results. The objective is to facilitate timely and proactive treatment for patients following the disclosure of results, thereby instilling confidence in the management of mCRC.

Effectiveness of an Impella Versus Intra-Aortic Balloon Pump in Patients Who Received Extracorporeal MembraneOxygenation.

It is unclear whether an intra-aortic balloon pump (IABP) or percutaneous ventricular assist device (Impella) in combination with extracorporeal membrane oxygenation (ECMO) is better. Using the Japanese Diagnosis Procedure Combination database from September 2016 to March 2022, we identified inpatients who received an Impella or IABP in combination with ECMO (ECPella or ECMO+IABP group, respectively). The primary outcome was in-hospital mortality, and the secondary outcomes included the length of hospital stay, length of ECMO, total hospitalization cost, complications, and durable mechanical circulatory support implantations. Propensity score matching was performed to compare the outcomes between the groups. Of 14 319 eligible patients, 590 (4.1%) received ECPella and 13 729 (96%) received ECMO+IABP. The mean age of patients was 65 years, 77% were men, and 57% had acute coronary syndrome. After propensity score matching, the patient characteristics were well balanced between the groups. The 14-day mortality rate was lower in the ECPella group than in the ECMO+IABP group (28.0% versus 36.8%; risk difference, -8.2% [95% CI, -13.8 to -2.7]), whereas there was no significant difference in in-hospital mortality between the groups (58.3% versus 56.6%; risk difference, 2.4% [95% CI, -3.5 to 8.2]). The ECPella group had a higher total hospitalization cost, increased renal replacement therapy during hospitalization, and more durable mechanical circulatory support implantations than the ECMO+IABP group. This nationwide inpatient database study showed no significant difference in in-hospital mortality between the groups, but ECPella was associated with a higher total hospitalization cost, increased renal replacement therapy during hospitalization, and more durable mechanical circulatory support implantations than ECMO+IABP.

Long-Term Impact of Early Subclinical Leaflet Thrombosis After Transcatheter Aortic Valve Implantation.

Hypoattenuated leaflet thickening (HALT) after transcatheter aortic valve implantation (TAVI) detected on multidetector computed tomography (MDCT) is considered leaflet thrombosis. However, its impact on long-term clinical outcomes remains unclear. This study aimed to investigate the impact of early HALT detection after TAVI on long-term clinical outcomes and structural valve deterioration beyond 6 years. Of the 672 consecutive patients who underwent TAVI between 2013 and 2018, 448 were treated with either SAPIEN XT or SAPIEN 3 and underwent MDCT analysis within 30 days after TAVI. MDCT results and echocardiographic data were analyzed annually. HALT was detected in 68 (15.2%) of 448 eligible patients within 30 days after TAVI. No significant difference in effective orifice area was observed by echocardiography within 30 days after TAVI between the HALT and the non-HALT groups in SAPIEN XT (HALT vs. non-HALT: 1.62 ± 0.66 cm2 vs. 1.72 ± 0.43 cm2; p = 0.26) and in SAPIEN 3 (1.42 ± 0.35 cm2 vs. 1.45 ± 0.34 cm2; p = 0.63). No significant differences in all-cause mortality (52.9% vs. 60.0%; hazard ratio (HR): 1.19; 95% confidence interval (CI): 0.83-1.70; p = 0.3), stroke incidence (5.9% vs. 7.1%; HR: 1.06; 95% CI: 0.08-13.7; p = 0.97), heart failure rehospitalization (10.3% vs. 15.0%; HR: 2.3; 95% CI: 0.89-5.99; p = 0.09), and structural valve deterioration (14.7% vs. 17.9%; HR: 0.89; 95% CI: 0.45-1.73; p = 0.73) were observed between the HALT and the non-HALT groups during the median follow-up of 1872 (interquartile range; 1203-2468) days. HALT within 30 days was not associated with clinical outcomes or hemodynamic performance during long-term follow-up.

Regional cerebral oxygen saturation during initial mobilization of critically ill patients is associated with clinical outcomes: a prospective observational study

BackgroundVital signs help determine the safety of early mobilization in critically ill patients in intensive care units. However, none of these variables directly assess cerebral circulation. Therefore, we aimed to investigate the relationship of regional cerebral oxygen saturation (rSO2) and vital signs with in-hospital death in critically ill patients.MethodsThis prospective study included critically ill patients admitted to the Uonuma Kikan Hospital Emergency Center who received physical therapy between June 2020 and December 2022. We continuously measured rSO2 during the initial mobilization using a wearable brain near-infrared spectroscopy device. With in-hospital death as the primary endpoint, the association between rSO2 and in-hospital death was assessed in Analysis 1 to determine the rSO2 cut-off value that predicts in-hospital death. In Analysis 2, patients were categorised into survival and non-survival groups to examine the temporal changes in vital signs and rSO2 associated with postural changes during mobilization.ResultsOf the 132 eligible patients, 98 were included in Analysis 1, and 70 were included in Analysis 2. Analysis 1 demonstrated that lower premobilization rSO2 was independently associated with in-hospital death (odds ratio 0.835, 95% confidence interval 0.724–0.961, p = 0.012). Receiver operating characteristic curve analysis identified an optimal rSO2 cut-off value of 57% for predicting in-hospital death (area under the curve 0.818, sensitivity 73%, specificity 83%). Analysis 2 showed that rSO2 changes during mobilization were unrelated to changes in vital signs, suggesting rSO2 as an independent prognostic marker.ConclusionsThe results suggest that rSO2 measured during initial mobilization is associated with in-hospital death in critically ill patients.

Neoadjuvant Chemotherapy in Muscle-Invasive Bladder Cancer: A Nationwide Analysis of Eligibility, Utilization, and Outcomes

Objectives: To investigate neoadjuvant chemotherapy (NAC) eligibility, utilization, and survival outcomes for muscle-invasive bladder cancer patients undergoing radical cystectomy (RC) in a Finnish population. Materials and Methods: Data from the Finnish National Cystectomy Database (2005–2017) was combined with Finnish Cancer Registry survival data. NAC utilization rates were reported, and downstaging rates were calculated based on final pathological staging. Logistic regression analyzed NAC usage and complete response (CR) predictors. Results: Since 2011, 29% of 1157 patients received NAC. Its usage remained consistent, and the number of eligible patients not receiving NAC decreased during the study period. Among NAC patients, pathology T-category was pT0 (34%), pT1-Ta-Tis (16%), pT2 (23%), pT3 (20%), and pT4 (7%) tumors, with pN0 in 82%. In the RC + NAC group, the 5-year overall survival (OS) rates were 89% for patients with no residual disease (pT0N0), 82% for those with organ-confined residual disease (pT1, Tis, Ta, T2/N0), and 49% for patients with non-organ-confined residual disease (pT3+/N+). The corresponding cancer-specific survival (CSS) rates were 93%, 86%, and 57%, respectively. Patients with organ-confined residual disease after NAC had survival outcomes comparable to those who underwent RC alone. Higher age; odds ratio (OR) 0.93, [95% Confidence Interval (CI): 0.90–0.95] and Charlson Co-morbidity Index–score [OR 0.88 (0.79–0.98)] reduced the likelihood of receiving NAC, while a smaller center size increased the probability [OR 1.82 (1.02–3.28)]. More treatment cycles [OR 0.70, (95% CI: 0.51–0.93)] and a favorable GFR [OR 0.38 (0.16–0.88)] were associated with achieving CR. Conclusion: We report that NAC is well-utilized across Finland, with CR rates comparable to recent trials. Additionally, our survival rates are reasonable, and even with organ-confined residual disease after NAC, survival outcomes are similar to those who underwent RC alone.

Comparative analysis of first-line treatment in NSCLC including unresectable stage III (IIIB/IIIC) and stage IV with low PD-L1 expression: Clinical trial eligible versus ineligible patients.

Clinical trial eligible patients with advanced non-small cell lung cancer (aNSCLC) and low programmed cell death ligand 1 (PD-L1) expression achieve greater benefit from immune checkpoint inhibitor (ICI) combination chemotherapy (ICI-Chemo) compared with Chemo alone. We examined whether patients ineligible for clinical trials may benefit from ICI-Chemo. This multicenter retrospective cohort study enrolled patients with aNSCLC, including unresectable Stage III (IIIB/IIIC) and IV disease with a PD-L1 tumor proportion score of 1-49% treated with ICI-Chemo or Chemo as first-line therapy from 2018 to 2023 in Japan. Treatment outcome and safety of ICI-Chemo versus Chemo groups in trial-eligible and trial-ineligible patients was compared based on criteria from previous phase III clinical trials. Overall, 728 patients were analyzed: 333 trial-eligible and 395 ineligible patients. The median overall survival was 25.1months in the ICI-Chemo group and 18.5months in the Chemo group for eligible patients (HR 0.73, 95%CI: 0.54-0.97) and was 18.2months in the ICI-Chemo group and 14.9months in the Chemo group for ineligible patients (HR 0.75, 95%CI: 0.59-0.95). Median progression-free survival was longer with ICI-Chemo in both groups. For ineligible patients, performance status (PS)≥2 and squamous cell carcinoma (SqCC) were clinical factors associated with worse survival prognosis, and survival outcomes with ICI-Chemo and Chemo were comparable. The ineligible group had no increase in severe adverse events compared to the eligible group. This study suggests a possible clinical benefit of receiving ICI-Chemo for trial-ineligible patients with low PD-L1 expression, excluding those with PS ≥2 or SqCC.

Intraperitoneal and intravenous paclitaxel plus S-1 versus intravenous paclitaxel plus S-1 in gastric cancer patients with peritoneal metastasis: Results from the multicenter, randomized, phase 3 DRAGON-01 trial.

327 Background: The optimal chemotherapeutic regimen for gastric cancer with peritoneal metastasis remains undefined. We evaluated the efficacy and safety of intraperitoneal and intravenous paclitaxel plus S-1 (NIPS Group) versus paclitaxel plus S-1 (PS Group) in gastric cancer patients with peritoneal metastasis. Methods: In this multicenter, randomized, controlled, phase 3 trial, patients were recruited from 9 cancer centers in China. Eligible patients were aged 18~75 years with an Eastern Cooperative Oncology Group performance status of 0~1, histologically confirmed gastric adenocarcinoma, peritoneal metastases from gastric cancer requiring definitive diagnosis by laparoscopy, without gastric outflow tract obstruction and intestinal obstruction, no prior treatment with chemotherapy, radiation therapy, targeted therapy or immunotherapy. Eligible patients were randomly assigned (2:1) to receive either intravenous paclitaxel at 50 mg/m² and intraperitoneal paclitaxel at 20 mg/m² on days 1 and 8, along with oral S-1 at a dose of 80 mg/m² on days 1~14, or intravenous paclitaxel at 70 mg/m² on days 1 and 8, along with oral S-1 at 80 mg/m² on days 1~14. The primary endpoint was overall survival in the intention-to-treat population. Safety was assessed in all participants. A sample size of 238 patients was calculated to provide 80% power with a one-sided alpha of 0.1, accounting for a 10% dropout rate. Survival was analyzed using Kaplan-Meier curves and compared with the log-rank test. Cox regression was used for multivariate analysis. A P -value &lt; 0.05 was considered statistically significant. Results: From May 10, 2017, to March 9, 2022, 246 patients were screened and 222 were included in the modified intention-to-treat population, of whom 148 patients were assigned to the NIPS Group and 74 to the PS group. As of data cutoff (March 9, 2024), the median survival time was 19.4 months (95% CI, 17.1~22.9), in the NIPS group and 13.9 months (95% CI, 10.3~16.1) in the PS group (HR = 0.66; 95% CI 0.49 - 0.88; P = 0.005). The 1-year and 2-year overall survival rates were 69.6% and 37.2% in the NIPS group, compared to 54.1% and 20.3% in the PS group. The most common grade 3~4 adverse events were leukopenia (21.7% in the NIPS group, and 24.7% in the PS group) and neutropenia (19.9% in the NIPS group, and 23.4% in the PS group). No treatment-related deaths were reported. Conclusions: Intraperitoneal and intravenous paclitaxel plus S-1 significantly improved the overall survival compared to intravenous paclitaxel plus S-1 in gastric cancer patients with peritoneal metastasis, with manageable toxicity. Clinical trial information: ChiCTR-IIR-16009802.

BREAKWATER: Analysis of first-line encorafenib + cetuximab + chemotherapy in BRAF V600E-mutant metastatic colorectal cancer.

16 Background: Encorafenib + cetuximab (EC) is approved for previously treated BRAF V600E-mutant metastatic colorectal cancer (mCRC) based on the BEACON phase 3 study (NCT02928224). Historically, first-line (1L) treatment of BRAF V600E-mutant mCRC with chemotherapy (chemo) regimens has had limited efficacy.BREAKWATER (NCT04607421) is an open-label, global, randomized, phase 3 study evaluating 1L EC with or without chemo vs standard of care (SOC; chemo with or without bevacizumab). Reported here are the primary analysis of objective response rate by blinded independent central review (ORR by BICR; dual primary endpoint [EP]), the first interim analysis of overall survival (OS; key secondary EP), other secondary EPs, and safety for the EC+FOLFOX (oxaliplatin, leucovorin, and 5-FU) vs SOC arms. Methods: Eligible patients (pts) had untreated BRAF V600E-mutant mCRC, measurable disease (RECIST 1.1), and ECOG PS 0-1. Pts were randomized 1:1:1 to receive EC, EC+FOLFOX, or SOC; EC arm enrollment was closed after a protocol amendment. Dual primary EPs were ORR (assessed in the first 110 pts randomized to each of the EC+FOLFOX and SOC arms) and progression-free survival by BICR (EC+FOLFOX vs SOC); OS was a key secondary EP (EC+FOLFOX vs SOC), other secondary EPs included response duration and time to response (TTR). Results: Four hundred seventy-nine pts were randomized to the EC+FOLFOX and SOC arms (EC+FOLFOX: n=236; SOC: n=243). Baseline demographics and disease characteristics were similar across arms (median age: 61.0 years; male: 50.5%; ECOG PS 0: 54.3%). At data cutoff (Dec 22, 2023), the EC+FOLFOX arm demonstrated a clinically meaningful and statistically significant improvement in confirmed ORR vs the SOC arm, 60.9% vs 40.0%, odds ratio=2.443, one-sided P -value=0.0008, meeting this dual primary EP. The response observed with EC+FOLFOX was rapid and durable. OS data were immature but indicated a sustained survival benefit with EC+FOLFOX vs SOC arm. Serious treatment-emergent adverse events (EC+FOLFOX: n=231; SOC: n=228) occurred in 37.7% vs 34.6% of pts in the respective arms. The safety profile was consistent with that known for each agent. Conclusions: BREAKWATER demonstrated a substantially improved response rate that was rapid and durable with EC+FOLFOX in BRAF V600E-mutant mCRC with manageable toxicities and no new safety signals. Clinical trial information: NCT04607421 . EC+FOLFOXn=110 SOCn=110 ORR by BICR % (95% CI) 60.9 (51.6, 69.5) 40.0 (31.3, 49.3) Odds ratio (95% CI) P -value a 2.443 (1.348, 4.380) 0.0008 n=67 n=44 Estimated median response duration by BICR (95% CI), mo 13.9 (8.5, NE) 11.1 (6.7, 12.7) Pts with a response duration of ≥6 mo, n (%)Pts with a response duration of ≥12 mo, n (%) 46 (68.7)15 (22.4) 15 (34.1)5 (11.4) Median TTR by BICR (range), weeks 7.1 (5.7-53.7) 7.3 (5.4-48.0) n=236 n=243 OS (95% CI), mo NE (19.8, NE) 14.6 (13.4, NE) Hazard ratio (95% CI) 0.47 (0.318, 0.691) a One-sided α=0.001. NE, not estimable.

Safety of Low-Dose Quetiapine for Insomnia in Older Adults.

Quetiapine is a Food and Drug Administration (FDA) approved second-generation antipsychotic. It is also commonly used at low dose for its sedative properties to treat insomnia in the older population. Quetiapine at standard doses has been associated with increased risk of cerebrovascular events, cognitive decline, and mortality in patients with dementia, especially within older adults. However, there are limited data describing its safety at lower doses, especially for the treatment of insomnia in older adults. This study aims to compare the safety of low-dose quetiapine versus trazodone or mirtazapine for insomnia in older adults in the USA. This was a retrospective cohort study that included patients aged 65 years or older who started low-dose quetiapine, trazodone, or mirtazapine for the treatment of insomnia from October 2018 to September 2021. The primary outcome was all-cause mortality and secondary outcomes included new incidences of stroke or transient ischemic attack, dementia, and falls with or without traumatic fractures. They were identified from electronic medical records using ICD-10-CM clinical diagnosis codes. Eligible patients were followed from the initiation of the drug until death, end of target drug exposure or escalation of dose, end of health plan membership, or 30 September 30 2022, whichever came first. Patients initiated mirtazapine or trazodone were matched to each patient who initiated quetiapine at a 4:1 ratio using propensity score matching method. We included 375 patients initiated on low-dose quetiapine, who were matched to 1500 patients started on trazodone and 1500 patients started on mirtazapine. Comparing patients who received quetiapine with trazodone, the quetiapine group had an increased risk of mortality (hazard ratio (HR) 3.1, 95% confidence interval (CI) 1.2-8.1; P < 0.05), dementia (HR 8.1, 95% CI 4.1-15.8; P < 0.05), and falls (HR 2.8, 95% CI 1.4-5.3; P < 0.05). When comparing quetiapine with mirtazapine, quetiapine group had an increased risk of dementia (HR 7.1, 95% CI 3.5-14.4; P < 0.05). No significant differences were detected in other outcomes. Caution should be taken in practice when using low-dose quetiapine for insomnia in older adults. It is associated with significantly higher rates of mortality, dementia, and falls when compared with trazodone and a higher dementia rate when compared with mirtazapine.

Preliminary result of a phase Ib study: Efficacy and safety of FG-M108 plus gemcitabine/nab-paclitaxel as first-line (1L) treatment in patients with Claudin18.2-positive locally advanced unresectable or metastatic (LA/m) pancreatic cancer.

729 Background: FG-M108, an ADCC-enhanced anti-CLDN18.2 monoclonal antibody, showed significant efficacy in 1L treatment of gastric cancer. Herein, we report the safety and efficacy results of FG-M108 in 1L treatment of pancreatic cancer (cohort C2&amp;D2). Methods: In this open-label, multicenter phase I/II study patients received FG-M108 (cohort C2: 300mg/m 2 or cohort D2: 600mg/m 2 Q3W) plus gemcitabine (1000mg/m 2 , d1, d8, Q3W) and nab-paclitaxel (125mg/m 2 , d1, d8, Q3W). Eligible patients were those with CLDN18.2 positive (IHC 1+/2+/3+≥10%) previously untreated LA/m pancreatic cancer. The primary endpoint were the incidence of adverse events (AEs) and preliminary clinical efficacy (ORR, DCR, DOR, PFS, and OS). Results: As of Sep 5 2024, 50 patients were enrolled and received FG-M108+gemcitabine/nab-paclitaxel treatment (39 patients in cohort C2, 11 patients in cohort D2). The median age was 61 (range 30-72). 47 (94%) patients were with CLDN18.2 moderate-high expression (IHC 2+/3+≥40%). Out of 50 patients, 44 patients had at least one tumor assessment after baseline and included in the efficacy analysis set. The results of ORR and DCR in cohort C2 were 32.4% and 100.0%, while that in cohort D2 were 30.0% and 90.0%, respectively. In cohort C2, the median PFS and median DOR were 6.8 months and 9.8 months, respectively. In the subgroup patients with CLDN18.2 moderate-high expression, the median PFS and median DOR were 7.6 months and 9.8 months, respectively. The median OS has not been reached. FG-M108 related AEs were observed in all patients, with 39 patients (78%) having Grade 3/4 AEs and no FG-M108 related fatal AE was observed. The most common FG-M108 related AEs in cohort C2 &amp; D2 were anemia (56.2% vs 63.6%), nausea (56.4% vs 36.4%), vomiting (48.7% vs 45.5%), and hypoalbuminemia (46.2% vs 54.5%). Conclusions: The combined therapy of FG-M108 plus chemotherapy as 1L treatment for patients with CLDN18.2 positive pancreatic cancer was well tolerated with encouraging survival especially in patients with CLDN18.2 moderate-high expression, deserving further investigation. Clinical trial information: NCT04894825 .

KIRROS: A phase II trial in progress of first-line atezolizumab (atezo) with or without bevacizumab (bev) in patients with unresectable hepatocellular carcinoma (HCC) and Child-Pugh B (CPB) cirrhosis.

TPS647 Background: HCC treatment is more complex for the sizable proportion of patients with CPB cirrhosis. These patients have poor survival due to both the cancer and underlying liver dysfunction. As such, they are typically excluded from pivotal clinical trials for first-line systemic therapy for unresectable HCC. The IMbrave150 trial established atezo + bev as a global standard of care for unresectable HCC, demonstrating a statistically significant improvement in overall survival (OS), progression-free survival (PFS) and confirmed objective response rate (ORR) of atezo + bev vs sorafenib (Finn N Engl J Med 2020; Cheng J Hepatol 2022). Real-world studies have consistently suggested benefit of atezo + bev in patients with HCC and CPB cirrhosis (e.g., Tanaka Hepatol Res 2022, D’Alessio Hepatol [Baltimore, Md] 2022). However, prospective clinical trial data are needed to comprehensively characterize safety and efficacy in this population. Single-agent immunotherapy is often used in patients with HCC and CPB cirrhosis given potential safety concerns of combination therapy. Safety data from real-world studies are limited by ascertainment and measurement biases. Therefore, a prospective study is warranted to address the unmet need for safety and efficacy data for first-line atezo ± bev in patients with CPB cirrhosis. Methods: KIRROS (NCT06096779) is a prospective, open-label, multicohort, multicenter phase II study in patients aged ≥18 years who have measurable and confirmed unresectable HCC, and CPB-7 or -8 cirrhosis who have not received prior systemic therapy. Eligible patients will be recruited into 2 cohorts for which endpoints will be non-comparatively assessed: Cohort A (n=60) patients will be treated with atezo 1200 mg intravenous (IV) + bev 15 mg/kg every 3 weeks (Q3W), and Cohort B (n=60) patients, those who do not meet Cohort A inclusion criteria (e.g., main portal vein tumor thrombus and proteinuria), will receive atezo 1200 mg IV Q3W only. Patients will receive treatment until unacceptable toxicity or loss of clinical benefit. The primary objective is to evaluate the safety of the treatment regimens as determined by incidence, nature and severity of adverse events and laboratory abnormalities graded per the National Cancer Institute Common Terminology Criteria for Adverse Events v5.0. Secondary objectives are to estimate efficacy with ORR, duration of response, and PFS per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 and HCC modified RECIST, as well as OS. Quality-of-life secondary endpoints include patient-reported tolerability of the treatment regimens assessed by PRO-CTCAE and EORTC IL46, and health-related quality of life per EORTC QLQ-C30 and QLQ-HCC18 scores. As of September 2024, the KIRROS study is recruiting patients at 40 sites in the US and Puerto Rico. Clinical trial information: NCT06096779 .