Boca Raton Regional Hospital is a 400-bed, not-for-profit health care organization located in Boca Raton, Florida. It was established in 1967 and provides patient care in areas such as cardiovascular, oncology, women's health, orthopedics, emergency medicine and the neurosciences. Presently, the hospital has 400 licensed beds, 800 physicians, a nursing and support staff of 2000 and 1200 volunteers.
We hypothesized that a time-limited frontline treatment strategy with abbreviated chemoimmunotherapy followed by targeted consolidation could achieve durable disease control with manageable toxicity in CLL. We evaluated the safety and efficacy of short-course bendamustine/rituximab (BR) induction followed by venetoclax/rituximab (VR) consolidation. In a multicenter, single-arm Phase 2 trial (NCT03609593), previously untreated CLL/SLL needing therapy received BR for three 28-day cycles followed by venetoclax ramp-up to 400 mg daily plus rituximab every 28 days for six cycles; venetoclax continued to 12 cycles (total treatment, 15 months). The primary endpoint was overall response rate (ORR); key secondary endpoints included uMRD, PFS/OS, and safety per CTCAE v4. Forty-two patients were enrolled (median age 61.5 years; 64% unmutated IGHV; 29% complex karyotype; 10% TP53 aberrancy); 93% completed all planned therapy. At end of treatment, ITT ORR was 86% (CR/CRi 64%, PR 21%); among efficacy-evaluable patients, ORR was 100% (CR/CRi 75%). End-of-therapy uMRD was achieved by 83% in bone marrow and 84% in blood among efficacy-evaluable patients. Three-year PFS and OS were 87.5% and 92.7%. TLS risk was downstaged after BR, and no TLS events occurred. Febrile neutropenia occurred in 12% of patients. Two on-study deaths due to COVID-19 occurred; no Richter transformation occurred. Time-limited BR-VR achieved high uMRD rates and durable remissions with a manageable safety profile. While the treatment landscape in CLL has largely shifted toward chemotherapy-free regimens, these data demonstrate the biological proof-of-concept that limited induction chemotherapy can effectively mitigate TLS risk and facilitate safe outpatient ramp-up of venetoclax.
BACKGROUND:Atrial fibrillation (AF) can lead to significant cardiovascular events and health care utilization. Continuous monitoring via insertable cardiac monitors (ICMs) and data analytics have the potential to improve care delivery. OBJECTIVE:The DEFINE Atrial Fibrillation (DEFINE AFib) study was designed to develop and evaluate novel algorithms using ICM data to predict AF-associated clinical actions (AFCAs) and guide AF management. METHODS:DEFINE AFib enrolled patients with an ICM (Reveal LINQ/LINQ II; Medtronic) and a history of AF. An Apple iPhone application collected AF-related quality of life (AFEQT) and EQ-5D data. ICM daily AF burden and Apple Watch (AW) irregular rhythm notification (IRN) data were also collected. AFCA was defined as an AF-related procedure or initiation of rate/rhythm control medication. Mutivariable logistic regression was used to identify ICM features in the last 30 days associated with first occurrence of AFCA in the next 30 days in a train and test approach (70%/30%). RESULTS:Among 864 patients (mean 69 ± 10 years; 56% male) meeting inclusion criteria, there were 8963 30-day evaluation windows that included 151 AFCAs. Area under the receiver operating characteristic curve (AUC) was 76% (train) and 70% (test). The model placed participants into high- vs low-risk AFCA groups. At the patient-level, 21% of participants crossing the high-risk threshold for their first time experienced an AFCA at a mean time of 195 ± 164 days compared with 5% in the low-risk group (AUC 65%). Increasing daily mean AF burden was associated with lower quality of life: <6 minutes (reference), 6 minutes to 5.5 hours (AFEQT -7.69; P < .001), and 5.5-12 hours (AFETQ -13.97, P < .001; ≥5.5 hours EQ-5D -0.03, P = .007). In a subanalysis of individuals with smart watch data (n = 53), the ICM model signaled high risk before AFCAs 85% of the time (AUC 57%) compared with 23% for AW IRN (P = .005; AUC 55%). CONCLUSION:DEFINE AFib transformed ICM diagnostic data to predict risk of AFCA with good discrimination, particularly compared with wearable data. These results highlight the potential advantages of ICM-based continuous monitoring for AF management and the utility of ICM prediction models that could help inform pre-emptive therapeutic strategies.
OBJECTIVE:Aneurysm behavior after fenestrated and branched endovascular aortic repair (F/B-EVAR) is a marker of treatment success and has been linked with long-term survival. This study aimed to characterize longitudinal changes in residual aneurysm sac behavior after F/B-EVAR and relate these changes to aortic outcomes. METHODS:We retrospectively analyzed F/B-EVARs performed in 10 sponsor-investigator investigational device exemption trials (2005-2024). Serial imaging after repair was evaluated for changes in residual aneurysm sac behavior. Changes in sac behavior over time were investigated with a multistate time-to-event survival model, and the time-dependent effect of sac behavior on outcomes was analyzed with a competing risks model for aortic events and nonaortic death. RESULTS:A total of 1932 patients met the study criteria; 1223 patients (63%) were treated for thoracoabdominal aneurysm with a median preoperative maximum aortic diameter of 61 mm (interquartile range [IQR], 57-67 mm). The median follow-up was 3.5 years (IQR, 2.3-4.6 years) with 3 surveillance imaging studies (IQR, 2-5 studies) available per patient. Endoleak occurred in 1043 patients (54%) and 343 (18%) underwent reintervention. At 1 year, the predicted probabilities of sac states were: 32% for regression (95% confidence interval [CI], 25-40), 42% stability (95% CI, 35-49), expansion 6% expansion (95% CI, 4-7), and 7% death (95% CI, 6-9); the probability of the aneurysm state not yet observed was 14% (95% CI, 10-20). The presence and absence of endoleak at any time in follow-up were associated with the risks of transition to a state of sac expansion (hazard ratio [HR], 1.3; 95% CI, 1.1-1.6; log-rank P = .003) or regression (HR, 2.1; 95% CI, 1.6-2.9; log-rank P < .0001), respectively. Aortic events, including rupture, dissection, and death, occurred in 78 patients (4%). Sac expansion demonstrated at any time after F/B-EVAR was associated with the cause-specific hazards of an aortic event (HR, 3.2; 95% CI, 1.6-6.4; log-rank P = .009), as well as nonaortic death (HR, 1.3; 95% CI, 1-1.6; log-rank P = .02). The hazard of an aortic event did not differ between states of stability and regression, but the presence of an endoleak significantly modified the hazard of aortic event with sac stability (HR, 2.2; 95% CI, 1.1-4.6; log-rank P = .04). CONCLUSIONS:Residual aneurysm sac behavior after F/B-EVAR is dynamic and influenced by the presence of an endoleak. Sac expansion, even when occurring later in follow-up, was associated with increased hazards of both aortic events and nonaortic death. These findings underscore the importance of diligent surveillance and timely intervention for endoleaks after F/B-EVAR.
Abstract Background Outpatient medication dispensing kiosks that contain antibiotics are proliferating. This study aimed to evaluate how their implementation in urgent care centers (UCC) alongside antimicrobial stewardship program (ASP) collaborative engagement can influence antibiotic prescribing. Methods This retrospective cohort study included 20 UCCs, evaluating antibiotic electronic prescriptions (eRX) ordered in January - June 2019 (pre-period) versus January - June 2024 (post-period). In late-2019 kiosks containing antibiotics were placed into UCCs with initial kiosk inventories based off historical eRx volumes. Serendipitously an outpatient ASP collaborative was established around the same time. Between the pre-/post-periods numerous programmatic interventions were implemented to promote rational antibiotic prescribing, including kiosk inventory modifications, education, and stakeholder engagement. Data on eRx prescribing for 12 antibiotics were obtained. The primary outcome was antibiotic duration of therapy (DOT) in days per eRx. Secondary outcomes included antibiotic-specific changes, kiosk utilization, and an estimate of intervention impact. Findings In the pre-period 38,593 eRx were included with 325,400 DOTs, as compared to 45,608 eRx with 355,502 DOTs in the post-period (8.4 DOT/prescription versus 7.8 DOT/prescription, respectively, p < 0.001). In the pre-period 8,649 eRx (22%) were routed to a kiosk compared to 25,414 eRx (56%) in the post-period, p < 0.001. There was an estimated 33,340 DOT avoided in the post-period. Interpretation Engagement of an antimicrobial stewardship collaborative along with implementation of UCC kiosks containing antibiotics may support prescriber practices that align with stewardship principles and safer outpatient antibiotic use. For health systems considering kiosk adoption, early and sustained ASP involvement in inventory decisions appears critical, which this manuscript may serve to support as a template.
