Background: Vascular access is a core component of hemodialysis and may influence both clinical outcomes and patient-reported quality of life. This study examined the association between vascular access type and quality of life among patients receiving maintenance hemodialysis in multiple nephrology centers. Methods: We conducted a multicenter, cross-sectional observational study of 152 adults with end-stage kidney disease undergoing hemodialysis in public and private dialysis units in the Attica region, Greece (January–May 2022). Data were collected using a demographic/clinical questionnaire, the 36-Item Short Form Health Survey (SF-36), the Dialysis Patient Satisfaction Questionnaire (SDIALOR), and the Missoula VITAS Quality of Life Index (MVQOLI). Multivariable linear regression models were fitted for SF-36 and MVQOLI domain scores. Results: Most participants reported being very (40.8%) or quite (53.3%) satisfied with their current vascular access, and 69.5% considered an arteriovenous fistula (AVF) the most appropriate option. SF-36 scores were generally lower than those reported for the general population, except for the mental health domain. Compared with AVF, permanent catheter use was associated with lower SF-36 physical functioning scores, and graft use was associated with lower vitality scores. Lower vascular access satisfaction was consistently associated with lower HRQoL: compared with being “very” satisfied, being “quite” satisfied was associated with lower general health, vitality, social functioning, mental health, and lower PCS/MCS scores, while being “a little/not at all” satisfied was associated with lower general health and worse bodily pain scores. On MVQOLI, living alone and lower access satisfaction were associated with lower interpersonal relationships, transcendence/spirituality, and overall quality-of-life scores, while obesity was associated with lower function scores. Conclusions: Vascular access type, particularly AVF versus catheter, is associated with meaningful differences in quality of life among hemodialysis patients. Patient satisfaction with access and sociodemographic characteristics should be considered in patient-centered access planning and follow-up.

Background: Severe obesity is associated with an increased prevalence of hiatal hernias (HH) and gastroesophageal reflux disease (GERD). Both fundoplication (FP) and gastric bypass (GB) are utilized in this population, but comparative outcomes are not well-established. This review aims to compare surgical outcomes of FP versus GB for managing GERD and HH in adults with severe obesity. Methods: A systematic search was conducted for studies published up to June 2025. Inclusion criteria: adult patients with obesity (BMI ≥ 30) with HH/GERD undergoing first FP or GB. Key outcomes were postoperative reflux, complications, recurrence, and reoperation. Results: Five studies met inclusion criteria. Both FP and GB effectively manage GERD. In a propensity-matched cohort, GB significantly reduced early hernia recurrences compared to FP, but long-term recurrence and reoperation rates were similar between groups. Another study found similar recurrence rates between GB and FP; however, fewer symptomatic recurrences occurred with GB. A large retrospective study reported a lower complication rate for GB versus FP (7% vs. 10%, p < 0.05) and no significant differences in reflux scores. Conclusions: Both FP and GB offer benefits in managing GERD and HH in patients with severe obesity. Future research should focus on comparing efficacy, standardizing outcome measures, and evaluating patient-centered outcomes.

ABSTRACT OBJECTIVES Prehospital programs for Medications for Opioid Use Disorder (MOUD) have gained significant traction over the past few years. Data describing statewide implementation of MOUD programs are limited. Our objective was to describe the current practices within active prehospital MOUD programs in North Carolina and to compare these data with previously published best practices to assist in standardizing future MOUD programs. METHODS This was a cross-sectional study of 21 counties in North Carolina (NC) with an active prehospital MOUD program at the time of the study. Using virtual and phone interviews, counties were asked a set of predefined qualitative and quantitative questions related to their program structure and elements which were then analyzed using descriptive statistics and combined into a comparative format based on current best practice consensus recommendations. RESULTS A total of 21 counties in NC had an active prehospital MOUD program, defined as having administered at least 1 induction dose. Of these active programs, 19 offered bridge dosing and 18 (86%) had administered at least 1 bridge dose. Inclusion criteria for patients were the same for all 21 active MOUD programs. In 20 counties (95%), only Community Paramedics (CPs) or other specialized personnel like EMS Supervisors were authorized to administer MOUD, while 1 county (5%) allowed any paramedic in the system to administer MOUD. With regards to induction therapy and the consensus recommendation of a 16mg dose, 9 counties (43%) utilized this dose for patients experiencing opiate withdrawal, and 13 (62%) counties used this dosing for patients experiencing withdrawal post overdose reversal with naloxone. CONCLUSIONS Prehospital MOUD programs in North Carolina demonstrated broad consistency with only small variations with respect to dosing, funding sources, hours of available treatment, and team composition. This study demonstrated significant consistency with regards to the approaches of NC EMS systems in the care of OUD, providing replicable models other states can use to drive forward prehospital MOUD programs and create a national standard of care. Further studies are needed to link these efforts to associated patient centered outcomes.

Minimally invasive surgery has emerged as a promising approach to the management of advanced-stage epithelial ovarian cancer, particularly in the setting of interval debulking surgery following neoadjuvant chemotherapy. Although primary cytoreduction has traditionally been performed via laparotomy, growing evidence supports the use of neoadjuvant chemotherapy to reduce surgical morbidity without compromising survival, creating new opportunities for minimally invasive surgery. Retrospective and prospective studies consistently report perioperative advantages with minimally invasive surgery, including less blood loss, shorter hospital stay, faster recovery, and earlier resumption of chemotherapy, when applied in carefully selected patients. Importantly, these benefits have yet to be supported by definitive data on long-term oncologic outcomes, underscoring the need for high-quality randomized trials of minimally invasive surgery, which are ongoing. Patient selection remains central to the safe application of minimally invasive surgery. Candidates are typically characterized by favorable response to chemotherapy, limited residual disease, and absence of extensive upper abdominal involvement, with pre-operative assessment supported by imaging, measurement biomarkers such as CA-125, and diagnostic laparoscopy. Despite encouraging feasibility data, adherence to oncologic principles and readiness to convert to laparotomy remain essential safeguards. Parallel technologic advances are expanding the scope of minimally invasive surgery. For example, robotic platforms improve dexterity and ergonomics, whereas intra-operative fluorescence imaging, ultrasound, and augmented-reality navigation offer new ways to identify residual disease and guide cytoreduction. Computational tools, including predictive models, artificial intelligence, and radiomic/pathomic integration, are emerging to refine triage and surgical planning. These innovations, although largely investigational, illustrate the potential of multi-modal integration to enhance both the precision and safety of minimally invasive surgery. Looking forward, the future of minimally invasive surgery will depend on maturation of evidence from randomized trials, broader incorporation of patient-centered outcomes, and integration with precision oncology and adjunct therapies. Minimally invasive surgery holds significant promise to reduce the morbidity of and improve recovery from advanced epithelial ovarian cancer, but its widespread adoption must await confirmation of oncologic equivalence to the open approach.

Outcomes assessed in clinical trials concerning orthodontic retention: A scoping review.

Federally qualified health centers and look-alikes are outpatient care settings that provide primary care and other health services in health professional shortage areas and to their populations. Compiling and disseminating data from these centers that is accessible for patient-centered outcomes research (PCOR) is critical to understanding health care provided at these settings. To describe the National Ambulatory Medical Care Survey Health Center (NAMCS HC) Component, and how this redesigned survey can be utilized to understand health care provided at health centers, improve data capacity, and facilitate PCOR. Beginning in 2021, the NAMCS HC Component began collecting visit data through electronic health record (EHR) submission from a nationally representative sample of FQHCs and FQHC look-alikes. Resulting datasets are made available for researchers to analyze, used to produce readily available interactive data visualizations, and linked to external datasets. The NAMCS HC Component and its resulting data resources are described. Availability of restricted and public datafiles is highlighted, with an example of how these can be used to study visits across different patient characteristics. Interactive dashboards are presented, including how researchers, health centers, and patients can view biannual preliminary visit rates/counts. Finally, linkages between the NAMCS HC Component and external data sources are highlighted, including how these linkages can be used to study health outcomes among different populations. EHR data collected from FQHCs and look-alikes through the redesigned NAMCS HC Component fills a gap to improve PCOR capacity at these unique settings.

Cost Comparison of 2 Different Targets for Glycemic Control in Women With Gestational Diabetes: Evaluation From the TARGET Stepped-Wedge Randomized Trial.

Innovation is no longer optional in health services it is essential. In the face of rising costs, workforce shortages, digital transformation, and increasing public expectations, healthcare systems must move beyond traditional models. Innovation represents a strategic effort to improve quality, enhance efficiency, and ensure long-term sustainability. Achieving high-quality care today requires balancing patient-centered outcomes with responsible resource management. Innovation integrates these goals by redesigning systems, strengthening leadership and collaboration, and leveraging digital and data-driven solutions. From telehealth to community-based prevention, innovation reshapes service delivery to improve resilience and accountability. Sustainable progress demands that innovation be evidence-based, ethical, and equity-oriented. The future of health services depends not on incremental adjustments, but on responsible and strategic innovation that secures lasting impact.

Accurate renal dosing of high dose melphalan as conditioning chemotherapy is critical for patients with multiple myeloma undergoing autologous stem cell transplant (ASCT). In clinical practice, serum creatinine (sCr) is used to eGFR for dosing calculations. The objective of our study was to compare sCr based eGFR to serum cystatin C based eGFR for melphalan dosing in patients undergoing ASCT for multiple myeloma to determine discrepancies in dosing and the effect on patient centered outcomes including chemotherapy-related toxicity, hospitalization and to assess IMWG response criteria at 3 and 12 months. We conducted a retrospective study including 76 patients with multiple myeloma who received melphalan conditioning before ASCT. Melphalan dosing in all patients was based on pre-transplant eGFR calculated from sCr (200 mg/m2 for eGFR >50 mL/min, 140 mg/m2 for eGFR < 50 mL/min). We calculated eGFR using both sCr and cystatin C levels prior to transplantation and observed the 30-day hospitalization from symptoms of melphalan toxicity. We identified a discordant patient group, whose cystatin C eGFR was calculated less than 50 mL/min compared to sCr eGFR >50 mL/min and would have qualified for a reduced melphalan dose. Of 76 patients, 13 (17%) were identified as having received a higher than intended dose of melphalan when eGFR was estimated using sCr rather than cystatin C (200 mg/m2 rather than 140 mg/m2, "discordant dosing"). 100% of discordant patients were hospitalized within 30 days of melphalan dosing compared to 60% of the concordant patients whose eGFR was greater than 50 mL/min with both cystatin C and sCr based eGFR, with melphalan dosing 200 mg/m2 (p = 0.006). Furthermore, patients with discordant dosing had a significantly longer hospitalization duration of 7days compared to 2.5 days in patients with concordant dosing (p=0.0014). More patients qualified for dose reduction using cystatin C based eGFR compared to combined sCr-cystatin C based eGFR (p=0.02). Discordance between creatinine- and cystatin C-based eGFR calculations in ASCT patients was linked to inconsistent melphalan dosing and associated with an increase in adverse outcomes.

Fluid overload (FO) is a common and modifiable risk factor in critically ill neonates. FO is associated with prolonged mechanical ventilation, multi-organ dysfunction, and increased mortality. Despite substantial observational evidence and consensus-driven guidelines, standardized fluid management strategies are inconsistently applied across neonatal intensive care units (NICUs). A critical knowledge gap exists between evidence and practice. Early single-center studies suggest bundle feasibility and effectiveness but are limited in scope and generalizability. Incorporating implementation science frameworks and electronic health record (EHR) data pipeline integration can strengthen adoption, fidelity, adaptation, and sustainability of these interventions across diverse NICU settings. Pragmatic, multicenter studies that utilize EHR-based approaches are needed to help determine how to best implement functional fluid management strategies that improve patient-centered outcomes. Such bundles integrate evidence-based interventions that collectively identify high-risk patients, track, prevent, and treat FO. A structured pathway is needed to enhance scalability and uptake, systematically address barriers, tailor strategies to local contexts, and engage interdisciplinary teams. Bridging the gap between evidence and implementation through collaborative, pragmatic research has the potential to meaningfully reduce FO-related morbidity and mortality and advance neonatal critical care.

Background: Communication failures cause most serious medical errors, with non-acute care environments being particularly vulnerable. While situation-background-assessment-recommendation (SBAR) is proven in acute settings, its safety impact in non-acute clinical settings remains unclear. Methods: This systematic review followed PRISMA 2020 guidelines and a pre-registered protocol (PROSPERO CRD420251139601). We searched PubMed, CINAHL, Cochrane Library, and Ichushi-Web through September 2025. Studies evaluating SBAR interventions for healthcare professionals in non-acute settings were eligible. Two reviewers independently performed selection, extraction, and risk-of-bias assessment (RoB 2, ROBINS-I). Evidence certainty was evaluated using GRADE. Results: Eleven studies (1 RCT, 10 quasi-experimental) were included. SBAR implementation improved structured communication adherence (43.6%-91.0% in long-term care; 4.0%-79.0% in psychiatry). One hemodialysis study reported reduced incidents (36-9 events), but an RCT found no reduction in adverse events despite improved INR control. Staff satisfaction generally improved (87.5% nurses reporting utility). Evidence for patient-centered outcomes was very limited. GRADE certainty was very low. Successful implementation required leadership support, clinical champions, context-specific adaptation, and iterative PDSA cycles; barriers included time constraints and hierarchical culture. Conclusions: SBAR is feasible for standardizing communication in non-acute settings; however, robust evidence of clinical effectiveness is lacking. Successful adoption requires active, context-sensitive strategies guided by implementation science frameworks.

Modern anesthesia is a high-frequency control problem: clinicians must continuously titrate hypnotics, opioids, fluids, and vasopressors to achieve adequate hypnosis/analgesia while avoiding hemodynamic instability and downstream organ injury. Artificial intelligence (AI), machine learning, and classical control engineering are increasingly embedded in perioperative monitors and drug delivery platforms, enabling decision support and closed-loop control. Randomized trials and meta-analyses indicate that closed-loop systems for hypnosis (typically processed EEG targets such as BIS) improve time-in-target and reduce overshoot/undershoot compared with manual titration. Multi-variable systems that co-manage hypnosis, analgesia, and fluids are feasible and may improve short-term recovery outcomes in selected settings. On the hemodynamic side, intraoperative hypotension is common and associated with myocardial and kidney injury, AI-based early warning systems using arterial waveforms can predict hypotension minutes before onset and, when paired with treatment protocols, may reduce hypotension burden in some trials. Closed-loop vasopressor and fluid systems improve protocol adherence and reduce hypotension in perioperative and early postoperative care. AI-enabled decision support and closed-loop controllers can improve stability of anesthesia and blood pressure management, but they should be implemented as supervised systems with clear safety constraints, manual override, and ongoing performance monitoring. Future multicenter trials should prioritize patient-centered outcomes, external validation, and transparent reporting.

Opioid-related iatrogenic harms, including opioid use disorder, overdose, and opioid-induced respiratory depression, constitute a major patient safety challenge. Although clinicians document key safety signals in unstructured clinical narratives, many of these indicators are not readily captured by conventional surveillance approaches that rely on structured administrative data. This clinically focused narrative review synthesizes 47 empirical studies published between 2009 and 2025 that applied artificial intelligence (AI) methods to identify opioid-related harms from clinical text and to address the resulting ascertainment gap. Across studies, administrative coding systems, including ICD-10, often under-ascertain opioid-related events, whereas text-based AI can identify additional cases and contextual details often documented primarily in narrative records, such as fluctuating mental status, suspected drug causality, and responses to naloxone. Methodologically, the literature has progressed from interpretable rule-based lexicons to machine learning and deep learning models and, more recently, to transformer-based approaches, including large language models (LLMs) for classification and schema-driven extraction. Rule-based systems established the feasibility of transparent surveillance and frequently recovered clinically documented cases missed by billing codes. Subsequent supervised and deep learning approaches expanded scalability and, in a smaller subset of studies, were integrated into electronic health record workflows with operational metrics reported. More recent transformer- and LLM-based studies emphasize richer extraction schemas and benchmark development, including characterization of overdose context and intentionality and identification of potential prodromal neurocognitive signals, although external validation, calibration, and prospective outcome evaluation remain inconsistently reported. Given that the evidence base is predominantly retrospective and that clinical workflow studies remain comparatively few, a pragmatic near-term clinical role is to provide detection-to-triage decision support rather than autonomous diagnosis, in which systems surface candidate cases with reviewable evidence for clinician adjudication. Future progress will require greater standardization of phenotype definitions, routine equity auditing and subgroup reporting, stronger external validation and calibration at operational thresholds, and a shift from retrospective discrimination metrics toward prospective assessments of the clinical workflow impact, clinical utility, and patient-centered outcomes.

Palliative care provides person-centred support to alleviate suffering in people with serious illnesses. However, common misconceptions that it is only for end-of-life care often delays timely access. This study aimed to co-design a framework and use it to co-produce resources that enhance public communication and engagement around patient-centred outcomes in palliative care-a field frequently overlooked despite its broader role in improving quality of life throughout the course of illness. Two online co-design workshops, guided by the Knowledge-to-Action framework, engaged patients, public and senior leaders from health and social care systems. Public participants were recruited from the Cicely Saunders Institute Public Involvement Forum, while senior leaders were recruited from integrated care systems and their partners. Both workshops focused on presenting evidence from the CovPall study-a national multicentre cohort study that examined symptom changes in 572 severely ill or dying patients with COVID-19 who received palliative care. As many patients were too unwell to self-report due to the severity of illness, a proxy-reported version of the Integrated Palliative Outcome Scale adapted for COVID-19 was used. Workshops shared these findings and explored effective communication strategies, dissemination formats, stakeholder engagement, and ways to evaluate the impact of such communication. Discussions were analysed using thematic analysis. Eighteen members of the public-including patients, carers, and individuals with lived experience of both roles-along with two local board members and one representative from a statutory health and social care body, participated and were actively involved in developing the framework and co-producing outputs through structured small-group discussions. Key findings highlighted the value of using clear, accessible, and culturally sensitive formats-such as short films and infographics-to reframe public understanding of palliative care as a holistic approach that addresses complex needs beyond just end-of-life care. Participants emphasised the importance of using insights from patient-centred outcomes and Patient-Reported outcome (PRO) data to build workforce capacity, improve services, and strengthen the connection between clinical and personal outcomes to maximise impact. As part of the study, we co-produced two resources that applied this framework in practice, demonstrating its potential to support more effective communication and public engagement. While based on COVID-19 outcome data, the co-produced framework and resources were developed to support communication that is relevant across broader palliative care settings. This study found that communication of patient-centred outcomes and Patient-Reported outcome (PRO) evidence can be strengthened through meaningful patient and public involvement and engagement (PPIE). This approach helps to reframe public understanding of palliative care, highlighting its broader relevance beyond end-of-life settings. The findings show how PPIE can amplify the impact of patient-centred research by engaging wider audiences, promoting timely access to care, and supporting better use of data. While developed in the context of palliative care, the framework offers transferable strategies for communicating complex outcomes in other often misunderstood or stigmatised areas, such as mental health and dementia care.

Same-day, colocated multidisciplinary clinics (MDCs) aim to expedite complex cancer care, yet their added value over sequential referral remains uncertain. We systematically reviewed comparative studies to assess their effects on treatment decisions, timelines, guideline adherence, and survival in newly diagnosed solid tumors. We searched MEDLINE, Embase, and CENTRAL through April 15, 2025, for studies comparing MDCs with routine care. Eligible studies involved same-day, on-site evaluation by ≥2 oncology specialties and at least one clinical or patient-centered outcome. Risk of bias was assessed with Risk of Bias in Non-randomized Studies of Interventions (ROBINS-I). Twenty-seven observational cohorts (>18,000 patients) met inclusion criteria: 17 studies (63%) were rated serious risk of bias and 10 (37%) were rated critical risk on ROBINS-I. Across studies, MDCs shortened the diagnosis-to-treatment interval and improved guideline concordance. A pooled analysis of two comparable cohorts showed that therapy began 9.5 days sooner (95% CI, -16.2 to -2.7 days; I2 = 0%). Guideline adherence averaged 91% with MDCs versus 68% with routine pathways. Eleven series reported management change rates of 24%-52%, most often escalation to multimodality therapy or evidence-based de-escalation. Patient-reported satisfaction exceeded 90% in all five studies capturing this outcome, and two economic analyses documented reduced diagnostic expenditures without shifting cost to patients. A random-effects meta-analysis of two risk-adjusted cohorts showed improved overall survival (pooled hazard ratio, 0.77 [95% CI, 0.68 to 0.87]; τ2 = 0.004; I2 = 51%). Observational evidence suggests that same-day MDCs compress care timelines, raise guideline adherence, and may improve survival, while maintaining high patient satisfaction and neutral out-of-pocket costs. Randomized or quasi-experimental designs are needed to confirm causality and identify the clinic features that drive benefit.

The purpose of this narrative review is to survey the use of diuretic therapy in hospitalized patients with the goal of synthesizing relevant data and describing common strategies for the individualized management of diuresis and de-resuscitation. Careful fluid management is essential for optimizing patient-centered outcomes in hospitalized patients, particularly in those with critical illness. Intravenous fluids are one of the most commonly administered medications in hospitalized patients, but fluids are not benign. Fluid overload is associated with significant adverse events; therefore, the need for fluid stewardship has been recognized in recent years. The majority of research has been devoted to the selection and dosing of fluids in the resuscitation phase to achieve hemodynamic stability. Yet, achieving subsequent euvolemia through de-resuscitation efforts is vital for patient outcomes. Individualization of care and precision medicine are increasingly recognized as important due to the inherent heterogeneity of hospitalized patients. While general de-resuscitation guidance has been developed, a detailed review of the pharmacological management of de-resuscitation (ie, diuretics) in hospitalized patients with the goal to improve diuretic selection and implementation has not been undertaken. Consideration of acute and chronic comorbidities is necessary to properly manage diuretics for de-resuscitation in hospitalized patients, particularly in those with critical illness. More research is needed to determine optimal strategies for individualizing de-resuscitation.

Local public health departments (LHD) geographic distribution and scope of practice result in them as a primary source of care for rural older adults. The 4M's framework (What Matters, Medications, Mentation, Mobility) was developed to assess their needs. Public health is a good fit for implementing the 4M's framework. Phase 1) develop and implement a quality improvement project; Phase 2) adapt the project as needed and measure implementation outcomes (percentage of older adults assessed using the 4Ms; continued agency funding after project end) METHODS: The project utilized the Institute for Healthcare Improvement Plan-Do-Study-Act (PDSA) process to design and measure change. Seven PDSA cycles were conducted over a seven-month period at LHD clinics. 285 participants accessed a clinic with 80 participants completing the 4M's assessment tool for a 28% completion rate. Leadership identified four existing funding sources to reallocate and five potential new grants to sustain the project. Utilizing LHDs is an innovative approach for 4M's implementation. Obtaining data provides valuable information on what is important to older adults. Expansion of the 4M's to other programs, connecting older adults to resources, and tying results to patient-centered outcomes will be important next steps.

This review highlights the growing need for coordinated, multidisciplinary survivorship models for individuals treated for head and neck cancer (HNC), as modern treatments have improved survival for the group but also led to a higher prevalence of complex, multisystem late sequelae. The importance of authorities and academic societies in incorporating rehabilitation as part of treatment in national cancer plans is reviewed. As healthcare systems strive to integrate hospital-based and community-based services, the balance between centralisation of specialisation and the desire for patient-centred care is challenged. The Copenhagen Model for HNC Rehabilitation, provides a structured and standardised framework for assessing patient needs, enhancing care coordination across sectors, and deliver specialised, patient-centred rehabilitation from the early postoperative period through late sequelae, salvage treatment, and advance care planning. Dysphagia remains one of the most frequent and burdensome late sequelae after treatment of HNC, contributing to impaired quality of life, airway protection problems, nutritional concerns, and emotional distress. The Copenhagen Model offers a structured model for managing late sequelae after surgically treated HNC by systematic patient stratification, home-based visits, and multidisciplinary efforts with comprehensive clinical assessments, identifying unmet rehabilitation needs and initiating interventions. This systematic approach has contributed to creating an increased focus on palliative care and advanced care planning and to a greater degree of refraining from treatment. Insights from this model suggest that structured, multidisciplinary team-based rehabilitation can enhance the detection of late effects, promote well tolerated and effective therapeutic strategies, and strengthen patient-centred outcomes in survivorship care. The clinical experience underscores the need for ongoing research to refine interventions, assess long-term functional outcomes, and optimise multidisciplinary collaboration in HNC rehabilitation. Additionally, patients' posttreatment experiences influence clinicians' perspectives on the scope of future treatments, underscoring the need for surgeons' participation in rehabilitation and importance of research into prehabilitation assessment and communication.

Abstract Background Many cancer drugs have been FDA approved based on a drug development paradigm using a maximum tolerated dose (MTD) approach. For targeted anticancer agents, including CDK4/6is, the MTD approach is less relevant, as the optimal biological dose may be lower than the MTD. CDK4/6is are commonly combined with endocrine therapy (ET) for treatment (tx) of HR+/HER2- MBC. Clinical trials and real-world data show that CDK4/6is are commonly dose-reduced to manage side effects and improve tolerability, without loss of efficacy. Benefits of CDK4/6i therapy are similar in younger and older patients (pts); however, toxicity can be worse in older pts leading to more dose reductions, tx interruptions, and discontinuations. We hypothesize that titrated dosing (i.e., initiating tx at lower doses and escalating as tolerated) may enable older pts to remain on tx longer with fewer adverse events (AEs). The CDK Study (NCT06377852), a multicenter, pragmatic, randomized trial, was developed to determine if titrated dosing of palbociclib (P) or ribociclib (R) in pts aged ≥65 years with HR+/HER2- MBC would allow pts to stay on tx longer than the standard FDA-approved indicated dosing approach. This study is funded through a Patient-Centered Outcomes Research Institute (PCORI) Award (BPS-2022C3-26451). Trial Design For CDK4/6i dosing, pts are randomized 1:1 to: Arm 1 (Indicated): FDA-approved dose (P 125 mg or R 600 mg), or Arm 2 (Titrated): provider-choice lower starting dose (P 75 or 100 mg, or R 200 or 400 mg) with escalation to full dose as tolerated. All pts receive CDK4/6i (P or R) for 21 days in a 28-day cycle plus ET (aromatase inhibitor (AI) or fulvestrant (F)), agent selection is by physician choice. Subsequent dose reduction and discontinuation in both arms is per standard-of-care management. Main Eligibility Criteria Eligible pts are ≥65 years old with HR+/HER2- MBC, adequate organ function, and planned ET initiation in combination with first use of P or R in the metastatic setting. Specific Aims The primary aim is to compare time to discontinuation (TTD), on the indicated dosing arm vs. the titrated dosing arm. Secondary aims include evaluation of progression-free survival, overall survival, toxicity, dose intensity, quality of life (PROMIS-29 and FACT-G, AEs, health care utilization), and associations of baseline factors with outcomes. Statistical Methods Randomization is stratified by CDK4/6i (P vs. R), age (65-74 vs. &amp;gt;75 yrs), and ET (AI vs. F). The primary analysis will estimate the hazard ratio (HR) comparing TTD in the two arms using a stratified Cox proportional hazards model. The null hypothesis will be rejected if the 2-sided p-value for the HR is &amp;lt;0.05. A sample size of 500 was based on 80% power to detect a HR of 0.75. Present Accrual and Target Accrual As of July 7, 2025, 30 pts of 500 total pts have enrolled at 13 US clinical centers (80+ locations). Final analysis will occur either after 379 discontinuation events or 24 months after last enrollment. Conclusion The CDK Study will generate evidence to help oncologists and pts make decisions about the optimal dose and dosing strategy for CDK4/6is in older pts. Trial progress demonstrates the feasibility of trials evaluating alternative dosing strategies for FDA-approved anticancer regimens in older adults. Acknowledgements The authors thank Anne Loeser and Bridgette Hempstead, dedicated pt advocates, for their leadership in developing the CDK Study. The statements in this publication are solely the responsibility of the authors and do not necessarily represent the views of PCORI, its Board of Governors or Methodology Committee. Contact Information For more information about the CDK Study (NCT06377852), please contact CDKstudy@asco.org or visit www.cdkstudy.org. Citation Format: A. Gregory, E. L. Mayer, D. Hershman, J. Cowden, R. D. Harvey, K. Kalinsky, A. Magnuson, P. Manohar, T. Pollastro, M. Sedrak, P. A. Spears, R. Thota, D. A. Walker, A. Boose, E. Garrett-Mayer, G. Grantham, D. Hinshaw, C. MacInnis, P. Mangat, J. Perez, J. Gralow. CDK4/6 inhibitor (CDK4/6i) dosing knowledge (CDK) study: A pragmatic randomized trial of indicated vs. titrated CDK4/6i dosing in older adults with HR+/HER2- metastatic breast cancer (MBC) [abstract]. In: Proceedings of the San Antonio Breast Cancer Symposium 2025; 2025 Dec 9-12; San Antonio, TX. Philadelphia (PA): AACR; Clin Cancer Res 2026;32(4 Suppl):Abstract nr PS5-07-08.

Blood pressure is closely monitored during anaesthesia, yet the optimal intraoperative target remains uncertain. This narrative review synthesizes contemporary observational and randomized evidence and explores emerging strategies for individualized haemodynamic management. We reviewed major observational cohort studies, randomized controlled trials (RCTs), consensus statements, and recent technological developments addressing intraoperative hypotension, MAP thresholds, and strategies to prevent perioperative organ injury in adult noncardiac surgery. Large observational datasets consistently demonstrate graded, duration-dependent associations between intraoperative MAP 60-70 mmHg and postoperative myocardial injury, acute kidney injury, and mortality . These findings have informed international recommendations to avoid MAP below 60-65 mmHg. However, contemporary multicentre RCTs enrolling more than 13,000 patients show that targeting higher or individualized MAP thresholds does not improve patient-centred outcomes compared with routine care (typically MAP ≥ 65 mmHg) . Only one small trial reported benefit with individualized systolic targets. Emerging evidence suggests that hypotension reflects heterogeneous haemodynamic endotypes (vasodilation, hypovolaemia, myocardial depression, bradycardia), potentially explaining why uniform pressure targets fail to improve outcomes. Continuous blood pressure monitoring, proactive norepinephrine infusion, predictive analytics, and closed-loop vasopressor systems reliably reduce hypotension exposure, although definitive outcome benefits remain unproven. Observational and randomized data are concordant: MAP ≥ 60-65 mmHg appears sufficient for most noncardiac surgical patients. Future progress will likely depend on mechanistic endotyping, integration of advanced monitoring, and precision-guided haemodynamic strategies rather than escalation of universal MAP targets alone.