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Traditional paradigms for clinical translation are challenged in settings where multiple contemporaneous therapeutic strategies have been identified as potentially beneficial. Platform trials have emerged as an approach for sequentially comparing multiple trials using a single protocol. The Ebola virus disease outbreak in West Africa represents one recent example which utilized a platform design. Specifically, the PREVAIL II master protocol sequentially tested new combinations of therapies against the concurrent, optimal standard of care (oSOC) strategy. Once a treatment demonstrated sufficient evidence of benefit, the treatment was added to the oSOC for all future comparisons (denoted as segments throughout the manuscript). In the interest of avoiding bias stemming from population drift, PREVAIL II considered only within-segment comparisons between the oSOC and novel treatments and failed to leverage data from oSOC patients in prior segments. This article describes adaptive design methodology aimed at boosting statistical power through Bayesian modeling and adaptive randomization. Specifically, the design uses multi-source exchangeability models to combine data from multiple segments and adaptive randomization to achieve information balance within a segment. When compared to the PREVAIL II design, we demonstrate that our proposed adaptive platform design improves power by as much as 51% with limited type-I error inflation. Further, the adaptive platform effectuates more balance with respect to the distribution of acquired information among study arms, with more patients randomized to experimental regimens.

Overuse of continuous cardiac monitoring can lead to poor patient experience, increased costs, and decreased efficiency. Because significant variation in continuous cardiac monitoring ordering exists, implementation strategies that promote care in alignment with practice standards and an examination of use cases that fall outside of standards are needed. The purpose of this study, therefore, was to evaluate if implementation of American Heart Association (AHA) practice standards on continuous cardiac monitoring could reduce utilization without jeopardizing patient safety. We conducted a prospective pre-post study including a 2 year prospectively collected baseline against a 10-month post intervention period within a 10-hospital health system. An electronic health record (EHR) order set was implemented to align care with AHA continuous cardiac monitoring practice standards. We compared continuous cardiac monitoring utilization, adherence to standards, as well as clinical outcomes including mortality and length of stay. Finally, we investigated the rate and impact of hemodynamically significant events (hypotension, bradycardia, and tachycardia) before and after the intervention. We compared 117,814 hospitalizations pre-implementation against 49,006 post implementation finding significant reductions in total telemetry use, and no significant change in outcomes. Overall, patients with telemetry use outside of standards had higher mortality, longer length of stay, and higher readmission rates. The intervention was associated with a higher rate of hypotensive events which occurred off cardiac monitoring. This was not associated with worse outcomes. An EHR tool to align care with continuous cardiac monitoring practice standards safely reduced overall continuous cardiac monitoring utilization. Use outside of practice standards persisted and was primarily focused on monitoring for potential hemodynamic instability. We found no evidence that continuous cardiac monitoring was associated with improved outcomes in unstable patients. Continuous cardiac monitoring for potentially unstable patients can likely be replaced for non-cardiac indications with continuous heart rate monitoring.

Cervical cancer poses a significant threat to Korean American women, who are reported to have one of the highest cervical cancer mortality rates in the United States. Studies consistently report that Korean American women have the lowest Pap test screening rates across US ethnic groups. In response to the need to enhance cervical cancer screening in this vulnerable population, we developed and tested a 7-day mobile phone text message-based cervical cancer Screening (mScreening) intervention designed to promote the receipt of Pap tests by young Korean American women. We developed and assessed the acceptability and feasibility of a 1-week mScreening intervention to increase knowledge of cervical cancer screening, intent to receive screening, and the receipt of a Pap test. Fogg's Behavior Model was the conceptual framework that guided the development of the mScreening intervention. A series of focus groups were conducted to inform the development of the intervention. The messages were individually tailored for each participant and delivered to them for a 7-day period at each participant's preferred time. A quasi-experimental research design of 30 Korean American women aged 21 to 29 years was utilized with baseline, post (1 week after the completion of mScreening), and follow-up (3 months after the completion of mScreening) testing. Findings revealed a significant increase in participants' knowledge of cervical cancer (P<.001) and guidelines for cervical cancer screening (P=.006). A total of 23% (7/30) (95% CI 9.9-42.3) of the mScreening participants received a Pap test; 83% (25/30) of the participants expressed satisfaction with the intervention and 97% (29/30) reported that they would recommend the program to their friends, indicating excellent acceptability and feasibility of the intervention. This study provides evidence of the effectiveness and feasibility of the mScreening intervention. Mobile technology is a promising tool to increase both knowledge and receipt of cervical cancer screening. Given the widespread usage of mobile phones among young adults, a mobile phone-based health intervention could be a low-cost and effective method of reaching populations with low cervical cancer screening rates, using individually tailored messages that cover broad content areas and overcome restrictions to place and time of delivery.

IntroductionApproximately, 20 million older adults undergo major elective surgery annually, yet less than 10% engage in advance care planning (ACP). This is a critical missed opportunity to optimally engage in patient-aligned medical decisions and communications in the perioperative setting. The PREPARE ACP programme (easy-to-read advance directives (ADs) and a patient-directed, online ACP programme) has been shown to increase ACP documentation and patient and clinician empowerment to discuss ACP. Yet, a gap remains in extending PREPARE’s use to surgical populations. We hypothesise that by delivering PREPARE in a patient-facing electronic health record (EHR) centric presurgery workflow for older adults, supported by automated patient reminders and outreach from a healthcare navigator (HCN), we can enable patients and/or surgical teams to engage in ACP discussions.Methods and analysisThis is a three-site, single-blinded, pragmatic randomised trial comparing increasing intensity of ACP-focused, patient-facing EHR messaging and HCN support. The outreach occurs prior to a new presurgical clinic visit. We will enrol 6000 patients (2000 each site) aged 65 and older and randomise them equally to the following study arms: (Arm 1) ACP-related cover letter and PREPARE URL information sent via patient portal and postal mail (includes cover letter, AD and PREPARE pamphlet); (Arm 2) Arm 1 plus reminder message via text or MyChart message and (Arm 3) Arm 2 plus HCN outreach and support. The primary outcome is clinically meaningful ACP documentation in the EHR (ie, surrogate designation, documented discussions and ADs) within 6 months of the new surgical visit. The rate of ACP documentation will be compared between treatment groups using generalised estimating equations. Secondary outcomes include a validated four-item ACP engagement survey, administered 2 weeks after the presurgical visit and 6 months later. All analyses will follow the intention-to-treat principle and recent Consolidated Standards of Reporting Trials guidelines.Ethics and disseminationThe study will be conducted according to the Declaration of Helsinki, Protection of Human Volunteers (21 Code of Federal Regulations (CFR) 50), Institutional Review Boards (21 CFR 56) and Obligations of Clinical Investigators (21 CFR 312). The protocol and consent form were reviewed and approved by Advarra, an National Insitutes of Health (NIH)-approved, commercial, centralised Institutional Review Board (IRB). The IRB/Independent Ethics Committee of each participating centre reviewed and approved the protocol and consent and obtained reliance agreements with Advarra prior to study initiation. The study is guided by input from patient and clinical advisory boards and a data safety monitoring board. The results of the study will be disseminated to both academic and community stakeholders, complying with all applicable privacy laws.Trial registration numberClinicalTrials.gov ID: NCT06090552.Protocol numberAdvarra Pro 00070994.University of California, San Francisco IRB iRIS number23-38948.Protocol Date: 24 October 2024. Protocol Version: 4.

Background Senescent immune cells exhibit altered gene expression and resistance to apoptosis. The prevalence of these cells increases with age and emerging data implicate senescence-associated maladaptive signaling as a potential contributor to sepsis and septic shock. The senolytic drug fisetin promotes clearance of senescent cells and is hypothesized to mitigate septic responses to infection. Methods We are conducting a multi-center, randomized, double-blinded, adaptive allocation phase 2 clinical trial to assess the efficacy of the senolytic drug fisetin in preventing clinical deterioration of elderly patients diagnosed with sepsis. We intend to enroll and randomize 220 elderly patients (age > 65) with the clinical diagnosis of sepsis to receive either fisetin as a single oral dose of 20 mg/kg, fisetin in two oral doses of 20 mg/kg each spaced 1 day apart, or placebo. The primary outcome will be changed in the composite of cardiovascular, respiratory, and renal sequential organ failure assessment scores at 7 days from enrollment. Secondary outcomes include quantification of senescent CD3 + cells at 7 days, and 28-day assessments of organ failure-free days, days in an intensive care unit, and all-cause mortality. Discussion This multi-center, randomized, double-blinded trial will assess the efficacy of fisetin in preventing clinical deterioration in elderly patients with sepsis and measure the effects of this drug on the prevalence of senescent immune cells. We intend that the results of this phase 2 trial will inform the design of a larger phase 3 study. Trial registration This trial is registered to ClinicalTrials.gov under identifier NCT05758246, first posted on March 7, 2023.

Positron Emission Tomography-Computed Tomography (PET-CT) is routinely used for staging and monitoring of human cancer patients and is becoming increasingly available in veterinary medicine. In this study, 18-fluorodeoxyglucose (18FDG)-PET-CT was used in dogs with naturally occurring splenic hemangiosarcoma (HSA) to assess its utility as a staging and monitoring modality as compared to standard radiography and ultrasonography. Nine dogs with stage-2 HSA underwent 18FDG-PET-CT following splenectomy and prior to commencement of chemotherapy. Routine staging (thoracic radiography and abdominal ultrasonography) was performed prior to 18FDG-PET-CT in all dogs. When abnormalities not identified on routine tests were noted on 18FDG-PET-CT, owners were given the option to repeat a PET-CT following treatment with eBAT. A PET-CT scan was repeated on Day 21 in three dogs. Abnormalities not observed on conventional staging tools, and most consistent with malignant disease based on location, appearance, and outcome, were detected in two dogs and included a right atrial mass and a hepatic nodule, respectively. These lesions were larger and had higher metabolic activity on the second scans. 18FDG-PET-CT has potential to provide important prognostic information and influence treatment recommendations for dogs with stage-2 HSA. Additional studies will be needed to precisely define the value of this imaging tool for staging and therapy monitoring in dogs with this and other cancers.

Human papillomavirus (HPV) is a common sexually transmitted infection, causing multiple cancers, including cervical, penile, and anal. Infection and subsequent health risks caused by HPV can be diminished by HPV vaccination. Unfortunately, vaccination rates among Hmong Americans are substantially lower than those among other racial and ethnic groups, despite having higher cervical cancer rates than non-Hispanic White women. Such disparities and sparse literature highlight the need for innovative and culturally appropriate educational interventions to improve HPV vaccine rates in Hmong Americans. We aimed to develop and evaluate the effectiveness and usability of an innovative web-based eHealth educational website, the Hmong Promoting Vaccines website (HmongHPV website), for Hmong-American parents and adolescents to improve their knowledge, self-efficacy, and decision-making capacities to obtain HPV vaccinations. Through social cognitive theory and community-based participatory action research process, we created a theory-driven and culturally and linguistically appropriate website for Hmong parents and adolescents. We conducted a pre-post intervention pilot study to assess the website's effectiveness and usability. Overall, 30 Hmong-American parent and adolescent dyads responded to questions about HPV and HPV vaccine knowledge, self-efficacy, and decision-making at preintervention, 1 week after intervention, and at the 5-week follow-up. Participants responded to survey questions about website content and processes at 1 and 5 weeks, and a subset of 20 dyad participants participated in telephone interviews 6 weeks later. We used paired t tests (2-tailed) to measure the change in knowledge, self-efficacy, and decision-making processes, and used template analysis to identify a priori themes for website usability. Participants' HPV and HPV vaccine knowledge improved significantly from pre- to postintervention stage and follow-up. Knowledge scores increased from preintervention to 1 week after intervention for both parents (HPV knowledge, P=.01; vaccine knowledge, P=.01) and children (HPV knowledge, P=.01; vaccine knowledge, P<.001), which were sustained at the 5-week follow-up. Parents' average self-efficacy score increased from 21.6 at baseline to 23.9 (P=.007) at post intervention and 23.5 (P=.054) at follow-up. Similar improvements were observed in the teenagers' self-efficacy scores (from 30.3 at baseline to 35.6, P=.009, at post intervention and 35.9, P=.006, at follow-up). Collaborative decision-making between parents and adolescents improved immediately after using the website (P=.002) and at follow-up (P=.02). The interview data also revealed that the website's content was informative and engaging; in particular, participants enjoyed the web-based quizzes and vaccine reminders. This theory-driven, community-based participatory action research-designed and culturally and linguistically appropriate educational website was well received. It improved Hmong parents' and adolescents' knowledge, self-efficacy, and decision-making processes regarding HPV vaccination. Future studies should examine the website's impact on HPV vaccine uptake and its potential for broader use across various settings (eg, clinics and schools).

Background Currently, there are no FDA approved screening tools for detecting early stage ovarian cancer in the general population. Development of a biomarker-based assay for early detection would significantly improve the survival of ovarian cancer patients. Methods We used a multiplex approach to identify protein biomarkers for detecting early stage ovarian cancer. This new technology (Proseek ® Multiplex Oncology Plates) can simultaneously measure the expression of 92 proteins in serum based on a proximity extension assay. We analyzed serum samples from 81 women representing healthy, benign pathology, early, and advanced stage serous ovarian cancer patients. Results Principle component analysis and unsupervised hierarchical clustering separated patients into cancer versus non-cancer subgroups. Data from the Proseek ® plate for CA125 levels exhibited a strong correlation with current clinical assays for CA125 (correlation coefficient of 0.89, 95% CI 0.83, 0.93). CA125 and HE4 were present at very low levels in healthy controls and benign cases, while higher levels were found in early stage cases, with highest levels found in the advanced stage cases. Overall, significant trends were observed for 38 of the 92 proteins (p < 0.001), many of which are novel candidate serum biomarkers for ovarian cancer. The area under the ROC curve (AUC) for CA125 was 0.98 and the AUC for HE4 was 0.85 when comparing early stage ovarian cancer versus healthy controls. In total, 23 proteins had an estimated AUC of 0.7 or greater. Using a naïve Bayes classifier that combined 12 proteins, we improved the sensitivity corresponding to 95% specificity from 93 to 95% when compared to CA125 alone. Although small, a 2% increase would have a significant effect on the number of women correctly identified when screening a large population. Conclusions These data demonstrate that the Proseek ® technology can replicate the results established by conventional clinical assays for known biomarkers, identify new candidate biomarkers, and improve the sensitivity and specificity of CA125 alone. Additional studies using a larger cohort of patients will allow for validation of these biomarkers and lead to the development of a screening tool for detecting early stage ovarian cancer in the general population.

Ebola virus causes a devastating clinical illness that is associated with high mortality. In this trial conducted primarily in West Africa during an outbreak, ZMapp (a cocktail of three monoclonal antibodies against Ebola) showed some clinical activity. The 2014–2016 Ebola outbreak in West Africa was unprecedented in sheer scope, duration, and number of human casualties. 1 , 2 The outbreak resulted in more than 28,000 suspected or confirmed cases of Ebola virus disease (EVD) and more than 11,000 deaths. 3 Fragile health care infrastructures that were often already severely compromised by past years of civil strife played a substantial role in the propagation of the outbreak. Although the final postmortem analysis of the global response has yet to be written, there can be little doubt that the lack of therapeutic agents and vaccines with proven efficacy against EVD further contributed . . .

The Food and Drug Administration has the authority to reduce the nicotine content of cigarettes. In this randomized trial, participants assigned to reduced-nicotine cigarettes smoked fewer cigarettes than those assigned to standard-nicotine cigarettes. Twenty years ago, Benowitz and Henningfield published a landmark commentary that coincided with initial attempts by the Food and Drug Administration (FDA) to regulate tobacco products. 1 They reasoned that if the nicotine content of cigarettes were limited to approximately 0.5 mg per cigarette (approximately 0.7 mg per gram of tobacco), cigarettes would be rendered nonaddictive. Although a reduction in nicotine content was endorsed by representatives of the medical community, 2 in 2000, the FDA lost its initial argument to regulate cigarettes in a hearing before the Supreme Court, and the proposal ultimately languished. 3 In the past 8 years, the prospect of . . .