Risk of Stroke or Systemic Embolism According to Baseline Frequency and Duration of Subclinical Atrial Fibrillation: Insights From the ARTESiA Trial.

BACKGROUND: In the ARTESiA trial (Apixaban for the Reduction of Thromboembolism in Patients With Device-Detected Subclinical Atrial Fibrillation), apixaban, compared with aspirin, reduced stroke or systemic embolism in patients with device-detected subclinical atrial fibrillation (SCAF). Clinical guidelines recommend considering SCAF episode duration when deciding whether to prescribe oral anticoagulation for this population. METHODS: We performed a retrospective cohort study in ARTESiA. Using Cox regression adjusted for CHA2DS2-VASc score and treatment allocation (apixaban or aspirin), we assessed frequency of SCAF episodes and duration of the longest SCAF episode in the 6 months before randomization as predictors of stroke risk and of apixaban treatment effect. RESULTS: Among 3986 patients with complete baseline SCAF data, 703 (17.6%) had no SCAF episode ≥6 minutes in the 6 months before enrollment. Among 3283 patients (82.4%) with ≥1 episode of SCAF ≥6 minutes in the 6 months before enrollment, 2542 (77.4%) had up to 5 episodes, and 741 (22.6%) had ≥6 episodes. The longest episode lasted <1 hour in 1030 patients (31.4%), 1 to <6 hours in 1421 patients (43.3%), and >6 hours in 832 patients (25.3%). Higher baseline SCAF frequency was not associated with increased risk of stroke or systemic embolism: 1.1% for 1 to 5 episodes versus 1.2%/patient-year for ≥6 episodes (adjusted hazard ratio, 0.89 [95% CI, 0.59-1.34]). In an exploratory analysis, patients with previous SCAF but no episode ≥6 minutes in the 6 months before enrollment had a lower risk of stroke or systemic embolism than patients with at least one episode during that period (0.5% versus 1.1%/patient-year; adjusted hazard ratio, 0.48 [95% CI, 0.27-0.85]). The frequency of SCAF did not modify the reduction in stroke or systemic embolism with apixaban (Pinteraction=0.1). The duration of the longest SCAF episode in the 6 months before enrollment was not associated with the risk of stroke or systemic embolism during follow-up (<1 hour: 1.0%/patient-year [reference]; 1-6 hours: 1.2%/patient-year [adjusted hazard ratio, 1.27 (95% CI, 0.85-1.90)]; >6 hours: 1.0%/patient-year [adjusted hazard ratio, 1.02 (95% CI, 0.63-1.66)]). SCAF duration did not modify the reduction in stroke or systemic embolism with apixaban (Ptrend=0.1). CONCLUSIONS: In ARTESiA, baseline SCAF frequency and longest episode duration were not associated with risk of stroke or systemic embolism and did not modify the effect of apixaban on reduction of stroke or systemic embolism. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT01938248.

Standard operating protocol for utilizing energy-based devices in aesthetic practice.

BACKGROUND: Lasers and other energy-based devices are increasingly becoming popular in aesthetic practice. Many centers employ doctors or technicians to perform these procedures where treating doctor and operating doctor may be different. Hence the need for standard operative protocols, to be followed while performing these procedures to avoid mistakes, complications and to get optimum results. In the current review article, group of doctors who have worked with these energy-based devices over many years worked together and suggested the protocols to be followed for the most commonly used energy-based procedures. AIM: To provide Standard operating protocols for the operator and staff to ensure, efficacy, safety, for the patient and for the devices. METHODS: The following protocols have been drafted based on the best practices followed by the authors in their clinics and reflect their consensus opinion. The objective is to provide operating protocols in a standard format, which can be of use by practicing dermatologists and their staff. The protocols include both general guidelines for the laser room and specific protocols for different machines. The draft follows the following schema: General instructions for all the energy-based devices. Specific protocols for different devices: Laser hair removal, fractional lasers, Q-switched lasers, fractional microneedling radiofrequency and cryolipolysis. CONCLUSIONS: The protocols proposed help to maintain the uniformity and avoid complications. However, these instructions are generalized and not machine or lesion specific. There may be variations in the protocols depending on the treatment lesion and treating doctor as well as machine.

INDIVIDUAL ARTICLE: Real-World Patient Cases Using Triple Lipid-Containing Cream for Cutaneous Healing Post Laser or Microneedling Radiofrequency Treatment.

Lipids play an essential role in skin barrier health. With age, there is a natural reduction of physiological lipids such as fatty acids, ceramides, and cholesterol. The triple lipid restore cream is a moisturizer that contains an optimized lipid ratio for aging skin. The cream contains a 2:4:2 ratio of ceramides, cholesterol, and fatty acids that have been shown to best support aging skin. The triple lipid restore cream has been used in combination with energy-based procedures, to provide patients with comprehensive integrated skincare regimens. With limited clinical data and guidelines available in regenerative medicine, real-world cases serve as an invaluable guide for patients and dermatologists in navigating rejuvenation treatment plans. J Drugs Dermatol. 2024;23:9(Suppl 1):s3-14.

AI assistance in aesthetic medicine-A consensus on objective medical standards.

BACKGROUND: Aesthetic medicine has traditionally relied on clinical scales for the objective assessment of baseline appearance and treatment outcomes. However, the scales focus on limited aesthetic areas mostly and subjective interpretation inherent in these scales can lead to variability, which undermines standardization efforts. OBJECTIVE: The consensus meeting aimed to establish guidelines for AI application in aesthetic medicine. MATERIALS AND METHODS: In February 2024, the AI Consensus Group, comprising international experts in various specialties, convened to deliberate on AI in aesthetic medicine. The methodology included a pre-consensus survey and an iterative consensus process during the meeting. RESULTS: AI's implementation in Aesthetic Medicine has achieved full consensus for enhancing patient assessment and consultation, ensuring standardized care. AI's role in preventing overcorrection is recognized, alongside the need for validated objective facial assessments. Emphasis is placed on comprehensive facial aesthetic evaluations using indices such as the Facial Aesthetic Index (FAI), Facial Youth Index (FYI), and Skin Quality Index (SQI). These evaluations are to be gender-specific and exclude makeup-covered skin at baseline. Age and gender, as well as patients' ancestral roots, are to be considered integral to the AI assessment process, underlining the move towards personalized, precise treatments. CONCLUSION: The consensus meeting established that AI will significantly improve aesthetic medicine by standardizing patient assessments and consultations, with a strong endorsement for preventing overcorrection and advocating for validated, objective facial assessments. Utilizing indices such as the FAI, FYI, and SQI allows for gender-specific, age adjusted evaluations and insists on a makeup-free baseline for accuracy.

"Effectiveness of minimally invasive injectable modalities in the management of androgenetic alopecia among adults-A systematic review".

BACKGROUND: Androgenetic alopecia is the most common cause of hair loss that affects over 50% of the world population. It is a condition that is multifactorial in origin, with no specific causative factor, making treatment an enervating experience for the patient as well as the doctor. In recent times, a number of modalities have been introduced for the treatment of alopecia. However, the evidence supporting them is unstructured and sparse. Therefore, this article aims to explore the current trends in minimally invasive treatments for the management of androgenetic alopecia. METHODS: An in-depth literature search on injectables used in the treatment of alopecia in PubMed/MEDLINE, Embase, PsycINFO, TRIP Cochrane Library, and Cochrane Skin databases between January 2000 and May 2023 was performed. The studies included were randomized controlled trials, non-randomized trials, quasi trials, single arm interventions, and cohort studies. RESULTS: Sixteen of the 1071 studies that were found during the original search were accepted in accordance with the inclusion criteria. Twelve studies assessed the effectiveness of the injectable group by comparing it to a control group consisting of saline, distilled water, and topical minoxidil. In the treatment of alopecia, dutasteride and injectable growth factor formulations achieved clinically significant results. CONCLUSION: The usage of injectables and topical medicines to treat hair loss has increased in the recent years. Overall results from clinical investigations, pilot studies, and trials looking at the efficacy and safety of these growth factors in the AGA show satisfactory efficacy.

Two-year post-treatment outcomes following peanut oral immunotherapy in the Probiotic and Peanut Oral Immunotherapy-003 Long-Term (PPOIT-003LT) study.

BACKGROUND: Few studies have examined long-term outcomes following oral immunotherapy (OIT); none have examined long-term risks and benefits associated with distinct clinical outcomes (desensitization, remission). METHODS: Participants completing the probiotic and peanut oral immunotherapy (PPOIT) -003 randomized trial were enrolled in a follow-on study, PPOIT-003LT. Peanut ingestion, reactions, and health-related quality of life (HRQOL) were monitored prospectively. Outcomes at 1-year and 2-years post-treatment were examined by treatment group and by post-OIT clinical outcome (remission, desensitization without remission [DWR], allergic). RESULTS: 86% (151/176) of eligible children enrolled. Post-treatment peanut ingestion at 2-years post-treatment were similar for PPOIT (86.7%) and OIT (78.7%) groups, both higher than placebo (10.3%). Reactions reduced over time for all treatment and clinical outcome groups (PPOIT 31.7% to 23.3%, OIT 37.7% to 19.7%, placebo 13.8% to 6.9%; remission 27.5% to 15.9%; DWR 57.9% to 36.8%; allergic 11.6% to 7%). At 2-years post-treatment, similar proportions of remission and allergic participants reported reactions (RD 0.09 (95%CI -0.03, 0.20), p = .127), whereas more DWR participants reported reactions than remission (remission vs DWR: RD -0.21 (95%CI -0.39; -0.03), p = .02) and allergic (DWR vs allergic: RD 0.30 (95%CI 0.13, 0.47), p = .001) participants. At 2-years post-treatment, 0% remission versus 5.3% DWR versus 2.3% allergic participants reported adrenaline injector usage. Remission participants had significantly greater HRQOL improvement (adjusted for baseline) compared with both DWR (MD -0.54 (95%CI -0.99, -0.10), p = .017) and allergic (MD -0.82 (95%CI -1.25, -0.38), p < .001). CONCLUSION: By 2-years post-treatment, remission participants reported fewer reactions, less severe reactions and greater HRQOL improvement compared with DWR and allergic participants, indicating that remission is the patient-preferred treatment outcome over desensitization or remaining allergic.

Advancements in laser technologies for skin rejuvenation: A comprehensive review of efficacy and safety.

INTRODUCTION: Laser technology has fundamentally transformed the landscape of dermatology, offering nuanced solutions for skin rejuvenation and resurfacing. This paper aims to explore the spectrum of laser technologies, from ablative to non-ablative and fractional lasers, their mechanisms, benefits, and tailored applications for diverse skin conditions. As we delve into the intricacies of each technology, we also consider the scientific advancements that have made these treatments safer and more effective, promising a new horizon in skin rejuvenation. OBJECTIVE: This comprehensive analysis seeks to evaluate recent advancements in laser technology for skin rejuvenation, focusing on efficacy, safety, and patient satisfaction. METHODS: The selection criteria for studies in this publication focused on recent, peer-reviewed articles from the last 20 years, emphasizing advancements in laser technologies for skin rejuvenation. Our comprehensive review involved searches in PubMed, Cochrane, Scopus and Google Scholar using keywords like "skin rejuvenation," "laser technology," "efficacy," "safety," and "dermatology." This approach focused on inclusion of recent research and perspectives on the efficacy and safety of laser treatments in the field of dermatology. RESULTS: Our literature review reveals advancements in laser skin resurfacing technologies, notably fractional lasers for minimal downtime rejuvenation, ablative lasers for precise tissue vaporization, and non-ablative lasers for coagulation effect promoting collagen with reduced recovery. Hybrid and picosecond lasers are highlighted for their versatility and effectiveness in addressing a wide array of skin concerns. The findings also emphasize the development of safer treatment protocols for ethnic skin, significantly reducing risks like hyperpigmentation and scarring, thus broadening the scope of effective dermatological solutions. CONCLUSION: This extensive review of advancements in laser technologies for skin rejuvenation underscores a remarkable evolution in dermatological treatments, offering an expansive overview of the efficacy, safety, and patient satisfaction associated with these interventions. Furthermore, the exploration of combination treatments and laser-assisted drug delivery represents a frontier in dermatological practice, offering synergistic effects that could amplify the therapeutic benefits of laser treatments.

A Plain Language Summary of "Dostarlimab for primary advanced or recurrent endometrial cancer".

What is this summary about? Dostarlimab, also known by the brand name JEMPERLI, is a medicine that uses a patient's own immune system to treat endometrial cancer. Dostarlimab is a type of medicine called an immunotherapy. Immunotherapies help the immune system find and attack cancer cells. Dostarlimab stops cancer cells from being able to hide from the immune system, which allows the patient to have a boosted immune response against their cancer.The RUBY study is a phase 3 clinical study of primary advanced (cancer that has spread outside the uterus) or recurrent (cancer that has come back) endometrial cancer. A phase 3 clinical study looks at how well a new treatment works compared to the standard, or usual, treatment in a large patient population. The RUBY study is testing how well dostarlimab given with chemotherapy, followed by dostarlimab alone, works at delaying primary advanced or recurrent endometrial cancer from getting worse and preventing patients from dying, compared to chemotherapy given alone (the current standard treatment for primary advanced or recurrent endometrial cancer).What were the results? When dostarlimab was given with chemotherapy, this combination was found to delay primary advanced or recurrent endometrial cancer from getting worse and to prevent patients from dying, compared with chemotherapy given alone (without dostarlimab). Patients in the study who received dostarlimab with chemotherapy had a 36% lower risk of dying or having their cancer get worse.What do the results mean? The results from this study contributed to the approval of dostarlimab with chemotherapy as a new treatment option for patients with mismatch repair deficient/microsatellite instability-high primary advanced or recurrent endometrial cancer. As of the publication of this plain language summary of publication (PLSP), this combination of dostarlimab with chemotherapy has been approved in the United States of America, the United Kingdom, the European Union and Hong Kong.Clinical Trial Registration: NCT03981796 (RUBY).

Facilitating the use of the target product profile in academic research: a systematic review.

BACKGROUND: The Target Product Profile (TPP) is a tool used in industry to guide development strategies by addressing user needs and fostering effective communication among stakeholders. However, they are not frequently used in academic research, where they may be equally useful. This systematic review aims to extract the features of accessible TPPs, to identify commonalities and facilitate their integration in academic research methodology. METHODS: We searched peer-reviewed papers published in English developing TPPs for different products and health conditions in four biomedical databases. Interrater agreement, computed on random abstract and paper sets (Cohen's Kappa; percentage agreement with zero tolerance) was > 0.91. We interviewed experts from industry contexts to gain insight on the process of TPP development, and extracted general and specific features on TPP use and structure. RESULTS: 138 papers were eligible for data extraction. Of them, 92% (n = 128) developed a new TPP, with 41.3% (n = 57) focusing on therapeutics. The addressed disease categories were diverse; the largest (47.1%, n = 65) was infectious diseases. Only one TPP was identified for several fields, including global priorities like dementia. Our analyses found that 56.5% of papers (n = 78) was authored by academics, and 57.8% of TPPs (n = 80) featured one threshold level of product performance. The number of TPP features varied widely across and within product types (n = 3-44). Common features included purpose/context of use, shelf life for drug stability and validation aspects. Most papers did not describe the methods used to develop the TPP. We identified aspects to be taken into account to build and report TPPs, as a starting point for more focused initiatives guiding use by academics. DISCUSSION: TPPs are used in academic research mostly for infectious diseases and have heterogeneous features. Our extraction of key features and common structures helps to understand the tool and widen its use in academia. This is of particular relevance for areas of notable unmet needs, like dementia. Collaboration between stakeholders is key for innovation. Tools to streamline communication such as TPPs would support the development of products and services in academia as well as industry.

Outcomes of Cardiac Resynchronization Therapy by New York Heart Association Class: A Patient-Level Meta-Analysis.

BACKGROUND: Data on the benefits of cardiac resynchronization therapy (CRT) in patients with severe heart failure symptoms are limited. We investigated the relative effects of CRT in patients with ambulatory New York Heart Association (NYHA) IV versus III functional class at the time of device implantation. METHODS AND RESULTS: In this meta-analysis, we pooled patient-level data from the MIRACLE (Multicenter InSync Randomized Clinical Evaluation), MIRACLE-ICD (Multicenter InSync Implantable Cardioversion Defibrillation Randomized Clinical Evaluation), and COMPANION (Comparison of Medical Therapy, Pacing, and Defibrillation in Heart Failure) trials. Outcomes evaluated were time to the composite end point of the first heart failure hospitalization or all-cause mortality, and time to all-cause mortality alone. The association between CRT and outcomes was evaluated using a Bayesian hierarchical Weibull survival regression model. We assessed if this association differed between NYHA III and IV groups by adding an interaction term between CRT and NYHA class as a random effect. A sensitivity analysis was performed by including data from RAFT (Resynchronization-Defibrillation for Ambulatory Heart Failure). Our pooled analysis included 2309 patients. Overall, CRT was associated with a longer time to heart failure hospitalization or all-cause mortality (adjusted hazard ratio [aHR], 0.79 [95% credible interval [CI], 0.64-0.99]; posterior probability or P=0.044), with a similar association with time to all-cause mortality (aHR, 0.78 [95% CI, 0.59-1.03]; P=0.083). Associations of CRT with outcomes were not significantly different for those in NYHA III and IV classes (ratio of aHR, 0.72 [95% CI, 0.30-1.27]; P=0.23 for heart failure hospitalization/mortality; ratio of aHR, 0.70 [95% CI, 0.35-1.34]; P=0.27 for all-cause mortality alone). The sensitivity analysis, including RAFT data, did not show a significant relative CRT benefit between NYHA III and IV classes. CONCLUSIONS: Overall, there was no significant difference in the association of CRT with either outcome for patients in NYHA functional class III compared with functional class IV.

Enhanced skin regeneration and therapeutic delivery using novel diamond-augmented zinc oxide.

BACKGROUND: Recent advancements in dermatological therapeutics have highlighted the need for treatments that enhance skin regeneration and healing. Diamond-Augmented Zinc Oxide (ND-ZnO) technology combines zinc oxide with diamond particles in a unique core-shell structure, offering a multifaceted approach to overall skin health. AIMS: This study evaluates the efficacy of ND-ZnO in promoting human dermal fibroblast migration and growth, enhancing total collagen synthesis, and improving transdermal delivery of active ingredients as a daily comprehensive skin regeneration topical therapy. PATIENTS/METHODS: In vitro assays assessed wound healing, collagen production, and skin absorption. Human Dermal Fibroblasts (HDFs) were used in scratch wound assays. Collagen synthesis was quantified using enzyme-linked immunosorbent assays (ELISA). Permeation tests were performed on reconstructed human epidermal tissues to evaluate niacinamide absorption. Clinical case studies validated ND-ZnO efficacy in post-CO2 laser treatments and Actinic Keratosis removal recovery. RESULTS: ND-ZnO increased HDF migration by 198% compared to controls. Collagen synthesis assays showed a 71.3% restoration of collagen production in aged HDFs. Skin permeation studies revealed a 203% increase in niacinamide skin absorption with ND-ZnO. Clinical case studies demonstrated faster and more effective healing post-ablative CO2 laser and significant improvements in Actinic Keratosis recovery. CONCLUSIONS: ND-ZnO technology enhances wound healing, collagen synthesis, and active ingredient delivery, offering substantial benefits for daily skin regeneration and other dermatological applications. This innovative approach holds promise for advancing dermatological therapeutics, providing comprehensive skin care solutions that address both protective and regenerative needs.

Leadless Ultrasound-Based Cardiac Resynchronization System in Heart Failure.

Importance: Approximately 40% of patients with heart failure (HF) who are eligible for cardiac resynchronization therapy (CRT) either fail to respond or are untreatable due to anatomical constraints. Objective: To assess the safety and efficacy of a novel, leadless, left ventricular (LV) endocardial pacing system for patients at high risk for a CRT upgrade or whose coronary sinus (CS) lead placement/pacing with a conventional CRT system failed. Design, Setting, and Participants: The SOLVE-CRT study was a prospective multicenter trial, enrolling January 2018 through September 2022, with follow-up in March 2023. Data were analyzed from DATE MONTH, YEAR, through DATE MONTH, YEAR. The trial combined data from an initial randomized, double-blind study (n = 108) and a subsequent single-arm part (n = 75). It took place at 36 centers across Australia, Europe, and the US. Participants were nonresponders, previously untreatable (PU), or high-risk upgrades (HRU). All participants contributed to the safety analysis. The primary efficacy analysis (n = 100) included 75 PU-HRU patients from the single-arm part and 25 PU-HRU patients from the randomized treatment arm. Interventions: Patients were implanted with the WiSE CRT System (EBR Systems) consisting of a leadless LV endocardial pacing electrode stimulated with ultrasound energy delivered by a subcutaneously implanted transmitter and battery. Main Outcomes and Measures: The primary safety end point was freedom from type I complications. The primary efficacy end point was a reduction in mean LV end systolic volume (LVESV). Results: The study included 183 participants; mean age was 68.1 (SD, 10.3) years and 141 were male (77%). The trial was terminated at an interim analysis for meeting prespecified stopping criteria. In the safety population, patients were either New York Heart Association Class II (34.6%) or III (65.4%). The primary efficacy end point was met with a 16.4% (95% CI, -21.0% to -11.7%) reduction in mean LVESV (P = .003). The primary safety end point was met with an 80.9% rate of freedom from type I complications (P < .001), which included 12 study device system events (6.6%), 5 vascular events (2.7%), 3 strokes (1.6%), and 7 cardiac perforations which mostly occurred early in the study (3.8%). Conclusions and Relevance: The SOLVE-CRT study has demonstrated that leadless LV endocardial pacing with the WiSE CRT system is associated with a reduction in LVESV in patients with HF. This novel system may represent an alternative to conventional CRT implants in some HF patient populations. Trial Registration: ClinicalTrials.gov Identifier: NCT0292203.

A global perspective on the treatment and maintenance of mature skin using gentle cleansers and moisturizers.

Xerosis is highly prevalent in the population aged over 50 years and substantially impacts quality of life due to the associated stigma, related pruritus, and potential sequelae. We propose that the term mature xerosis be used for subjects over 50 who suffer from age-related xerosis and replace senile xerosis to describe the phenomenon. The etiology of xerosis depends on genetic and environmental factors that affect stratum corneum hydration and skin barrier function. Skincare to restore barrier function is essential in xerosis treatment and is relevant for maintaining and preventing its progression. Many moisturizers and cleansers are available for xerosis; however, they are underutilized by patients with mature xerosis. A panel of eight global dermatologists reviewed the unique aspects of xerosis in mature skin and discussed the specific needs, relevance, and considerations for skincare selection to prevent, treat, and maintain skin with mature xerosis. The panel selected five statements based on evidence from a literature review and the panel's clinical experience to provide clinical considerations and recommendations for dermatologists and other healthcare providers treating patients with mature xerosis. Increased recognition of the burden of xerosis in mature skin is warranted. Gentle cleansers and barrier-restoring ceramide-containing moisturizers are essential to xerosis management, reducing signs and symptoms of xerosis, including associated pruritus.

Association Between the Use of an Adaptive Cardiac Resynchronization Therapy Algorithm and Health Care Use and Cost.

OBJECTIVES: To assess the association between the use of adaptive pacing on clinical and economic outcomes of cardiac resynchronization therapy (CRT) recipients in a real-world analysis. BACKGROUND: The adaptivCRT (aCRT) algorithm was shown in prior subgroup analyses of prospective trials to achieve clinical benefits, but a large prospective trial showed nonsignificant changes in the endpoint of mortality or hospitalizations due to heart failure. METHODS: CRT-implanted patients from the Optum Clinformatics database with ≥ 90 days of follow-up were included. Remote monitoring data were used to classify patients based on CRT setting-adaptive biventricular and left ventricular pacing (aCRT) vs standard biventricular pacing (Standard CRT). Inverse probability of treatment weighting was used to adjust for baseline differences between groups. Mortality, 30-day readmissions, health care use, and payer and patients' costs were evaluated post-implantation. RESULTS: This study included 2412 aCRT and 1638 Standard CRT patients (mean follow-up: 2.4 ± 1.4 years), with balanced baseline characteristics after adjustment. The aCRT group was associated with lower all-cause mortality rates (adjusted hazard ratio = 0.88 [95% confidence interval (CI):0.80, 0.96]), fewer all-cause 30-day readmissions (adjusted incidence rate ratio = 0.87 [CI:0.81, 0.94]), and fewer all-cause and HF-related inpatient, outpatient and emergency department visits. The aCRT cohort was also associated with lower all-cause outpatient payer-paid amounts and lower all-cause and HF-related inpatient and emergency department patient-paid amounts. CONCLUSIONS: In this retrospective analysis of a large real-world cohort, the use of an adaptive CRT algorithm was associated with lower mortality rates, reduced health care resource use and lower payer and patient costs.

Apixaban vs Aspirin According to CHA2DS2-VASc Score in Subclinical Atrial Fibrillation: Insights From ARTESiA.

BACKGROUND: ARTESiA (Apixaban for the Reduction of Thrombo-Embolism in Patients With Device-Detected Sub-Clinical Atrial Fibrillation) demonstrated that apixaban, compared with aspirin, significantly reduced stroke and systemic embolism (SE) but increased major bleeding in patients with subclinical atrial fibrillation. OBJECTIVES: To help inform decision making, the authors evaluated the efficacy and safety of apixaban according to baseline CHA2DS2-VASc score. METHODS: We performed a subgroup analysis according to baseline CHA2DS2-VASc score and assessed both the relative and absolute differences in stroke/SE and major bleeding. RESULTS: Baseline CHA2DS2-VASc scores were <4 in 1,578 (39.4%) patients, 4 in 1,349 (33.6%), and >4 in 1,085 (27.0%). For patients with CHA2DS2-VASc >4, the rate of stroke was 0.98%/year with apixaban and 2.25%/year with aspirin; compared with aspirin, apixaban prevented 1.28 (95% CI: 0.43-2.12) strokes/SE per 100 patient-years and caused 0.68 (95% CI: -0.23 to 1.57) major bleeds. For CHA2DS2-VASc <4, the stroke/SE rate was 0.85%/year with apixaban and 0.97%/year with aspirin. Apixaban prevented 0.12 (95% CI: -0.38 to 0.62) strokes/SE per 100 patient-years and caused 0.33 (95% CI: -0.27 to 0.92) major bleeds. For patients with CHA2DS2-VASc =4, apixaban prevented 0.32 (95% CI: -0.16 to 0.79) strokes/SE per 100 patient-years and caused 0.28 (95% CI: -0.30 to 0.86) major bleeds. CONCLUSIONS: One in 4 patients in ARTESiA with subclinical atrial fibrillation had a CHA2DS2-VASc score >4 and a stroke/SE risk of 2.2% per year. For these patients, the benefits of treatment with apixaban in preventing stroke/SE are greater than the risks. The opposite is true for patients with CHA2DS2-VASc score <4. A substantial intermediate group (CHA2DS2-VASc =4) exists in which patient preferences will inform treatment decisions. (Apixaban for the Reduction of Thrombo-Embolism in Patients With Device-Detected Sub-Clinical Atrial Fibrillation; NCT01938248).

Efficacy and Safety of RelabotulinumtoxinA, a New Ready-to-Use Liquid Formulation Botulinum Toxin: Results From the READY-1 Double-Blind, Randomized, Placebo-Controlled Phase 3 Trial in Glabellar Lines.

BACKGROUND: RelabotulinumtoxinA (RelaBoNT-A, Galderma, Uppsala, Sweden) is an innovative, ready-to-use liquid botulinum toxin A, produced using PEARLTM manufacturing technology that yields a potent, complex-free formulation. OBJECTIVES: The READY-1 study examined efficacy and safety outcomes following a single RelaBoNT-A treatment for glabellar line correction. METHODS: Adults with moderate-to-severe glabellar lines received RelaBoNT-A (50 U) or placebo in a 3:1 randomized, 6-month, Phase 3, multicenter, double-blind study. Primary endpoints (examined at Month 1, maximum frown) comprised the composite ≥2-grade response, defined as ≥2-grades' improvement from baseline on concurrent investigator (GL-ILA) and subject (GL-SLA) severity scales (US endpoint), and the investigator-reported responder rate for subjects scored as 0 (none) or 1 (mild) (GL-ILA scale only; EU endpoint). Subject satisfaction and treatment-emergent adverse events (TEAEs) were reported. RESULTS: Overall, 297 adults were randomized and treated. Month 1 composite ≥2-grade responder rate was 82.9% (RelaBoNT-A, N=199) versus 0% (placebo, N=67; p<0.001). Month 1 investigator-reported none-or-mild responder rate was 96.3% (RelaBoNT-A) versus 4.5% (placebo; p<0.001). GL-ILA scores (none-or-mild; ≥1-grade improvement) remained higher with RelaBoNT-A (23.6%; 58.1%) versus placebo (1.5%; 10.4%) through Month 6 (p<0.001). In the Kaplan-Meier analysis, 75% still showed GL-ILA and GL-SLA improvements from baseline at 169 days (end-of-study). Subjects reported onset of effect from Day 1 (39%) and satisfaction with natural-looking results (96.8%; Month 1). RelaBoNT-A-related TEAEs were low (3.6%) and typically mild. CONCLUSIONS: A single RelaBoNT-A treatment was effective and demonstrated a favorable safety profile. RelaBoNT-A provided significant improvements in glabellar line severity, high satisfaction, rapid onset, and enduring effectiveness throughout the 6-month study period.

Immunogenicity, reactogenicity, and IgE-mediated immune responses of a mixed whole-cell and acellular pertussis vaccine schedule in Australian infants: A randomised, double-blind, noninferiority trial.

BACKGROUND: In many countries, infant vaccination with acellular pertussis (aP) vaccines has replaced use of more reactogenic whole-cell pertussis (wP) vaccines. Based on immunological and epidemiological evidence, we hypothesised that substituting the first aP dose in the routine vaccination schedule with wP vaccine might protect against IgE-mediated food allergy. We aimed to compare reactogenicity, immunogenicity, and IgE-mediated responses of a mixed wP/aP primary schedule versus the standard aP-only schedule. METHODS AND FINDINGS: OPTIMUM is a Bayesian, 2-stage, double-blind, randomised trial. In stage one, infants were assigned (1:1) to either a first dose of a pentavalent wP combination vaccine (DTwP-Hib-HepB, Pentabio PT Bio Farma, Indonesia) or a hexavalent aP vaccine (DTaP-Hib-HepB-IPV, Infanrix hexa, GlaxoSmithKline, Australia) at approximately 6 weeks old. Subsequently, all infants received the hexavalent aP vaccine at 4 and 6 months old as well as an aP vaccine at 18 months old (DTaP-IPV, Infanrix-IPV, GlaxoSmithKline, Australia). Stage two is ongoing and follows the above randomisation strategy and vaccination schedule. Ahead of ascertainment of the primary clinical outcome of allergist-confirmed IgE-mediated food allergy by 12 months old, here we present the results of secondary immunogenicity, reactogenicity, tetanus toxoid IgE-mediated immune responses, and parental acceptability endpoints. Serum IgG responses to diphtheria, tetanus, and pertussis antigens were measured using a multiplex fluorescent bead-based immunoassay; total and specific IgE were measured in plasma by means of the ImmunoCAP assay (Thermo Fisher Scientific). The immunogenicity of the mixed schedule was defined as being noninferior to that of the aP-only schedule using a noninferiority margin of 2/3 on the ratio of the geometric mean concentrations (GMR) of pertussis toxin (PT)-IgG 1 month after the 6-month aP. Solicited adverse reactions were summarised by study arm and included all children who received the first dose of either wP or aP. Parental acceptance was assessed using a 5-point Likert scale. The primary analyses were based on intention-to-treat (ITT); secondary per-protocol (PP) analyses were also performed. The trial is registered with ANZCTR (ACTRN12617000065392p). Between March 7, 2018 and January 13, 2020, 150 infants were randomised (75 per arm). PT-IgG responses of the mixed schedule were noninferior to the aP-only schedule at approximately 1 month after the 6-month aP dose [GMR = 0·98, 95% credible interval (0·77 to 1·26); probability (GMR > 2/3) > 0·99; ITT analysis]. At 7 months old, the posterior median probability of quantitation for tetanus toxoid IgE was 0·22 (95% credible interval 0·12 to 0·34) in both the mixed schedule group and in the aP-only group. Despite exclusions, the results were consistent in the PP analysis. At 6 weeks old, irritability was the most common systemic solicited reaction reported in wP (65 [88%] of 74) versus aP (59 [82%] of 72) vaccinees. At the same age, severe systemic reactions were reported among 14 (19%) of 74 infants after wP and 8 (11%) of 72 infants after aP. There were 7 SAEs among 5 participants within the first 6 months of follow-up; on blinded assessment, none were deemed to be related to the study vaccines. Parental acceptance of mixed and aP-only schedules was high (71 [97%] of 73 versus 69 [96%] of 72 would agree to have the same schedule again). CONCLUSIONS: Compared to the aP-only schedule, the mixed schedule evoked noninferior PT-IgG responses, was associated with more severe reactions, but was well accepted by parents. Tetanus toxoid IgE responses did not differ across the study groups. TRIAL REGISTRATION: Trial registered at the Australian and New Zealand Clinical 207 Trial Registry (ACTRN12617000065392p).