Short-term health system responses to epidemics across hard to reach areas in sub-Saharan Africa: A scoping review protocol.

Epidemics and Pandemics (disease outbreaks) are the occurrence of cases of disease in excess of what would be normally expected. Epidemic-prone diseases, including emerging and re-emerging diseases, constitute the greatest threat to public health security and disruption of social and economic development. When outbreaks are diagnosed in specific areas, an outbreak response is triggered to stop the spread rapidly. In the past 20 years, the sub-Saharan region has witnessed a marked increase in the number of outbreaks in pandemics, such as cholera, dengue, A/H5N 1 influenza among others. While efforts toward containment have been individually studied, we have no recent studies that examine them collectively in order to draw appropriate comparisons, no recent studies that have especially focused on hard-to-reach areas, and none that have applied a health systems lens. This study thus details a scoping review of short-term health system responses to epidemics across hard-to-reach areas in sub-Saharan Africa. The scoping review will be undertaken following PRISMA guidelines. A modified Donabedian framework will be used to understand the different approaches used while responding to epidemics. The review will focus on published and unpublished studies that report short-term health systems responses to epidemics in hard to reach areas. These will be gleaned from PubMed, google scholar and Cochrane, supplemented by a Google advanced search. In addition, manual searches will be carried out through related articles and websites. Data will be charted, coded, and narratively synthesized. our exclusion criteria will include; protocols, book chapters and countries not identified as hard to reach areas in SSA. We anticipate developing a document that will show the different approaches health systems in different countries used when responding to epidemics. The information generated will contribute to strengthening future epidemic responses by identifying best practices and innovative ideas as well as highlighting knowledge gaps.

The socio-cultural contexts shaping health-seeking behaviours among community members regarding childhood cancer in Tanzania: A qualitative study.

BACKGROUND: Timely diagnosis of childhood cancer, early hospital presentation and completion of treatment significantly improve outcomes. Unfortunately, in Tanzania, thousands of children die of cancer each year without ever being diagnosed or treated. To reduce childhood death from cancer, it is important to understand the social-cultural context, values and beliefs that influence healthcare-seeking behaviours among the Tanzanian community. METHODS: This was a cross-sectional qualitative study conducted in Mwanza, Kilimanjaro and Dar-es-Salaam regions between March and June 2021. We purposively selected community members aged ≥18 years from three rural and three urban settings to participate in seven focus group discussions (each with eight to 12 respondents). The participants were from communities without any affiliation to the treatment of children with cancer or treatment facilities. We transcribed, coded and analyzed data using a thematic-content approach with the support of NVIVO 12 software. RESULTS: Many had heard of breast or cervical cancer; however, most were unaware of childhood cancer. Adults believe that cancer in children is caused by witchcraft and cannot be cured by modern medicines available at hospitals. These beliefs lead parents to first seek care from traditional healers, which hence delay presentation to the hospital. Other community concerns included the cost of transportation, investigation-related costs, and the long duration of treatment. These have an influence on treatment adherence leading to seeking alternative treatment, such as spiritual or traditional treatment. CONCLUSION: Low community awareness, late hospital presentation, and treatment abandonment remain a challenge in childhood cancer in most parts of Tanzania. Belief about childhood cancer being a result of witchcraft and superstition contributes to limited health-seeking behaviours. Cultural and contextually relevant awareness campaign interventions are needed to increase cancer knowledge in Tanzanian communities.

Robotic-assisted coronary artery bypass grafting: how I teach it.

The first robotic cardiac operation was performed more than two decades ago. This paper describes the distinct steps and components necessary for teaching robotic-assisted minimally invasive direct coronary artery bypass (R-MIDCAB). It also provides a general overview of the surgical robotic setup and ways to troubleshoot potential complications. The focus of robotic training is not only on the surgeon but includes an entire dedicated cardiac team and administrative institutional support. This team approach ensures that R-MIDCAB can be performed safely and reproducibly. Meticulous planning, incremental learning, and teamwork are the main factors leading to program success and optimal patient outcomes. Robotic-assisted internal mammary artery (IMA) harvesting and coronary revascularization via a small, anterior mini-thoracotomy has provided an alternative to sternotomy in selected patients with coronary artery disease (CAD). Benefits include less postoperative atrial fibrillation, fewer blood transfusion, less time in the operating room (OR), less ventilatory support, fewer strokes, decreased intensive care unit stay and shortened postoperative length of stay all of which manifests as a decrease in institutional resource utilization. Recent data show that R-MIDCAB and hybrid coronary revascularization provides good long-term outcomes. In addition to patient satisfaction, there is an additional overall cost benefit to R-MIDCAB over traditional sternotomy coronary artery bypass grafting (CABG), secondary to decreased hospital length of stay. Robotically harvesting the IMA, operating on a beating heart, and performing anastomoses through a small incision all require advanced training and incremental learning. Increased experience generally leads to shortened surgical times and fewer complications.

Human tactile sensing and sensorimotor mechanism: from afferent tactile signals to efferent motor control.

In tactile sensing, decoding the journey from afferent tactile signals to efferent motor commands is a significant challenge primarily due to the difficulty in capturing population-level afferent nerve signals during active touch. This study integrates a finite element hand model with a neural dynamic model by using microneurography data to predict neural responses based on contact biomechanics and membrane transduction dynamics. This research focuses specifically on tactile sensation and its direct translation into motor actions. Evaluations of muscle synergy during in -vivo experiments revealed transduction functions linking tactile signals and muscle activation. These functions suggest similar sensorimotor strategies for grasping influenced by object size and weight. The decoded transduction mechanism was validated by restoring human-like sensorimotor performance on a tendon-driven biomimetic hand. This research advances our understanding of translating tactile sensation into motor actions, offering valuable insights into prosthetic design, robotics, and the development of next-generation prosthetics with neuromorphic tactile feedback.

Navigating the Web of Influence: A Bibliometric Analysis of Social Media Addiction.

Social media addiction is a behavioral dependency characterized by excessive and compulsive use of social media platforms, leading to negative impacts on various aspects of an individual's life. Bibliometric analysis is a research method used to quantitatively analyze academic literature, such as articles, books, and conference papers. It involves the application of statistical and mathematical tools to study the patterns and trends in scientific publications. This bibliometric study provides a comprehensive analysis of the literature on social media addiction, revealing patterns and dynamics within the field. Utilizing Web of Science for bibliographic data, the study employs advanced bibliometric tools like Biblioshiny and CiteSpace to map the scientific landscape. Annual scientific production, top contributing authors, key sources, trending topics, and thematic maps were identified using Biblioshiny. Additionally, network visualizations, such as co-citation networks of authors, time zone network visualizations of keyword co-occurrence, and timeline network visualizations of country collaborations, were created using CiteSpace. Our findings present an increasing trend in publications over the years, highlighting a growing recognition of social media addiction's significance. We detail the most relevant authors and sources, pinpointing key contributors and influential journals that shape the discourse. Trend topics analysis uncovers the prevalent themes, with "internet addiction" and "adolescents" at the forefront, reflecting the field's concentration on the younger population. The thematic map categorizes the research into motor themes (driving research areas), basic themes (fundamental and well-established areas), and niche themes (specialized and emerging topics), providing insight into the central and evolving topics. The study also delves into the co-occurrence of all keywords and the co-citation of authors, illustrating the interconnected nature of the research community. A timeline network visualization of country collaborations underscores the global scope of research efforts. Importantly, the study identifies critical research gaps such as underexplored demographics and emerging digital concerns and discusses practical implications, including the need for targeted intervention programs and informed policy-making. Collectively, this study charts the trajectory of social media addiction research and lays a foundation for future explorations to address identified lacunae.

Longitudinal trials illustrate interactive effects between declining Bt efficacy against Helicoverpa zea (Lepidoptera: Noctuidae) and planting dates of corn.

Helicoverpa zea (Boddie) (Lepidoptera: Noctuidae) has evolved resistance to insecticidal toxins from Bacillus thuringiensis (Bt) Berliner (Bacillales: Bacillaceae) expressed in genetically engineered corn, Zea mays L. This study provides an overview of field trials from Georgia, North Carolina, and South Carolina evaluating Bt and non-Bt corn hybrids from 2009 to 2022 to show changes in susceptibility in H. zea to Bt corn. The reduction in kernel injury relative to a non-Bt hybrid averaged across planting dates generally declined over time for Cry1A.105 + Cry2Ab2 corn. In addition, there was a significant interaction with planting date used as a covariate. The reduction in kernel injury remained above 80% and did not vary with planting date from 2009 to 2014, whereas a significant decline with planting date was found in this reduction from 2015 to 2022. For Cry1Ab + Cry1F corn, the reduction in kernel injury relative to a non-Bt hybrid averaged across planting dates did not vary among years. The reduction in kernel injury significantly declined with planting date from 2012 to 2022. Kernel injury as a proxy for H. zea pressure was greater in late-planted trials in non-Bt corn hybrids. Our study showed that Bt hybrids expressing Cry1A.105 + Cry2Ab2 are now less effective in later planted trials in reducing H. zea injury; however, this was not the case during the earlier years of adoption of corn expressing these 2 toxins when resistance alleles were likely less frequent in H. zea populations. The implications for management of H. zea and for insect resistance management are discussed.

Characterizing a complex CT-rich haplotype in intron 4 of SNCA using large-scale targeted amplicon long-read sequencing.

Parkinson's disease (PD) is a common neurodegenerative disorder with a significant risk proportion driven by genetics. While much progress has been made, most of the heritability remains unknown. This is in-part because previous genetic studies have focused on the contribution of single nucleotide variants. More complex forms of variation, such as structural variants and tandem repeats, are already associated with several synucleinopathies. However, because more sophisticated sequencing methods are usually required to detect these regions, little is understood regarding their contribution to PD. One example is a polymorphic CT-rich region in intron 4 of the SNCA gene. This haplotype has been suggested to be associated with risk of Lewy Body (LB) pathology in Alzheimer's Disease and SNCA gene expression, but is yet to be investigated in PD. Here, we attempt to resolve this CT-rich haplotype and investigate its role in PD. We performed targeted PacBio HiFi sequencing of the region in 1375 PD cases and 959 controls. We replicate the previously reported associations and a novel association between two PD risk SNVs (rs356182 and rs5019538) and haplotype 4, the largest haplotype. Through quantitative trait locus analyzes we identify a significant haplotype 4 association with alternative CAGE transcriptional start site usage, not leading to significant differential SNCA gene expression in post-mortem frontal cortex brain tissue. Therefore, disease association in this locus might not be biologically driven by this CT-rich repeat region. Our data demonstrates the complexity of this SNCA region and highlights that further follow up functional studies are warranted.

Enhancing precision: A predictive model for 177Lu-DOTATATE treatment response in neuroendocrine tumors using quantitative 68Ga-DOTATATE PET and clinicopathological biomarkers.

Purpose: This study aims to elucidate the role of quantitative SSTR-PET metrics and clinicopathological biomarkers in the progression-free survival (PFS) and overall survival (OS) of neuroendocrine tumors (NETs) treated with peptide receptor radionuclide therapy (PRRT). Methods: A retrospective analysis including 91 NET patients (M47/F44; age 66 years, range 34-90 years) who completed four cycles of standard 177Lu-DOTATATE was conducted. SSTR-avid tumors were segmented from pretherapy SSTR-PET images using a semiautomatic workflow with the tumors labeled based on the anatomical regions. Multiple image-based features including total and organ-specific tumor volume and SSTR density along with clinicopathological biomarkers including Ki-67, chromogranin A (CgA) and alkaline phosphatase (ALP) were analyzed with respect to the PRRT response. Results: The median OS was 39.4 months (95% CI: 33.1-NA months), while the median PFS was 23.9 months (95% CI: 19.3-32.4 months). Total SSTR-avid tumor volume (HR = 3.6; P = 0.07) and bone tumor volume (HR = 1.5; P = 0.003) were associated with shorter OS. Also, total tumor volume (HR = 4.3; P = 0.01), liver tumor volume (HR = 1.8; P = 0.05) and bone tumor volume (HR = 1.4; P = 0.01) were associated with shorter PFS. Furthermore, the presence of large lesion volume with low SSTR uptake was correlated with worse OS (HR = 1.4; P = 0.03) and PFS (HR = 1.5; P = 0.003). Among the biomarkers, elevated baseline CgA and ALP showed a negative association with both OS (CgA: HR = 4.9; P = 0.003, ALP: HR = 52.6; P = 0.004) and PFS (CgA: HR = 4.2; P = 0.002, ALP: HR = 9.4; P = 0.06). Similarly, number of prior systemic treatments was associated with shorter OS (HR = 1.4; P = 0.003) and PFS (HR = 1.2; P = 0.05). Additionally, tumors originating from the midgut primary site demonstrated longer PFS, compared to the pancreas (HR = 1.6; P = 0.16), and those categorized as unknown primary (HR = 3.0; P = 0.002). Conclusion: Image-based features such as SSTR-avid tumor volume, bone tumor involvement, and the presence of large tumors with low SSTR expression demonstrated significant predictive value for PFS, suggesting potential clinical utility in NETs management. Moreover, elevated CgA and ALP, along with an increased number of prior systemic treatments, emerged as significant factors associated with worse PRRT outcomes.

Competition between brown stink bug (Hemiptera: Pentatomidae) and corn earworm (Lepidoptera: Noctuidae) in field corn.

Interspecific competition is an important ecological concept which can play a major role in insect population dynamics. In the southeastern United States, a complex of stink bugs (Hemiptera: Pentatomidae), primarily the brown stink bug, Euschistus servus (Say), and corn earworm, Helicoverpa zea (Boddie) (Lepidoptera: Noctuidae), are the 2 most common pests of field corn, Zea mays L. (Poales: Poaceae). Stink bugs have the greatest potential for economic injury during the late stages of vegetative corn development when feeding can result in deformed or "banana-shaped" ears and reduced grain yield. Corn earworm moths lay eggs on corn silks during the first stages of reproductive development. A 2-year field study was conducted to determine the impact of feeding by the brown stink bug during late-vegetative stages on subsequent corn earworm oviposition, larval infestations, and grain yield. Brown stink bug feeding prior to tasseling caused deformed ears and reduced overall grain yield by up to 92%. Across all trials, varying levels of brown stink bug density and injury reduced the number of corn earworm larvae by 29-100% and larval feeding by 46-85%. Averaged across brown stink bug densities, later planted corn experienced a 9-fold increase in number of corn earworm larvae. This is the first study demonstrating a competitive interaction between these major pests in a field corn setting, and these results have potential implications for insect resistance management.

Continued decline in sublethal effects of Bt toxins on Helicoverpa zea (Lepidoptera: Noctuidae) in field corn.

The majority of field corn, Zea mays L., in the southeastern United States has been genetically engineered to express insecticidal toxins produced by the soil bacterium, Bacillus thuringiensis (Bt). Field corn is the most important mid-season host for corn earworm, Helicoverpa zea (Boddie) (Lepidoptera: Noctuidae), which has developed resistance to all Cry toxins in Bt corn. From 2020 to 2023, corn earworm pupae were collected from early- and late-planted pyramided hybrids expressing Bt toxins and non-Bt near-isolines in North and South Carolina (16 trials). A total of 5,856 pupae were collected across all trials, with 55 and 88% more pupae collected in later-planted trials relative to early plantings in North and South Carolina, respectively. Only 20 pupae were collected from hybrids expressing Cry1F + Cry1Ab + Vip3A20 across all trials. Averaged across trials, Cry1A.105 + Cry2Ab2 hybrids reduced pupal weight by 6 and 9% in North and South Carolina, respectively, relative to the non-Bt near-isoline. Cry1F + Cry1Ab hybrids reduced pupal weight on average by 3 and 8% in North and South Carolina, respectively, relative to the non-Bt near-isoline. The impact of the Bt toxins on pupal weight varied among trials. When combined with data from 2014 to 2019 from previous studies, a significant decline in the percent reduction in pupal weight over time was found in both states and hybrid families. This study demonstrates a continued decline in the sublethal impacts of Bt toxins on corn earworm, emphasizing the importance of insect resistance management practices.

A case of hybrid robotic-assisted coronary artery bypass grafting and valve-in-valve transcatheter aortic valve replacement.

We report a hybrid procedure of robotic-assisted coronary artery bypass grafting and transcatheter aortic valve-in-valve implantation for left main disease and prosthetic aortic valve stenosis. Robotic-assisted coronary artery bypass grafting using a left internal mammary artery graft was preferred to percutaneous coronary intervention because of the complex anatomy of the coronary lesion and concerns about dual antiplatelet therapy tolerance. This was followed by a valve-in-valve procedure five days later, allowing the patient to be discharged the next day. This innovative, less invasive approach demonstrates the feasibility and potential for early recovery in appropriately selected patients with complex coronary and aortic valve disease. Learning objective: Hybrid robotic-assisted coronary artery bypass grafting (CABG) and transcatheter aortic valve replacement (AVR) is a feasible and less invasive approach for appropriately selected patients with complex coronary and aortic valve disease who are not good candidates for percutaneous coronary intervention or conventional CABG and surgical AVR.

Emerging Themes and Research Frontiers in Suicide Prediction: A Scientometric Analysis.

Suicide remains a critical global health issue despite advancements in mental health treatment. The purpose of this analysis is to emphasize the development, patterns, and noteworthy outcomes of suicide prediction research. It also helps to uncover gaps and areas of under-researched topics within suicide prediction. A scientometric analysis was conducted using Biblioshiny and VOSviewer. To thoroughly assess the academic literature on suicide prediction, various scientometric methodologies such as trend analysis and citation analysis were employed. We utilized the temporal features of the Web of Science to analyze publication trends over time. Author affiliation data were used to investigate the geographic distribution of research. Cluster analysis was performed by grouping related keywords into clusters to identify overarching themes within the literature. A total of 1,703 articles from 828 different sources, spanning from 1942 to 2023, were collected for the analysis. Machine learning techniques might have a big influence on suicide-related event prediction, which would enhance attempts at suicide prevention and intervention. The conceptual understanding of suicide prediction is enhanced by scientometric analysis, which further uncovers the research gap and literature in this area. Suicide prediction research underscores that suicidal behavior is not caused by a single factor but is the result of a complex interplay of multiple factors. These factors may include biological, psychological, social, and environmental factors. Understanding and integrating these factors into predictive models is a theoretical advancement in the field. Unlike previous bibliometric studies in the field of suicide prediction that have typically focused on specific subtopics or data sources, our analysis offers a comprehensive mapping of the entire landscape. We encompass a wide range of suicide prediction literature, including research from medical, psychological, and social science domains, thus providing a holistic overview.

Health Care Utilization Prior to Ovarian Cancer Diagnosis in Publicly Insured Individuals in New York State.

Background: Women with early-stage ovarian cancer may be asymptomatic or present with nonspecific symptoms. We examined health care utilization prior to ovarian cancer diagnosis to assess whether women with higher utilization differed in their prognosis and outcomes compared to women with low utilization. Methods: Using Medicaid, Medicare, and New York State Cancer Registry data for ovarian cancer cases diagnosed in 2006-2015, we examined selected health care visits that occurred 1-6 months before ovarian cancer diagnosis. We used multivariable-adjusted logistic regression to estimate odds ratios (ORs) and 95% CIs for associations of sociodemographic factors with number of prediagnostic visits and number of visits with tumor characteristics, and Cox proportional hazards regression to examine differences in survival by number of visits. Results: Women with >5 vs 0 prediagnostic visits were statistically significantly less likely to be diagnosed with distant vs local stage disease (OR, 0.72; 95% CI, 0.54-0.96), and women with 3-5 or >5 vs 0 prediagnostic visits had better overall survival (hazard ratio [HR], 0.88; 95% CI, 0.80-0.96 and HR, 0.90; 95% CI, 0.83-0.98, respectively). In stratified analyses, the association with improved survival was observed only among cases with regional or distant stage disease. Conclusions: Women with high health care utilization prior to ovarian cancer diagnosis may have better prognosis and survival, possibly because of earlier detection or better access to care throughout treatment. Women and their health care providers should not ignore symptoms potentially indicative of ovarian cancer and should be persistent in following up on symptoms that do not resolve.

An investigation into gender distributions in scholarly publications among dental faculty members in Iran.

BACKGROUND: Research on gender inequality is crucial as it unveils the pervasive disparities that persist across various domains, shedding light on societal imbalances and providing a foundation for informed policy-making. AIM: To investigate gender differences in scientometric indices among faculty members in dental schools across Iran. This included overall data and speciality-specific data. METHODS: The publication profiles of academic staff in all dental schools were examined using the Iranian Scientometric Information Database (ISID, http://isid.research.ac.ir). Variables analyzed were working field, academic degree, the total number of papers, papers per year, total number of citations, percentage of self-citation, h-index, g-index, citations per paper, gender, university type, number of years publishing, proportion of international papers, first-author papers, and corresponding-author papers. Mann-Whitney and Kruskal-Wallis nonparametric tests were used to analyze the relationship between background characteristics and scientometric indicators. The extracted data were analyzed using R v4.0.1. RESULTS: The database included 1850 faculty members, of which about 60% (1104 of 1850) were women. Men (n = 746) had a higher number of papers (6583 vs. 6255) and citations (60410 vs. 39559) compared with women; 234 of the 376 faculty members with no papers were women. Almost half of the women (N = 517 of 1104) were in Type 2 universities, and nearly half of the men (N = 361 of the 746) were faculty members at Type 1 universities (Type 1 universities ranking higher than Type 2 and 3 universities). The medians of scientometric indices were higher in men, except for self-citation percentage (0 (IQR = 2) vs. 0 (IQR = 3), P = 0.083), international papers percentage (0 (IQR = 7.5) vs. 0 (IQR = 16.7), P<0.001). The proportion of corresponding-author papers was more than 62% higher in women (25 (IQR = 50) vs. 15.4 (IQR = 40), P<0.001). Men had a two-fold higher median h-index (2 (IQR = 4) vs. 1 (IQR = 3), P<0.001). Restorative dentistry and pediatric dentistry had the highest men-to-women ratios (1.5 for both). Dental materials and oral and maxillofacial surgery showed the lowest men-to-women ratios (0.42 and 0.5, respectively). CONCLUSIONS: Women made up the majority of dental faculty members in Iran. Nevertheless, men showed better scientometric results in several significant indices. Having identified scientometric information reflecting differences across faculty members, further research is now needed to better understand the drivers of these differences.

A framework for understanding climate change impacts through non-compensatory intra- and interspecific climate change responses.

Understanding and predicting population responses to climate change is a crucial challenge. A key component of population responses to climate change are cases in which focal biological rates (e.g., population growth rates) change in response to climate change due to non-compensatory effects of changes in the underlying components (e.g., birth and death rates) determining the focal rates. We refer to these responses as non-compensatory climate change effects. As differential responses of biological rates to climate change have been documented in a variety of systems and arise at multiple levels of organization within and across species, non-compensatory effects may be nearly ubiquitous. Yet, how non-compensatory climate change responses combine and scale to influence the demographics of populations is often unclear and requires mapping them to the birth and death rates underlying population change. We provide a flexible framework for incorporating non-compensatory changes in upstream rates within and among species and mapping their consequences for additional downstream rates across scales to their eventual effects on population growth rates. Throughout, we provide specific examples and potential applications of the framework. We hope this framework helps to enhance our understanding of and unify research on population responses to climate change.

Utility of bioselection with neoadjuvant chemotherapy for organ preservation in patients with T4 laryngeal cancer.

BACKGROUND: Neoadjuvant chemotherapy for induction selection of definitive treatment (IS) protocols have shown excellent outcomes for organ preservation and survival in patients with T3 laryngeal squamous cell carcinoma (LSCC). We seek to evaluate survival and organ preservation outcomes in T4 LSCC patients treated with IS protocols. METHODS: Retrospective cohort of advanced T3 and T4 LSCC patients who underwent IS protocols based upon potential for preserving a functional larynx. Patients received one neoadjuvant cycle of platinum-based chemotherapy with either 5-fluorouracil or docetaxel or with two cycles of platinum-based chemotherapy with docetaxel and a Bcl-2 inhibitor. Patients who achieved ≥ 50 % response as determined by radiographic review and/or endoscopic evaluation received definitive chemoradiation. Patients who had < 50 % response after IS underwent total laryngectomy (TL) followed by post-operative radiation +/- chemotherapy. RESULTS: Amongst T4 patients, 114 met inclusion criteria including 89 who underwent IS protocols and 25 who received an upfront TL. In total, 76.0 % of T3 patients and 71.9 % of T4 patients responded to IS and underwent definitive chemoradiation. There was no significant difference in hazard of death between T4 IS and T4 TL patients (HR: 0.9, p = 0.86). Among responders, there was no significant difference in 5-year laryngectomy-free survival (T3 - 59.6 %, T4 44.3 %, p = 0.15) or laryngeal preservation by T stage (T3 - 72.8 %, T4 - 73.0 %, p = 0.84). CONCLUSIONS: Select T4 patients may benefit from organ preservation using IS protocols with similar response rates to patients with T3 tumors, without compromising survival when compared to upfront TL.

Observational study protocol for an arrhythmia notification feature.

INTRODUCTION: Screening for atrial fibrillation (AF) in the general population may help identify individuals at risk, enabling further assessment of risk factors and institution of appropriate treatment. Algorithms deployed on wearable technologies such as smartwatches and fitness bands may be trained to screen for such arrhythmias. However, their performance needs to be assessed for safety and accuracy prior to wide-scale implementation. METHODS AND ANALYSIS: This study will assess the ability of the WHOOP strap to detect AF using its WHOOP Arrhythmia Notification Feature (WARN) algorithm in an enriched cohort with a 2:1 distribution of previously diagnosed AF (persistent and paroxysmal) and healthy controls. Recruited participants will collect data for 7 days with the WHOOP wrist-strap and BioTel ePatch (electrocardiography gold-standard). Primary outcome will be participant level sensitivity and specificity of the WARN algorithm in detecting AF in analysable windows compared with the ECG gold-standard. Similar analyses will be performed on an available epoch-level basis as well as comparison of these findings in important subgroups. ETHICS AND DISSEMINATION: The study was approved by the ethics board at the study site. Participants will be enrolled after signing an online informed consent document. Updates will be shared via clinicaltrials.gov. The data obtained from the conclusion of this study will be presented in national and international conferences with publication in clinical research journals. TRIAL REGISTRATION NUMBER: NCT05809362.

Vandetanib in locally advanced or metastatic differentiated thyroid cancer refractory to radioiodine therapy.

The VERIFY study aimed to determine the efficacy of vandetanib in patients with differentiated thyroid cancer (DTC) that is either locally advanced or metastatic and refractory to radioiodine (RAI) therapy. Specifically, VERIFY is a randomized, double-blind, multicenter phase III trial aimed to determine the efficacy and safety of vandetanib in tyrosine kinase inhibitor-naive patients with locally advanced or metastatic RAI-refractory DTC with documented progression (NCT01876784). Patients were randomized 1:1 to vandetanib or placebo. The primary endpoint was progression-free survival (PFS). Secondary endpoints included best objective response rate, overall survival (OS), safety, and tolerability. Patients continued to receive randomized treatment until disease progression or for as long as they were receiving clinical benefit unless criteria for treatment discontinuation were met. Following randomization, 117 patients received vandetanib, and 118 patients received a placebo. Median PFS was 10.0 months in the vandetanib group and 5.7 months in the placebo group (hazard ratio: 0.75; 95% CI: 0.55-1.03; P = 0.080). OS was not significantly different between treatment arms. Common Terminology Criteria for Adverse Events (CTCAE) of grade ≥3 were reported in 55.6% of patients in the vandetanib arm and 25.4% in the placebo arm. Thirty-three deaths (28.2%; one related to study treatment) occurred in the vandetanib arm compared with 16 deaths (13.6%; two related to treatment) in the placebo arm. No statistically significant improvement was observed in PFS in treatment versus placebo in patients with locally advanced or metastatic, RAI-refractory DTC. Moreover, active treatment was associated with more adverse events and more deaths than placebo, though the difference in OS was not statistically significant.

A phase I/II trial of sapanisertib in advanced anaplastic and radioiodine refractory differentiated thyroid carcinoma.

BACKGROUND: There are limited therapeutic options for patients with recurrent/metastatic anaplastic thyroid carcinoma (ATC), and radioiodine refractory (RAIR) differentiated thyroid carcinoma (DTC) refractory to multi-kinase inhibitors. This multi-center trial evaluated sapanisertib, a next generation oral kinase inhibitor of mTOR complexes 1/2, in ATC and RAIR DTC. METHODS: A safety run-in phase I was followed by non-randomized phase II trial in ATC, with an exploratory cohort in RAIR DTC. Primary endpoint was proportion of patients with ATC who were without disease progression at 4 months. Safety and survival outcomes were key secondary endpoints. RESULTS: Forty-six patients (20 ATC; 26 DTC) were enrolled including 40 (18 ATC; 22 DTC) who received recommended phase II dose of 5 mg daily. Eleven percent (2/18, 95% C.I.: 1.4-34.7%) of patients with ATC were progression-free at 4 months, 22.2% (4/18) had stable disease as best response. Enrollment in the ATC cohort stopped early with 18 patients out of proposed 23 due to overall futility. One confirmed partial response (4.5%, 1/22) occurred in RAIR DTC, with stable disease in 63.6% (14/22) patients. Median progression-free survival was 1.6 (95% C.I.: 0.9-2.8) months and 7.8 (2.0-not reached) months in ATC and DTC, respectively. Grade 3 treatment related adverse events occurred in 30% of patients who received the phase II dose, most common being anorexia, nausea, diarrhea, fatigue, skin rash and hyperglycemia. Genomic alterations in the PI3 K/AKT/mTOR pathway were not associated with response or PFS. CONCLUSIONS: Sapanisertib monotherapy did not meet the primary endpoint of this trial (proportion progression-free at 4 months) in ATC, and did not show clinically meaningfully activity. Clinical trials with alternative therapeutic strategies are needed. CLINICAL TRIAL REGISTRATION: NCT02244463.