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Background Lung cancer is the leading cause of cancer death for both men and women in the United States. The National Lung Screening Trial (NLST) demonstrated that low-dose computed tomography (LDCT) screening can reduce lung cancer mortality among high-risk individuals, but uptake of lung screening remains low. Social media platforms have the potential to reach a large number of people, including those who are at high risk for lung cancer but who may not be aware of or have access to lung screening. Methods This paper discusses the protocol for a randomized controlled trial (RCT) that leverages FBTA to reach screening-eligible individuals in the community at large and intervene with a public-facing, tailored health communication intervention ( LungTalk ) to increase awareness of, and knowledge about, lung screening. Discussion This study will provide important information to inform the ability to refine implementation processes for national population efforts to scale a public-facing health communication focused intervention using social media to increase screening uptake of appropriate, high-risk individuals. Trial registration The trial is registered at clinicaltrials.gov (#NCT05824273).

Taxi and for-hire vehicle (FHV) drivers are a largely immigrant, low-income occupational group at increased cardiovascular disease (CVD) risk. Poor dental health is a CVD risk factor, and dental care access is an unexamined taxi/FHV driver CVD risk factor. A cross-sectional survey was administered to 422 taxi/FHV drivers (2016–2017) to identify predictors of access to dental health care among drivers. One-third (n = 128, 30.3%) reported needing dental care/tests/treatment within the past six months, and nearly one-half (n = 61, 48%) were delayed/unable to obtain care. Only 57.6% (n = 241) had past-year dental cleanings. Not having enough money to cover household expenses was a significant predictor of being delayed/unable to obtain needed dental care/tests/treatment in the prior six months (0.5 OR; 95% CI, 0.28–0.89; p  < .05). Lack of dental insurance coverage (2.72 OR; 95% CI, 1.60–4.63; p  < .001) or lack of primary care provider (2.72 OR; 95% CI, 1.60–4.63; p  < .001) were associated with lack of past-year dental cleaning. Seventeen percent of drivers with Medicaid were unaware of their dental coverage, which was associated with both inability to access needed dental care/tests/treatment in the past 6 months ( p  = .026) and no past-year dental cleaning ( p  < .001). Limited understanding of dental coverage was associated with both an inability to access needed dental care/tests/treatment in the past 6 months ( p  = .028) and lack of past-year dental cleaning ( p  = .014). Our findings can inform targeted intervention development to increase taxi/FHV driver dental care access/uptake, potentially improving their CVD risk.

Background Rett syndrome (RTT) is a severe X-linked neurodevelopmental disorder associated with multiple neurologic impairments. Previous studies have shown challenges to the quality of life of individuals with RTT and their caregivers. However, instruments applied to quantify disease burden have not adequately captured the impact of these impairments on affected individuals and their families. Consequently, an international collaboration of stakeholders aimed at evaluating Burden of Illness (BOI) in RTT was organized. Methods Based on literature reviews and qualitative interviews with parents of children and adults with RTT, a caregiver questionnaire was constructed to evaluate 22 problems (inclusive of core characteristics, functional impairments, and comorbidities) often experienced with RTT, rated mainly with a 5-level Likert scale. The questionnaire was administered anonymously online to an international sample of 756 caregivers (predominantly parents) of girls and women with RTT. Descriptive statistics were used to identify problems of high frequency and impact on affected individuals and caregivers. Chi-square tests characterized the relationship between problem severity and impact responses, while nonparametric ANOVAs of raw and z-score adjusted scores identified agreement between severity and impact on individual and caregiver. Secondary inferential tests were used to determine the roles of age, clinical type, and country of residence on BOI in RTT. Results There was variability in reported frequency of problems, with the most prevalent, severe and impactful being those related to the core features of RTT (i.e., communication and fine and gross motor impairments). Chi-square analyses demonstrated interdependence between severity and impact responses, while ANOVAs showed that many problems had disproportionately greater impact than severity, either on affected individuals (e.g., hand stereotypies) or their caregivers (e.g., sleep difficulties, seizures, pain, and behavioral abnormalities). With certain exceptions (e.g., breath-holding, seizures), age, clinical type, or country of residence did not influence these BOI profiles. Conclusions Our data demonstrate that core features and related impairments are particularly impactful in RTT. However, problems with mild severity can also have disproportionate impact on affected individuals and, particularly, on their caregivers. Future analyses will examine the role of factors such as treatment outcomes, healthcare services, and healthcare provider’s perspectives, in these BOI profiles.

Patients with severe malaria or sepsis are at risk of developing life-threatening acute respiratory distress syndrome (ARDS). The objective of this study was to evaluate point-of-care lung ultrasound as a novel tool to determine the prevalence and early signs of ARDS in a resource-limited setting among patients with severe malaria or sepsis. Serial point-of-care lung ultrasound studies were performed on four consecutive days in a planned sub study of an observational cohort of patients with malaria or sepsis in Bangladesh. We quantified aeration patterns across 12 lung regions. ARDS was defined according to the Kigali Modification of the Berlin Definition. Of 102 patients enrolled, 71 had sepsis and 31 had malaria. Normal lung ultrasound findings were observed in 44 patients on enrolment and associated with 7% case fatality. ARDS was detected in 10 patients on enrolment and associated with 90% case fatality. All patients with ARDS had sepsis, 4 had underlying pneumonia. Two patients developing ARDS during hospitalisation already had reduced aeration patterns on enrolment. The SpO2/FiO2 ratio combined with the number of regions with reduced aeration was a strong prognosticator for mortality in patients with sepsis (AUROC 91.5% (95% Confidence Interval: 84.6%-98.4%)). This study demonstrates the potential usefulness of point-of-care lung ultrasound to detect lung abnormalities in patients with malaria or sepsis in a resource-constrained hospital setting. LUS was highly feasible and allowed to accurately identify patients at risk of death in a resource limited setting.

Background Pulmonary oedema is a feared and difficult to predict complication of severe malaria that can emerge after start of antimalarial treatment. Proinflammatory mediators are thought to play a central role in its pathogenesis. Methods An exploratory study was conducted to evaluate the predictive capacity of biomarkers for development of clinical pulmonary oedema in patients with severe falciparum malaria at two hospitals in Bangladesh. Plasma concentrations of interleukin-6 (IL-6), IL-8, tumour necrosis factor (TNF), soluble Receptor of Advanced Glycation End-products (sRAGE), surfactant protein-D (SP-D), club cell secretory protein (CC16), and Krebs von den Lungen-6 (KL-6) on admission were compared with healthy controls. Correlations between these biomarker and plasma lactate and Plasmodium falciparum histidine-rich protein 2 (PfHRP2) levels were evaluated. Receiver Operating Characteristic (ROC) curves were constructed to assess the predictive capacity for clinical pulmonary oedema of the biomarkers of interest. Results Of 106 screened patients with falciparum malaria, 56 were classified as having severe malaria with a mortality rate of 29%. Nine (16%) patients developed clinical pulmonary oedema after admission. Plasma levels of the biomarkers of interest were higher in patients compared to healthy controls. IL-6, IL-8, TNF, sRAGE, and CC16 levels correlated well with plasma PfHRP2 levels ( r s = 0.39; P  = 0.004, r s = 0.43; P  = 0.001, r s = 0.54; P  < 0.001, r s = 0.44; P  < 0.001, r s = 0.43; P  = 0.001, respectively). Furthermore, IL-6 and IL-8 levels correlated well with plasma lactate levels ( r s = 0.37; P  = 0.005, r s = 0.47; P  < 0.001, respectively). None of the biomarkers of interest had predictive capacity for development of clinical pulmonary oedema. Conclusions IL-6, IL-8, TNF, sRAGE, SP-D, CC16 and KL-6 cannot be used in predicting clinical pulmonary oedema in severe malaria patients.

Invasive species are a leading driver of global change, with consequences for biodiversity and society. Because of extraordinary rates of endemism, introduction, and extinction, Hawaii offers a rich platform for exploring the cross-disciplinary challenges of managing invasive species in a dynamic world. We highlight key successes and shortcomings to share lessons learned and inspire innovation and action in and beyond the archipelago. We then discuss thematic challenges and opportunities of broad relevance to invaded ecosystems and human communities. Important research needs and possible actions include eradicating mammals from mainland island sanctuaries, assessing hidden threats from poorly known introduced species, harnessing genomic tools to eradicate disease vectors, structured decision-making to achieve common objectives among diverse stakeholders, and enhancing capacity through nontraditional funding streams and progressive legislation. By shining a spotlight on invasive species at the front lines in Hawaii, we hope to catalyze strategic research and practice to help inform scientists and policymakers.

Abstract Background Acidosis in severe Plasmodium falciparum malaria is associated with high mortality, yet the pathogenesis remains incompletely understood. The aim of this study was to determine the nature and source of metabolic acids contributing to acidosis in patients with severe falciparum malaria. Methods A prospective observational study was conducted to characterize circulating acids in adults with P. falciparum malaria (n = 107) and healthy controls (n = 45) from Bangladesh using high-resolution liquid chromatography–mass spectrometry metabolomics. Additional in vitro P. falciparum culture studies were performed to determine if parasites release the acids detected in plasma from patients with severe malaria acidosis. Results We identified previously unmeasured plasma acids strongly associated with acidosis in severe malaria. Metabolomic analysis of P. falciparum parasites in vitro showed no evidence that these acids are released by the parasite during its life cycle. Instead, 10 of the plasma acids could be mapped to a gut microbial origin. Patients with malaria had low L-citrulline levels, a plasma marker indicating reduced gut barrier integrity. Longitudinal data showed the clearance of these newly identified acids was delayed in fatal cases. Conclusions These data suggest that a compromise in intestinal barrier function may contribute significantly to the pathogenesis of life-threatening acidosis in severe falciparum malaria. Clinical Trials Registration NCT02451904. Acidosis in severe falciparum malaria is associated with an accumulation of unidentified acids in blood plasma. Clinical and in vitro metabolomic studies identify a potential role for translocation of bacterial acids from the gut into the bloodstream.

Clinical trials in severe falciparum malaria require a large sample size to detect clinically meaningful differences in mortality. This means few interventions can be evaluated at any time. Using a validated surrogate endpoint for mortality would provide a useful alternative allowing a smaller sample size. Here we evaluate changes in coma score and plasma lactate as surrogate endpoints for mortality in severe falciparum malaria. Three datasets of clinical studies in severe malaria were re-evaluated: studies from Chittagong, Bangladesh (adults), the African 'AQUAMAT' trial comparing artesunate and quinine (children), and the Vietnamese 'AQ' study (adults) comparing artemether with quinine. The absolute change, relative change, slope of the normalization over time, and time to normalization were derived from sequential measurements of plasma lactate and coma score, and validated for their use as surrogate endpoint, including the proportion of treatment effect on mortality explained (PTE) by these surrogate measures. Improvements in lactate concentration or coma scores over the first 24 hours of admission, were strongly prognostic for survival in all datasets. In hyperlactataemic patients in the AQ study (n = 173), lower mortality with artemether compared to quinine closely correlated with faster reduction in plasma lactate concentration, with a high PTE of the relative change in plasma lactate at 8 and 12 hours of 0.81 and 0.75, respectively. In paediatric patients enrolled in the 'AQUAMAT' study with cerebral malaria (n = 785), mortality was lower with artesunate compared to quinine, but this was not associated with faster coma recovery. The relative changes in plasma lactate concentration assessed at 8 or 12 hours after admission are valid surrogate endpoints for severe malaria studies on antimalarial drugs or adjuvant treatments aiming at improving the microcirculation. Measures of coma recovery are not valid surrogate endpoints for mortality.

Cardiovascular disease remains the leading cause of mortality and healthcare expenditures in the United States. It is also a major contributor to premature mortality, years lived with disability, and rising healthcare costs around the world. Despite the availability of proven therapies and interventions that could vastly decrease the burden of cardiovascular disease and cardiometabolic conditions, their implementation is poor, with generally less than half of patients being treated with the most effective therapies. Implementation science offers promise in bridging this gap and mitigating disparities. However, even though small studies have shown that there are effective methods to improve the implementation of evidence-based therapies, these methods have not been scaled to make an impact at the level of health systems or nationally. A coordinated, multi-stakeholder approach is essential to identify barriers to implementation on a broad scale and, more critically, to develop and deploy practical solutions. The Duke Clinical Research Institute conducted an Implementation Summit entitled “Scalability, Spread, and Sustainability” to explore strategies for advancing the uptake of evidence-based interventions for cardiometabolic diseases in healthcare in the United States. This manuscript presents the participants’ multi-stakeholder perspective on the steps necessary to improve the implementation of evidence-based therapies in cardiometabolic disease. Key recommendations include focused efforts on evidence generation around broad implementation strategies, dissemination of the evidence generated, uptake of evidence into usual care settings, and investment in training the current and next generations of leaders in implementation.

Amino acid derangements are common in severe falciparum malaria and have been associated with endothelial dysfunction (L-arginine), metabolic acidosis (alanine and lactate), and disease severity (phenylalanine and tryptophan metabolites). Whether these amino acid perturbations reflect isolated pathogenic mechanisms or if they are part of overall changes in amino acid metabolism is unclear. To investigate this, we prospectively simultaneously quantified a broad range of plasma free amino acids (PFAA) using HPLC-MRM-Mass spectrometry in relation to presenting symptoms in adults with severe malaria (n = 88), septicaemia (n = 88), uncomplicated malaria (n = 71), and healthy controls (n = 48) from Bangladesh. The total plasma concentration of measured amino acids was significantly reduced in each of the patient groups when compared to normal levels observed in healthy local controls: uncomplicated malaria −54%, severe malaria −23%, and sepsis −32%, (p = <0.001). Inspection of amino acid profiles revealed that in each group the majority of amino acids were below normal levels, except for phenylalanine. Among patients with severe malaria, L-lactate was strongly associated with an increase of the total amino acid concentration, likely because this reflects tissue hypoxia. Our data confirm previously described amino acid abnormalities, likely resulting from overall changes in the concentration of PFAA.