DVT Surveillance Program in the ICU: Analysis of Cost-Effectiveness

Background Venous Thrombo-embolism (VTE – Deep venous thrombosis (DVT) and/or pulmonary embolism (PE) – in traumatized patients causes significant morbidity and mortality. The current study evaluates the effectiveness of DVT surveillance in reducing PE, and performs a cost-effectiveness analysis. Methods All traumatized patients admitted to the adult ICU underwent twice weekly DVT surveillance by bilateral lower extremity venous Duplex examination (48-month surveillance period – SP). The rates of DVT and PE were recorded and compared to the rates observed in the 36-month pre-surveillance period (PSP). All patients in both periods received mechanical and pharmacologic prophylaxis unless contraindicated. Total costs – diagnostic, therapeutic and surveillance – for both periods were recorded and the incremental cost for each Quality Adjusted Life Year (QALY) gained was calculated. Results 4234 patients were eligible (PSP – 1422 and SP – 2812). Rate of DVT in SP (2.8%) was significantly higher than in PSP (1.3%) – p Conclusions Surveillance of traumatized ICU patients increases DVT detection and reduces PE incidence. Costs in terms of QALY gained compares favorably with other interventions accepted by society

Distinctive receptor binding properties of the surface glycoprotein of a natural Feline Leukemia Virus isolate with unusual disease spectrum

<p>Abstract</p> <p>Background</p> <p>Feline leukemia virus (FeLV)-945, a member of the FeLV-A subgroup, was previously isolated from a cohort of naturally infected cats. An unusual multicentric lymphoma of non-T-cell origin was observed in natural and experimental infection with FeLV-945. Previous studies implicated the FeLV-945 surface glycoprotein (SU) as a determinant of disease outcome by an as yet unknown mechanism. The present studies demonstrate that FeLV-945 SU confers distinctive properties of binding to the cell surface receptor.</p> <p>Results</p> <p>Virions bearing the FeLV-945 Env protein were observed to bind the cell surface receptor with significantly increased efficiency, as was soluble FeLV-945 SU protein, as compared to the corresponding virions or soluble protein from a prototype FeLV-A isolate. SU proteins cloned from other cohort isolates exhibited increased binding efficiency comparable to or greater than FeLV-945 SU. Mutational analysis implicated a domain containing variable region B (VRB) to be the major determinant of increased receptor binding, and identified a single residue, valine 186, to be responsible for the effect.</p> <p>Conclusions</p> <p>The FeLV-945 SU protein binds its cell surface receptor, feTHTR1, with significantly greater efficiency than does that of prototype FeLV-A (FeLV-A/61E) when present on the surface of virus particles or in soluble form, demonstrating a 2-fold difference in the relative dissociation constant. The results implicate a single residue, valine 186, as the major determinant of increased binding affinity. Computational modeling suggests a molecular mechanism by which residue 186 interacts with the receptor-binding domain through residue glutamine 110 to effect increased binding affinity. Through its increased receptor binding affinity, FeLV-945 SU might function in pathogenesis by increasing the rate of virus entry and spread <it>in vivo</it>, or by facilitating entry into a novel target cell with a low receptor density.</p

Misrepresentation and Nonadherence Regarding COVID-19 Public Health Measures

IMPORTANCE: The effectiveness of public health measures implemented to mitigate the spread and impact of SARS-CoV-2 relies heavily on honesty and adherence from the general public. OBJECTIVE: To examine the frequency of, reasons for, and factors associated with misrepresentation and nonadherence regarding COVID-19 public health measures. DESIGN, SETTING, AND PARTICIPANTS: This survey study recruited a national, nonprobability sample of US adults to participate in an online survey using Qualtrics online panels (participation rate, 1811 of 2260 [80.1%]) from December 8 to 23, 2021. The survey contained screening questions to allow for a targeted sample of one-third who had had COVID-19, one-third who had not had COVID-19 and were vaccinated, and one-third who had not had COVID-19 and were unvaccinated. MAIN OUTCOME MEASURES: The survey assessed 9 different types of misrepresentation and nonadherence related to COVID-19 public health measures and the reasons underlying such behaviors. Additional questions measured COVID-19–related beliefs and behaviors and demographic characteristics. RESULTS: The final sample included 1733 participants. The mean (SD) participant age was 41 (15) years and the sample predominantly identified as female (1143 of 1732 [66.0%]) and non-Hispanic White (1151 of 1733 [66.4%]). Seven hundred twenty-one participants (41.6%) reported misrepresentation and/or nonadherence in at least 1 of the 9 items; telling someone they were with or about to be with in person that they were taking more COVID-19 preventive measures than they actually were (420 of 1726 [24.3%]) and breaking quarantine rules (190 of 845 [22.5%]) were the most common manifestations. The most commonly endorsed reasons included wanting life to feel normal and wanting to exercise personal freedom. All age groups younger than 60 years (eg, odds ratio for those aged 18-29 years, 4.87 [95% CI, 3.27-7.34]) and those who had greater distrust in science (odds ratio, 1.14 [95% CI, 1.05-1.23]) had significantly higher odds of misrepresentation and/or nonadherence for at least 1 of the 9 items. CONCLUSIONS: In this survey study of US adults, nearly half of participants reported misrepresentation and/or nonadherence regarding public health measures against COVID-19. Future work is needed to examine strategies for communicating the consequences of misrepresentation and nonadherence and to address contributing factors

Impacts of Climate Change on indirect human exposure to pathogens and chemicals from agriculture

Objective: Climate change is likely to affect the nature of pathogens and chemicals in the environment and their fate and transport. Future risks of pathogens and chemicals could therefore be very different from those of today. In this review, we assess the implications of climate change for changes in human exposures to pathogens and chemicals in agricultural systems in the United Kingdom and discuss the subsequent effects on health impacts. Data sources: In this review, we used expert input and considered literature on climate change ; health effects resulting from exposure to pathogens and chemicals arising from agriculture ; inputs of chemicals and pathogens to agricultural systems ; and human exposure pathways for pathogens and chemicals in agricultural systems. Data synthesis: We established the current evidence base for health effects of chemicals and pathogens in the agricultural environment ; determined the potential implications of climate change on chemical and pathogen inputs in agricultural systems ; and explored the effects of climate change on environmental transport and fate of different contaminant types. We combined these data to assess the implications of climate change in terms of indirect human exposure to pathogens and chemicals in agricultural systems. We then developed recommendations on future research and policy changes to manage any adverse increases in risks. Conclusions: Overall, climate change is likely to increase human exposures to agricultural contaminants. The magnitude of the increases will be highly dependent on the contaminant type. Risks from many pathogens and particulate and particle-associated contaminants could increase significantly. These increases in exposure can, however, be managed for the most part through targeted research and policy changes

Idarucizumab for Dabigatran Reversal - Full Cohort Analysis.

BACKGROUND: Idarucizumab, a monoclonal antibody fragment, was developed to reverse the anticoagulant effect of dabigatran. METHODS: We performed a multicenter, prospective, open-label study to determine whether 5 g of intravenous idarucizumab would be able to reverse the anticoagulant effect of dabigatran in patients who had uncontrolled bleeding (group A) or were about to undergo an urgent procedure (group B). The primary end point was the maximum percentage reversal of the anticoagulant effect of dabigatran within 4 hours after the administration of idarucizumab, on the basis of the diluted thrombin time or ecarin clotting time. Secondary end points included the restoration of hemostasis and safety measures. RESULTS: A total of 503 patients were enrolled: 301 in group A, and 202 in group B. The median maximum percentage reversal of dabigatran was 100% (95% confidence interval, 100 to 100), on the basis of either the diluted thrombin time or the ecarin clotting time. In group A, 137 patients (45.5%) presented with gastrointestinal bleeding and 98 (32.6%) presented with intracranial hemorrhage; among the patients who could be assessed, the median time to the cessation of bleeding was 2.5 hours. In group B, the median time to the initiation of the intended procedure was 1.6 hours; periprocedural hemostasis was assessed as normal in 93.4% of the patients, mildly abnormal in 5.1%, and moderately abnormal in 1.5%. At 90 days, thrombotic events had occurred in 6.3% of the patients in group A and in 7.4% in group B, and the mortality rate was 18.8% and 18.9%, respectively. There were no serious adverse safety signals. CONCLUSIONS: In emergency situations, idarucizumab rapidly, durably, and safely reversed the anticoagulant effect of dabigatran. (Funded by Boehringer Ingelheim; RE-VERSE AD ClinicalTrials.gov number, NCT02104947 .)

Engaging with community researchers for exposure science: lessons learned from a pesticide biomonitoring study

A major challenge in biomonitoring studies with members of the general public is ensuring their continued involvement throughout the necessary length of the research. The paper presents evidence on the use of community researchers, recruited from local study areas, as a mechanism for ensuring effective recruitment and retention of farmer and resident participants for a pesticides biomonitoring study. The evidence presented suggests that community researchers' abilities to build and sustain trusting relationships with participants enhanced the rigour of the study as a result of their on-the-ground responsiveness and flexibility resulting in data collection beyond targets expected

Separating the influences of prereading skills on early word and nonword reading

The essential first step for a beginning reader is to learn to match printed forms to phonological representations. For a new word, this is an effortful process where each grapheme must be translated individually (serial decoding). The role of phonological awareness in developing a decoding strategy is well known. We examined whether beginning readers recruit different skills depending on the nature of the words being read (familiar words vs. nonwords). Print knowledge, phoneme and rhyme awareness, rapid automatized naming (RAN), phonological short-term memory (STM), nonverbal reasoning, vocabulary, auditory skills, and visual attention were measured in 392 prereaders 4 and 5 years of age. Word and nonword reading were measured 9 months later. We used structural equation modeling to examine the skills–reading relationship and modeled correlations between our two reading outcomes and among all prereading skills. We found that a broad range of skills were associated with reading outcomes: early print knowledge, phonological STM, phoneme awareness and RAN. Whereas all of these skills were directly predictive of nonword reading, early print knowledge was the only direct predictor of word reading. Our findings suggest that beginning readers draw most heavily on their existing print knowledge to read familiar words

Cellular model system to dissect the isoform-selectivity of Akt inhibitors

The protein kinase Akt plays a pivotal role in cellular processes. However, its isoforms’ distinct functions have not been resolved to date, mainly due to the lack of suitable biochemical and cellular tools. Against this background, we present the development of an isoform-dependent Ba/F3 model system to translate biochemical results on isoform specificity to the cellular level. Our cellular model system complemented by protein X-ray crystallography and structure-based ligand design results in covalent-allosteric Akt inhibitors with unique selectivity profiles. In a first proof-of-concept, the developed molecules allow studies on isoform-selective effects of Akt inhibition in cancer cells. Thus, this study will pave the way to resolve isoform-selective roles in health and disease and foster the development of next-generation therapeutics with superior on-target properties