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Photovoice is a form of participatory action research and community-based participatory research and often used in social sciences to understand the needs of others and uncover the challenges and assets that may exist. Photovoice engages participants in the research process by inviting them to share their experiences through photographs and personal narratives. This act of storytelling and group discussion provides emotional connections among the participant cohort. Through the discussion of shared experience, common themes may arise. This column provides and overview of the photovoice methodology and highlights some of the benefits and limitations one might experience when leading photovoice based projects. Photovoice is a powerful tool that can prove useful for design researchers and practitioners alike as they seek to understand the challenges facing others. It is through this understanding that transformation to improve situations can occur.
Uncovering Social Issues Through Photovoice: A Comprehensive Methodology.
We performed the technique of uniportal thoracoscopic McKeown esophagectomy. The incision was located in the fourth intercostal space on the right axillary midline. The right recurrent laryngeal nerve lymph nodes were dissected. Four hemlocks were applied to clamp the proximal and distal ends of the aortic arch. The esophagus was suspended with purse-string at the level of the azygos vein arch to assist the dissection of the left recurrent laryngeal nerve lymph nodes. A silk thread was drawn out from the incision in order to remove the subcarinal lymph nodes. A thoracic drainage tube was placed at the back of the incision at the end.
Uniportal Thoracoscopic McKeown Esophagectomy
Bioelectrodes mediated by metal oxide nanoparticles have facilitated the development of new sensors in medical diagnosis. High-purity TiO(2) nanoparticles (NPs) were synthesized through thermal plasma and deposited directly on an interdigitated electrode. The surface of the TiO(2)-deposited electrode was activated with (3-aminopropyl) triethoxysilane (APTES) followed by fixing the single-stranded probe deoxyribonucleic acid (DNA) to fabricate the DNA biosensor. The structural properties of the deposited TiO(2) nanoparticles were analyzed using a transmission electron microscope (TEM), X-ray diffraction (XRD), and a dynamic light scattering (DLS) system. The chemical composition and structural properties of the TiO(2) nanoparticle layer and the fixed layer were analyzed by X-ray photoelectron spectroscopy (XPS) and scanning electron microscopy (SEM). E. coli O157:H7, a well-known pernicious pathogenic bacterial species, was detected as a target DNA of the prepared DNA biosensor, and the characteristics of DNA detection were determined by the current change using a picoammeter. The degree of binding between the probe DNA and the target DNA was converted into an electrical signal using the picoammeter method to quantitatively analyze the concentration of the target DNA. With the specificity experiment, it was confirmed that the biosensor was able to discriminate between nucleotides with mismatched, non-complementary, or complementary sequences.
Interdigitated Electrode Biosensor Based on Plasma-Deposited TiO(2) Nanoparticles for Detecting DNA
The field of animal-assisted therapy is advancing quickly throughout the world gaining popularity as a complementary therapy. Several countries, especially in the East, are still in their nascent phase in utilizing animal-assisted therapy and a more realistic presentation of their status should drive them towards effective initiatives to promote the field. The primary objective of this paper is to throw light on the current scenario of animal-assisted therapy in India. The relevant databases such as Scopus, Google Scholar, Proquest, PubMed, and JSTOR were searched to identify the research literature. The organizational websites, news, and blog articles, as well as institutional repositories, were explored to maximize the evidence. A total of 24 articles were found which included published research articles as well as unpublished conference papers. Results found a dearth of practice and research throughout the country indicating an urgent need to direct steps in promoting the growth of the field. The contemporary issues in the implementation of animal-assisted therapy such as cultural and religious beliefs, lack of awareness, lack of practising organizations and therapists warrant immediate attention. Reducing the research and practice gap alongside focusing on creating awareness, changing public perception, introducing coursework in educational institutions, the publication of evidence-based research will help in the acceptance and growth of this novel therapeutic field.
A Reflection on the Current Status of Animal-Assisted Therapy in India
Data are limited regarding 2 new human polyomaviruses, KI polyomavirus (KIPyV) and WU polyomavirus (WUPyV), in immunocompromised patients. We used real-time PCR to test for these and 12 respiratory viruses in 2,732 nasal wash samples collected during the first year after allogeneic hematopoietic cell transplantation from 222 patients. Specimens were collected weekly until day 100; then at least every 3 months. One year after hematopoietic cell transplantation, the cumulative incidence estimate was 26% for KIPyV and 8% for WUPyV. Age <20 years predicted detection of KIPyV (hazard ratio [HR] 4.6) and WUPyV (HR 4.4), and detection of a respiratory virus in the previous 2 weeks predicted KIPyV detection (HR 3.4). Sputum production and wheezing were associated with detection of KIPyV in the past week and WUPyV in the past month. There were no associations with polyomavirus detection and acute graft versus host disease, cytomegalovirus reactivation, neutropenia, lymphopenia, hospitalization, or death.
WU and KI Polyomaviruses in Respiratory Samples from Allogeneic Hematopoietic Cell Transplant Recipients
Emergency medical services providers, including emergency medical services students are among healthcare professionals on the front line to fight coronavirus disease 2019 and are under a greater risk of exposure. Preparing emergency medical services students to safely provide healthcare during the pandemic is vital. Therefore, this study assesses the emergency medical services student's preparedness for coronavirus disease 2019 in Saudi Arabia. A descriptive cross-sectional survey was conducted. This study was conducted at Prince Sultan Bin Abdulaziz College for Emergency Medical Services in King Saud University in Riyadh, Saudi Arabia. In this study, 198 students participated. The emergency medical services students thought they are insufficiently prepared to face situations, such coronavirus disease 2019 (2.50 +/- 1.57). Regarding knowledge, the emergency medical services students thought that they are insufficiently prepared for coronavirus disease 2019. The emergency medical services students thought that they are insufficiently contributing to local or national-level efforts associated with coronavirus disease 2019 (2.40 +/- 1.34). Among the emergency medical services students, 83 % (n=132) presented a feeling that they were not satisfactorily equipped to counter coronavirus disease 2019 situation. Furthermore, 87 % (n=138) of the emergency medical services students thought that embedding coronavirus disease 2019 related topics in the emergency medical services curriculum and theory and practical training would help prepare them. The emergency medical services students have moderately inadequate knowledge and skills related to coronavirus disease 2019. Moreover, they indicated that they are uncertain about their ability to respond adequately to, or participate satisfactorily in, pandemic-related events. The emergency medical services students have expressed the need for more knowledge and skills related to coronavirus disease 2019 to be embedded in the emergency medical services program curriculum.
The Preparedness of Emergency Medical Services Students for Coronavirus Disease 2019: A Cross-Sectional Study among Paramedic Students
Objectives: A proper description of the immune response to SARS-CoV-2 will be critical for the assessment of protection elicited after both infection and vaccination. Uncoupled T and B cell responses have been described in acute and convalescent patients and exposed individuals. We aimed to assess the potential usefulness of whole blood stimulation assays to identify functional cellular immune responses to SARS-CoV-2. Methods: Blood from COVID-19 recovered individuals (5 months after infection) and negative subjects was stimulated for 24 hours with HLA predicted peptide megapools of the Spike and Nucleoprotein, or the mixture of them. After stimulation, cytokines were quantified using a beads-based multiplex assay. Results: Interleukin-2 and IFN-{gamma} were found to be specific biomarkers of SARS-CoV-2 cellular response. Using the Spike and Nucleoprotein mixture, 91.3% of COVID-19 recovered individuals presented an IL-2 stimulation index over the cut-off, while 82.6% showed IFN-{gamma}. All the negative individuals presented an IL-2 response under the cut-off, while 5.3% of these subjects presented positive IFN-{gamma} stimulation indexes. Moreover, IL-2 production correlated with IgG levels for Spike 1, RBD, and Nucleocapsid. Conclusion: We demonstrate the potential of whole blood stimulation assays and the quantification of IL-2 and IFN-{gamma} for the analysis of SARS-CoV-2 functional cellular responses.
IL-2 and IFN- are biomarkers of SARS-CoV-2 specific cellular response in whole blood stimulation assays
To investigate the role of Hantaan virus envelope glycoprotein in infection, a panel of monoclonal antibodies (MAbs) was examined in vitro with several serological tests and in vivo by passive transfer experiments in mice. An antigenic site, specific for the inhibition of infected cell focus was detected with the focus inhibition neutralization test (FINT), in addition to the neutralization related antigenic sites, which were revealed by the ordinary focus reduction neutralization test (FRNT). Suckling mice were given the MAbs by passive transfer followed by lethal Hantaan virus challenge. All neutralizing MAbs detected by either FRNT or FINT protected all mice from lethal infection, confirming the importance of the antigenic sites as a protective antigen. Mice given non-neutralizing MAbs by passive transfer, however, began to die earlier than the control group; mean time to death (18.22.1 to 21.52.8 days) being significantly shorter than that of the control group (25.81.8, p<0.01, Mann-Whitney,U probability test). Virus titers in brains of mice which died early, were about 10 times higher than those of control mice. These results indicated the early death phenomenon of mice which was mediated by the antivirus antibody.
Protective role of antigenic sites on the envelope protein of Hantaan virus defined by monoclonal antibodies
Abstract COVID-19 has officially consumed every nurse leader's time and efforts. The purpose of this article is to share early learnings from the west coast of the United States, where the first U.S case was cared for. In this article, I describe the emerging principles allowing us to respond to an unprecedented crisis: Prevent, Protect, and Control. By the time this crisis is over, I do not doubt that we will have additional science and experience to support our frontline nurses and our nurse leaders. That said, I felt it was important to share our expertise in real-time for others to benefit from. I would also point out that writing about what you are feeling is catharticI encourage my colleagues to join me in writing about what you are experiencing.
Leading on the Edge of Insanity
While peptides can be excellent therapeutics for several conditions, their limited in vivo half-lives have been a major bottleneck in the development of therapeutic peptides. Conjugating the peptide to an inert chemical moiety is a strategy that has repeatedly proven to be successful in extending the half-life of some therapeutics. This systematic review and meta-analysis was conducted to examine the available literature and assess it in an unbiased manner to determine which conjugates, both biological and synthetic, provide the greatest increase in therapeutic peptide half-life. Systematic searches run on PubMed, Scopus and SciFinder databases resulted in 845 studies pertaining to the topic, 16 of these were included in this review after assessment against pre-specified inclusion criteria registered on PROSPERO (#CRD42020222579). The most common reasons for exclusion were non-IV administration and large peptide size. Of the 16 studies that were included, a diverse suite of conjugates that increased half-life from 0.1 h to 33.57 h was identified. Amongst these peptides, the largest increase in half-life was seen when conjugated with glycosaminoglycans. A meta-analysis of studies that contained fatty acid conjugates indicated that acylation contributed to a statistically significant extension of half-life. Additionally, another meta-analysis followed by a sensitivity analysis suggested that conjugation with specifically engineered recombinant peptides might contribute to a more efficient extension of peptide half-life as compared to PEGylation. Moreover, we confirmed that while polyethylene glycol is a good synthetic conjugate, its chain length likely has an impact on its effectiveness in extending half-life. Furthermore, we found that most animal studies do not include as much detail when reporting findings as compared to human studies. Inclusion of additional experimental detail on aspects such as independent assessment and randomization may be an easily accomplished strategy to drive more conjugated peptides towards clinical studies.
Conjugates for use in peptide therapeutics: a systematic review and meta-analysis
We have combined molecular beacon (MB) probes with barcoded metal nanowires to enable no-wash, sealed chamber, multiplexed detection of nucleic acids. Probe design and experimental parameters important in nanowire-based MB assays are discussed. Loop regions of 24 bases and 5 base pair stem regions in the beacon probes gave optimal performance. Our results suggest that thermodynamic predictions for secondary structure stability of solution-phase MB can guide probe design for nanowire-based assays. Dengue virus-specific probes with predicted solution-phase DeltaG of folding in 500 mM buffered NaCl of approximately -4 kcal/mol performed better than those with DeltaG > -2 or < -6 kcal/mol. Buffered 300-500 mM NaCl was selected after comparison of several buffers previously reported for similar types of assays, and 200-500 mM NaCl was found to be the optimal ionic strength for the hybridization temperatures (25 and 50 degrees C) and probe designs used here. Target binding to the surface as a function of solution concentration fit a Sips isotherm with Kd = 1.7 +/- 0.3 nM. The detection limit was approximately 100 pM, limited by incomplete quenching. Single base mismatches could be discriminated from fully complementary targets. Oligonucleotide target sequences specific for human immunodeficiency, hepatitis C, and severe acute respiratory viruses were assayed simultaneously in a no-wash, sealed chamber, multiplexed experiment in which each of three probe sequences was attached to a different pattern of encoded nanowires. Finally, we demonstrated that probe-coated nanowires retain their selectivity and sensitivity in a triplexed assay after storage for over 3 months.
Coupling molecular beacons to barcoded metal nanowires for multiplexed, sealed chamber DNA bioassays.
Given the links between the built environment and loneliness, there is interest in using place-based approaches (addressing built environment characteristics and related socio-spatial factors) in local communities to tackle loneliness and mental health problems. However, few studies have described the effectiveness, acceptability, or potential harms of such interventions. This review aimed to synthesize the literature describing local community-based interventions that target place-based factors to address loneliness and mental health problems, informing the development of future public health approaches. We searched PsycINFO, Medline, and Embase using a structured search strategy to identify English-language studies evaluating the effectiveness, acceptability, and potential harms of place-based community interventions in addressing loneliness and mental health problems, both in general and clinical populations. Seven studies met the inclusion criteria, classified as evaluating provision of community facilities (such as clubhouses), active engagement in local green spaces, and housing regeneration. None were randomised trials. Quantitative and qualitative findings suggested promising effects and/or acceptability of six interventions, with minimal potential harms. There is a clear need for randomised trials or quasi-experimental studies of place-based interventions to describe their effectiveness in addressing loneliness and mental health problems, as well as complementary qualitative work investigating acceptability. This will inform future policy development.
A Systematic Review of Studies Describing the Effectiveness, Acceptability, and Potential Harms of Place-Based Interventions to Address Loneliness and Mental Health Problems
BACKGROUND: A novel coronavirus, SARS-CoV-2 (known as COVID-19), spread rapidly around the world, affecting all and creating an ongoing global pandemic. Across the United States, Latinx and Indigenous populations have been disproportionately affected by COVID-19 cases and death rates. An examination of the perceptions and beliefs about the spread of the virus, COVID-19 testing, and vaccination amongst racial-ethnic minority groups, specifically Latinx and Indigenous Latin American immigrant communities, is needed to alleviate the widespread disparity in new cases and deaths. METHODS: This study was carried out from August 2020 to January 2021 and used community-based participatory research to engage community partners and build the capacity of community health workers (i.e., promotores de salud) and pre-medical and medical students in conducting qualitative research. The objective of the study was to examine the structural and social determinants of health on perceptions of the coronavirus, its spread, and decisions around COVID-19 testing and vaccination. Data collection included ethnography involving observations in public settings and focus groups with members of Latinx and Indigenous Mexican farm-working communities in the Eastern Coachella Valley, located in the Inland Southern California desert region. A total of seven focus groups, six in Spanish and one in Purpecha, with a total of 55 participants were conducted. Topics covered include perceptions of the coronavirus and its spread, as well as COVID-19 testing and vaccination. RESULTS: Using theme identification techniques, the findings identify structural and social factors that underly perceptions held by Latinx and Indigenous Mexican immigrants about the virus and COVID-19, which, in turn, shape attitudes and behaviors related to COVID-19 testing and vaccination. Common themes that emerged across focus groups include misinformation, lack of trust in institutions, and insecurity around employment and residency. CONCLUSIONS: This immigrant population is structurally vulnerable to historical and present-day inequalities that put them at increased risk of COVID-19 exposure, morbidity, and mortality. Study findings indicate a significant need for interventions that decrease structural vulnerabilities by addressing issues of (dis)trust in government and public health among this population.
Perceptions of the Coronavirus and COVID-19 testing and vaccination in Latinx and Indigenous Mexican immigrant communities in the Eastern Coachella Valley
OBJECTIVES: (1) To demonstrate how a risk assessment tool modified to account for the COVID-19 virus during the current global pandemic is able to provide risk assessment for low-energy geriatric hip fracture patients. (2) To provide a treatment algorithm for care of COVID-19 positive/suspected hip fractures patients that accounts for their increased risk of morbidity and mortality. SETTING: One academic medical center including 4 Level 1 trauma centers, 1 university-based tertiary care referral hospital, and 1 orthopaedic specialty hospital. PATIENTS/PARTICIPANTS: One thousand two hundred seventy-eight patients treated for hip fractures between October 2014 and April 2020, including 136 patients treated during the COVID-19 pandemic between February 1, 2020 and April 15, 2020. INTERVENTION: The Score for Trauma Triage in the Geriatric and Middle-Aged ORIGINAL (STTGMAORIGINAL) score was modified by adding COVID-19 virus as a risk factor for mortality to create the STTGMACOVID score. Patients were stratified into quartiles to demonstrate differences in risk distribution between the scores. MAIN OUTCOME MEASUREMENTS: Inpatient and 30-day mortality, major, and minor complications. RESULTS: Both STTGMA score and COVID-19 positive/suspected status are independent predictors of inpatient mortality, confirming their use in risk assessment models for geriatric hip fracture patients. Compared with STTGMAORIGINAL, where COVID-19 patients are haphazardly distributed among the risk groups and COVID-19 inpatient and 30 days mortalities comprise 50% deaths in the minimal-risk and low-risk cohorts, the STTGMACOVID tool is able to triage 100% of COVID-19 patients and 100% of COVID-19 inpatient and 30 days mortalities into the highest risk quartile, where it was demonstrated that these patients have a 55% rate of pneumonia, a 35% rate of acute respiratory distress syndrome, a 22% rate of inpatient mortality, and a 35% rate of 30 days mortality. COVID-19 patients who are symptomatic on presentation to the emergency department and undergo surgical fixation have a 30% inpatient mortality rate compared with 12.5% for patients who are initially asymptomatic but later develop symptoms. CONCLUSION: The STTGMA tool can be modified for specific disease processes, in this case to account for the COVID-19 virus and provide a robust risk stratification tool that accounts for a heretofore unknown risk factor. COVID-19 positive/suspected status portends a poor outcome in this susceptible trauma population and should be included in risk assessment models. These patients should be considered a high risk for perioperative morbidity and mortality. Patients with COVID-19 symptoms on presentation should have surgery deferred until symptoms improve or resolve and should be reassessed for surgical treatment versus definitive nonoperative treatment with palliative care and/or hospice care. LEVEL OF EVIDENCE: Prognostic Level III. See Instructions for Authors for a complete description of Levels of Evidence.
Modification of a Validated Risk Stratification Tool to Characterize Geriatric Hip Fracture Outcomes and Optimize Care in a Post-COVID-19 World
BACKGROUND Targeted radionuclide therapy with high-energy beta-emitters is generally considered suboptimal to cure small tumours (<300 mg). Tumour targeting of the CCK2 receptor-binding minigastrin analogue PP-F11 was determined in a tumour-bearing mouse model at increasing peptide amounts. The optimal therapy was analysed for PP-F11 labelled with (90)Y, (177)Lu or (213)Bi, accounting for the radionuclide specific activities (SAs), the tumour absorbed doses and tumour (radio) biology. METHODS Tumour uptake of (111)In-PP-F11 was determined in nude mice bearing CCK2 receptor-transfected A431 xenografts at 1 and 4 h post-injection for escalating peptide masses of 0.03 to 15 nmol/mouse. The absorbed tumour dose was estimated, assuming comparable biodistributions of the (90)Y, (177)Lu or (213)Bi radiolabelled peptides. The linear-quadratic (LQ) model was used to calculate the tumour control probabilities (TCP) as a function of tumour mass and growth. RESULTS Practically achievable maximum SAs for PP-F11 labelled with (90)Y and (177)Lu were 400 MBq (90)Y/nmol and 120 MBq(177)Lu/nmol. Both the large elution volume from the 220 MBq (225)Ac generator used and reaction kinetics diminished the maximum achieved (213)Bi SA in practice: 40 MBq (213)Bi/nmol. Tumour uptakes decreased rapidly with increasing peptide amounts, following a logarithmic curve with ED50 = 0.5 nmol. At 0.03 nmol peptide, the (300 mg) tumour dose was 9 Gy after 12 MBq (90)Y-PP-F11, and for (111)In and (177)Lu, this was 1 Gy. A curative dose of 60 Gy could be achieved with a single administration of 111 MBq (90)Y labelled to 0.28 nmol PP-F11 or with 4 17 MBq (213)Bi (0.41 nmol) when its -radiation relative biological effectiveness (RBE) was assumed to be 3.4. Repeated dosing is preferable to avoid complete tumour receptor saturation. Tumours larger than 200 mg are curable with (90)Y-PP-F11; the other radionuclides perform better in smaller tumours. Furthermore, (177)Lu is not optimal for curing fast-growing tumours. CONCLUSIONS Receptor saturation, specific radiopharmaceutical activities and absorbed doses in the tumour together favour therapy with the CCK2 receptor-binding peptide PP-F11 labelled with (90)Y, despite its longer -particle range in tissue, certainly for tumours larger than 300 mg. The predicted TCPs are of theoretical nature and need to be compared with the outcome of targeted radionuclide experiments.
Therapeutic application of CCK2R-targeting PP-F11: influence of particle range, activity and peptide amount.
Two major casualties to our programme have been the loss of the annual wreath-laying ceremony in Westminster Abbey and the Fellowships London Conference: both of these had a special significance in this 150th anniversary of Dickenss death (which we mark in this issue). Notwithstanding the outbreaks of strident nationalism in various parts of the world, this Covid pandemic has had the paradoxical effect of reinforcing the sense of a close global community almost in inverse ratio to its necessary impositions of physical and social aloofness. When Dickens met his audience in person for the last time, at his final reading, he promised them that after he had left the public stage he would be back with them, in their private homes, as an invisible presence to accompany the 'new series of readings' of his fictional worlds.
From the Editor
Objective: The objective of this study was to determine if different infertility diagnoses impacted patients scores on the FertiQol questionnaire, Insomnia Severity Index (ISI), and Perceived Stress Scale (PSS) during the COVID-19 pandemic The study also investigated if patients who were forced to discontinue their fertility treatment during the COVID-19 pandemic had different FertiQol scores than patients who were able to continue Design: Surveys were administered to 220 patients at a fertility clinic in Manhattan during the COVID-19 pandemic The surveys included a 36-item FertiQol questionnaire assessing Fertility Quality of Life in men and women experiencing fertility problems The surveys also asked patients to specify their infertility diagnoses (polycystic ovary syndrome, diminished ovarian reserve, uterine factor, endometriosis, or male infertility) Patients were further given a 7-item ISI questionnaire and a 10-item PSS questionnaire Finally, the surveys asked whether patients were forced to disrupt their fertility treatment plans due to the COVID-19 pandemic Materials and Methods: Using multiple linear regression, we looked for statistically significant relationships between different infertility diagnoses and FertiQol scores For this regression, we excluded all individuals who did not know their infertility diagnosis, had unexplained infertility issues, answered that they were fertile, or did not answer the FertiQol questionnaire We also used multiple linear regression to look for statistically significant relationships between different infertility diagnoses and levels of insomnia and between different infertility diagnoses and perceived stress Next, using Welchs t-test, we investigated if patients who discontinued their fertility treatments during the COVID-19 pandemic had a different mean FertiQol score from patients who continued treatment We excluded all individuals who were not currently undergoing treatment and who did not answer the FertiQol questionnaire A p-value less than 0 05 was considered statistically significant Results: The majority of the IVF patients sampled self-reported moderate stress (66 9%) There was no statistically significant relationship between the exact etiology of an IVF patients infertility diagnosis and the patients FertiQol score There was also no statistically significant relationship between the exact etiology of an IVF patients infertility diagnosis and the patients ISI nor PSS scores Patients who discontinued their fertility treatments during COVID-19 did not have different FertiQol scores from patients who were able to continue Conclusions: The majority of the IVF patients sampled self-reported moderate stress during the COVID-19 pandemic Interestingly, the exact etiology of an IVF patients infertility diagnosis did not have a statistically significant impact upon his or her Fertility Quality of Life, ISI, and PSS scores during this time period Patients who were forced to discontinue their fertility treatments due to COVID-19 did not have different FertiQol scores from patients who were able to continue
Relationships between Specific Infertility Diagnoses and Fertility Quality of Life (fertiqol), Insomnia, and Perceived Stress during Covid-19 Pandemic
Concomitant use of direct oral anticoagulants (DOACs) and medications with inhibition/induction effect on P-gp/CYP3A might increase risk of bleeding/treatment failure, respectively. We designed a nested case-control study within a Clalit cohort of atrial fibrillation (AF) patients and a cohort of venous thromboembolic patients, new users of a DOAC (1.1.2010-24.8.2020). Propensity scores were constructed from demographic, clinical and medications at cohort entry. Each case of: 1) serious bleeding event; 2) stroke/systemic emboli (SE) in AF patients; 3) recurrent thromboembolism in thromboembolic patients, was matched by age, sex, length of follow up, year of cohort entry, DOAC type, and DOAC indication, to up to 20 controls. Within 89284 AF and venous thromboembolic patients and 126,302 patient-years of follow up, there were 1587 serious bleeding events. Risk of serious bleeding increased in association with concurrent prescription of P-gp/CYP3A4 inhibitors. Specifically, higher bleeding risk was associated with dabigatran-verapamil, rivaroxaban-verapamil, and rivaroxaban-amiodarone concurrent prescriptions: adjusted ORs 2.29 (1.13-4.60), 2.18 (1.07-4.40), 1.68 (1.14-2.49), respectively. There were 1116 events of stroke/SE, in 79302 DOAC-treated AF patients and 118,124 patient-years of follow up. Concomitant use of phenytoin, carbamazepine, valproic acid, or levetiracetam was associated with risk for stroke/SE: adjusted OR 2.18 (1.55-3.10). Risk of recurrent venous thromboembolism could not be assessed due to low number of cases. Concurrent prescriptions of dabigatran or rivaroxaban with verapamil, and of rivaroxaban with amiodarone, are associated with increased risk for serious bleeding. Higher risk for stroke/SE in AF patients is associated with concurrent prescriptions of DOACs with phenytoin, carbamazepine, valproic acid, or levetiracetam.
Association between Use of Pharmacokinetic-Interacting Drugs and Effectiveness and Safety of Direct Acting Oral Anticoagulants: Nested Case-Control Study.
Understanding the mechanisms of modulators action on enzymes is crucial for optimizing and designing pharmaceutical substances. The acute inflammatory response, in particular, is regulated mainly by a disintegrin and metalloproteinase (ADAM) 17. ADAM17 processes several disease mediators such as TNF and APP, releasing their soluble ectodomains (shedding). A malfunction of this process leads to a disturbed inflammatory response. Chemical protease inhibitors such as TAPI-1 were used in the past to inhibit ADAM17 proteolytic activity. However, due to ADAM17s broad expression and activity profile, the development of active-site-directed ADAM17 inhibitor was discontinued. New exosite (secondary substrate binding site) inhibitors with substrate selectivity raised the hope of a substrate-selective modulation as a promising approach for inflammatory disease therapy. This work aimed to develop a high-throughput screen for potential ADAM17 modulators as therapeutic drugs. By combining experimental and in silico methods (structural modeling and docking), we modeled the kinetics of ADAM17 inhibitor. The results explain ADAM17 inhibition mechanisms and give a methodology for studying selective inhibition towards the design of pharmaceutical substances with higher selectivity.
In Silico and Experimental ADAM17 Kinetic Modeling as Basis for Future Screening System for Modulators
During the current COVID-19 global pandemic, the major efforts are channeled toward containing and minimizing the spread and maintaining the healthcare providers' safety. One of the major aspects of effective infection control and prevention is healthcare team training and system troubleshooting. Simulation-based education appears to be a practical and flexible instructional design to achieve variable levels of knowledge, skills, and attitude training. In this paper, we aim is to provide a brief scheme on how simulation-based training can be employed in COVID-19 pandemic preparedness efforts. In addition, we will be sharing our multidisciplinary simulation experience in critical care at the National Guard Health Affairs, Saudi Arabia.
Simulation role in preparing for COVID-19