An evaluation of the usability and durability of 3D printed versus standard suture materials.

The capability to produce suture material using three-dimensional (3D) printing technology may have applications in remote health facilities where rapid restocking of supplies is not an option. This is a feasibility study evaluating the usability of 3D-printed sutures in the repair of a laceration wound when compared with standard suture material. The 3D-printed suture material was manufactured using a fused deposition modelling 3D printer and nylon 3D printing filament. Study participants were tasked with performing laceration repairs on the pigs' feet, first with 3-0 WeGo nylon suture material, followed by the 3D-printed nylon suture material. Twenty-six participants were enrolled in the study. Survey data demonstrated statistical significance with how well the 3D suture material performed with knot tying, 8.9 versus 7.5 (p = 0.0018). Statistical significance was observed in the 3D-printed suture's ultimate tensile strength when compared to the 3-0 Novafil suture (274.8 vs. 199.8 MPa, p = 0.0096). The 3D-printed suture also demonstrated statistical significance in ultimate extension when compared to commercial 3-0 WeGo nylon suture (49% vs. 37%, p = 0.0215). This study was successful in using 3D printing technology to manufacture suture material and provided insight into its usability when compared to standard suture material.

Oral bemnifosbuvir (AT-527) vs placebo in patients with mild-to-moderate COVID-19 in an outpatient setting (MORNINGSKY).

Aim: This phase III study assessed the efficacy/safety/antiviral activity/pharmacokinetics of bemnifosbuvir, a novel, oral nucleotide analog to treat COVID-19. Patients & methods: Outpatient adults/adolescents with mild-to-moderate COVID-19 were randomized 2:1 to bemnifosbuvir/placebo. Time to symptom alleviation/improvement (primary outcome), risk of hospitalization/death, viral load and safety were evaluated. Results: Although the study was discontinued prematurely and did not meet its primary end point, bemnifosbuvir treatment resulted in fewer hospitalizations (71% relative risk reduction), COVID-19-related medically attended hospital visits, and COVID-19-related complications compared with placebo. No reduction in viral load was observed. The proportion of patients with adverse events was similar; no deaths occurred. Conclusion: Bemnifosbuvir showed hospitalization reduction in patients with variable disease progression risk and was well tolerated. Clinical Trial Registration: NCT04889040 (ClinicalTrials.gov).

Oral Nirmatrelvir for High-Risk, Nonhospitalized Adults with Covid-19.

BACKGROUND: Nirmatrelvir is an orally administered severe acute respiratory syndrome coronavirus 2 main protease (Mpro) inhibitor with potent pan-human-coronavirus activity in vitro. METHODS: We conducted a phase 2-3 double-blind, randomized, controlled trial in which symptomatic, unvaccinated, nonhospitalized adults at high risk for progression to severe coronavirus disease 2019 (Covid-19) were assigned in a 1:1 ratio to receive either 300 mg of nirmatrelvir plus 100 mg of ritonavir (a pharmacokinetic enhancer) or placebo every 12 hours for 5 days. Covid-19-related hospitalization or death from any cause through day 28, viral load, and safety were evaluated. RESULTS: A total of 2246 patients underwent randomization; 1120 patients received nirmatrelvir plus ritonavir (nirmatrelvir group) and 1126 received placebo (placebo group). In the planned interim analysis of patients treated within 3 days after symptom onset (modified intention-to treat population, comprising 774 of the 1361 patients in the full analysis population), the incidence of Covid-19-related hospitalization or death by day 28 was lower in the nirmatrelvir group than in the placebo group by 6.32 percentage points (95% confidence interval [CI], -9.04 to -3.59; P<0.001; relative risk reduction, 89.1%); the incidence was 0.77% (3 of 389 patients) in the nirmatrelvir group, with 0 deaths, as compared with 7.01% (27 of 385 patients) in the placebo group, with 7 deaths. Efficacy was maintained in the final analysis involving the 1379 patients in the modified intention-to-treat population, with a difference of -5.81 percentage points (95% CI, -7.78 to -3.84; P<0.001; relative risk reduction, 88.9%). All 13 deaths occurred in the placebo group. The viral load was lower with nirmatrelvir plus ritonavir than with placebo at day 5 of treatment, with an adjusted mean difference of -0.868 log10 copies per milliliter when treatment was initiated within 3 days after the onset of symptoms. The incidence of adverse events that emerged during the treatment period was similar in the two groups (any adverse event, 22.6% with nirmatrelvir plus ritonavir vs. 23.9% with placebo; serious adverse events, 1.6% vs. 6.6%; and adverse events leading to discontinuation of the drugs or placebo, 2.1% vs. 4.2%). Dysgeusia (5.6% vs. 0.3%) and diarrhea (3.1% vs. 1.6%) occurred more frequently with nirmatrelvir plus ritonavir than with placebo. CONCLUSIONS: Treatment of symptomatic Covid-19 with nirmatrelvir plus ritonavir resulted in a risk of progression to severe Covid-19 that was 89% lower than the risk with placebo, without evident safety concerns. (Supported by Pfizer; ClinicalTrials.gov number, NCT04960202.).

The Association of Death Notification and Related Training with Burnout among Emergency Medical Services Professionals.

INTRODUCTION: Death notification is a difficult task commonly encountered during prehospital care and may lead to burnout among EMS professionals. Lack of training could potentiate the relationship between death notification and burnout. The first objective of this study was to describe EMS professionals' experience with death notification and related training. The secondary objective was to assess the associations between death notification delivery, training, and burnout. Methods: We administered an electronic questionnaire to a random sample of nationally-certified EMS professionals. Work-related burnout was measured using the validated Copenhagen Burnout Inventory. Analysis was stratified by certification level to basic life support (BLS) and advanced life support (ALS). The association between the number of adult (≥18 years) patient death notifications delivered in the prior 12 months and burnout was assessed using multivariable logistic regression to adjust for confounding variables. Multivariable logistic regression modeling was used to assess the adjusted association between training and burnout among those who reported delivering at least one death notification in the prior 12 months. Adjusted odds ratios (aOR) and 95% confidence intervals are reported (95% CI). Results: We received 2,333/19,330 (12%) responses and 1,514 were included in the analysis. Most ALS respondents (77%) and one-third of BLS respondents (33%) reported at least one adult death notification in the past year. Approximately half of respondents reported receiving death notification training as part of their initial EMS education program (51% BLS; 52% ALS) and fewer reported receiving continuing education (30% BLS; 44% ALS). Delivering a greater number of death notifications was associated with increased odds of burnout. Among those who delivered at least one death notification, continuing education was associated with reduced odds of burnout. Conclusion: Many EMS professionals reported delivering at least one death notification within the past year. Yet, fewer than half reported training related to death notification during initial EMS education and even fewer reported receiving continuing education. More of those who delivered death notifications experienced burnout, while continuing education was associated with reduced odds of burnout. Future work is needed to develop and evaluate death notification training specifically for EMS professionals.

Neurocognition and the Suicidal Process.

Early thinking about cognitive process and suicidal behaviors tended to focus on the immediate situation surrounding the individual - typically the underlying psychiatric condition that was seen as leading to his or her distress. However, we now know that the cognitive processes involved in a range of suicidal thoughts and behaviors can exert a significant impact on the expression or development of these behaviors, even without an environmental stressor or psychiatric condition. In this chapter, we summarize theoretical perspectives that led to this realization and explore the current understanding of the link between cognition and suicide from recent research and clinical findings. We present these findings first by psychiatric disorder, then by cognitive domains, and finally by specific suicidal construct in order to highlight the importance of these factors in determining the role of cognition in the suicidal process.Within and across psychiatric disorders, certain cognitive processes - negativistic thinking, impulsivity, cognitive rigidity, and altered emotional processing - are frequently found to be linked to suicidal thoughts and behaviors. Overall cognitive performance, decreased processing speed, executive dysfunction, and negative biases in memory and attention have also been linked to suicidal thoughts and behaviors. However, these findings do not hold true for all populations. There seems to be a role both for cognitive distortions (such as hopelessness) and neurocognitive deficits (such as poor overall cognitive performance, slower processing speed, and executive dysfunction) in the suicidal process, which warrant further exploration both separately and together.

Obesity is not associated with increased difficulty placing peripheral IVs in trauma activation patients.

INTRODUCTION: Previous studies have identified obesity as a risk factor for difficult IV access, but this has not been studied in the acute trauma setting. The primary objective was to determine if obesity is associated with increased difficulty placing peripheral IVs in trauma patients. Secondary analysis evaluated IV difficulty and associations with nursing self-competence ratings, trauma experience, and patient demographics. METHODS: Prospective, observational study at academic level I trauma center with 58,000 annual visits. Trauma activation patients between January and October of 2016 were included. Each nurse who attempted IV placement, completed anonymous 7 question survey, including trauma experience (years), self-competence and IV difficulty (Likert scales 1-5), and attempts. Demographic and clinical information was retrospectively collected from the EMR and nursing surveys. Descriptive statistics, chi-square tests, and spearman correlations were used. RESULTS: 200 patients included in the study with 185 BMI calculations. 110 overweight (BMI > 25) and 48 obese (BMI > 30). 70 (35%) female, 149 (75%) white, average age 48. Increased BMI and IV difficulty displayed spearman correlation (ρ) of 0.026 (P = 0.72) suggesting against significant association. Increased trauma experience and self-competence ratings significantly correlated with decreased IV difficulty, ρ = -0.173 and -0.162 (P = 0.010 and 0.014). There was no statistically significant association with IV difficulty in regards to patient race, age, sex, or location of IV placement. CONCLUSION: Obesity was not associated with increased difficulty in placing peripheral IVs in trauma activation patients. Nurses with greater trauma experience and higher self-competence ratings, had less difficulty inserting IVs.

The Current Genomic Landscape of Western South America: Andes, Amazonia, and Pacific Coast.

Studies of Native South American genetic diversity have helped to shed light on the peopling and differentiation of the continent, but available data are sparse for the major ecogeographic domains. These include the Pacific Coast, a potential early migration route; the Andes, home to the most expansive complex societies and to one of the most widely spoken indigenous language families of the continent (Quechua); and Amazonia, with its understudied population structure and rich cultural diversity. Here, we explore the genetic structure of 176 individuals from these three domains, genotyped with the Affymetrix Human Origins array. We infer multiple sources of ancestry within the Native American ancestry component; one with clear predominance on the Coast and in the Andes, and at least two distinct substrates in neighboring Amazonia, including a previously undetected ancestry characteristic of northern Ecuador and Colombia. Amazonian populations are also involved in recent gene-flow with each other and across ecogeographic domains, which does not accord with the traditional view of small, isolated groups. Long-distance genetic connections between speakers of the same language family suggest that indigenous languages here were spread not by cultural contact alone. Finally, Native American populations admixed with post-Columbian European and African sources at different times, with few cases of prolonged isolation. With our results we emphasize the importance of including understudied regions of the continent in high-resolution genetic studies, and we illustrate the potential of SNP chip arrays for informative regional-scale analysis.

Fosdagrocorat (PF-04171327) versus prednisone or placebo in rheumatoid arthritis: a randomised, double-blind, multicentre, phase IIb study.

Objectives: Glucocorticoids have anti-inflammatory, transrepression-mediated effects, although adverse events (AEs; transactivation-mediated effects) limit long-term use in patients with rheumatoid arthritis (RA). We evaluated the efficacy and safety of fosdagrocorat (PF-04171327), a dissociated agonist of the glucocorticoid receptor, versus prednisone or placebo. Methods: In this 12-week, phase II, randomised controlled trial, 323 patients with moderate to severe RA were randomised 1:1:1:1:1:1:1 to fosdagrocorat (1 mg, 5 mg, 10 mg or 15 mg), prednisone (5 mg or 10 mg) or placebo, once daily. The primary endpoints (week 8) were American College of Rheumatology 20% improvement criteria (ACR20) responses, and percentage changes from baseline in biomarkers of bone formation (procollagen type 1 N-terminal peptide [P1NP]) and resorption (urinary N-telopeptide to urinary creatinine ratio [uNTx:uCr]). Safety was assessed. Results: ACR20 responses with fosdagrocorat 10 mg and 15 mg were superior to placebo, and fosdagrocorat 15 mg was non-inferior to prednisone 10 mg (week 8 model-predicted ACR20 responses: 47%, 61%, 69% and 73% vs 51%, 71% and 37% with fosdagrocorat 1 mg, 5 mg, 10 mg and 15 mg vs prednisone 5 mg, 10 mg and placebo, respectively). Percentage changes from baseline in P1NP with fosdagrocorat 1 mg, 5 mg and 10 mg met non-inferiority criteria to prednisone 5 mg. Corresponding changes in uNTx:uCr varied considerably. All fosdagrocorat doses reduced glycosylated haemoglobin levels. AEs were similar between groups; 63 (19.5%) patients reported treatment-related AEs; 9 (2.8%) patients reported serious AEs. No patients had adrenal insufficiency, treatment-related significant infections or laboratory abnormalities. No deaths were reported. Conclusion: In patients with RA, fosdagrocorat 10 mg and 15 mg demonstrated efficacy similar to prednisone 10 mg and safety similar to prednisone 5 mg. Trial registration number: NCT01393639.