Efficacy of texture and color enhancement imaging for the visibility and diagnostic accuracy of non-polypoid colorectal lesions.

Objective: A newly launched endoscopy system (EVIS X1, CV-1500; Olympus) is equipped with texture and color enhancement imaging (TXI). We aimed to investigate the efficacy of TXI for the visibility and diagnostic accuracy of non-polypoid colorectal lesions. Methods: We examined 100 non-polypoid lesions in 42 patients from the same position, angle, and distance of the view in three modes: white light imaging (WLI), narrow-band imaging (NBI), and TXI. The primary outcome was to compare polyp visibility in the three modes using subjective polyp visibility score and objective color difference values. The secondary outcome was to compare the diagnostic accuracy without magnification. Results: Overall, the visibility score of TXI was significantly higher than that of WLI (3.7 ± 1.1 vs. 3.6 ± 1.1; p = 0.008) and lower than that of NBI (3.7 ± 1.1 vs. 3.8 ± 1.1; p = 0.013). Color difference values of TXI were higher than those of WLI (11.5 ± 6.9 vs. 9.1 ± 5.4; p < 0.001) and lower than those of NBI (11.5 ± 6.9 vs. 13.1 ± 7.7; p = 0.002). No significant differences in TXI and NBI (visibility score: 3.7 ± 1.0 vs. 3.8 ± 1.1; p = 0.833, color difference values: 11.6 ± 7.1 vs. 12.9 ± 8.3; p = 0.099) were observed for neoplastic lesions. Moreover, the diagnostic accuracy of TXI was significantly higher than that of NBI (65.5% vs. 57.6%, p = 0.012) for neoplastic lesions. Conclusions: TXI demonstrated higher visibility than that of WLI and lower than that of NBI. Further investigations are warranted to validate the performance of the TXI mode comprehensively.

Effectiveness of digital health interventions for telemedicine/telehealth for managing blood pressure in adults: a systematic review and meta-analysis.

This systematic review and meta-analysis included randomized controlled trials or observational studies that compare digital health interventions (DHIs) for telemedicine/telehealth versus usual care for managing blood pressure (BP) in adults. We searched PubMed, Cochrane CENTRAL, and IchuShi-Web, and used a random-effects meta-analysis of the weighted mean difference (MD) between the comparison groups to pool data from the included studies. The outcome included the pooled MD of office BP from baseline to each follow-up period. This meta-analysis considered 117 studies with 68677 participants as eligible. The 3-month intervention period reduced office systolic BP (SBP) compared with usual care in 38 studies (MD: -3.21 mmHg [95% confidence interval: -4.51 to -1.90]), with evidence of heterogeneity. Office SBP across intervention periods demonstrated comparable effects (3-, 6- [54 studies], 12- [43 studies], and >12-month periods [9 studies]). The benefits for office diastolic BP were similar to those for office SBP. Additionally, the interventions significantly reduced the office SBP compared with the control, regardless of the mode of intervention delivery (smartphone apps [38 studies], text messages [35 studies], and websites [34 studies]) or type of facility (medical [74 studies] vs. non-medical [33 studies]). The interventions were more effective in 41 hypertension cohorts compared with 66 non-hypertension cohorts (-4.81 mmHg [-6.33, -3.29] vs. -2.17 mmHg [-3.15, -1.19], P = 0.006 for heterogeneity). In conclusion, DHIs for telemedicine/telehealth improved BP management compared with usual care. The effectiveness with heterogeneity should be considered, as prudent for implementing evidence-based medicine. This meta-analysis considered 117 studies with 68677 participants eligible. The DHIs for telemedicine/telehealth reduced office BP compared with usual care, regardless of intervention duration, intervention delivery mode, facility type, and cohort type. Additionally, the DHIs reduced the risk of uncontrolled BP compared with usual care, regardless of intervention duration, intervention delivery mode, and facility type. BP blood pressure, DHI digital health intervention, MD mean difference, RR risk ratio, SBP systolic blood pressure.

Childhood PFAS exposure and immunotoxicity: a systematic review and meta-analysis of human studies.

BACKGROUND: Exposure to poly- and perfluoroalkyl substances (PFAS) may affect infant and childhood health through immunosuppression. However, the findings of epidemiological literature examining relationships between prenatal/childhood PFAS exposure and vaccine response and infection in humans are still inconclusive. The aim of this review was to examine the effects of PFAS exposure on vaccine antibody response and infection in humans. METHODS: The MEDLINE/Pubmed database was searched for publications until 1 February 2023 to identify human studies on PFAS exposure and human health. Eligible for inclusion studies had to have an epidemiological study design and must have performed logistic regression analyses of gestational or childhood exposure to PFAS against either antibody levels for pediatric vaccines or the occurrence of children's infectious diseases. Information on baseline exposure to PFAS (in ng/mL), the age of PFAS exposure (gestational or in years), and the outcome was measured, potentially leading to multiple exposure-outcome comparisons within each study was collected. Percentage change and standard errors of antibody titers and occurrence of infectious diseases per doubling of PFAS exposure were calculated, and a quality assessment of each study was performed. RESULTS: Seventeen articles were identified matching the inclusion criteria and were included in the meta-analysis. In general, a small decrease in antibody response and some associations between PFAS exposure and childhood infections were observed. CONCLUSIONS: This meta-analysis summarizes the findings of PFAS effects on infant and childhood immune health. The immunosuppression findings for infections yielded suggestive evidence related to PFAS exposure, particularly PFOS, PFOA, PFHxS, and PFNA but moderate to no evidence regarding antibody titer reduction. SYSTEMATIC REVIEW REGISTRATION: The research protocol of this systematic review is registered and accessible at the Open Science Framework ( https://doi.org/10.17605/OSF.IO/5M2VU ).

Supply of nirmatrelvir/ritonavir and molnupiravir for patients with COVID-19 in the first eight months since listing on the Australian Pharmaceutical Benefits Scheme: A retrospective observational study.

OBJECTIVES: To compare the supply of molnupiravir and nirmatrelvir/ritonavir in relation to patient characteristics and other co-prescribed medicines and to estimate the number of patients without contraindications to nirmatrelvir/ritonavir who were treated with molnupiravir. STUDY DESIGN, SETTING: Retrospective observational study of patients identified in the Pharmaceutical Benefits Scheme (PBS) 10 % sample dataset who were supplied with either molnupiravir or nirmatrelvir/ritonavir between May and December 2022. We supplemented the PBS dataset with aggregated counts from published literature to determine prevalence of clinical contraindications to nirmatrelvir/ritonavir. MAIN OUTCOME MEASURES: We used multivariable Poisson regression to estimate risk ratios (RR) of receiving nirmatrelvir/ritonavir over molnupiravir. RESULTS: We identified 54,550 patients who received either nirmatrelvir/ritonavir (26.8 %) or molnupiravir (73.2 %). Their average age was 71.6 (SD = 13.4) years and 57.1 % were female. Patients were less likely to receive nirmatrelvir/ritonavir with increasing age (RR = 0.50; 95 % CI: 0.48-0.53; for ages 85 + compared to < 65 years) or who had received medicines contraindicated for use with nirmatrelvir/ritonavir (RR = 0.66; 95 % CI: 0.64-0.68). During the study period, we estimated that between 28.4 % and 45.4 % of patients aged ≥ 65 years had received molnupiravir in the absence of pharmacological and clinical contraindications to nirmatrelvir/ritonavir. CONCLUSION: Many prescriptions were written for molnupiravir where there were no contraindications to nirmatrelvir/ritonavir. The benefits that followed from prompt government action in approving and obtaining nirmatrelvir/ritonavir were therefore likely to be less than they could potentially have been. Governments should consider investing in quality improvement systems to ensure the best outcomes in terms of efficacy and safety.

Morphometric Characteristics and Species Identification of Bed Bugs (Hemiptera: Cimicidae) in Eastern Iran.

Background: The common bed bugs, Cimex lectularius, and tropical bed bugs, Cimex hemipterus are the primary species of public health importance in the family Cimicidae. This study aimed to determine the morphometric criteria and prevalent species of bed bugs in eastern Iran. Methods: Bed bugs were collected from March 2021 to June 2022 from infested residential buildings and apartments in eastern Iran, including North Khorasan, Khorasan Razavi, and Sistan and Baluchistan Provinces. The morphological and morphometrical characteristics were used to identify collected bed bugs at inter- and intra-specific levels. Results: A total of 34 isolates comprising 127 adult bed bugs were collected from Bojnord, Mashhad, Neishabur, Taibad, Sabzevar, Kashmer, Zahedan, Saravan, Rask, Pishin and Chabahar. Of these, 33 isolates (n=124) were found to be tropical bed bugs, C. hemipterus, and one population (n=3) was identified as C. lectularius. The index pronotal width/length ratio was calculated from 2.72 to 2.94 and 1.98 to 2.47 for C. lectularius and C. hemipterus, respectively. The length/width ratio of the hind femur was 3.365 in C. hemipterus and 4.267 in C. lectularius. The ratio of length/width of the third femur (F3 l/w) between populations of C. hemipterus was different, and this difference was statistically significant (P< 0.05). Conclusion: The results of this study indicated that C. hemipterus was the dominant bed bug species in the east of Iran and provided more morphometric criteria of C. hemipterus for researchers to identify the species and determine the intraspecific variations in the present and future.

A most aggressive bear: Safari videos document sloth bear defense against tiger predation.

Sloth bears are non-carnivorous yet they attack more people than any other bear. They often stand up and charge explosively if a person mistakenly gets too close. Here, we argue that their aggression toward humans is an extension of their behavior toward tigers, which are their only natural predator. Interactions between sloth bears and tigers have not previously been studied because scientists have rarely observed such events. We collected and examined 43 videos or photo documentations of sloth bear-tiger interactions posted on the internet or social media from 2011 to 2023, mainly by tourists visiting tiger parks in India. We observed that sloth bears were most likely to stand up and charge if they first became aware of the tiger at close range (<3 m away). This aggressive-defensive strategy, intended to dissuade the tiger from attacking, appeared to be successful, in that 86% of interactions ended with no contact, whereas four (9%) culminated in the bear's death. We propose that a myrmecophagous diet led to this species' aggressive behavior: (1) their long, blunt front claws, well adapted for digging termites and ants, hamper their ability to climb trees for escape, and (2) they walk with their head down focused on scents underground, and make considerable noise digging and blowing soil, enabling tigers to approach quite closely without being detected. Sloth bears have coexisted with tigers or other (now extinct) large felid predators for their entire evolutionary history. Whereas their aggressive behavior has served them well for millions of years, more recently, people's fear of and retaliation against sloth bears represents a major threat to their survival. Understanding how sloth bears react to tigers provides guidance for reducing attacks on humans, thereby contributing to sloth bear conservation. Our investigation was made possible by passive citizen scientists, who unknowingly collected valuable data.

Indomethacin Does Not Reduce Post-ERCP Pancreatitis in High-Risk Patients Receiving Pancreatic Stenting.

BACKGROUND: Rectal indomethacin reduces pancreatitis following endoscopic retrograde cholangiopancreatography (ERCP). However, there is insufficient evidence regarding its added benefits in patients already receiving prophylactic pancreatic stenting. Our goal was to evaluate the impact of indomethacin in high-risk patients undergoing pancreatic stenting. METHODS: A cohort study was conducted on all patients who underwent the rescue cannulation technique for challenging bile duct cannulation (selected high-risk patients). Patients were split into two groups based on the prophylaxis method for post-ERCP pancreatitis (PEP): one receiving a combination of indomethacin and pancreatic stenting, while the other received pancreatic stenting alone. Comparative analyses were carried out on PEP, hyperamylasemia, gastrointestinal bleeding, and postoperative hospital stay among post-ERCP pancreatitis patients. RESULTS: Between November 2017 and May 2023, a total of 607 patients with native papillae were enrolled, with 140 grouped into the indomethacin plus stent group and 467 into the stent alone group. The overall PEP rate was 4.4% in the entire cohort, with no statistical differences observed between the groups in terms of PEP rates (P = 0.407), mild PEP (P = 0.340), moderate to severe PEP (P = 1.000), hyperamylasemia (P = 0.543), gastrointestinal bleeding (P = 0.392), and postoperative hospital stay (P = 0.521). Furthermore, sensitivity analysis using multivariable analysis also validated these findings. CONCLUSIONS: Indomethacin did not reduce the incidence or severity of PEP in high-risk patients who routinely received prophylactic pancreatic stent placement. Therefore, the additional administration of rectal indomethacin to further mitigate PEP appears to be not necessary.

Effect of Nitrate Supplementation on Oxygen Saturation Levels for Acute Mountain Sickness Prevention: A Systematic Review and Meta-Analysis.

PURPOSE: This study aimed to systematically review the effect of nitrate supplementation on blood oxygen saturation. METHODS: We searched PubMed, Scopus, and Cochrane Library databases from their inception up to October 2022. Two reviewers independently conducted two stages of the screening process to include a randomized controlled trial with nitrate supplementation versus placebo intervention assessing oxygen saturation among lowlanders going to either real or simulated high altitude environments. We used the Cochrane Risk of Bias 2.0 tool to assess the risk of bias in the included studies. Fixed-effect model meta-analyses were conducted for laboratory-based studies. Random-effect meta-analyses were conducted for real-world studies. RESULTS: We found 7 trials that met the eligibility criteria. A meta-analysis of studies with some bias concerns showed an increase of 1.26% in the SpO2 with 44% I2 during submaximal exercise at simulated high altitudes (GRADE: low). On the contrary, a meta-analysis of studies without heterogeneity showed that nitrate supplementation aggravated oxygen saturation decline (-2.64%, p=0.03, GRADE: high) during rest in real high-altitude environments. A meta-analysis also showed that nitrate supplementation did not affect Acute Mountain Sickness (AMS) symptoms (GRADE: high). CONCLUSION: Our results suggest that nitrate supplementation did not provide benefits for AMS prevention during rest at high altitudes. The low-quality evidence showing small beneficial effects of nitrate supplementation during exercise calls for further studies.

Family-Centered Care Experiences in Elderly with Chronic Diseases in Communities: Qualitative Study of Patients, Families, Nurses, and Volunteers.

Introduction: The family, at community, must be an important part of elderly care. However, most of the elderly experience a decrease in psychological well-being and quality of life. This is not in accordance with the concept of the family-centered care (FCC) model and can endanger the continuity of the elderly with chronic illnesses. Objective: The aim of this study was to explore experience of FCC among patients with chronic illness, nurses, families, and volunteers. Methods: This study examines the contextual-based FCC model qualitatively. In-depth interviews and focus group discussions were conducted by 12 elderly people, 3 nurses, 10 family members, and 3 volunteers. In total, 36 people, where several were FGD participants, were also interviewed in depth. Data were analyzed using thematic analysis, with codes organized into larger themes. Result: In total, 36 interviews and FGDs were conducted. The concept of information interaction, the phenomenon of emotional interaction, the practical interaction, and various factors that can either facilitate or impede interaction, were considered the four significant themes. Conclusion: FCC acceptance is found in interactions between parents, nurses, family, and volunteers who are not optimistic. Lack of communication and collaboration was noted between community nurses and volunteers. Offer a new perspective on developing and implementing interventions that facilitate positive interactions, reduce family burdens, provide high-quality treatment for parents with chronic diseases, and improve the quality of care for those with advanced chronic conditions. Recommendation: These insights provide a fresh perspective on how to develop and implement effective interventions in this context. It is recommended that future research should employ multiple methodologies to investigate FCC across diverse health practices for the elderly population.

Effects of Lacticaseibacillus rhamnosus HA-114 probiotic supplementation on circulating IGFBP-2 levels during a calorie-restricted diet in overweight humans.

Background and aim: Gut microbiota influences energy homeostasis in part through circulating hormones. Insulin-like growth factor-binding protein (IGFBP)-2 is a biomarker whose increase in systemic circulation is associated with positive effects on body weight and metabolism. In a recent clinical trial, probiotic Lacticaseibacillus rhamnosus HA-114 supplementation showed positive effects on eating behaviors and insulin resistance in overweight participants undergoing a weight-loss intervention. In this context, this ancillary study aimed at assessing the impact of L. rhamnosus HA-114 supplementation on plasma IGFBP-2 levels in these individuals, and whether this modulation correlated with changes in fat mass, energy metabolism, and eating behaviors. Methods: Fasting plasma IGFBP-2 concentrations were quantified in 100 overweight or obese men and women enrolled in a 12-week diet-based weight reduction program (-500 kcal/day), in combination with probiotic L. rhamnosus HA-114 or placebo supplementation. Baseline and changes in circulating IGFBP-2 concentrations were correlated with anthropometric parameter, glucose and lipid metabolism, cardiorespiratory function and eating behaviors. Results: On average, the intervention reduced BMI by 4.6 % and increased IGFBP-2 by 13 %, regardless of supplementation group. Individuals who presented an increase in IGFBP-2 levels had significantly greater reductions in BMI. Changes in IGFBP-2 levels were correlated with loss in fat mass (r = 0.2, p < 0.001) in the probiotic-supplemented group, but not with other metabolic parameters or eating behaviors. Baseline IGFBP-2 levels were not associated with weight loss or improvements in cardiometabolic parameters. Conclusion: Probiotic supplementation with L. rhamnosus HA-114 did not modulate plasma IGFBP-2 levels. Changes in IGFBP-2 levels were correlated with greater reductions in BMI, but not with other metabolic parameters or eating behaviors, indicating that the benefits of HA-114 on eating behaviors are likely independent of IGFBP-2. Additional changes in microbiota might be required to modulate IGFBP-2 and observe its associations with eating behaviors and cardiometabolic improvements.

BSE risk posed by ruminant collagen and gelatine derived from bones.

The European Commission requested an estimation of the BSE risk (C-, L- and H-BSE) from gelatine and collagen derived from ovine, caprine or bovine bones, and produced in accordance with Regulation (EC) No 853/2004, or Regulation (EC) No 1069/2009 and its implementing Regulation (EU) No 142/2011. A quantitative risk assessment was developed to estimate the BSE infectivity, measured in cattle oral infectious dose 50 (CoID50), in a small size batch of gelatine including one BSE-infected bovine or ovine animal at the clinical stage. The model was built on a scenario where all ruminant bones could be used for the production of gelatine and high-infectivity tissues remained attached to the skull (brain) and vertebral column (spinal cord). The risk and exposure pathways defined for humans and animals, respectively, were identified. Exposure routes other than oral via food and feed were considered and discussed but not assessed quantitatively. Other aspects were also considered as integrating evidence, like the epidemiological situation of the disease, the species barrier, the susceptibility of species to BSE and the assumption of an exponential dose-response relationship to determine the probability of BSE infection in ruminants. Exposure to infectivity in humans cannot be directly translated to risk of disease because the transmission barrier has not yet been quantified, although it is considered to be substantial, i.e. much greater amounts of infectivity would be needed to successfully infect a human and greater in the oral than in the parenteral route of exposure. The probability that no new case of BSE in the cattle or small ruminant population would be generated through oral exposure to gelatine made of ruminant bones is 99%-100% (almost certain) This conclusion is based on the current state of knowledge, the epidemiological situation of the disease and the current practices, and is also valid for collagen.

Handedness in Animals and Plants.

Structural and functional asymmetries are traceable in every form of life, and some lateralities are homologous. Functionally speaking, the division of labour between the two halves of the brain is a basic characteristic of the nervous system that arose even before the appearance of vertebrates. The most well-known expression of this specialisation in humans is hand dominance, also known as handedness. Even if hand/limb/paw dominance is far more commonly associated with the presence of a nervous system, it is also observed in its own form in aneural organisms, such as plants. To date, little is known regarding the possible functional significance of this dominance in plants, and many questions remain open (among them, whether it reflects a generalised behavioural asymmetry). Here, we propose a comparative approach to the study of handedness, including plants, by taking advantage of the experimental models and paradigms already used to study laterality in humans and various animal species. By taking this approach, we aim to enrich our knowledge of the concept of handedness across natural kingdoms.

The effect of mailed outreach on FIT completion among patients aged 45-50 in a safety net healthcare system.

PURPOSE: Colorectal cancer screening is recommended starting at age 45, but there has been little research on strategies to promote screening in patients younger than 50. METHODS: An outreach program quasi-randomly assigned patients aged 45-50 without recent fecal immunochemical test (FIT), colonoscopy or contraindications to screening to two intervention arms: electronic outreach with email and text (electronic outreach only) versus electronic outreach plus mailed outreach with FIT, an instructional letter and a prepaid return envelope (mailed + electronic outreach). In response to known disparities in screening uptake, all Black patients were assigned to receive mailed + electronic outreach. RESULTS: Among patients quasi-randomly assigned to an intervention (non-Black patients), the 180-day FIT completion rate was 18.8% in the electronic outreach only group (n = 1,318) and 25.0% in the mailed + electronic outreach group (n = 1,364) (difference 6.2% [95% CI 3.0, 9.4]). FIT completion was 16.6% among Black patients (n = 469), 8.4% (95% CI 4.1, 12.6) lower than among non-Black patients also assigned to mailed + electronic outreach. CONCLUSION: Among patients aged 45-50, mailed + electronic outreach had a greater effect on FIT completion than electronic outreach alone. Crossover between intervention groups likely lead to an underestimation of the effect of mailed outreach.

The recommendations and the way forward to fight human infections caused by influenza A (H1N1) in Brazil.

Many recent outbreaks of influenza A (H1N1) in the world, especially in Brazil, it has become clear that the severity of the disease is not known in the same form. On Wednesday, June 7, 2023, Brazil notified the WHO of a fatal case of human infection with a variant of the influenza A(H1N1) virus of swine origin, this case was confirmed in a laboratory in the region of the interior state of Paraná. This is the first human infection caused by an influenza A (H1N1) virus reported in 2023 nationwide in Brazil. To mitigate H1N1 flu in Brazil, we urge the Brazillian government through its Ministry of Health to improve on mass awareness about the signs and symptoms of H1N1 flu among the Brazillians. The Brazillian government should also implement the One Health approach towards the control of H1N1 flu in Brazil, as we believe that these recommendations would go a long way in preventing future cases and the spread of H1N1 flu in Brazil. This article aims to present the clinical presentations of the H1N1 flu and the implications, recommendations and the way forward to protect the Brazilian population against the H1N1 flu.

Leptospirosis in India: insights on circulating serovars, research lacunae and proposed strategies to control through one health approach.

Leptospirosis is one of the most neglected zoonotic infections of public health concern worldwide and a remerging infection in tropical countries such as India. The infection least explored disease and the epidemiological and other critical data are scarce for the disease rate reported and to control the infection. Leptospirosis as sapronosis is as underrated as the infection itself, and this article aims to explore the significance of this aspect of the disease. The research review aimed at the epidemiological understanding of the infection to control the negative impact of the disease. A mixed review and analysis were carried out to understand the knowledge published on the critical and understudied areas like epidemiology, transmission, diagnosis, treatment, and control of infection. A systematic analysis was carried out to extract information about the reported circulating strains, and research lacunae in India with the published data available in PubMed. The article elaborately discusses crucial inference areas of infection transmission and addresses lacunae in critically unacclaimed areas of infection to control the spread of infection using one health approach (OHA), and strategies to control leptospiral infection are proposed. The article also reviewed how and why Leptospirosis can be best studied and controlled by "One health approach" in India.

Nancy S. Jecker, Zohar Lederman, and Anita Ho reply.

This letter replies to the letter "Colonial and Neocolonial Barriers to Companion Digital Humans in Africa," by Luís Cordeiro-Rodrigues, in the same, May-June 2024, issue of the Hastings Center Report.

Colonial and Neocolonial Barriers to Companion Digital Humans in Africa.

This letter responds to the essay "Digital Humans to Combat Loneliness and Social Isolation: Ethics Concerns and Policy Recommendation," by Nancy S. Jecker, Robert Sparrow, Zohar Lederman, and Anita Ho, in the January-February 2024 issue of the Hastings Center Report.

An international survey assessing the effects of the duration of attack-free period on health-related quality of life for patients with hereditary angioedema.

BACKGROUND: Hereditary angioedema (HAE) is characterized by unpredictable and often severe cutaneous and mucosal swelling that affects the extremities, face, larynx, gastrointestinal tract, or genitourinary area. Introduction of novel long-term prophylactic treatment options (lanadelumab, berotralstat, and C1-esterase inhibitor SC [human]) into the treatment armamentarium has substantially reduced HAE attacks, allowing patients to be attack free for longer with improvements to their quality of life. Using data drawn from a wide-ranging survey of patients with HAE, we examined the relationship between duration of time attack free and health-related quality of life (HRQoL), exploring the possibility that there is an association between observed improvement in HRQoL and attack-free duration. METHODS: A survey among patients with HAE on long-term prophylaxis (LTP) in six countries (the US, Australia, Canada, UK, Germany, and Japan) assessed the relationship between attack-free duration and mean Angioedema Quality of Life (AE-QoL) scores, quality of life benefits, and rescue medication used. Analysis of covariance (ANCOVA) was used to assess the roles of LTP and attack-free period (< 1 month, 1- < 6 months, ≥ 6 months) on total AE-QoL scores. Results include descriptive p-values for strength of association, without control for multiplicity. Descriptive statistics were used to show the relationship between time attack free and quality of life benefits. RESULTS: Longer durations of time for which participants reported being attack free at the time of the survey correlated with better AE-QoL scores and less use of rescue medication. The mean total AE-QoL scores were 51.8, 33.2, and 19.9 for those who reported having been attack free for < 1 month, 1- < 6 months, and ≥ 6 months, respectively, with higher scores reflecting more impairment. The ANCOVA results showed a strong association between attack-free duration and AE-QoL total score. CONCLUSION: This study shows that longer attack-free duration has an influential role for better HRQoL in patients receiving LTP. Prolonging the attack-free period is an important goal of therapy and recent advances in LTP have increased attack-free duration. However, opportunities exist for new treatments to further increase attack-free duration and improve HRQoL for all patients with HAE.

Association between volume of lung damage and endoplasmic reticulum stress expression among severe COVID-19 ICU patients.

Introduction: Links have been established between SARS-CoV-2 and endoplasmic reticulum stress (ERS). However, the relationships between inflammation, ERS, and the volume of organ damage are not well known in humans. The aim of this study was to explore whether ERS explains lung damage volume (LDV) among COVID-19 patients admitted to the intensive care unit (ICU). Materials and methods: We conducted a single-center retrospective study (ancillary analysis of a prospective cohort) including severe COVID-19 ICU patients who had a chest computed tomography (CT) scan 24 h before/after admission to assess LDV. We performed two multivariate linear regression models to identify factors associated with plasma levels of 78 kDa-Glucose-Regulated Protein (GRP78; ERS marker) and Interleukin-6 (IL-6; inflammation marker) at admission. Results: Among 63 patients analyzed, GRP78 plasma level was associated with LDV in both multivariate models (ß = 22.23 [4.08;40.38]; p = 0.0179, ß = 20.47 [0.74;40.20]; p = 0.0423) but not with organ failure (Sequential Organ Failure Assessment (SOFA) score) at admission (r = 0.03 [-0.22;0.28]; p = 0.2559). GRP78 plasma level was lower among ICU survivors (1539.4 [1139.2;1941.1] vs. 1714.2 [1555.2;2579.1] pg./mL. respectively; p = 0.0297). IL-6 plasma level was associated with SOFA score at admission in both multivariate models (ß = 136.60 [65.50;207.70]; p = 0.0003, ß = 193.70 [116.60;270.90]; p < 0.0001) but not with LDV (r = 0.13 [-0.14;0.39]; p = 0.3219). IL-6 plasma level was not different between ICU survivors and non-survivors (12.2 [6.0;43.7] vs. 30.4 [12.9;69.7] pg./mL. respectively; p = 0.1857). There was no correlation between GRP78 and IL-6 plasma levels (r = 0.13 [-0.13;0.37]; p = 0.3106). Conclusion: Among severe COVID-19 patients, ERS was associated with LDV but not with systemic inflammation, while systemic inflammation was associated with organ failure but not with LDV.