Spontaneous coronary artery dissection (SCAD) and takotsubo cardiomyopathy (TCM) - A potential association.

Background: Spontaneous coronary artery dissection and takotsubo cardiomyopathy are increasingly recognized in the last two decades. Case reports have shown both entities can present concomitantly - however, little is known about their association. Methods: In this retrospective study we aimed to explore a potential association between SCAD and TCM using the Nationwide Inpatient Sample. The odds of having TCM among patients with SCAD compared with those who did not have SCAD were calculated as an odds ratio. Conversely, the odds of having SCAD among patients with TCM compared with those who did not have TCM were also calculated. The primary outcome was the odds of TCM among patients with a primary diagnosis of SCAD and vice versa. The secondary endpoint was the odds of in-hospital mortality among patients with SCAD, and/or TCM. Results: Hospitalized patients who had SCAD were 7.12 (95 % CI: 6.28-8.08) times more likely to also have TCM than those who did not have SCAD (p < 0.0001).), while patients with TCM were 6.91 (95 % CI: 6.07-7.85) times more likely to have SCAD compared to those who didn't have TCM adjusted for age, gender, race, hypertension, hyperlipidemia, and diabetes mellitus (p < 0.0001). Conclusion: This data indicate that patients with either SCAD or TCM are seven times more likely to be diagnosed concomitantly with both, compared to the patients without either diagnosis [after adjusting for age, gender, race, hypertension, hyperlipidemia, and diabetes mellitus]. Our data are consistent with the growing body of evidence supporting an association between SCAD and TCM and raise the question of a common pathophysiologic mechanism.

From rejection to the Nobel Prize: Karikó and Weissman's pioneering work on mRNA vaccines, and the need for diversity and inclusion in translational immunology.

Katalin Karikó and Drew Weissman were given the 2023 Nobel Prize in Physiology or Medicine for their findings of nucleoside base modifications that lead to the development of effective mRNA vaccines against COVID-19. This was a remarkable achievement, given that their initial manuscript was rejected by Nature and Science in 2005. The development of mRNA vaccines lagged for more than a decade for several reasons, including the lack of funding, the perceived risks of the technology, and the scepticism of many scientists. Furthermore, Karikó and Weissman's study appeared to be technical and difficult to understand. The COVID-19 pandemic, on the other hand, has shown the importance of mRNA vaccine technology. COVID-19 mRNA vaccines have been highly effective in preventing serious illness, hospitalization, and death. The Nobel Prize for Karikó and Weissman highlights the importance of perseverance, diversity, and inclusion in translational immunology. We need to build a more inclusive scientific community, where scientists from all backgrounds are supported and their work is valued. This will result in more scientific breakthroughs and better healthcare for everyone.

Risk assessment and antibody responses to SARS-CoV-2 in healthcare workers.

Background: Preventing infection in healthcare workers (HCWs) is crucial for protecting healthcare systems during the COVID-19 pandemic. Here, we investigated the seroepidemiology of SARS-CoV-2 in HCWs in Norway with low-transmission settings. Methods: From March 2020, we recruited HCWs at four medical centres. We determined infection by SARS-CoV-2 RT-PCR and serological testing and evaluated the association between infection and exposure variables, comparing our findings with global data in a meta-analysis. Anti-spike IgG antibodies were measured after infection and/or vaccination in a longitudinal cohort until June 2021. Results: We identified a prevalence of 10.5% (95% confidence interval, CI: 8.8-12.3) in 2020 and an incidence rate of 15.0 cases per 100 person-years (95% CI: 12.5-17.8) among 1,214 HCWs with 848 person-years of follow-up time. Following infection, HCWs (n = 63) mounted durable anti-spike IgG antibodies with a half-life of 4.3 months since their seropositivity. HCWs infected with SARS-CoV-2 in 2020 (n = 46) had higher anti-spike IgG titres than naive HCWs (n = 186) throughout the 5 months after vaccination with BNT162b2 and/or ChAdOx1-S COVID-19 vaccines in 2021. In a meta-analysis including 20 studies, the odds ratio (OR) for SARS-CoV-2 seropositivity was significantly higher with household contact (OR 12.6; 95% CI: 4.5-35.1) and occupational exposure (OR 2.2; 95% CI: 1.4-3.2). Conclusion: We found high and modest risks of SARS-CoV-2 infection with household and occupational exposure, respectively, in HCWs, suggesting the need to strengthen infection prevention strategies within households and medical centres. Infection generated long-lasting antibodies in most HCWs; therefore, we support delaying COVID-19 vaccination in primed HCWs, prioritising the non-infected high-risk HCWs amid vaccine shortage.

Progress in drug delivery and diagnostic applications of carbon dots: a systematic review.

Carbon dots (CDs), which have particle size of less than 10 nm, are carbon-based nanomaterials that are used in a wide range of applications in the area of novel drug delivery in cancer, ocular diseases, infectious diseases, and brain disorders. CDs are biocompatible, eco-friendly, easy to synthesize, and less toxic with excellent chemical inertness, which makes them very good nanocarrier system to deliver multi-functional drugs effectively. A huge number of researchers worldwide are working on CDs-based drug delivery systems to evaluate their versatility and efficacy in the field of pharmaceuticals. As a result, there is a tremendous increase in our understanding of the physicochemical properties, diagnostic and drug delivery aspects of CDs, which consequently has led us to design and develop CDs-based theranostic system for the treatment of multiple disorders. In this review, we aim to summarize the advances in application of CDs as nanocarrier including gene delivery, vaccine delivery and antiviral delivery, that has been carried out in the last 5 years.

Atrial Speckle Tracking Echocardiography for Detecting Atrial Fibrillation in Cryptogenic Stroke: A Meta-Analysis.

Cryptogenic stroke (CS) accounts for approximately 25% of ischemic stroke cases, with atrial fibrillation (AF) accounting for 30% of CS cases. We investigated the utility of left atrial (LA) speckle-tracking echocardiography in identifying patients at high risk of AF after CS and potentially guiding patients who will benefit from long-term rhythm monitoring devices. Cochrane Library, MEDLINE, and EMBASE were searched for relevant studies. We included studies that examined patients with new CS without a history of AF and further examined LA strain parameters (peak and/or reservoir strain). Continuous data were pooled as a mean difference (MD) comparing patients who developed AF vs no AF.  We used the inverse variance method with the DerSimonian-Laird estimator for tau2 and Hartung-Knapp adjustment for random effect analysis. I2 was used to assess heterogeneity. Thirteen observational studies met our criteria and included 3031 patients with new CS. Of those, 420 patients developed AF on follow-up, and 2611 patients did not develop AF. The AF group vs. no AF had significantly reduced LA reservoir strain (LARS) [MD: -8.61; 95% CI: -10.76, -6.47, I2 = 85%, p < 0.01] at presentation. LARS is significantly lower in patients who developed AF after CS. More studies are needed to validate this data.

Indicators of Self-Determination in Therapeutic Songwriting Lyrics Created by Adults with High LDL Cholesterol.

Individuals with low-density lipoprotein cholesterol ≥190 mg/dL are at high risk for atherosclerotic cardiovascular disease events. Our goal was to determine if adults with this condition would express important psychological, health, and motivation themes when generating lyrics during music therapy. Thirty-one participants each created their own original song with the help of a music therapist. The lyrics were analyzed using a deductive approach guided by Self-Determination Theory (specifically the satisfaction or frustration of basic psychological needs): (1) for each entire song (macro-analysis) and (2) line-by-line (micro-analysis). Song lyrics generated during music therapy sessions by patients with a low-density lipoprotein cholesterol ≥190 mg/dL revealed the presence of the three basic needs (autonomy, competence, and relatedness) of Self-Determination Theory. The most prevalent theme identified in the macro-analysis of songs was autonomy satisfaction, coded in 25 songs (27.17% of all macro codes), and followed by competence satisfaction in 17 songs (18.48%) and relatedness satisfaction in 15 songs (16.3%). Line-by-line micro-analysis of lyrics revealed that at least one basic need of Self-Determination Theory was present in 277 of the unique lyric lines (50%); 107 (19%) for relatedness, 101 (18%) for autonomy, and 69 (13%) for competence. Need satisfaction occurred more frequently than need frustration in both analyses. However, depending on the level of analysis (macro or micro), results differed as to which themes were most prevalent. These results indicate that therapeutic songwriting may be a unique way to identify the basic psychological needs that, when satisfied, indicate self-determination.

A Comparison of the Quality of Life of People With Epilepsy Receiving Home-Based and Clinic-Based Epilepsy Care Using the European Quality of Life Five-Dimension Three-Level (EQ-5D-3L) Scale.

Background and objective Epilepsy is a chronic neurological condition that, both physically and psychologically, puts a person at risk for poor quality of life (QOL). People with epilepsy (PWE) may experience shame, fear, and rejection and feel discriminated against, hence avoiding social interactions. To avoid being labeled as having epilepsy, patients may conceal their disease and refuse medical attention, which can lead to treatment discontinuation and significantly impact the quality of life. Epilepsy care in India has fallen back on primary care physicians because there are not enough neurologists available to treat the condition. Home-based care (HBC) may overcome many barriers by providing free antiepileptic drugs (AEDs), eliminating the "distance to a health facility," and providing correct information that may improve QOL. This study is therefore conducted to compare the QOL between people with epilepsy receiving home-based care (HBC) and routine clinic-based care (CBC). Methodology The people with epilepsy enrolled in this study were already part of a community-based randomized controlled trial conducted to compare the effect of regular home-based epilepsy care with routine clinic-based epilepsy care on antiepileptic adherence among urban and peri-urban areas of Ludhiana, Punjab, India (explained further in the study). The present study is a cohort study where the two cohorts, one receiving home-based epilepsy care (n = 97) and the other receiving routine clinic-based epilepsy care (n = 76), were compared for QOL at two points in time, i.e., at baseline (at enrolment) and after 24 months of receiving epilepsy care, using the European Quality of Life Five-Dimension Three-Level (EQ-5D-3L) scale. Results The mean EQ-5D-3L index scores for the HBC group at baseline were 0.88 ± 0.15, and after 24 months, the scores increased to 0.94 ± 0.17. The baseline mean index scores for the CBC group were 0.89 ± 0.21, and after 24 months, the value increased to 0.90 ± 0.19. The mean difference in QOL in the HBC group showed a higher difference than in the CBC group (0.06 ± 0.1 versus 0.01 ± 0.1), but the difference was found to be statistically not significant (p = 0.067). As per the five dimensions of the EQ-5D-3L scale, i.e., mobility, self-care, usual activities, pain/discomfort, and anxiety/depression, there was a decrease in the number of PWE reporting problems among both groups after 24 months of epilepsy care. Sociodemographic and clinical variables such as level of education, working status, age at the onset of seizures, frequency of seizures, treatment regimen, presence of comorbidities, and adverse drug reactions significantly affect the QOL of people with epilepsy at p < 0.05. Conclusion The results of the study emphasize that epilepsy has a negative impact on QOL. The results showed a higher QOL among the people in the HBC group as compared to the CBC group, but the difference was not statistically significant. There was an improvement in QOL from baseline after dedicated care in both groups. The problems related to mobility, self-care, usual activities, pain/discomfort, and anxiety/depression have been significantly reduced in the HBC group. Having low levels of education, not having a job, starting to have seizures at a young age, having seizures more often, receiving more than one type of treatment, and the presence of other health problems and side effects are factors associated with poor QOL among people with epilepsy.

Durable immune responses after BNT162b2 vaccination in home-dwelling old adults.

Objectives: Elderly are an understudied, high-risk group vulnerable to severe COVID-19. We comprehensively analyzed the durability of humoral and cellular immune responses after BNT162b2 vaccination and SARS-CoV-2 infection in elderly and younger adults. Methods: Home-dwelling old (n = 100, median 86 years) and younger adults (n = 449, median 38 years) were vaccinated with two doses of BNT162b2 vaccine at 3-week intervals and followed for 9-months. Vaccine-induced responses were compared to home-isolated COVID-19 patients (n = 183, median 47 years). Our analysis included neutralizing antibodies, spike-specific IgG, memory B-cells, IFN-γ and IL-2 secreting T-cells and sequencing of the T-cell receptor (TCR) repertoire. Results: Spike-specific breadth and depth of the CD4+ and CD8+ TCR repertoires were significantly lower in the elderly after one and two vaccinations. Both vaccinations boosted IFN-γ and IL-2 secreting spike-specific T-cells responses, with 96 % of the elderly and 100 % of the younger adults responding after the second dose, although responses were not maintained at 9-months. In contrast, T-cell responses persisted up to 12-months in infected patients. Spike-specific memory B-cells were induced after the first dose in 87 % of the younger adults compared to 38 % of the elderly, which increased to 83 % after the second dose. Memory B-cells were maintained at 9-months post-vaccination in both vaccination groups. Neutralizing antibody titers were estimated to last for 1-year in younger adults but only 6-months in the older vaccinees. Interestingly, infected older patients (n = 15, median 75 years) had more durable neutralizing titers estimated to last 14-months, 8-months longer than the older vaccinees. Conclusions: Vaccine-induced spike-specific IgG and neutralizing antibodies were consistently lower in the older than younger vaccinees. Overall, our data provide valuable insights into the kinetics of the humoral and cellular immune response in the elderly after SARS-CoV-2 vaccination or infection, highlighting the need for two doses, which can guide future vaccine design.Clinical trials.gov; NCT04706390.

Cardiovascular positron emission tomography: established and emerging role in cardiovascular diseases.

Cardiac positron emission tomography (PET) imaging has established themselves firmly as excellent and reliable functional imaging modalities in assessment of the spectrum of coronary artery disease. With the explosion of technology advances and the dream of flow quantification now a reality, the value of PET is now well realized. Cardiac PET has proved itself as precise imaging modality that provides functional imaging of the heart in addition to anatomical imaging. It has established itself as one of the best available techniques for evaluation of myocardial viability. Hybrid PET/computed tomography provides simultaneous integration of coronary anatomy and function with myocardial perfusion and metabolism, thereby improving characterization of the dysfunctional area and chronic coronary artery disease. The availability of quantitative myocardial blood flow evaluation with PET provides additional prognostic information and increases diagnostic accuracy in the management of patients with coronary artery disease. Hybrid imaging seems to hold immense potential in optimizing management of cardiovascular diseases and furthering clinical research.

Preclinical evaluation of a microparticle-based transdermal vaccine patch against metastatic breast cancer.

Breast cancer is the number one cause of cancer-related deaths among females. Current chemotherapy targets both tumor and normal cells, leading to pronounced side effects. Therefore, therapeutic vaccines acting against specific cancer cells would be the choice of treatment. We prepared microparticles entrapping the antigens obtained from a murine metastatic breast cancer cell line, 4 T1 using the spray drying technology. These microparticles were incorporated into microneedle patches to deliver to the animals for the efficacy study. An antineoplastic drug, cyclophosphamide, in a very low dose has been found to inhibit the immunosuppressive regulatory T cells (Treg) (Le and Jaffee, 2012). In-vivo efficacy of the microparticulate vaccine given along with a low dose of cyclophosphamide was evaluated in a murine breast cancer model. Animals immunized with vaccine microparticles showed considerably slower tumor growth than animals that did not receive the vaccine. The results of the study showed that the Tumor-Associated Antigens (TAAs) within the microparticles were responsible for the delayed tumor growth in vaccinated animals. Vaccinated animals also showed an increase in the population of CD4 and CD8 T cells. Overall, our results demonstrated that immunotherapy with vaccine microparticles encapsulating TAA's could potentially be an effective treatment for metastatic breast cancer.

Anticoagulation and BMI: effect of high body weight on the safety and efficacy of direct oral anticoagulants.

Obesity is an epidemic with rising prevalence, and obese patients are predisposed to comorbid conditions that increase risk for thromboembolic events. It is critical to identify safe and effective anticoagulation therapy for use in this population. Direct oral anticoagulants (DOACs) are a preferred option for anticoagulation in patients of normal weight due to many benefits and equivalent safety and efficacy to their vitamin K antagonist counterparts. However, the safety and efficacy of DOACs in obese patients is not well understood. This review describes recent studies on the pharmacokinetics, safety and efficacy, and clinical outcomes of the DOACs apixaban, rivaroxaban, edoxaban and dabigatran in obese patient populations. DOACs may be a beneficial alternative to vitamin K antagonist therapy in obese patient populations.

The incidence of obesity within the USA is on the rise, as is that of the medical conditions that often accompany it. These include conditions that can predispose individuals to forming clots in the blood, such as atrial fibrillation, which is a form of an abnormal heartbeat, and nonalcoholic fatty liver disease, which is caused by fat buildup around the liver. Therefore, it is important that we have effective medicines that can prevent clotting in an obese patient population. Direct oral anticoagulants are a new, preferred medication option for this, but it is unclear how safe or effective they are in obese people; there is some concern that because of increased body weight, individuals may not get enough medicine to effectively prevent clots from forming, which would ultimately put them at risk for clotting and serious adverse health outcomes such as stroke. This review describes recent studies on the use of the direct oral anticoagulants apixaban, rivaroxaban, edoxaban and dabigatran in obese patients, and whether they are a safe and effective form of anticoagulation in this population.

Crafting Immunological Response Using Particulate Vaccines.

To achieve optimal immunogenicity, particulates present a promising vehicle for antigen delivery and have the potential to skew immune response. Particulate vaccine offers several advantages including targeting of antigen to sentinel cells, protection from degradation, sustained release, and itself acts an adjuvant mimics viral structure. Adjuvant presence is vital in overcoming the poor immunogenicity of vaccines, e.g., subunit vaccines. Adjuvants have antigen dose sparing potential and provide danger signals to alert the immune system. Various particulate carriers received attention in the delivery of vaccine antigens such as virus-like particles, liposomes, immunostimulating complexes, and polymeric particles. This review also discussed the properties of particles such as size, shape, and rigidity affecting the immunological outcome. It further highlights the cellular uptake of the particulate vaccine, antigen processing, and its presentation by antigen-presenting cells. For mass vaccination, especially in countries lacking resources, effect of storage temperature condition on stability of vaccine is pivotal. The current COVID-19 pandemic is not showing any signs of abatement and role of nanocarriers are highly relevant in SARS-CoV-2 pandemic as an effective immunization strategy. Eradication of pandemic demands the rapid evaluation of multiple approaches that can provides successful vaccination platform, enabling scalability and global distribution.

Trifecta and Pentafecta Outcomes in Laparoscopic and Robotic Nephron-Sparing Surgery for Highly Complex Renal Tumors: A Propensity Score-Matched Cohort Analysis.

Purpose: To compare the trifecta and pentafecta outcomes of laparoscopic partial nephrectomy (LPN) and robotic partial nephrectomy (RPN) in highly complex renal tumors (RENAL nephrometry score ≥10) using a matched cohort analysis. Methods: Patients undergoing LPN or RPN for renal tumors with RENAL score ≥10 between January 2014 and December 2019 were matched using 1:2 propensity score match analysis based on age, body mass index, gender, laterality of tumor, RENAL score, and American Society of Anesthesiologists (ASA) score. The two groups were compared for trifecta and pentafecta outcomes. Results: Thirty patients undergoing LPN (Group A) were matched with 60 patients undergoing RPN (Group B). The mean age (standard deviation) was 53.7 (12.9) years. The median (interquartile range) RENAL score was 10 (10-11). In comparison, the mean warm ischemia time in Group A was significantly longer than that in Group B (26.2 vs 23.0 minutes, p = 0.013). The overall complication rate was 36.7% in Group A as compared with 20% in Group B (p = 0.440). The trifecta outcomes could be achieved in 11 patients (36.7%) in Group A compared with 40 patients (66.7%) in Group B (p = 0.012). Moreover, 10 patients (33.3%) in Group A and 28 patients (46.7%) in Group B achieved pentafecta outcomes (p = 0.227). Conclusions: In a matched cohort of patients undergoing nephron-sparing surgery for highly complex renal tumors (RENAL score ≥10), the robotic approach offers a superior advantage in the achievement of trifecta outcomes as compared with the laparoscopic approach. However, both LPN and RPN can achieve similar pentafecta outcomes.

Functional and Binding H1N1pdm09-Specific Antibody Responses in Occasionally and Repeatedly Vaccinated Healthcare Workers: A Five-Year Study (2009-2014).

Background: In 2009, a novel influenza A/H1N1pdm09 emerged and caused a pandemic. This strain continued to circulate and was therefore included in the seasonal vaccines up to the 2016/2017-season. This provided a unique opportunity to study the long-term antibody responses to H1N1pdm09 in healthcare workers (HCW) with a different vaccination history. Methods: HCW at Haukeland University Hospital, Bergen, Norway were immunized with the AS03-adjuvanted H1N1pdm09 vaccine in 2009 (N=55) and divided into groups according to their vaccination history; one vaccination (N=10), two vaccinations (N=15), three vaccinations (N=5), four vaccinations (N=15) and five vaccinations (N=10). HCW are recommended for influenza vaccination to protect both themselves and their patients, but it is voluntary in Norway. Blood samples were collected pre- and at 21 days, 3, 6, and 12 months after each vaccination, or annually from 2010 HCW without vaccination. ELISA, haemagglutination inhibition (HI) and microneutralization (MN) assays were used to determine the antibody response. Results: Pandemic vaccination induced a significant increase in the H1N1-specific antibodies measured by ELISA, HI and MN. Seasonal vaccination boosted the antibody response, both in HCW with only the current vaccination and those with prior and current vaccination during 2010/11-2013/14. We observed a trend of increased antibody responses in HCW with only the current vaccination in 2013/14. A two- and three-year gap before vaccination in 2013/14 provided a more potent antibody response compared to annually vaccinated HCW. Conclusions: Our long term follow up study elucidates the antibody response in HCW with different vaccination histories. Our findings contribute to our understanding of the impact of repeated vaccination upon antibody responses.

Safety, Immunogenicity, Efficacy and Effectiveness of Inactivated Influenza Vaccines in Healthy Pregnant Women and Children Under 5 Years: An Evidence-Based Clinical Review.

Annual influenza vaccination is often recommended for pregnant women and young children to reduce the risk of severe influenza. However, most studies investigating the safety, immunogenicity, and efficacy or effectiveness of influenza vaccines are conducted in healthy adults. In this evidence-based clinical review, we provide an update on the safety profile, immunogenicity, and efficacy/effectiveness of inactivated influenza vaccines (IIVs) in healthy pregnant women and children <5 years old. Six electronic databases were searched until May 27, 2021. We identified 3,731 articles, of which 93 met the eligibility criteria and were included. The IIVs were generally well tolerated in pregnant women and young children, with low frequencies of adverse events following IIV administration; however, continuous vaccine safety monitoring systems are necessary to detect rare adverse events. IIVs generated good antibody responses, and the seroprotection rates after IIVs were moderate to high in pregnant women (range = 65%-96%) and young children (range = 50%-100%), varying between the different influenza types/subtypes and seasons. Studies show vaccine efficacy/effectiveness values of 50%-70% in pregnant women and 20%-90% in young children against lab-confirmed influenza, although the efficacy/effectiveness depended on the study design, host factors, vaccine type, manufacturing practices, and the antigenic match/mismatch between the influenza vaccine strains and the circulating strains. Current evidence suggests that the benefits of IIVs far outweigh the potential risks and that IIVs should be recommended for pregnant women and young children.

Formulation and Characterization of Microcapsules Encapsulating PC12 Cells as a Prospective Treatment Approach for Parkinson's Disease.

Parkinson's disease (PD) is the second most common neurological disorder, associated with decreased dopamine levels in the brain. The goal of this study was to assess the potential of a regenerative medicine-based cell therapy approach to increase dopamine levels. In this study, we used rat adrenal pheochromocytoma (PC12) cells that can produce, store, and secrete dopamine. These cells were microencapsulated in the selectively permeable polymer membrane to protect them from immune responses. For fabrication of the microcapsules, we used a modified Buchi spray dryer B-190 that allows for fast manufacturing of microcapsules and is industrially scalable. Size optimization of the microcapsules was performed by systematically varying key parameters of the spraying device. The short- and long-term stabilities of the microcapsules were assessed. In the in vitro study, the cells were found viable for a period of 30 days. Selective permeability of the microcapsules was confirmed via dopamine release assay and micro BCA protein assay. We found that the microcapsules were permeable to the small molecules including dopamine and were impermeable to the large molecules like BSA. Thus, they can provide the protection to the encapsulated cells from the immune cells. Griess's assay confirmed the non-immunogenicity of the microcapsules. These results demonstrate the effective fabrication of microcapsules encapsulating cells using an industrially scalable device. The microcapsules were stable, and the cells were viable inside the microcapsules and were found to release dopamine. Thus, these microcapsules have the potential to serve as the alternative or complementary treatment approach for PD.

Attack rates amongst household members of outpatients with confirmed COVID-19 in Bergen, Norway: A case-ascertained study.

BACKGROUND: Households studies reflect the natural spread of SARS-CoV-2 in immunologically naive populations with limited preventive measures to control transmission.We hypothesise that seropositivity provides more accurate household attack rates than RT-PCR. Here, we investigated the importance of age in household transmission dynamics. METHODS: We enroled 112 households (291 participants) in a case-ascertained study in Bergen, Norway from 28th February to 4th April 2020, collecting demographic and clinical data from index patients and household members. SARS-CoV-2-specific antibodies were measured in sera collected 6-8 weeks after index patient nasopharyngeal testing to define household attack rates. FINDINGS: The overall attack rate was 45% (95% CI 38-53) assessed by serology, and 47% when also including seronegative RT-PCR positives. Serology identified a higher number of infected household members than RT-PCR. Attack rates were equally high in children (48%) and young adults (42%). The attack rate was 16% in asymptomatic household members and 42% in RT-PCR negative contacts. Older adults had higher antibody titres than younger adults. The risk of household transmission was higher when the index patient had fever (aOR 3.31 [95% CI 1.52-7.24]; p = 0.003) or dyspnoea (aOR 2.25 [95% CI 1.80-4.62]; p = 0.027) during acute illness. INTERPRETATION: Serological assays provide more sensitive and robust estimates of household attack rates than RT-PCR. Children are equally susceptible to infection as young adults. Negative RT-PCR or lack of symptoms are not sufficient to rule out infection in household members. FUNDING: Helse Vest (F-11628), Trond Mohn Foundation (TMS2020TMT05).

Taste Masking of Granulated Acetaminophen by Water Insoluble Ethylcellulose Coating.

INTRODUCTION: Bitter tasting of drugs leads to non-compliance especially in the case of pediatric patients due to their inability to swal-low medication. AIM: In this study, we aimed to mask the bitter taste of acetaminophen (APAP) particles through coating. MATERIALS AND METHODS: A pH independent water insoluble ethylcellulose polymer was used to coat the APAP. The coating of water insoluble ethylcellulose on APAP can have a significant impact on the dissolution profile. Various grades of APAP were used for coating; fine grade, Compap L90% having wide particle size distribution (PSD), and a special granular (SG) APAP 1680 having narrow PSD. Coating was performed using top spray (Vector) for Compap L90% and SG APAP 1680 grade of APAP. RESULTS: Bitter taste of SG APAP was masked after spraying dispersion equivalent to a weight gain of 10% compared to 35% used for Compap L90%. Using bottom spray (Wurster coater, GPCP 2.0), coating was performed on SG APAP 1680 grade of APAP by spraying aqueous dispersion of ethylcellulose (Surelease) equivalent to a weight gain of 10%. The scalability of the top spray process was also evaluated in GPCG 30 and bitter taste was masked by using Surelease dispersion equivalent to a weight gain of 6%. Coated APAP was examined for particle size (PS), particle size distribution (PSD), flowability, and drug release profile. Dissolution was performed using USP apparatus 2 and 4 in phosphate buffer and evaluated for mechanism of drug release. Particle size obtained for coated SG APAP 1680 via top and bottom spray process was 404 µm d(90) and 487 µm d(90) respectively. CONCLUSIONS: The results of the study demonstrated the potential of Surelease dispersion in taste masking. The use of SG APAP 1680 having narrow PSD allowed taste masking to achieve at low weight gain without greatly affecting the dissolution profile.