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BACKGROUND: Pre-exposure prophylaxis for COVID-19 with tixagevimab/cilgavimab (T/C) received Emergency Use Authorization (EUA) based on results of a clinical trial conducted prior to the emergence of the Omicron variant. The clinical effectiveness of T/C has not been well described in the Omicron era. We examined the incidence of symptomatic illness and hospitalizations among T/C recipients when Omicron accounted for virtually all local cases. METHODS: Through retrospective electronic medical record chart review, we identified patients who received T/C between January 1 -July 31, 2022 within our quaternary referral health system. We determined the incidence of symptomatic COVID-19 infections and hospitalizations due to or presumed to be caused by early Omicron variants before and after receiving T/C (pre-T/C and post-T/C). Chi square and Mann-Whitney Wilcoxon two-sample tests were used to examine differences between the characteristics of those who got COVID-19 before or after T/C prophylaxis, and rate ratios (RR) and 95% confidence intervals (CI) were calculated to assess differences in hospitalization rates for the two groups. RESULTS: Of 1295 T/C recipients, 105 (8.1%) developed symptomatic COVID-19 infection before receiving T/C, and 102 (7.9%) developed symptomatic disease after receiving it. Of the 105 patients who developed symptomatic infection pre-T/C, 26 (24.8%) were hospitalized, compared with six of the 102 patients (5.9%) who were diagnosed with COVID-19 post-T/C (RR = 0.24; 95% CI = 0.10-0.55; p = 0.0002). Seven of the 105 (6.7%) patients infected pre-T/C, but none of the 102 infected post-T/C required ICU care. No COVID-related deaths occurred in either group. The majority of COVID-19 cases among those infected pre-T/C treatment occurred during the Omicron BA.1 surge, while the majority of post-T/C cases occurred when Omicron BA.5 was predominant. In both groups, having at least one dose of vaccine strongly protected against hospitalization (pre-T/C group RR = 0.31, 95% CI = 0.17-0.57, p = 0.02; post-T/C group RR = 0.15; 95% CI = 0.03-0.94; p = 0.04). CONCLUSION: We identified COVID-19 infections after T/C prophylaxis. Among patients who received T/C at our institution, COVID-19 Omicron cases occurring after T/C were one-fourth as likely to require hospitalization compared to those with Omicron prior to T/C. However, due to the presence of changing vaccine coverage, multiple therapies, and changing variants, the effectiveness of T/C in the Omicron era remains difficult to assess.

BACKGROUND: The supraclavicular fossa is the dominant location for human brown adipose tissue (BAT). Activation of BAT promotes non-shivering thermogenesis by utilization of glucose and free fatty acids and has been the focus of pharmacological and non-pharmacological approaches for modulation in order to improve body weight and glucose homeostasis. Sympathetic neural control of supraclavicular BAT has received much attention, but its innervation has not been extensively investigated in humans. METHODS: Dissection of the cervical region in human cadavers was performed to find the distribution of sympathetic nerve branches to supraclavicular fat pad. Furthermore, proximal segments of the 4th cervical nerve were evaluated histologically to assess its sympathetic components. RESULTS: Nerve branches terminating in supraclavicular fat pad were identified in all dissections, including those from the 3rd and 4th cervical nerves and from the cervical sympathetic plexus. Histology of the proximal segments of the 4th cervical nerves confirmed tyrosine hydroxylase positive thin nerve fibers in all fascicles with either a scattered or clustered distribution pattern. The scattered pattern was more predominant than the clustered pattern (80% vs. 20%) across cadavers. These sympathetic nerve fibers occupied only 2.48% of the nerve cross sectional area on average. CONCLUSIONS: Human sympathetic nerves use multiple pathways to innervate the supraclavicular fat pad. The present finding serves as a framework for future clinical approaches to activate human BAT in the supraclavicular region.

Sleep deprivation (SD), defined as an inability to get a minimum of 7 hours of regular sleep at night is a serious health problem that impacts the performance of medical professionals. This study aims to determine the impact of sleep deprivation on perceived performance among medical officers (MOs). A cross-sectional study design involved 231 MOs from six disciplines in Hospital Tuanku Ja'afar, a tertiary center in the south of Malaysia. A self-administered questionnaire was introduced in the English language. The questionnaire involved the sociodemographic characteristics; job-related factors, and the Sleep Deprivation Impact Scale (SDIS). The SDIS is a 12-question scale, rated on a 5-point Likert scale from strongly disagree to strongly agree. A higher SDIS score reflected a higher impact of sleep deprivation. A total of 206 MOs returned the completed questionnaire yielding a response rate of 89.17%. The mean age of respondents was 31.68 (±3.49) years. Most of the respondents were female, of Malay ethnicity, and married. More than three-quarters (78.64%) reported sleep deprivation. Being less effective in communication and formulating diagnosis (3 (1.01) vs 2.5 (1.15),p = 0.005); taking longer time to do things (3.44 (1.07) vs 2.8 (1.34),p = 0.001); and feeling unsafe while driving (3.56 (1.25) vs 2.93 (1.55),p = 0.006) manifested significantly higher mean among sleep-deprived respondents. In conclusion, sleep deprivation is a prevalent problem; that adversely affects crucial functioning domains that may endanger patients and healthcare providers alike. Radical countermeasures are required to ensure satisfactory sleep duration and address areas jeopardizing MO safety.

The objective of the review is to identify factors related to how East and Southeast Asian immigrant youth aged 12-24 and their families access mental health and substance use (MHSU) services. To address how East and Southeast Asian youth and their families access mental health and substance use services, a scoping review was conducted to identify studies in these databases: PubMed, MEDLINE (Ovid), EMBASE (Ovid), PsychINFO, CINAHL, and Sociology Collection. Qualitative content analysis was used to deductively identify themes and was guided by Bronfenbrenner's Ecological Systems Theory, the process-person-context-time (PPCT) model, and the five dimensions of care accessibility (approachability, acceptability, availability and accommodation, appropriateness, affordability). Seventy-three studies met the inclusion criteria. The dimensions of healthcare accessibility shaped the following themes: 1) Acceptability; 2) Appropriateness; 3) Approachability; 4) Availability and Accommodation. Bronfenbrenner's Ecological Systems Theory and the PPCT model informed the development of the following themes: 1) Immediate Environment/Proximal Processes (Familial Factors, Relationships with Peers; 2) Context (School-Based Services/Community Resources, Discrimination, Prevention, Virtual Care); 3) Person (Engagement in Services/Treatment/Research, Self-management); 4) Time (Immigration Status). The study suggests that there is a growing body of research (21 studies) focused on identifying acceptability factors, including Asian cultural values and the model minority stereotype impacting how East and Southeast Asian immigrant youth access MHSU services. This review also highlighted familial factors (16 studies), including family conflict, lack of MHSU literacy, reliance on family as support, and family-based interventions, as factors affecting how East and Southeast Asian immigrant youth access MHSU care. However, the study also highlighted a dearth of research examining how East and Southeast Asian youth with diverse identities access MHSU services. This review emphasizes the factors related to the access to MHSU services by East and Southeast Asian immigrant youth and families while providing insights that will improve cultural safety.

BackgroundMyopia, characterized by excessive axial elongation of the eyeball, increases risks of having sight-threatening diseases and impose a financial burden to healthcare system. Although myopic control interventions showed their effectiveness in slowing progression, the efficacy varies between individuals and does not completely halt progression. The study aims to investigate the efficacy of combining 0.01% atropine administered twice daily with optical defocus for myopia control in schoolchildren.Methods and designThis is a prospective, parallel-group, single-blinded, randomized, active-control trial (ClinicalTrials.gov identifier: NCT06358755). Myopic schoolchildren with no previous myopic control interventions aged between 7 to 12 years will be recruited. They will be randomly allocated into two groups (n = 56 per group) after baseline measurement. Both groups will receive 0.01% atropine twice per day for 18 months (one drop in the morning and the other drop at night before bedtime). Defocus incorporated multiple segments (DIMS) spectacle lenses will be prescribed in atropine plus optical defocus (ATD) treatment group while single vision spectacle lenses will be given in atropine only (AT) group. Cycloplegic refraction and axial lengths will be monitored every 6 months over 18-month study period. The primary outcomes are changes in cycloplegic refraction and axial lengths relative to the baseline over the study period.DiscussionThe result will examine the combination effect of low dose atropine and myopic defocus on myopia control in a randomized controlled study. The findings will also explore the potential benefits of applying 0.01% atropine twice per day on myopic control and its potential side effects.

BackgroundSuicide by road vehicle collision in Australia is under-explored with mixed findings. We aimed to address this research gap by examining time trends, different types of vehicle collision, and individual characteristics related to vehicle-collision suicide.MethodWe retrospectively analyzed deaths by suicide between 1st January 2001 and 31st December 2017 in Australia, using coronial records from the National Coronial Information System. The travel mode used and collision counterpart were retrieved from records of death by vehicle-collision suicide using all available information. We conducted negative binomial regression analysis to examine annual changes in suicide rate by vehicle collision on a public road (N = 640) and other methods of suicide (N = 41,890), and logistic regression analysis to examine individual characteristics associated with the likelihood of dying by suicide via road vehicle collision.ResultsOverall, the national suicide rate involving road vehicle collision significantly increased, while the rate by other methods significantly decreased. Drivers accounted for 61% of suicide events by vehicle collision, of which 72% were single-vehicle collisions (commonly involving a tree). For multiple-vehicle collision suicide events, 82% involved collision with a truck. Pedestrians accounted for more than one-third of suicide events, of which 58% involved collision with a truck and 23% involved collision with a car/van. Individuals who were male (odds ratio 1.15; 95% CI 0.88-1.50), aged ConclusionsThis study provides a better understanding of road vehicle collision suicide in Australia and informs future research directions on topic. Our findings can be used to inform suicide prevention initiatives to reduce vehicle-collision suicide deaths.

BackgroundIn Canada, there is a recognized underrepresentation of women in the field of surgery. However, the extent to which this trend applies across various surgical specialties is not well delineated. The aim of this study is to identify existing disparities and trends over time to inform the need for future interventions to make the match process more equitable for applicants.MethodsData regarding surgical specialty applicants was extracted from the Canadian Resident Matching Service (CaRMS)'s 2003 to 2022 reports.ResultsA total of 9,488 applicants ranked surgical specialties as their first choice from 2003-2022. Increases in the proportion of women applicants comparing periods 2003-2007 to 2018-2022 were significant for cardiac surgery (22% to 43%, p = 0.03), general surgery (46% to 60%, pConclusionsWhile the proportion of women applicants to surgical specialties in Canada has been increasing, women remain underrepresented in several surgical specialties. This underrepresentation cannot be solely attributed to fewer women applying to these specialties, as women experience lower success rates when matching to specific surgical specialties. Further research is essential to identify and address the underlying causes of these disparities.

The trends for sustainable lifestyle and marketing motivated natural product consumption, such as natural skin care products (NSCPs). Different personal, environmental, and sociocultural factors influence purchase intention (PI) for NSCPs. However, there is a lack of evidence on the role of consumers' ethnicity in the PI model. The present study investigated the moderated mediation role of ethnicity in the relationship between related factors, including environmental concern, subjective norms, health factor, Halal certificate, packaging design, past experience factor, price factor, and PI mediated by personal attitude. A web-based survey was utilized to capture quantitative data from a random sample of 330 multicultural consumer group participants. The results of the study indicated that consumers' ethnicity substantially moderated the mediation effect of personal attitude in the relationships between subjective norms, health factor, Halal certificate, packaging design, past experience factor, price factor, and PI in the model. The findings contributed to understanding of the factors that influenced the PI of consumers from diverse sociocultural contexts in the market for natural products. It contributed directly to natural product marketing and industry.

INTRODUCTION: Limited population-based data exist about children with primary nephrotic syndrome (NS). METHODS: We identified a cohort of children with primary NS receiving care in Kaiser Permanente Northern California, an integrated healthcare delivery system caring for >750,000 children. We identified all children 3500 mg/g, urine PCR>3.5 mg/mg, 24-hour urine protein>3500 mg or urine dipstick>300 mg/dL) in laboratory databases or a diagnosis of NS in electronic health records. Nephrologists reviewed health records for clinical presentation and laboratory and biopsy results to confirm primary NS. RESULTS: Among 365 cases of confirmed NS, 179 had confirmed primary NS attributed to presumed minimal change disease (MCD) (72%), focal segmental glomerulosclerosis (FSGS) (23%) or membranous nephropathy (MN) (5%). The overall incidence of primary NS was 1.47 (95% Confidence Interval:1.27-1.70) per 100,000 person-years. Biopsy data were available in 40% of cases. Median age for patients with primary NS was 6.9 (interquartile range:3.7 to 12.9) years, 43% were female and 26% were white, 13% black, 17% Asian/Pacific Islander, and 32% Hispanic. CONCLUSION: This population-based identification of children with primary NS leveraging electronic health records can provide a unique approach and platform for describing the natural history of NS and identifying determinants of outcomes in children with primary NS.

Background: Prior research has shown that patients with stable ischemic heart disease who undergo delayed coronary artery bypass graft (CABG) surgery face higher mortality rates than those who receive CABG within the time recommended by physicians. However, this research did not account for percutaneous coronary intervention (PCI), a widely available alternative to delayed CABG in many settings. We sought to establish whether there was a difference in mortality between timely PCI and delayed CABG. Methods: We identified 25,520 patients 60 years or older who underwent first-time non-emergency revascularization for angiographically-proven, stable left main or multi-vessel ischemic heart disease in British Columbia between January 1, 2001, and December 31, 2016. We estimated unadjusted and adjusted mortality after index revascularization or last staged PCI for patients undergoing delayed CABG compared to timely PCI. Findings: After adjustment with inverse probability of treatment weights, at three years, patients who underwent delayed CABG had a statistically significant lower mortality compared with patients who received timely PCI (4.3% delayed CABG, 13.5% timely PCI; risk ratio 0.32, 95% CI 0.24–0.40). Interpretation: Patients who undergo CABG with delay have a lower risk of death than patients who undergo PCI within appropriate time. Our results suggest that patients who wish to receive CABG as their revascularization treatment will receive a mortality benefit over PCI as an alternative strategy. [ABSTRACT FROM AUTHOR]

BackgroundThe supraclavicular fossa is the dominant location for human brown adipose tissue (BAT). Activation of BAT promotes non-shivering thermogenesis by utilization of glucose and free fatty acids and has been the focus of pharmacological and non-pharmacological approaches for modulation in order to improve body weight and glucose homeostasis. Sympathetic neural control of supraclavicular BAT has received much attention, but its innervation has not been extensively investigated in humans.MethodsDissection of the cervical region in human cadavers was performed to find the distribution of sympathetic nerve branches to supraclavicular fat pad. Furthermore, proximal segments of the 4th cervical nerve were evaluated histologically to assess its sympathetic components.ResultsNerve branches terminating in supraclavicular fat pad were identified in all dissections, including those from the 3rd and 4th cervical nerves and from the cervical sympathetic plexus. Histology of the proximal segments of the 4th cervical nerves confirmed tyrosine hydroxylase positive thin nerve fibers in all fascicles with either a scattered or clustered distribution pattern. The scattered pattern was more predominant than the clustered pattern (80% vs. 20%) across cadavers. These sympathetic nerve fibers occupied only 2.48% of the nerve cross sectional area on average.ConclusionsHuman sympathetic nerves use multiple pathways to innervate the supraclavicular fat pad. The present finding serves as a framework for future clinical approaches to activate human BAT in the supraclavicular region.

Introduction The Kingdom of Lesotho has one of the highest burdens of tuberculosis (TB) in the world. A national TB prevalence survey was conducted to estimate the prevalence of bacteriologically confirmed pulmonary TB disease among those ≥15 years of age in 2019. Method A multistage cluster-based cross-sectional survey where residents ≥15 years in 54 clusters sampled from across the country were eligible to participate. Survey participants were screened using a symptom screen questionnaire and digital chest X-ray (CXR). Respondents who acknowledged cough of any duration, fever, weight loss, night sweats and/or had any CXR abnormality in the lungs were asked to provide two spot sputum specimens. All sputum testing was conducted at the National TB Reference Laboratory (NTRL), where samples underwent Xpert MTB/RIF Ultra (1st sample) and MGIT culture (2nd sample). HIV counselling and testing was offered to all survey participants. TB cases were those with Mycobacterium tuberculosis complex-positive samples with culture; and where culture was not positive, Xpert MTB/RIF Ultra (Xpert Ultra) was positive with a CXR suggestive of active TB and no current or prior history of TB. Result A total of 39,902 individuals were enumerated, and of these, 26,857 (67.3%) were eligible to participate; 21,719 (80.9%) participated in the survey of which 8,599 (40%) were males and 13,120 (60%) were females. All 21,719 (100%) survey participants underwent symptom screening and a total of 21,344 participants (98.3%) had a CXR. Of the 7,584 (34.9%) participants who were eligible for sputum examination, 4,190 (55.2%) were eligible by CXR only, 1,455 (19.2%) by symptom screening, 1,630 by both, and 309 by CXR exemption. A total of 6,780 (89.4%) submitted two sputum specimens, and 311 (4.1%) submitted one sample only. From the 21,719 survey participants, HIV counseling and testing was offered to 17,048, and 3,915 (23.0%) were documented as HIV-positive. The survey identified 132 participants with bacteriologically confirmed pulmonary TB thus providing an estimated prevalence of 581 per 100,000 population (95% CI 466–696) for those ≥15 years in 2019. Using the survey results, TB incidence was re-estimated to be 654 per 100,000 (95% CI 406–959), which was comparable to the 2018 TB incidence rate of 611 per 100,000 (95% CI 395–872) reported by the World Health Organization (WHO). The highest TB burden was found in those ≥55 years and among men. The ratio of prevalence to case notification was estimated at 1.22. TB/HIV coinfection was identified in 39 (29.6%) participants. Out of the 1,825 participants who reported a cough, 50% of these participants, mostly men, did not seek care. Those who sought care predominantly went to the public health facilities. Conclusion The TB prevalence survey results confirmed that burden of TB and TB/HIV coinfection remains very high in Lesotho. Given that TB prevalence remains high, and there is a significant proportion of participants with confirmed TB that did not report TB suggestive symptoms. The National TB Programme will need to update its TB screening and treatment algorithms to achieve the End TB targets. A major focus will need to be placed on finding the “missing cases” i.e., undiagnosed or under-reported TB cases, or ensuring that not only TB symptomatic but also those who do not present with typical TB symptoms are promptly identified to reduce further onward transmission.

Background Ten percent of the school-aged population have speech, language, and communication needs (SLCN) that impact access to the curriculum. Successful implementation of classroom-based SLCN interventions can reduce barriers to learning, thereby improving educational outcomes for this vulnerable population. The challenges of implementing innovations in educational settings are well-documented, yet limited studies have addressed such considerations when developing, and piloting universal level SLCN interventions for use in Irish schools. Methods A qualitative exploratory study was undertaken to establish the acceptability, feasibility, and appropriateness of a universal level SLCN intervention. An advisory panel of teachers (n = 8) and children with SLCN (n = 2) were engaged as co-researchers in the study. The Communication Supporting Classrooms Observation Tool, developed as part of the Better Communication Project in the UK, was trialled across a diverse sample of school settings (n = 5). Semi-structured interviews were conducted with school practitioners and school leaders, and a deductive content analysis was undertaken using the domains of the Consolidation Framework for Implementation Research. Discussion The observation tool was viewed as acceptable with suggested additions. Integrating use of the tool within existing data-informed, school self-evaluation processes aimed at supporting school improvement was noted as a potential means of supporting implementation. A knowledge gap in relation to school-based models of support for SLCN was identified which may negatively impact implementation. An implementation strategy targeting coherence, cognitive engagement and contextual integration is indicated if the tool is to be normalised into routine practice in Irish classrooms. Implementation needs appeared to vary at the school level. Conclusions The importance of early-stage exploration to guide implementation planning with regards to developing and testing universal level interventions for SLCN in schools is highlighted. Engaging an advisory panel provides important insights to guide implementation decisions. Findings suggest an adaptive design is required when planning implementation studies targeting classroom setting.

IntroductionSarcopenia is common in men with metastatic castrate-resistant prostate cancer (mCRPC) and has been largely assessed opportunistically through computed-tomography (CT) scans, excluding measures of muscle function. Therefore, the impact of a comprehensive assessment of sarcopenia on clinical outcomes in men with mCRPC is poorly understood. The objectives of this study were to comprehensively assess sarcopenia through CT scans and measures of muscle function and examine its impact on severe treatment toxicity, time to first emergency room (ER) visit, disease progression, and overall mortality in men initiating chemotherapy or androgen receptor-targeted axis (ARAT) therapy for mCRPC.MethodsThis was a secondary analysis of a prospective observational study of men with mCRPC at the Princess Margaret Cancer Centre between July 2015-May 2021. Participants were classified as sarcopenic if they had CT-based low muscle mass or low muscle density, a grip strength and gait speed score of ResultsA total of 110 men (mean age: 74.6) were included in the analysis. At baseline, 30 (27.3%) were classified as sarcopenic. Sarcopenia was a significant predictor of severe toxicity (aOR = 6.26, 95%CI = 1.17-33.58, P = 0.032) and ER visits (aHR = 4.41, 95%CI = 1.26-15.43, p = 0.020) in men initiating ARAT but not in men initiating chemotherapy. Sarcopenia was also a predictor of radiographic progression (aHR = 2.39, 95%CI = 1.06-5.36, p = 0.035) and overall mortality (aHR = 2.44, 95%CI = 1.17-5.08, p = 0.018) regardless of treatment type.ConclusionsBaseline sarcopenia predicts radiographic progression and overall mortality in men with mCRPC regardless of the type of treatment and may also predict severe treatment toxicity and ER visits in men initiating ARAT.

IntroductionInternational humanitarian aid during disasters should be needs-based and coordinated in response to appeals from affected governments. We identify disaster and population factors associated with international aid appeal during disasters and hence guide preparation by international humanitarian aid providers.MethodsIn this retrospective database analysis, we searched the Emergency Events Database for all disasters from 1995 to 2015. Disasters with and without international aid appeals were compared by location, duration, type of disaster, deaths, number of people affected, and total estimated damage. Logistic regression was used to examine the association of each factor with international aid appeal.ResultsOf 13,961 disasters recorded from 1995 to 2015, 168 (1.2%) involved international aid appeals. Aid appeals were more likely to be triggered by disasters which killed more people (OR 1.29 [95% confidence interval (CI) 1.02-1.64] log10 persons), affected more people (OR 1.85 [95%CI 1.57-2.18] / log10 persons), and occurred in Africa (OR 1.67 [95%CI 1.06-2.62). Earthquakes (OR 4.07 [95%CI 2.16-7.67]), volcanic activity (OR 6.23 [95%CI 2.50-15.53]), and insect infestations (OR 12.14 [95%CI 3.05-48.35]) were more likely to trigger international aid appeals. International aid appeals were less likely to be triggered by disasters which occurred in Asia (OR 0.46 [95%CI 0.29-0.73]) and which were transport accidents (OR 0.12 [95%CI 0.02-0.89]).ConclusionInternational aid appeal during disasters was associated with greater magnitude of damage, disasters in Africa, and specific types of disasters such as earthquakes, volcanic activity, and insect infestations. Humanitarian aid providers can focus preparation on these identified factors.

BackgroundPre-exposure prophylaxis for COVID-19 with tixagevimab/cilgavimab (T/C) received Emergency Use Authorization (EUA) based on results of a clinical trial conducted prior to the emergence of the Omicron variant. The clinical effectiveness of T/C has not been well described in the Omicron era. We examined the incidence of symptomatic illness and hospitalizations among T/C recipients when Omicron accounted for virtually all local cases.MethodsThrough retrospective electronic medical record chart review, we identified patients who received T/C between January 1 -July 31, 2022 within our quaternary referral health system. We determined the incidence of symptomatic COVID-19 infections and hospitalizations due to or presumed to be caused by early Omicron variants before and after receiving T/C (pre-T/C and post-T/C). Chi square and Mann-Whitney Wilcoxon two-sample tests were used to examine differences between the characteristics of those who got COVID-19 before or after T/C prophylaxis, and rate ratios (RR) and 95% confidence intervals (CI) were calculated to assess differences in hospitalization rates for the two groups.ResultsOf 1295 T/C recipients, 105 (8.1%) developed symptomatic COVID-19 infection before receiving T/C, and 102 (7.9%) developed symptomatic disease after receiving it. Of the 105 patients who developed symptomatic infection pre-T/C, 26 (24.8%) were hospitalized, compared with six of the 102 patients (5.9%) who were diagnosed with COVID-19 post-T/C (RR = 0.24; 95% CI = 0.10-0.55; p = 0.0002). Seven of the 105 (6.7%) patients infected pre-T/C, but none of the 102 infected post-T/C required ICU care. No COVID-related deaths occurred in either group. The majority of COVID-19 cases among those infected pre-T/C treatment occurred during the Omicron BA.1 surge, while the majority of post-T/C cases occurred when Omicron BA.5 was predominant. In both groups, having at least one dose of vaccine strongly protected against hospitalization (pre-T/C group RR = 0.31, 95% CI = 0.17-0.57, p = 0.02; post-T/C group RR = 0.15; 95% CI = 0.03-0.94; p = 0.04).ConclusionWe identified COVID-19 infections after T/C prophylaxis. Among patients who received T/C at our institution, COVID-19 Omicron cases occurring after T/C were one-fourth as likely to require hospitalization compared to those with Omicron prior to T/C. However, due to the presence of changing vaccine coverage, multiple therapies, and changing variants, the effectiveness of T/C in the Omicron era remains difficult to assess.

This paper explores how ideas and practices of elder-care may be changing for the new Chinese middle class. This paper draws on in-depth interviews with the members of different generations of ten middle class families in the Chinese city of Tianjin. It explores how increased resources but also increased pressure are affecting the care of older people and the expectations around elder-care. Thematic analysis of transcripts entered into NVIVO revealed three findings. Firstly, that the generation born in the 1950s and 1960s are often negotiating their care responsibilities between their parents and their grandchildren. Secondly, the only viable elder-care solution for many families is to buy in support from an unregulated market-based home care sector. Thirdly driven by an increasingly postmodern culture, filial piety may be changing from a normative expectation to a set of new practices based on familial reciprocity. The paper concludes by reflecting on the issues that will arise from the proposed raising of the retirement age in China, and the increasing geographic dispersal of generations. Flexible working policies as well as investment in a regulated home care sector are recommended as solutions to be explored.

During the COVID-19 pandemic, young people have been exposed to distressing content about COVID-19 without knowing whether they can trust such content. This indicates a need to examine the effects of social media use on mental health and well-being. Existing research provides an inconsistent impression of such effects. Thus, we examined the relation between exposure to COVID-19 information on social media and well-being and assessed if trust in COVID-19 information on social media moderated this relationship. The sample consisted of 168 adolescents and young adults from the U.K. and U.S. (Mage = 17.4 years). Participants completed measures of exposure to, and trust in, COVID-19 information on social media platforms, and measures of emotional, psychological, and social well-being. Results revealed a null to positive relation between exposure to COVID-19 information on social media and well-being across measures. However, when trust was added to the models as a moderator, results indicated that, for adolescents with higher levels of trust in COVID-19 information found on social media, the relation between information encountered on social media and well-being was positive. In contrast, for adolescents with lower levels of trust, the association between information encountered on social media and well-being was null or sometimes negative. Given the lack of consensus about the impact of social media use on well-being, these results point to the importance of trust when assessing the relationship between exposure to COVID-19 information and well-being.

BackgroundThe COVID-19 pandemic caused disruptions across healthcare systems globally exposing the precarious state of patient engagement across all levels of healthcare. While evidence is emerging to describe how engagement was affected across various settings, insights about how some organizations at the policy and practice level of healthcare were able to sustain or adapt patient engagement activities is lacking.ObjectiveThis paper addresses the following research question: "How were healthcare, government, and patient partner organizations able to sustain or adapt patient engagement activities during the COVID-19 pandemic?"MethodsA qualitative descriptive study was conducted to understand how patient engagement activities were maintained or adapted in a variety of healthcare, government, and patient partner organizations in Canada throughout the pandemic. This analysis was part of a larger qualitative, multiple case study where one-to-one interviews were conducted with organizational leaders, managers and patient partners.ResultsThe following themes were identified as key aspects of maintaining or adapting patient engagement activities: 1) having an embedded organizational culture of patient engagement; 2) adapting patient engagement activities to focus on COVID-19 response efforts; 3) having patient partners who exercised leadership and advocacy to support patient care and experiences during the pandemic; and 4) leveraging virtual technology as a communication tool to engage patient partners.ConclusionThis paper highlights important insights that may be useful to other health care organizations on how to sustain or adapt patient engagement activities during a healthcare crisis. Having patient engagement embedded within an organization's culture supported by, but not limited to, infrastructure, resources, investments in dedicated staff and patient partner leadership, and communication strategies and tools enabled continued patient engagement activities during the pandemic.

"'Hypos' can strike twice" (HS2) is a pragmatic, leaflet-based referral intervention designed for administration by clinicians of the emergency medical services (EMS) to people they have attended and successfully treated for hypoglycaemia. Its main purpose is to encourage the recipient to engage with their general practitioner or diabetic nurse in order that improvements in medical management of their diabetes may be made, thereby reducing their risk of recurrent hypoglycaemia. Herein we build a de novo economic model for purposes of incremental analyses to compare, in 2018-19 prices, HS2 against standard care for recurrent hypoglycaemia in the fortnight following the initial attack from the perspective of the UK National Health Service (NHS). We found that per patient NHS costs incurred by people receiving the HS2 intervention over the fortnight following an initial hypoglycaemia average £49.79, and under standard care costs average £40.50. Target patient benefit assessed over that same period finds the probability of no recurrence of hypoglycaemia averaging 42.4% under HS2 and 39.4% under standard care, a 7.6% reduction in relative risk. We find that implementing HS2 will cost the NHS an additional £309.36 per episode of recurrent hypoglycaemia avoided. Contrary to the favourable support offered in Botan et al., we conclude that in its current form the HS2 intervention is not a cost-effective use of NHS resources when compared to standard NHS care in reducing the risk of hypoglycaemia recurring within a fortnight of an initial attack that was resolved at-scene by EMS ambulance clinicians.

BackgroundAlthough tuberculosis (TB) symptoms have limited sensitivity they remain an important entry point into the TB care cascade.ObjectivesTo investigate self-reported healthcare seeking for TB symptoms in participants in a community-based survey.MethodsWe compared reasons for not seeking care in participants reporting ≥1 of four TB screening symptoms (cough, weight loss, night sweats, fever) in the first South African national TB prevalence survey (2017-2019). We used logistic regression analyses to identify sociodemographic and clinical characteristics associated with healthcare seeking.Results5,168/35,191 (14.7%) survey participants reported TB symptoms and 3,442/5168 had not sought healthcare. 2,064/3,442(60.0%) participants intended to seek care, 912 (26.5%) regarded symptoms as benign, 399 (11.6%) reported access barriers(distance and cost), 36 (1.0%) took other medications and 20(0.6%) reported health system barriers. Of the 57/98 symptomatic participants diagnosed with bacteriologically confirmed TB who had not sought care: 38(66.7%) intended to do so, 8(14.0%) regarded symptoms as benign, and 6(10.5%) reported access barriers. Among these 98, those with unknown HIV status(OR 0.16 95% CI 0.03-0.82), p = 0.03 and those who smoked tobacco products(OR 0.39, 95% CI 0.17-0.89, p = 0.03) were significantly less likely to seek care.ConclusionsPeople with TB symptoms delayed seeking healthcare, many regarded symptoms as benign while others faced access barriers. Those with unknown HIV status were significantly less likely to seek care. Strengthening community-based TB awareness and screening programmes together with self-screening models could increase awareness of the significance of TB symptoms and contribute to improving healthcare seeking and enable many people with TB to enter the TB care cascade.

BackgroundIntroduction of risk stratification within population-based cancer screening programmes has the potential to optimise resource allocation by targeting screening towards members of the population who will benefit from it most. Endorsement from healthcare professionals is necessary to facilitate successful development and implementation of risk-stratified interventions. Therefore, this review aims to explore whether using risk stratification within population-based cancer screening programmes is acceptable to healthcare professionals and to identify any requirements for successful implementation.MethodsWe searched four electronic databases from January 2010 to October 2021 for quantitative, qualitative, or primary mixed methods studies reporting healthcare professional and/or other stakeholder opinions on acceptability of risk-stratified population-based cancer screening. Quality of the included studies was assessed using the Mixed Methods Appraisal Tool. Data were analysed using the Joanna Briggs Institute convergent integrated approach to mixed methods analysis and mapped onto the Consolidated Framework for Implementation Research using a 'best fit' approach. PROSPERO record CRD42021286667.ResultsA total of 12,039 papers were identified through the literature search and seven papers were included in the review, six in the context of breast cancer screening and one considering screening for ovarian cancer. Risk stratification was broadly considered acceptable, with the findings covering all five domains of the framework: intervention characteristics, outer setting, inner setting, characteristics of individuals, and process. Across these five domains, key areas that were identified as needing further consideration to support implementation were: a need for greater evidence, particularly for de-intensifying screening; resource limitations; need for staff training and clear communication; and the importance of public involvement.ConclusionsRisk stratification of population-based cancer screening programmes is largely acceptable to healthcare professionals, but support and training will be required to successfully facilitate implementation. Future research should focus on strengthening the evidence base for risk stratification, particularly in relation to reducing screening frequency among low-risk cohorts and the acceptability of this approach across different cancer types.

Sleep deprivation (SD), defined as an inability to get a minimum of 7 hours of regular sleep at night is a serious health problem that impacts the performance of medical professionals. This study aims to determine the impact of sleep deprivation on perceived performance among medical officers (MOs). A cross-sectional study design involved 231 MOs from six disciplines in Hospital Tuanku Ja'afar, a tertiary center in the south of Malaysia. A self-administered questionnaire was introduced in the English language. The questionnaire involved the sociodemographic characteristics; job-related factors, and the Sleep Deprivation Impact Scale (SDIS). The SDIS is a 12-question scale, rated on a 5-point Likert scale from strongly disagree to strongly agree. A higher SDIS score reflected a higher impact of sleep deprivation. A total of 206 MOs returned the completed questionnaire yielding a response rate of 89.17%. The mean age of respondents was 31.68 (±3.49) years. Most of the respondents were female, of Malay ethnicity, and married. More than three-quarters (78.64%) reported sleep deprivation. Being less effective in communication and formulating diagnosis (3 (1.01) vs 2.5 (1.15),p = 0.005); taking longer time to do things (3.44 (1.07) vs 2.8 (1.34),p = 0.001); and feeling unsafe while driving (3.56 (1.25) vs 2.93 (1.55),p = 0.006) manifested significantly higher mean among sleep-deprived respondents. In conclusion, sleep deprivation is a prevalent problem; that adversely affects crucial functioning domains that may endanger patients and healthcare providers alike. Radical countermeasures are required to ensure satisfactory sleep duration and address areas jeopardizing MO safety. [ABSTRACT FROM AUTHOR]

Background: Medical graduates applying to Residency through the Canadian Resident Matching System (CaRMS) utilize the internet to gather information on programs and their overarching Postgraduate Medical Education (PGME) Office. This study aims to evaluate how PGME websites across Canada convey their commitment to equity, diversity, and inclusion (EDI) through their website features. Methods: Cross-sectional analysis of the 17 Canadian PGME websites against 20 EDI criteria based on contemporary literature, across five domains: leadership and governance, recruitment, accommodations, community engagement, and pathways to entry. Non-parametric testing was conducted to explore the relationship between EDI performance and municipal population diversity and geographic region. Results: The evaluation of PGME websites, policies, reports, and plans revealed a mean score of 8.65/20 (SD = 3.00), with scores ranging from a minimum of 4/20 to a maximum of 13/20, indicating variability in EDI representation. Specifically, the domain of leadership and governance demonstrated the highest mean proportion of completed criteria (51%), while community engagement had the lowest (24%). Notably, 9 out of 17 PGME websites (53%) met at least 10 EDI criteria. Analysis by geographic region demonstrates significant mean differences (p = 0.02), with Ontario (10.50, SD = 2.17) and Western Provinces (11.00, SD = 0.00) scoring notably higher than Quebec (4.50, SD = 0.58), the Prairies (8.50, SD = 2.12), and the Atlantic region (8.00, SD = 2.83). Conclusions: The assessment of Canadian PGME websites reveals varying levels of commitment to EDI. While many programs exhibit strong EDI representation in mission statements, access to mental health services, and anti-discrimination policies, there are notable gaps in leadership messaging, diverse interview panels, family-friendly policies, and deliberate recruitment of underrepresented groups. Regional differences highlight the need for sharing best practices to promote inclusivity across the country. Improving EDI efforts on PGME websites can promote the recruitment and retention of a diverse resident population. [ABSTRACT FROM AUTHOR]

The objective of the review is to identify factors related to how East and Southeast Asian immigrant youth aged 12–24 and their families access mental health and substance use (MHSU) services. To address how East and Southeast Asian youth and their families access mental health and substance use services, a scoping review was conducted to identify studies in these databases: PubMed, MEDLINE (Ovid), EMBASE (Ovid), PsychINFO, CINAHL, and Sociology Collection. Qualitative content analysis was used to deductively identify themes and was guided by Bronfenbrenner's Ecological Systems Theory, the process-person-context-time (PPCT) model, and the five dimensions of care accessibility (approachability, acceptability, availability and accommodation, appropriateness, affordability). Seventy-three studies met the inclusion criteria. The dimensions of healthcare accessibility shaped the following themes: 1) Acceptability; 2) Appropriateness; 3) Approachability; 4) Availability and Accommodation. Bronfenbrenner's Ecological Systems Theory and the PPCT model informed the development of the following themes: 1) Immediate Environment/Proximal Processes (Familial Factors, Relationships with Peers; 2) Context (School-Based Services/Community Resources, Discrimination, Prevention, Virtual Care); 3) Person (Engagement in Services/Treatment/Research, Self-management); 4) Time (Immigration Status). The study suggests that there is a growing body of research (21 studies) focused on identifying acceptability factors, including Asian cultural values and the model minority stereotype impacting how East and Southeast Asian immigrant youth access MHSU services. This review also highlighted familial factors (16 studies), including family conflict, lack of MHSU literacy, reliance on family as support, and family-based interventions, as factors affecting how East and Southeast Asian immigrant youth access MHSU care. However, the study also highlighted a dearth of research examining how East and Southeast Asian youth with diverse identities access MHSU services. This review emphasizes the factors related to the access to MHSU services by East and Southeast Asian immigrant youth and families while providing insights that will improve cultural safety. [ABSTRACT FROM AUTHOR]

Background: Myopia, characterized by excessive axial elongation of the eyeball, increases risks of having sight-threatening diseases and impose a financial burden to healthcare system. Although myopic control interventions showed their effectiveness in slowing progression, the efficacy varies between individuals and does not completely halt progression. The study aims to investigate the efficacy of combining 0.01% atropine administered twice daily with optical defocus for myopia control in schoolchildren. Methods and design: This is a prospective, parallel-group, single-blinded, randomized, active-control trial (ClinicalTrials.gov identifier: NCT06358755). Myopic schoolchildren with no previous myopic control interventions aged between 7 to 12 years will be recruited. They will be randomly allocated into two groups (n = 56 per group) after baseline measurement. Both groups will receive 0.01% atropine twice per day for 18 months (one drop in the morning and the other drop at night before bedtime). Defocus incorporated multiple segments (DIMS) spectacle lenses will be prescribed in atropine plus optical defocus (ATD) treatment group while single vision spectacle lenses will be given in atropine only (AT) group. Cycloplegic refraction and axial lengths will be monitored every 6 months over 18-month study period. The primary outcomes are changes in cycloplegic refraction and axial lengths relative to the baseline over the study period. Discussion: The result will examine the combination effect of low dose atropine and myopic defocus on myopia control in a randomized controlled study. The findings will also explore the potential benefits of applying 0.01% atropine twice per day on myopic control and its potential side effects. [ABSTRACT FROM AUTHOR]

The Open Science (OS) movement is rapidly gaining traction among policy-makers, research funders, scientific journals and individual scientists. Despite these tendencies, the pace of implementing OS throughout the scientific process and across the scientific community remains slow. Thus, a better understanding of the conditions that affect OS engagement, and in particular, of how practitioners learn, use, conduct and share research openly can guide those seeking to implement OS more broadly. We surveyed participants at an OS workshop hosted by the Living Norway Ecological Data Network in 2020 to learn how they perceived OS and its importance in their research, supervision and teaching. Further, we wanted to know what OS practices they had encountered in their education and what they saw as hindering or helping their engagement with OS. The survey contained scaled-response and open-ended questions, allowing for a mixed-methods approach. We obtained survey responses from 60 out of 128 workshop participants (47%). Responses indicated that usage and sharing of open data and code, as well as open access publication, were the most frequent OS practices. Only a minority of respondents reported having encountered OS in their formal education. A majority also viewed OS as less important in their teaching than in their research and supervisory roles. The respondents' suggestions for what would facilitate greater OS engagement in the future included knowledge, guidelines, and resources, but also social and structural support. These are aspects that could be strengthened by promoting explicit implementation of OS practices in higher education and by nurturing a more inclusive and equitable OS culture. We argue that incorporating OS in teaching and learning of science can yield substantial benefits to the research community, student learning, and ultimately, to the wider societal objectives of science and higher education.

In response to pheromone, many proteins localize on the plasma membrane of yeast cell to reform it into a polarized shmoo structure. The adaptor protein Ste50p, known as a pheromone signal enhancer critical for shmoo polarization, has never been explored systematically for its localization and function in the polarization process. Time-lapse single-cell imaging and quantitation shown here characterizes Ste50p involvement in the establishment of cell polarity. We found that Ste50p patches on the cell cortex mark the point of shmoo initiation, these patches could move, and remain associated with the growing shmoo tip in a pheromone concentration time-dependent manner until shmoo maturation. A Ste50p mutant impaired in patch localization suffers a delay in polarization. By quantitative analysis we show that polarization correlates with the rising levels of Ste50p, enabling rapid cell responses to pheromone that correspond to a critical level of Ste50p at the initial G1 phase. We exploited the quantitative differences in the pattern of Ste50p expression to correlate with the cell-cell phenotypic heterogeneity, showing Ste50p involvement in the cellular differentiation choice. Taken together, these findings present Ste50p to be part of the early shmoo development phase, suggesting that Ste50p may be involved with the polarisome in the initiation of polarization, and plays a role in regulating the polarized growth of shmoo during pheromone response.

IntroductionThe use of anti-retroviral therapy (ART) has dramatically reduced HIV-1 associated morbidity and mortality. However, HIV-1 infected individuals have increased rates of morbidity and mortality compared to the non-HIV-1 infected population and this appears to be related to end-organ diseases collectively referred to as Serious Non-AIDS Events (SNAEs). Circulating miRNAs are reported as promising biomarkers for a number of human disease conditions including those that constitute SNAEs. Our study sought to investigate the potential of selected miRNAs in predicting mortality in HIV-1 infected ART treated individuals.Materials and methodsA set of miRNAs was chosen based on published associations with human disease conditions that constitute SNAEs. This case: control study compared 126 cases (individuals who died whilst on therapy), and 247 matched controls (individuals who remained alive). Cases and controls were ART treated participants of two pivotal HIV-1 trials. The relative abundance of each miRNA in serum was measured, by RTqPCR. Associations with mortality (all-cause, cardiovascular and malignancy) were assessed by logistic regression analysis. Correlations between miRNAs and CD4+ T cell count, hs-CRP, IL-6 and D-dimer were also assessed.ResultsNone of the selected miRNAs was associated with all-cause, cardiovascular or malignancy mortality. The levels of three miRNAs (miRs -21, -122 and -200a) correlated with IL-6 while miR-21 also correlated with D-dimer. Additionally, the abundance of miRs -31, -150 and -223, correlated with baseline CD4+ T cell count while the same three miRNAs plus miR-145 correlated with nadir CD4+ T cell count.DiscussionNo associations with mortality were found with any circulating miRNA studied. These results cast doubt onto the effectiveness of circulating miRNA as early predictors of mortality or the major underlying diseases that contribute to mortality in participants treated for HIV-1 infection.

Here we present vB_BanS-Tsamsa, a novel temperate phage isolated from Bacillus anthracis, the agent responsible for anthrax infections in wildlife, livestock and humans. Tsamsa phage is a giant siphovirus (order Caudovirales), featuring a long, flexible and non-contractile tail of 440 nm (not including baseplate structure) and an isometric head of 82 nm in diameter. We induced Tsamsa phage in samples from two different carcass sites in Etosha National Park, Namibia. The Tsamsa phage genome is the largest sequenced Bacillus siphovirus, containing 168,876 bp and 272 ORFs. The genome features an integrase/recombinase enzyme, indicative of a temperate lifestyle. Among bacterial strains tested, the phage infected only certain members of the Bacillus cereus sensu lato group (B. anthracis, B. cereus and B. thuringiensis) and exhibited moderate specificity for B. anthracis. Tsamsa lysed seven out of 25 B. cereus strains, two out of five B. thuringiensis strains and six out of seven B. anthracis strains tested. It did not lyse B. anthracis PAK-1, an atypical strain that is also resistant to both gamma phage and cherry phage. The Tsamsa endolysin features a broader lytic spectrum than the phage host range, indicating possible use of the enzyme in Bacillus biocontrol.

Background: Suicide by road vehicle collision in Australia is under-explored with mixed findings. We aimed to address this research gap by examining time trends, different types of vehicle collision, and individual characteristics related to vehicle-collision suicide. Method: We retrospectively analyzed deaths by suicide between 1st January 2001 and 31st December 2017 in Australia, using coronial records from the National Coronial Information System. The travel mode used and collision counterpart were retrieved from records of death by vehicle-collision suicide using all available information. We conducted negative binomial regression analysis to examine annual changes in suicide rate by vehicle collision on a public road (N = 640) and other methods of suicide (N = 41,890), and logistic regression analysis to examine individual characteristics associated with the likelihood of dying by suicide via road vehicle collision. Results: Overall, the national suicide rate involving road vehicle collision significantly increased, while the rate by other methods significantly decreased. Drivers accounted for 61% of suicide events by vehicle collision, of which 72% were single-vehicle collisions (commonly involving a tree). For multiple-vehicle collision suicide events, 82% involved collision with a truck. Pedestrians accounted for more than one-third of suicide events, of which 58% involved collision with a truck and 23% involved collision with a car/van. Individuals who were male (odds ratio 1.15; 95% CI 0.88–1.50), aged <25 years old (odds ratio 5.27; 95% CI 3.05–9.10), non-Indigenous (odds ratio 3.36; 95% CI 1.71–6.62), and born overseas (odds ratio 1.40; 95% CI 1.10–1.79) were more likely to die by vehicle-collision suicide than by other methods of suicide. Conclusions: This study provides a better understanding of road vehicle collision suicide in Australia and informs future research directions on topic. Our findings can be used to inform suicide prevention initiatives to reduce vehicle-collision suicide deaths. [ABSTRACT FROM AUTHOR]

The trends for sustainable lifestyle and marketing motivated natural product consumption, such as natural skin care products (NSCPs). Different personal, environmental, and sociocultural factors influence purchase intention (PI) for NSCPs. However, there is a lack of evidence on the role of consumers' ethnicity in the PI model. The present study investigated the moderated mediation role of ethnicity in the relationship between related factors, including environmental concern, subjective norms, health factor, Halal certificate, packaging design, past experience factor, price factor, and PI mediated by personal attitude. A web-based survey was utilized to capture quantitative data from a random sample of 330 multicultural consumer group participants. The results of the study indicated that consumers' ethnicity substantially moderated the mediation effect of personal attitude in the relationships between subjective norms, health factor, Halal certificate, packaging design, past experience factor, price factor, and PI in the model. The findings contributed to understanding of the factors that influenced the PI of consumers from diverse sociocultural contexts in the market for natural products. It contributed directly to natural product marketing and industry. [ABSTRACT FROM AUTHOR]

[This corrects the article DOI: 10.1371/journal.pone.0239224.].

BackgroundThe two biomarkers 2-[18F]FDG-PET and cerebrospinal fluid biomarkers are both recommended to support the diagnosis of Alzheimer's disease. However, there is a lack of knowledge for the comparison of the two biomarkers in a routine clinical setting.ObjectiveThe aim was to compare the clinical impact of 2-[18F]FDG-PET and cerebrospinal fluid biomarkers on diagnosis, prognosis, and patient management in patients suspected of Alzheimer's disease.MethodsEighty-one patients clinically suspected of Alzheimer's disease were retrospectively included from the Copenhagen Memory Clinic. As part of the clinical work-up all patients had a standard diagnostic program examination including MRI and ancillary investigations with 2-[18F]FDG-PET and cerebrospinal fluid biomarkers. An incremental study design was used to evaluate the clinical impact of the biomarkers. First, the diagnostic evaluation was based on the standard diagnostic program, then the diagnostic evaluation was revised after addition of either cerebrospinal fluid biomarkers or 2-[18F]FDG-PET. At each diagnostic evaluation, two blinded dementia specialists made a consensus decision on diagnosis, prediction of disease course, and change in patient management. Confidence in the decision was measured on a visual analogue scale (0-100). After 6 months, the diagnostic evaluation was performed with addition of the other biomarker. A clinical follow-up after 12 months was used as reference for diagnosis and disease course.ResultsThe two biomarkers had a similar clinical value across all diagnosis when added individually to the standard diagnostic program. However, for the correctly diagnosed patient with Alzheimer's disease cerebrospinal fluid biomarkers had a significantly higher impact on diagnostic confidence (mean scores±SD: 88±11 vs. 82±11, p = 0.046) and a significant reduction in the need for ancillary investigations (23 vs. 18 patients, p = 0.049) compared to 2-[18F]FDG-PET.ConclusionThe two biomarkers had similar clinical impact on diagnosis, but cerebrospinal fluid biomarkers had a more significant value in corroborating the diagnosis of Alzheimer's disease compared to 2-[18F]FDG-PET.

BackgroundSofosbuvir and ledipasvir-sofosbuvir are both newer direct-acting antiviral agents for the treatment of hepatitis C. The high list prices for both drugs have led to concern about the budget impact for public drug coverage programs. Therefore, we studied the impact of public prescription drug coverage for both drugs on utilization, adherence, and public and private expenditure in British Columbia, Canada.MethodsWe used provincial administrative claims data from January 2014 to June 2017 for all individuals historically tested for either hepatitis C and/or human immunodeficiency virus. Using interrupted time series analysis, we examined the impact of public insurance coverage on treatment uptake, adherence (proportion of days covered), and public and private expenditures.ResultsOver our study period, 4,462 treatment initiations were eligible for analysis (1,131 sofosbuvir and 3,331 ledipasvir-sofosbuvir, which include 19 patients initiated on both treatments). We found the start of public coverage for sofosbuvir and ledipasvir-sofosbuvir increased treatment uptake by 154%. Adherence rates were consistently high and did not change with public coverage. Finally, public expenditure increased after the policy change, and crowded out some private expenditure.ConclusionPublic coverage for high-cost drugs for hepatitis C dramatically increased use of these drugs, but did not reduce adherence. From a health policy perspective, public payers should be prepared for increased treatment uptake following the availability of public coverage. However, they should not be concerned that populations without private insurance coverage will be less adherent and not finish their treatment course.

Arginine deprivation cancer therapy targets certain types of malignancies with positive result in many studies and clinical trials. NEI-01 was designed as a novel arginine-depleting enzyme comprising an albumin binding domain capable of binding to human serum albumin to lengthen its half-life. In the present work, NEI-01 is shown to bind to serum albumin from various species, including mice, rat and human. Single intraperitoneal administration of NEI-01 to mice reduced plasma arginine to undetectable level for at least 9 days. Treatment of NEI-01 specifically inhibited cell viability of MIA PaCa-2 and PANC-1 cancer cell lines, which were ASS1 negative. Using a human pancreatic mouse xenograft model, NEI-01 treatment significantly reduced tumor volume and weight. Our data provides proof of principle for a cancer treatment strategy using NEI-01.

This study explored topic interest, perceived learning and actual recall of exhibit content in 979 children and adolescents and 1,184 adults who visited informal science learning sites and interacted with an adult or youth educator or just the exhibit itself as part of family visits to the sites. Children in early childhood reported greater topic interest and perceived learning, but actually recalled less content, than participants in middle childhood or adolescence. Youth visitors reported greater interest after interacting with a youth educator than just the exhibit, and perceived that they learn more if they interact with an educator (youth or adult). Participants in middle childhood recall more when they encounter a youth educator. Adult visitors reported greater interest after interaction with a youth educator than with the exhibit alone or an adult educator. They also perceived that they learn more if they interact with an educator (youth or adult) than just the exhibit and perceived that they learned more if they interacted with a youth educator than an adult educator. Results highlight the benefits of educators in informal science learning sites and document the importance of attention to developmental needs.

We have demonstrated that exposing human breast tumour xenografts to ultrasound-stimulated microbubbles enhances tumour cell death and vascular disruption resulting from hyperthermia treatment. The aim of this study was to investigate the effect of varying the hyperthermia and ultrasound-stimulated microbubbles treatment parameters in order to optimize treatment bioeffects. Human breast cancer (MDA-MB-231) tumour xenografts in severe combined immunodeficiency (SCID) mice were exposed to varying microbubble concentrations (0%, 0.1%, 1% or 3% v/v) and ultrasound sonication durations (0, 1, 3 or 5 min) at 570 kPa peak negative pressure and central frequency of 500 kHz. Five hours later, tumours were immersed in a 43°C water bath for varying hyperthermia treatment durations (0, 10, 20, 30, 40, 50 or 60 minutes). Results indicated a significant increase in tumour cell death reaching 64 ± 5% with combined treatment compared to 11 ± 3% and 26 ± 5% for untreated and USMB-only treated tumours, respectively. A similar but opposite trend was observed in the vascular density of the tumours receiving the combined treatment. Optimal treatment parameters were found to consist of 40 minutes of heat with low power ultrasound treatment microbubble parameters of 1 minute of sonification and a 1% microbubble concentration.

The use of ultrasound-stimulated microbubble therapy has successfully been used to target tumor vasculature and enhance the effects of radiation therapy in tumor xenografts in mice. Here, we further investigate this treatment using larger, more clinically relevant tumor models. New Zealand white rabbits bearing prostate tumor (PC3) xenografts received a single treatment of either ultrasound-stimulated microbubbles (USMB), ionizing radiation (XRT; 8Gy), or a combination of both treatments (USMB+XRT). Treatment outcome was evaluated 24 hours after treatment using histopathology, immunolabeling, 3D Doppler ultrasound and photoacoustic imaging. A second cohort of rabbits received multiple treatments over a period of three weeks, where USMB treatments were delivered twice weekly with daily XRT treatments to deliver a fractionated 2Gy dose five days per week. A significant decrease in vascular function, observed through immunolabeling of vascular endothelial cells, was observed in tumors receiving the combined treatment (USMB+XRT) compared to control and single treatment groups. This was associated with an increase in cell death as observed through in situ end labeling (ISEL), a decrease in vascular index measured by Power Doppler imaging, and a decrease in oxygen saturation. In rabbits undergoing the long-term fractionated combined treatment, a significant growth delay was observed after 1 week and a significant reduction in tumor size was observed after 3 weeks with combined therapy. Results demonstrated an enhancement of radiation effect and superior anti-tumor effect of the combination of USMB+XRT compared to the single treatments alone. Tumor growth was maximally inhibited with fractionated radiotherapy combined with the ultrasound-stimulated microbubble-based therapy.