Conectar
by Irene Boateng, Beth Stuart, Taeko Becque, Bruce Barrett, Jennifer Bostock, Robin Bruyndonckx, Lucy Carr-Knox, Emily J. Ciccone, Samuel Coenen, Mark Ebell, David Gillespie, Gail Hayward, Katarina Hedin, Kerenza Hood, Tin Man Mandy Lau, Paul Little, Dan Merenstein, Edgar Mulogo, Jose Ordóñez-Mena, Peter Muir, Kirsty Samuel, Nader Shaikh, Sharon Tonner, Alike W. van der Velden, Theo Verheij, Kay Wang, Alastair D. Hay, Nick Francis
BackgroundResistance to antibiotics is rising and threatens future antibiotic effectiveness. ‘Antibiotic targeting’ ensures patients who may benefit from antibiotics receive them, while being safely withheld from those who may not. Point-of-care tests may assist with antibiotic targeting by allowing primary care clinicians to establish if symptomatic patients have a viral, bacterial, combined, or no infection. However, because organisms can be harmlessly carried, it is important to know if the presence of the virus/bacteria is related to the illness for which the patient is being assessed. One way to do this is to look for associations with more severe/prolonged symptoms and test results. Previous research to answer this question for acute respiratory tract infections has given conflicting results with studies has not having enough participants to provide statistical confidence.
AimTo undertake a synthesis of IPD from both randomised controlled trials (RCTs) and observational cohort studies of respiratory tract infections (RTI) in order to investigate the prognostic value of microbiological data in addition to, or instead of, clinical symptoms and signs.
MethodsA systematic search of Cochrane Central Register of Controlled Trials, Ovid Medline and Ovid Embase will be carried out for studies of acute respiratory infection in primary care settings. The outcomes of interest are duration of disease, severity of disease, repeated consultation with new/worsening illness and complications requiring hospitalisation. Authors of eligible studies will be contacted to provide anonymised individual participant data. The data will be harmonised and aggregated. Multilevel regression analysis will be conducted to determine key outcome measures for different potential pathogens and whether these offer any additional information on prognosis beyond clinical symptoms and signs.
Trial registrationPROSPERO Registration number: CRD42023376769.
by Omar Al Omari, Gerald Amandu, Samir Al-Adawi, Zubaida Shebani, Ibtisam Al Harthy, Arwa Obeidat, Khloud Al Dameery, Mohammad Al Qadire, Iman Al Hashmi, Abduallh Al Khawldeh, Mohammed ALBashtawy, Maen Aljezawi
There is currently limited knowledge about the firsthand experiences of adolescents and young adults with mental health problems and the meanings they ascribe to these experiences, particularly within Arab countries. This study, therefore, aimed to explore the lived experience of Omani adolescents and young adults with a mental health problem. A sample of 15 participants aged 13–22 diagnosed with a range of mental health problems took part in the study. A qualitative interview guide consisting of open-ended questions was used to allow participants to speak in-depth about their experiences. Using the thematic analysis approach to uncover patterns in the data, three major themes emerged: “living in darkness”, “perilous journey” and “uncertain future”. Results show that the progress of adolescents and young adults with mental health problems is characterized by several challenges; the most significant of which is having insufficient knowledge about their illness, leading to unnecessary delays in their treatment. These findings shed light on the breadth and depth of the experience of adolescents and young adults with mental health problems and lay the groundwork for further examinations. Implications lie in the development of approaches for preventing or mitigating difficulties faced by adolescents and young adults with mental health problems.by Ajaya Basnet, Basanta Tamang, Mahendra Raj Shrestha, Lok Bahadur Shrestha, Junu Richhinbung Rai, Rajendra Maharjan, Sushila Dahal, Pradip Shrestha, Shiba Kumar Rai
IntroductionThe lack of standardized methods for detecting biofilms continues to pose a challenge to microbiological diagnostics since biofilm-mediated infections induce persistent and recurrent infections in humans that often defy treatment with common antibiotics. This study aimed to evaluate diagnostic parameters of four in vitro phenotypic biofilm detection assays in relation to antimicrobial resistance in aerobic clinical bacterial isolates.
MethodsIn this cross-sectional study, bacterial strains from clinical samples were isolated and identified following the standard microbiological guidelines. The antibiotic resistance profile was assessed through the Kirby-Bauer disc diffusion method. Biofilm formation was detected by gold standard tissue culture plate method (TCPM), tube method (TM), Congo red agar (CRA), and modified Congo red agar (MCRA). Statistical analyses were performed using SPSS version 17.0, with a significant association considered at p Result
Among the total isolates (n = 226), TCPM detected 140 (61.95%) biofilm producers, with CoNS (9/9) (p Conclusion
It is suggested that TM be used for biofilm detection, after TCPM. Unlike MCRA, black pigmentation in colonies formed on CRA declined with time. MDR- and XDR-biofilm formers were frequent among the clinical isolates.
by Nataliya Rybnikova, Dani Broitman, Murielle Mary-Krause, Maria Melchior, Yakov Ben-Haim
Questionnaires are among the most basic and widespread tools to assess the mental health of a population in epidemiological and public health studies. Their most obvious advantage (firsthand self-report) is also the source of their main problems: the raw data requires interpretation, and are a snapshot of the specific sample’s status at a given time. Efforts to deal with both issues created a bi-dimensional space defined by two orthogonal axes, in which most of the quantitative mental health research can be located. Methods aimed to assure that mental health diagnoses are solidly grounded on existing raw data are part of the individual validity axis. Tools allowing the generalization of the results across the entire population compose the collective validity axis. This paper raises a different question. Since one goal of mental health assessments is to obtain results that can be generalized to some extent, an important question is how robust is a questionnaire result when applied to a different population or to the same population at a different time. In this case, there is deep uncertainty, without any a priori probabilistic information. The main claim of this paper is that this task requires the development of a new robustness to deep uncertainty axis, defining a three-dimensional research space. We demonstrate the analysis of deep uncertainty using the concept of robustness in info-gap decision theory. Based on data from questionnaires collected before and during the Covid-19 pandemic, we first locate a mental health assessment in the space defined by the individual validity axis and the collective validity axis. Then we develop a model of info-gap robustness to uncertainty in mental health assessment, showing how the robustness to deep uncertainty axis interacts with the other two axes, highlighting the contributions and the limitations of this approach. The ability to measure robustness to deep uncertainty in the mental health realm is important particularly in troubled and changing times. In this paper, we provide the basic methodological building blocks of the suggested approach using the outbreak of Covid-19 as a recent example.by Laurie Simard, Julie Bouchard, Martin Lavallière, Tommy Chevrette
This article discussed the issue of low PA levels among school-aged children and highlights the promising approach of school-based interventions, including physically active learning (PAL), to increase PA levels. The study aimed to co-design and to assess the implementation of a PAL program for 8 weeks in 4 elementary classrooms (82 students and 7 teachers), emphasizing the potential of integrating PA with academic learning and the importance of co-designing programs with teachers to maximize their effectiveness. Technology was found to support PAL practices in promoting PA and academic achievement. The study underscores the need for further research to explore the societal implications of PAL programs, including their potential to improve the health and well-being of children while promoting positive academic outcomes.by Abarna Nadeshkumar, Gitanjali Sathiadas, Shalini Sri Ranganathan
IntroductionOral liquid dosage forms remain popular in several middle income countries. The accuracy of liquid dosage form dosing depends on the accuracy and availability of measuring devices. Lack of quality oral liquid measuring devices will lead to medication errors. Hence there is an urgent need to describe the quality of manufacturer supplied measuring devices enclosed with paediatric oral liquid dosage forms currently registered in Sri Lanka.
MethodologyStandards for measuring devices were developed after a detailed literature search. Multidisciplinary panel rated each standard for the necessity criteria on a 9 point Likert scale. Standards with overall panel median score of ≥ 7 with agreement were selected. A cross-sectional study was done. All the measuring devices, labels and instructions enclosed with the registered products were assessed against the standards developed. Three volumes of liquid antibacterials were measured using the enclosed measuring device. Accuracy of the volumes was measured.
ResultsOf the total products (n = 202) only 126 were packed with a dosing device. Around quarter of the oral liquid dosage forms (n = 36) did not have a measuring device. More than half of the measuring devices aligned with all the standards developed. Out of 44 oral liquid paediatric antimicrobials measuring cups (n = 25, 56.8%, 95% CI: 41%-72%) were enclosed more and less error was seen with measuring cups.
ConclusionThe quality of oral liquid measuring devices were not satisfactory. Quality could be further improved if the regulatory body request the manufactures/importers to adhere to the standards developed. Correct volumes were not measured using the measuring devices provided with the liquid antimicrobial agents
by Samar Fatima, Madiha Ismail, Taymmia Ejaz, Zarnain Shah, Summaya Fatima, Mohammad Shahzaib, Hassan Masood Jafri
ObjectiveThere is a lack of estimates regarding the at-risk population associated with long COVID in Pakistan due to the absence of prospective longitudinal studies. This study aimed to determine the prevalence of long COVID and its association with disease severity and vaccination status of the patient.
Design and data sourcesThis prospective cohort study was conducted at the Aga Khan University Hospital and recruited patients aged > 18 years who were admitted between February 1 and June 7, 2021. During this time, 901 individuals were admitted, after excluding patients with missing data, a total of 481 confirmed cases were enrolled.
ResultsThe mean age of the study population was 56.9±14.3 years. Among patients with known vaccination status (n = 474), 19%(n = 90) and 19.2%(n = 91) were fully and partially vaccinated, respectively. Severe/critical disease was present in 64%(n = 312). The mortality rate following discharge was 4.58%(n = 22). Around 18.9%(n = 91) of the population required readmission to the hospital, with respiratory failure (31.8%, n = 29) as the leading cause. Long COVID symptoms were present in 29.9%(n = 144), and these symptoms were more prevalent in the severe/critical (35.5%, n = 111) and unvaccinated (37.9%, n = 105) cohort. The most prominent symptoms were fatigue (26.2%, n = 126) and shortness of breath (24.1%, n = 116), followed by cough (15.2%, n = 73). Vaccinated as compared to unvaccinated patients had lower readmissions (13.8% vs. 21.51%) and post-COVID pulmonary complications (15.4% vs. 24.2%). On multivariable analysis, after adjusting for age, gender, co-morbidity, and disease severity, lack of vaccination was found to be an independent predictor of long COVID with an Odds ratio of 2.42(95% CI 1.52–3.84). Fully and partially vaccinated patients had 62% and 56% reduced risk of developing long COVID respectively.
ConclusionsThis study reports that the patients continued to have debilitating symptoms related to long COVID, one year after discharge, and most of its effects were observed in patients with severe/critical disease and unvaccinated patients.
by Samina Ali, Claudia Maki, Asa Rahimi, Keon Ma, Maryna Yaskina, Helen Wong, Antonia Stang, Tania Principi, Naveen Poonai, Serge Gouin, Sylvia Froese R. N., Paul Clerc, Redjana Carciumaru, Waleed Alqurashi, Manasi Rajagopal, Elise Kammerer, Julie Leung, Bruce Wright, Shannon D. Scott, on behalf of the Pediatric Emergency Research Canada Family Needs Study Group
ObjectivesTo describe the extent to which caregivers’ emotional and communication needs were met during pediatric emergency department (PED) visits. Secondary objectives included describing the association of caregiver emotional needs, satisfaction with care, and comfort in caring for their child’s illness at the time of discharge with demographic characteristics, caregiver experiences, and ED visit details.
Study designElectronic surveys with medical record review were deployed at ten Canadian PEDs from October 2018 –March 2020. A convenience sample of families with children Results
This study recruited 2005 caregivers who self-identified as mothers (74.3%, 1462/1969); mean age was 37.8 years (SD 7.7). 71.7% (1081/1507) of caregivers felt their emotional needs were met. 86.4% (1293/1496) identified communication with the doctor as good/very good and 83.4% (1249/1498) with their child’s nurse. Caregiver involvement in their child’s care was reported as good/very good 85.6% (1271/1485) of the time. 81.8% (1074/1313) of caregivers felt comfortable in caring for their child at home at the time of discharge. Lower caregiver anxiety scores, caregiver involvement in their child’s care, satisfactory updates, and having questions adequately addressed positively impacted caregiver emotional needs and increased caregiver comfort in caring for their child’s illness at home.
ConclusionApproximately 30% of caregivers presenting to PEDs have unmet emotional needs, over 15% had unmet communication needs, and 15% felt inadequately involved in their child’s care. Family caregiver involvement in care and good communication from PED staff are key elements in improving overall patient experience and satisfaction.
by Emily J. Ward, Maren S. Fragala, Charles E. Birse, Matt Hawrilenko, Casey Smolka, Geetu Ambwani, Millard Brown, John H. Krystal, Philip R. Corlett, Adam Chekroud
Mental health issues are a growing concern in the workplace, linked to negative outcomes including reduced productivity, increased absenteeism, and increased turnover. Employer-sponsored mental health benefits that are accessible and proactive may help address these concerns. The aim of this retrospective cohort study was to evaluate the impact of a digital mental health benefit (Spring Health) on frontline healthcare service workers’ clinical and workplace outcomes. The benefit was sponsored by a national health services company from 2021–2022 and included mental health screening, care navigation, psychotherapy and/or medication management. We hypothesized program use would be associated with improvements in depression and anxiety symptoms, and increased productivity and retention. Participants were employees enrolled in the benefit program, had at least moderate anxiety or depression, at least 1 treatment appointment, and at least 2 outcome assessments. Clinical improvement measures were PHQ-9 scale (range, 0–27) for depression and GAD-7 scale (range, 0–21) for anxiety; workplace measures were employee retention and the Sheehan Disability Scale (SDS) for functional impairment. A total of 686 participants were included. Participants using the mental health benefit had a 5.60 point (95% CI, 4.40–6.79, d = 1.28) reduction in depression and a 5.48 point (95% CI, 3.88–7.08, d = 1.64) reduction in anxiety across 6 months. 69.9% (95% CI, 61.8%–78.1%) of participants reliably improved (≥5 point change) and 84.1% (95% CI, 78.2%–90.1%) achieved reliable improvement or recovery (by Laura Capitán-Moyano, Nerea Cañellas-Iniesta, María Arias-Fernández, Miquel Bennasar-Veny, Aina M. Yáñez, Enrique Castro-Sánchez
Food insecurity in recent years has increased worldwide due to many planetary events such as the COVID-19 pandemic, geopolitical conflicts, the climate crisis, and globalization of markets. Adolescents are a particularly vulnerable group to food insecurity, as they enter adulthood with less parental supervision and greater personal autonomy, but less legislative or institutional protection. The experience of food insecurity in adolescents is influenced by several environmental factors at different levels (interpersonal, organizational, community, and societal), although they are not usually addressed in the design of interventions, prioritizing the individual behavioural factors. We present a scoping review protocol for assessing and identifying the environmental factors that could influence adolescents’ food insecurity. We used the Preferred Reporting Items for Systematic Reviews and Meta-Analysis Protocols (PRISMA-P) and the PRISMA guidelines for Scoping Reviews (PRISMA-ScR) to prepare the protocol. The search strategy will be performed in the following databases: Pubmed/Medline, EMBASE, Biblioteca Virtual de Salud, EBSCOHost, Scopus, Web of Science, and Cochrane Library Plus. The reference list of the included studies will also be hand-searched. Grey literature will be search through the electronic database Grey Literature Report, and local, provincial, national, and international organisations’ websites. Assessment of eligibility after screening of titles, abstract and full text, and the resolution of discrepancies will be performed by three independent reviewers. This scoping review will contribute to refine the “logic model of the problem” which constitutes the first step in the intervention mapping protocol. The “logic model of the problem” from the intervention mapping protocol will serve to classify and analyse the environmental factors. The findings from this review will be presented to relevant stakeholders that have a role in shaping the environmental factors.by Kelsey McOwat, Snehal M. Pinto Pereira, Manjula D. Nugawela, Shamez N. Ladhani, Fiona Newlands, Terence Stephenson, Ruth Simmons, Malcolm G. Semple, Terry Segal, Marta Buszewicz, Isobel Heyman, Trudie Chalder, Tamsin Ford, Emma Dalrymple, Consortium , Roz Shafran
BackgroundDuring the COVID-19 pandemic children and young people (CYP) were socially restricted during a stage of life crucial to development, potentially putting an already vulnerable population at higher risk of loneliness, social isolation, and poorer wellbeing. The objectives of this study are to conduct an exploratory analysis into loneliness before and during the pandemic, and determine which self-reported factors are associated with loneliness.
Methods and findingsParticipants from The Children with Long COVID (CLoCk) national study were invited to take part via an online survey, with a total of 31,017 participants taking part, 31,016 of which reported on their experience of loneliness. Participants retrospectively answered questions on demographics, lifestyle, physical health and mental health and loneliness before the pandemic and at the time of answering the survey. Before the pandemic 6.5% (2,006/31,016) of participants reported experiencing loneliness “Often/Always” and at the time of survey completion 17.4% (5,395/31,016) reported feeling lonelier. There was an association between meeting the research definition of long COVID and loneliness [3.49 OR, 95%CI 3.28–3.72]. CYP who reported feeling lonelier at the time of the survey than before the pandemic were assigned female at birth, older CYP, those from Black/African/Caribbean/Black British or other ethnicity groups, those that had 3–4 siblings and lived in more deprived areas.
ConclusionsWe demonstrate associations between multiple factors and experiences of loneliness during the pandemic. There is a need for a multi-faceted integrated approach when developing interventions targeted at loneliness. It is important to follow up the CYP involved at regular intervals to investigate the progression of their experience of loneliness over time.
by Chiara Marraccini, Lucia Merolle, Davide Schiroli, Agnese Razzoli, Gaia Gavioli, Barbara Iotti, Roberto Baricchi, Marta Ottone, Pamela Mancuso, Paolo Giorgi Rossi
To investigate the association between biochemical and blood parameters collected before the pandemic in a large cohort of Italian blood donors with the risk of infection and severe disease. We also focused on the differences between the pre- and post-Omicron spread in Italy (i.e., pre- and post-January 01, 2022) on the observed associations. We conducted an observational cohort study on 13750 blood donors was conducted using data archived up to 5 years before the pandemic. A t-test or chi-squared test was used to compare differences between groups. Hazard ratios with 95% confidence intervals for SARS-CoV-2 infection and severe disease were estimated using Cox proportional hazards models. Subgroup analyses stratified by sex, age and epidemic phase of first infection (pre- and post-Omicron spread) were examined. We confirmed a protective effect of groups B and O, while groups A and AB had a higher likelihood of infection and severe disease. However, these associations were only significant in the pre-Omicron period. We found an opposite behavior after Omicron spread, with the O phenotype having a higher probability of infection. When stratified by variant, A antigen appeared to protect against Omicron infection, whereas it was associated with an increased risk of infection by earlier variants. We were able to stratify for the SARS CoV-2 dominant variant, which revealed a causal association between blood group and probability of infection, as evidenced by the strong effect modification observed between the pre- and post-Omicron spread. The mechanism by which group A acts on the probability of infection should consider this strong effect modification.by Sukanya G. Gakare, Jay M. Bhatt, Kishore Kumar S. Narasimhan, Shashank M. Dravid
In this study, we investigated the role of glutamate delta 1 receptor (GluD1) in oligodendrocyte progenitor cell (OPC)-mediated myelination during basal (development) and pathophysiological (cuprizone-induced demyelination) conditions. Initially, we sought to determine the expression pattern of GluD1 in OPCs and found a significant colocalization of GluD1 puncta with neuron-glial antigen 2 (NG2, OPC marker) in the motor cortex and dorsal striatum. Importantly, we found that the ablation of GluD1 led to an increase in the number of myelin-associated glycoprotein (MAG+) cells in the corpus callosum and motor cortex at P40 without affecting the number of NG2+ OPCs, suggesting that GluD1 loss selectively facilitates OPC differentiation rather than proliferation. Further, deletion of GluD1 enhanced myelination in the corpus callosum and motor cortex, as indicated by increased myelin basic protein (MBP) staining at P40, suggesting that GluD1 may play an essential role in the developmental regulation of myelination during the critical window period. In contrast, in cuprizone-induced demyelination, we observed reduced MBP staining in the corpus callosum of GluD1 KO mice. Furthermore, cuprizone-fed GluD1 KO mice showed more robust motor deficits. Collectively, our results demonstrate that GluD1 plays a critical role in OPC regulation and myelination in normal and demyelinating conditions.by Chalachew Kassaw, Valeriia Demareva
BackgroundAcademic success is a measure of students’ ability to attain their educational objectives, often assessed through regular evaluations or examinations. To establish effective policies and programs that align with academic accomplishments, conducting comprehensive data analysis is pivotal. Hence, this systematic review aimed to synthesize the factors impeding the academic achievements of Ethiopian students in higher education.
MethodsA comprehensive review was conducted on studies involving Ethiopian university students from 2013 to 2022. The review encompassed 24 papers that were gathered from different databases like PubMed, Google Scholar, African Journals Online, Scopus, and Web of Science.
ResultsThe findings of this research revealed that inadequate classroom environments, experiencing dysmenorrhea, and engaging in excessive social media usage were all linked to a decline in academic performance. Conversely, adopting healthy sleep habits, achieving high scores in entrance exams, and avoiding recent substance abuse were all factors positively influencing academic success. In addition, there was a positive correlation between academic excellence and being a health science college student and age range of 20 to 24 years old.
ConclusionTo enhance academic performance, it is crucial to address the negative factors identified, such as inadequate classroom environments, dysmenorrhea, and excessive social media usage, while promoting positive factors like healthy sleep habits, high scores in exams, and avoiding substance abuse. Additionally, being a health science college student and belonging to the age range of 20 to 24 were found to be associated with academic excellence.
by Shafaq Fatima, Ayesha Afzal, Hamna Rashid, Saba Iqbal, Rosheen Zafar, Komal Khalid, Ayman Rauf, Maryam Majeed, Aqsa Malik, Chris G. Carter
This experiment aimed to investigate the effects of partial substitution of crude protein from soybean meal (SBM) with black soldier fly (Hermetia illucens) larvae meal (BSFLM) in juvenile rohu (Labeo rohita) and catla (Catla catla). Four isonitrogenous diets (23% crude protein) were formulated to replace 0% (T0), 40% (T40), 80% (T80) and 100% (T100) crude protein from SBM with BSFLM. Triplicate groups of each species (10 fish per replicate) were fed in an eight week growth experiment. After final sampling (n = 20 fish per dietary group), the remaining fish were exposed to bacterial (Staphylococcus aureus) challenge (0.80 CFU/ml) for 15 days. Rohu fed with BSFLM substituted diets showed significantly higher growth and feed conversion ratio as compared to those in T0. Catla fed with BSFLM substituted diets showed slightly higher growth indices. The growth response of rohu to BSFLM substitution was better than that noted in catla in all groups. The chemical composition, amino acids and fatty acids profile, haematological and biochemical parameters, levels of liver function enzymes measured in T0, T40, T80 and T100 were similar between four dietary groups in both species. However, the maximum value of cholesterol and triglycerides were noted in T100 both in catla and rohu. The values of lauric acid, α-linolenic acid, decosahexanoic acid, n3:n6 fatty acids ratio progressively increased with dietary increase of BSFLM in both species. At end of the growth experiment, the levels of catalase, superoxide dismutase and lysozyme increased linearly with the inclusion of BSFLM in both species while malondialdehyde showed similar values between different groups. However, catalase, and superoxide dismutase increased (T0by Victoria Anne Archer, Samira Samiee-Zafarghandy, Forough Farrokyhar, Daniel Briatico, Luis H. Braga, J. Mark Walton
BackgroundIn neonates, uncontrolled pain and opioid exposure are both correlated with short- and long-term adverse events. Therefore, managing pain using opioid-sparing approaches is critical in neonatal populations. Multimodal pain control offers the opportunity to manage pain while reducing short- and long-term opioid-related adverse events. Intravenous (IV) acetaminophen may represent an appropriate adjunct to opioid-based postoperative pain control regimes. However, no trials assess this drug in patients less than 36 weeks post-conceptual age or weighing less than 1500 g.
ObjectiveThe proposed study aims to determine the feasibility of conducting a randomized control trial to compare IV acetaminophen and fentanyl to a saline placebo and fentanyl for patients admitted to the neonatal intensive care unit (NICU) undergoing major abdominal or thoracic surgery.
Methods and designThis protocol is for a single-centre, external pilot randomized controlled trial (RCT). Infants in the NICU who have undergone major thoracic or abdominal surgery will be enrolled. Sixty participants will undergo 1:1 randomization to receive intravenous acetaminophen and fentanyl or saline placebo and fentanyl. After surgery, IV acetaminophen or placebo will be given routinely for eight days (192 hours). Appropriate dosing will be determined based on the participant’s gestational age. Patients will be followed for eight days after surgery and will undergo a chart review at 90 days. Primarily feasibility outcomes include recruitment rate, follow-up rate, compliance, and blinding index. Secondary clinical outcomes will be collected as well.
ConclusionThis external pilot RCT will assess the feasibility of performing a multicenter RCT comparing IV acetaminophen and fentanyl to a saline placebo and fentanyl in NICU patients following major abdominal and thoracic surgery. The results will inform the design of a multicenter RCT, which will have the appropriate power to determine the efficacy of this treatment.
Trial registrationClinicalTrials.gov NCT05678244, Registered December 6, 2022.
by Katayi Mwila-Kazimbaya, Samuel Bosomprah, Obvious Nchimunya Chilyabanyama, Caroline Cleopatra Chisenga, Mwelwa Chibuye, Natasha Makabilo Laban, Michelo Simuyandi, Bert Huffer Jr, Miren Iturriza-Gomara, Robert K. M. Choy, Roma Chilengi
BackgroundRotavirus gastroenteritis remains a leading cause of morbidity and mortality despite the introduction of vaccines. Research shows there are several factors contributing to the reduced efficacy of rotavirus vaccines in low- and middle-income settings. Proposed factors include environmental enteric dysfunction (EED), malnutrition, and immune dysfunction. This study aimed to assess the effect of these factors on vaccine responses using a machine learning lasso approach.
MethodsSerum samples from two rotavirus clinical trials (CVIA 066 n = 99 and CVIA 061 n = 124) were assessed for 11 analytes using the novel Micronutrient and EED Assessment Tool (MEEDAT) multiplex ELISA. Immune responses to oral rotavirus vaccines (Rotarix, Rotavac, and Rotavac 5D) as well as a parenteral rotavirus vaccine (trivalent P2-VP8) were also measured and machine learning using the lasso approach was then applied to investigate any associations between immune responses and environmental enteric dysfunction, systemic inflammation, and growth hormone resistance biomarkers.
ResultsBoth oral and parenteral rotavirus vaccine responses were negatively associated with retinol binding protein 4 (RBP4), albeit only weakly for oral vaccines. The parenteral vaccine responses were positively associated with thyroglobulin (Tg) and histidine-rich protein 2 (HRP2) for all three serotypes (P8, P6 and P4), whilst intestinal fatty acid binding protein (I-FABP) was negatively associated with P6 and P4, but not P8, and soluble transferrin receptor (sTfR) was positively associated with P6 only.
ConclusionMEEDAT successfully measured biomarkers of growth, systemic inflammation, and EED in infants undergoing vaccination, with RBP4 being the only analyte associated with both oral and parenteral rotavirus vaccine responses. Tg and HRP2 were associated with responses to all three serotypes in the parenteral vaccine, while I-FABP and sTfR results indicated possible strain specific immune responses to parenteral immunization.
by Silvia A. Purro, Michael Farmer, Elizabeth Noble, Claire J. Sarell, Megan Powell, Daniel Yip, Lauren Giggins, Leila Zakka, David X. Thomas, Mark Farrow, Andrew J. Nicoll, Dominic Walsh, John Collinge
Oligomers formed from monomers of the amyloid β-protein (Aβ) are thought to be central to the pathogenesis of Alzheimer’s disease (AD). Unsurprisingly for a complex disease, current mouse models of AD fail to fully mimic the clinical disease in humans. Moreover, results obtained in a given mouse model are not always reproduced in a different model. Cellular prion protein (PrPC) is now an established receptor for Aβ oligomers. However, studies of the Aβ-PrPC interaction in different mouse models have yielded contradictory results. Here we performed a longitudinal study assessing a range of biochemical and histological features in the commonly used J20 and APP-PS1 mouse models. Our analysis demonstrated that PrPC ablation had no effect on amyloid accumulation or oligomer production. However, we found that APP-PS1 mice had higher levels of oligomers, that these could bind to recombinant PrPC, and were recognised by the OC antibody which distinguishes parallel, in register fibrils. On the other hand, J20 mice had a lower level of Aβ oligomers, which did not interact with PrPC when tested in vitro and were OC-negative. These results suggest the two mouse models produce diverse Aβ assemblies that could interact with different targets, highlighting the necessity to characterise the conformation of the Aβ oligomers concomitantly with the toxic cascade elicited by them. Our results provide an explanation for the apparent contradictory results found in APP-PS1 mice and the J20 mouse line in regards to Aβ toxicity mediated by PrPC.by Andreas W. Oehm, Yury Zablotski, Martina Hoedemaker, Amely Campe, Christina Strube, Daniela Jordan, Andrea Springer, Markus Klawitter, Gabriela Knubben-Schweizer
Fasciola hepatica is one of the economically most important endoparasites in cattle production. The aim of the present work was to evaluate the relevance of production level on the associations of on-farm presence of F. hepatica with farm-level milk yield, milk fat, and milk protein in Holstein cows, a specialised dairy breed, and in Simmental cows, a dual purpose breed. Furthermore, we investigated whether differential associations were present depending on breed. Data from 560 dairy farms across Germany housing 93,672 cows were analysed. The presence of F. hepatica antibodies was determined via ELISA on bulk tank milk samples. Quantile regression was applied to model the median difference in milk yield, milk fat, and milk protein depending on the interaction of breed and fluke occurrence. Whereas a reduction in milk yield (-1,206 kg, p F. hepatica positive German Holstein farms, only milk fat (-33.8 kg, p = 0.01) and milk protein (-22.6 kg, p = 0.03) were affected on F. hepatica positive German Simmental farms. Subsequently, production traits were modelled within each of the two breeds for low, medium, and high producing farms in the presence of F. hepatica antibodies and of confounders. On Holstein farms, the presence of F. hepatica seropositivity was associated with lower production, while on German Simmental farms such an association was less evident. This work demonstrates that production level is relevant when assessing the associations between the exposure to F. hepatica with production characteristics. Moreover, both models indicate a breed dependence. This could point towards a differential F. hepatica resilience of specialised dairy breeds in comparison with dual purpose breeds.by Ana Šemrov, Valerija Tadić, Mario Cortina-Borja, Jugnoo Sangeeta Rahi, on behalf of The Resilience and Childhood Visual Impairment Study Group
Childhood visual impairment can have a significant impact on an individual’s development. To improve clinical care and develop appropriate psychosocial interventions of these patients, it is necessary to understand the contributing and modifiable factors that both identify individuals in greater need and could be targeted in interventions. Here we investigate the broader individual, family, and environmental factors associated with vision-related quality of life (VQoL) of children and young people with visual impairment (CYP-VI). Data for this cross-sectional study were collected from September 2014 to May 2017 to develop and validate two vision-specific patient-reported outcome measures (PROMs) for CYP-VI. Patients were recruited from 22 hospitals in the United Kingdom and were aged 7–18 years with visual impairment as per WHO criteria. Participants self-completed the two PROMs, VQoL and Functional Vision Questionnaires. Clinical characteristics were extracted from medical records. Their carers provided information on family sociodemographic backgrounds. Associations between the VQoL scores and other factors were examined using Spearman’s correlation, Kruskal-Wallis, Wilcoxon rank-sum tests, and quantile regression models. The sample consisted of 152 CYP-VI (67 females). Better VQoL was significantly associated with better functional vision overall (rSpearman = –0.52), parent-reported absence of additional chronic conditions (dCohen = 0.46), attending mainstream (versus other) school (dCohen = 0.44), higher socio-economic status (rSpearman = 0.17) and higher parental education level (rSpearman = 0.20). No other investigated factors were significantly associated with VQoL. The final quantile regression model included functional vision scores and the presence of additional health condition. Variation in self-reported VQoL in CYP-VI can be partly accounted for by factors relating to the clinical status of the affected child and, more importantly, by non-health-related factors. This needs to be considered in clinical practice when assessing vision-specific outcomes and providing support to CYP-VI, as well as in the development of future interventions.
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