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Michael Weekes

and 11 more

Nick K. Jones1,2*, Lucy Rivett1,2*, Chris Workman3, Mark Ferris3, Ashley Shaw1, Cambridge COVID-19 Collaboration1,4, Paul J. Lehner1,4, Rob Howes5, Giles Wright3, Nicholas J. Matheson1,4,6¶, Michael P. Weekes1,7¶1 Cambridge University NHS Hospitals Foundation Trust, Cambridge, UK2 Clinical Microbiology & Public Health Laboratory, Public Health England, Cambridge, UK3 Occupational Health and Wellbeing, Cambridge Biomedical Campus, Cambridge, UK4 Cambridge Institute of Therapeutic Immunology & Infectious Disease, University of Cambridge, Cambridge, UK5 Cambridge COVID-19 Testing Centre and AstraZeneca, Anne Mclaren Building, Cambridge, UK6 NHS Blood and Transplant, Cambridge, UK7 Cambridge Institute for Medical Research, University of Cambridge, Cambridge, UK*Joint first authorship¶Joint last authorshipCorrespondence: [email protected] UK has initiated mass COVID-19 immunisation, with healthcare workers (HCWs) given early priority because of the potential for workplace exposure and risk of onward transmission to patients. The UK’s Joint Committee on Vaccination and Immunisation has recommended maximising the number of people vaccinated with first doses at the expense of early booster vaccinations, based on single dose efficacy against symptomatic COVID-19 disease.1-3At the time of writing, three COVID-19 vaccines have been granted emergency use authorisation in the UK, including the BNT162b2 mRNA COVID-19 vaccine (Pfizer-BioNTech). A vital outstanding question is whether this vaccine prevents or promotes asymptomatic SARS-CoV-2 infection, rather than symptomatic COVID-19 disease, because sub-clinical infection following vaccination could continue to drive transmission. This is especially important because many UK HCWs have received this vaccine, and nosocomial COVID-19 infection has been a persistent problem.Through the implementation of a 24 h-turnaround PCR-based comprehensive HCW screening programme at Cambridge University Hospitals NHS Foundation Trust (CUHNFT), we previously demonstrated the frequent presence of pauci- and asymptomatic infection amongst HCWs during the UK’s first wave of the COVID-19 pandemic.4 Here, we evaluate the effect of first-dose BNT162b2 vaccination on test positivity rates and cycle threshold (Ct) values in the asymptomatic arm of our programme, which now offers weekly screening to all staff.Vaccination of HCWs at CUHNFT began on 8th December 2020, with mass vaccination from 8th January 2021. Here, we analyse data from the two weeks spanning 18thto 31st January 2021, during which: (a) the prevalence of COVID-19 amongst HCWs remained approximately constant; and (b) we screened comparable numbers of vaccinated and unvaccinated HCWs. Over this period, 4,408 (week 1) and 4,411 (week 2) PCR tests were performed from individuals reporting well to work. We stratified HCWs <12 days or > 12 days post-vaccination because this was the point at which protection against symptomatic infection began to appear in phase III clinical trial.226/3,252 (0·80%) tests from unvaccinated HCWs were positive (Ct<36), compared to 13/3,535 (0·37%) from HCWs <12 days post-vaccination and 4/1,989 (0·20%) tests from HCWs ≥12 days post-vaccination (p=0·023 and p=0·004, respectively; Fisher’s exact test, Figure). This suggests a four-fold decrease in the risk of asymptomatic SARS-CoV-2 infection amongst HCWs ≥12 days post-vaccination, compared to unvaccinated HCWs, with an intermediate effect amongst HCWs <12 days post-vaccination.A marked reduction in infections was also seen when analyses were repeated with: (a) inclusion of HCWs testing positive through both the symptomatic and asymptomatic arms of the programme (56/3,282 (1·71%) unvaccinated vs 8/1,997 (0·40%) ≥12 days post-vaccination, 4·3-fold reduction, p=0·00001); (b) inclusion of PCR tests which were positive at the limit of detection (Ct>36, 42/3,268 (1·29%) vs 15/2,000 (0·75%), 1·7-fold reduction, p=0·075); and (c) extension of the period of analysis to include six weeks from December 28th to February 7th 2021 (113/14,083 (0·80%) vs 5/4,872 (0·10%), 7·8-fold reduction, p=1x10-9). In addition, the median Ct value of positive tests showed a non-significant trend towards increase between unvaccinated HCWs and HCWs > 12 days post-vaccination (23·3 to 30·3, Figure), suggesting that samples from vaccinated individuals had lower viral loads.We therefore provide real-world evidence for a high level of protection against asymptomatic SARS-CoV-2 infection after a single dose of BNT162b2 vaccine, at a time of predominant transmission of the UK COVID-19 variant of concern 202012/01 (lineage B.1.1.7), and amongst a population with a relatively low frequency of prior infection (7.2% antibody positive).5This work was funded by a Wellcome Senior Clinical Research Fellowship to MPW (108070/Z/15/Z), a Wellcome Principal Research Fellowship to PJL (210688/Z/18/Z), and an MRC Clinician Scientist Fellowship (MR/P008801/1) and NHSBT workpackage (WPA15-02) to NJM. Funding was also received from Addenbrooke’s Charitable Trust and the Cambridge Biomedical Research Centre. We also acknowledge contributions from all staff at CUHNFT Occupational Health and Wellbeing and the Cambridge COVID-19 Testing Centre.

Guangming Wang

and 4 more

Tam Hunt

and 1 more

Tam Hunt [1], Jonathan SchoolerUniversity of California Santa Barbara Synchronization, harmonization, vibrations, or simply resonance in its most general sense seems to have an integral relationship with consciousness itself. One of the possible “neural correlates of consciousness” in mammalian brains is a combination of gamma, beta and theta synchrony. More broadly, we see similar kinds of resonance patterns in living and non-living structures of many types. What clues can resonance provide about the nature of consciousness more generally? This paper provides an overview of resonating structures in the fields of neuroscience, biology and physics and attempts to coalesce these data into a solution to what we see as the “easy part” of the Hard Problem, which is generally known as the “combination problem” or the “binding problem.” The combination problem asks: how do micro-conscious entities combine into a higher-level macro-consciousness? The proposed solution in the context of mammalian consciousness suggests that a shared resonance is what allows different parts of the brain to achieve a phase transition in the speed and bandwidth of information flows between the constituent parts. This phase transition allows for richer varieties of consciousness to arise, with the character and content of that consciousness in each moment determined by the particular set of constituent neurons. We also offer more general insights into the ontology of consciousness and suggest that consciousness manifests as a relatively smooth continuum of increasing richness in all physical processes, distinguishing our view from emergentist materialism. We refer to this approach as a (general) resonance theory of consciousness and offer some responses to Chalmers’ questions about the different kinds of “combination problem.”  At the heart of the universe is a steady, insistent beat: the sound of cycles in sync…. [T]hese feats of synchrony occur spontaneously, almost as if nature has an eerie yearning for order. Steven Strogatz, Sync: How Order Emerges From Chaos in the Universe, Nature and Daily Life (2003) If you want to find the secrets of the universe, think in terms of energy, frequency and vibration.Nikola Tesla (1942) I.               Introduction Is there an “easy part” and a “hard part” to the Hard Problem of consciousness? In this paper, we suggest that there is. The harder part is arriving at a philosophical position with respect to the relationship of matter and mind. This paper is about the “easy part” of the Hard Problem but we address the “hard part” briefly in this introduction.  We have both arrived, after much deliberation, at the position of panpsychism or panexperientialism (all matter has at least some associated mind/experience and vice versa). This is the view that all things and processes have both mental and physical aspects. Matter and mind are two sides of the same coin.  Panpsychism is one of many possible approaches that addresses the “hard part” of the Hard Problem. We adopt this position for all the reasons various authors have listed (Chalmers 1996, Griffin 1997, Hunt 2011, Goff 2017). This first step is particularly powerful if we adopt the Whiteheadian version of panpsychism (Whitehead 1929).  Reaching a position on this fundamental question of how mind relates to matter must be based on a “weight of plausibility” approach, rather than on definitive evidence, because establishing definitive evidence with respect to the presence of mind/experience is difficult. We must generally rely on examining various “behavioral correlates of consciousness” in judging whether entities other than ourselves are conscious – even with respect to other humans—since the only consciousness we can know with certainty is our own. Positing that matter and mind are two sides of the same coin explains the problem of consciousness insofar as it avoids the problems of emergence because under this approach consciousness doesn’t emerge. Consciousness is, rather, always present, at some level, even in the simplest of processes, but it “complexifies” as matter complexifies, and vice versa. Consciousness starts very simple and becomes more complex and rich under the right conditions, which in our proposed framework rely on resonance mechanisms. Matter and mind are two sides of the coin. Neither is primary; they are coequal.  We acknowledge the challenges of adopting this perspective, but encourage readers to consider the many compelling reasons to consider it that are reviewed elsewhere (Chalmers 1996, Griffin 1998, Hunt 2011, Goff 2017, Schooler, Schooler, & Hunt, 2011; Schooler, 2015).  Taking a position on the overarching ontology is the first step in addressing the Hard Problem. But this leads to the related questions: at what level of organization does consciousness reside in any particular process? Is a rock conscious? A chair? An ant? A bacterium? Or are only the smaller constituents, such as atoms or molecules, of these entities conscious? And if there is some degree of consciousness even in atoms and molecules, as panpsychism suggests (albeit of a very rudimentary nature, an important point to remember), how do these micro-conscious entities combine into the higher-level and obvious consciousness we witness in entities like humans and other mammals?  This set of questions is known as the “combination problem,” another now-classic problem in the philosophy of mind, and is what we describe here as the “easy part” of the Hard Problem. Our characterization of this part of the problem as “easy”[2] is, of course, more than a little tongue in cheek. The authors have discussed frequently with each other what part of the Hard Problem should be labeled the easier part and which the harder part. Regardless of the labels we choose, however, this paper focuses on our suggested solution to the combination problem.  Various solutions to the combination problem have been proposed but none have gained widespread acceptance. This paper further elaborates a proposed solution to the combination problem that we first described in Hunt 2011 and Schooler, Hunt, and Schooler 2011. The proposed solution rests on the idea of resonance, a shared vibratory frequency, which can also be called synchrony or field coherence. We will generally use resonance and “sync,” short for synchrony, interchangeably in this paper. We describe the approach as a general resonance theory of consciousness or just “general resonance theory” (GRT). GRT is a field theory of consciousness wherein the various specific fields associated with matter and energy are the seat of conscious awareness.  A summary of our approach appears in Appendix 1.  All things in our universe are constantly in motion, in process. Even objects that appear to be stationary are in fact vibrating, oscillating, resonating, at specific frequencies. So all things are actually processes. Resonance is a specific type of motion, characterized by synchronized oscillation between two states.  An interesting phenomenon occurs when different vibrating processes come into proximity: they will often start vibrating together at the same frequency. They “sync up,” sometimes in ways that can seem mysterious, and allow for richer and faster information and energy flows (Figure 1 offers a schematic). Examining this phenomenon leads to potentially deep insights about the nature of consciousness in both the human/mammalian context but also at a deeper ontological level.

Susanne Schilling*^

and 9 more

Jessica mead

and 6 more

The construct of wellbeing has been criticised as a neoliberal construction of western individualism that ignores wider systemic issues including increasing burden of chronic disease, widening inequality, concerns over environmental degradation and anthropogenic climate change. While these criticisms overlook recent developments, there remains a need for biopsychosocial models that extend theoretical grounding beyond individual wellbeing, incorporating overlapping contextual issues relating to community and environment. Our first GENIAL model \cite{Kemp_2017} provided a more expansive view of pathways to longevity in the context of individual health and wellbeing, emphasising bidirectional links to positive social ties and the impact of sociocultural factors. In this paper, we build on these ideas and propose GENIAL 2.0, focusing on intersecting individual-community-environmental contributions to health and wellbeing, and laying an evidence-based, theoretical framework on which future research and innovative therapeutic innovations could be based. We suggest that our transdisciplinary model of wellbeing - focusing on individual, community and environmental contributions to personal wellbeing - will help to move the research field forward. In reconceptualising wellbeing, GENIAL 2.0 bridges the gap between psychological science and population health health systems, and presents opportunities for enhancing the health and wellbeing of people living with chronic conditions. Implications for future generations including the very survival of our species are discussed.  

Mark Ferris

and 14 more

IntroductionConsistent with World Health Organization (WHO) advice [1], UK Infection Protection Control guidance recommends that healthcare workers (HCWs) caring for patients with coronavirus disease 2019 (COVID-19) should use fluid resistant surgical masks type IIR (FRSMs) as respiratory protective equipment (RPE), unless aerosol generating procedures (AGPs) are being undertaken or are likely, when a filtering face piece 3 (FFP3) respirator should be used [2]. In a recent update, an FFP3 respirator is recommended if “an unacceptable risk of transmission remains following rigorous application of the hierarchy of control” [3]. Conversely, guidance from the Centers for Disease Control and Prevention (CDC) recommends that HCWs caring for patients with COVID-19 should use an N95 or higher level respirator [4]. WHO guidance suggests that a respirator, such as FFP3, may be used for HCWs in the absence of AGPs if availability or cost is not an issue [1].A recent systematic review undertaken for PHE concluded that: “patients with SARS-CoV-2 infection who are breathing, talking or coughing generate both respiratory droplets and aerosols, but FRSM (and where required, eye protection) are considered to provide adequate staff protection” [5]. Nevertheless, FFP3 respirators are more effective in preventing aerosol transmission than FRSMs, and observational data suggests that they may improve protection for HCWs [6]. It has therefore been suggested that respirators should be considered as a means of affording the best available protection [7], and some organisations have decided to provide FFP3 (or equivalent) respirators to HCWs caring for COVID-19 patients, despite a lack of mandate from local or national guidelines [8].Data from the HCW testing programme at Cambridge University Hospitals NHS Foundation Trust (CUHNFT) during the first wave of the UK severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic indicated a higher incidence of infection amongst HCWs caring for patients with COVID-19, compared with those who did not [9]. Subsequent studies have confirmed this observation [10, 11]. This disparity persisted at CUHNFT in December 2020, despite control measures consistent with PHE guidance and audits indicating good compliance. The CUHNFT infection control committee therefore implemented a change of RPE for staff on “red” (COVID-19) wards from FRSMs to FFP3 respirators. In this study, we analyse the incidence of SARS-CoV-2 infection in HCWs before and after this transition.

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Aim: To investigate the prevalence of depressive symptoms among adults living in the UAE during the COVID-19 pandemic. Methods: This cross-sectional study used a self-administered anonymous online questionnaire distributed in both Arabic and English via social media platforms. A total of 261 adults living in the UAE were included in the study. Patients clinically diagnosed with depression were excluded from this study. Results: Overall, the prevalence of depression among our studied population was 63%. Several parameters were correlated with depression to assess their associations. A lower household income was found to be linked to a greater likelihood of developing depression, as 74.6% of depressed subjects had an income lower than 20,000 Dhs (p=0.003). Age also had a significant correlation[](https://d.docs.live.net/c230006d1f964528/%D8%B3%D8%B7%D8%AD%20%D8%A7%D9%84%D9%85%D9%83%D8%AA%D8%A8/Covid-19%20and%20depression%20-%20second%20draft%20-%20AK%20comments%5b1%5d.docx)(95% CI, p=0.003) with depression, and those in the younger age group (18-25 years) had a greater prevalence of depression than did those in the older age group. Difficulty performing daily activities, restless sleep, feeling lonely, feeling sad, feeling inadequate, and losing hope were the most commonly reported symptoms in depressed subjects. A total of 78.21% of our participants did not know about hotlines when they were depressed; however, this difference was not statistically significant (95% CI, p=0.178). Conclusions: Depression was prevalent in 63% of our participants. A lower household income and younger age were associated with a greater risk of depression. We believe that our findings will encourage institutions and government authorities to implement awareness programs about depression awareness and screening for depression.

Sandra Marman

and 1 more

This study investigates grapheme encoding in Croatian as a second language among Farsi speakers after twenty hours of learning. Three phases of encoding tasks were administered: 1) dictation of individual phonemes, 2) dictation of words beginning with those phonemes, and 3) dictation of simple sentences with words from the previous phase. Respondents used "-" to denote unencoded items. Eleven Afghan respondents at the beginner level (A1 according to CEFRL), aged 18 to 63, were sampled conveniently. The study aims to assess: a) accuracy in encoding individual graphemes and words, b) problematic graphemes, and c) accuracy in encoding complete words. The results will illuminate initial decoding specifics for this group, confronting the added complexity of differing graphic systems between L1 and L2. Furthermore, implications for Croatian orthography acquisition as L2 will be discussed. Analysis of encoding by Farsi-speaking Croatian learners showed overall success with sentences but difficulty with individual graphemes, possibly due to reliance on lexical rather than phonological knowledge. Notably, struggles were observed with "nj," unlike with "c" as seen previously. This might be because "nj" is less common in Croatian, especially early on. Transfer errors from Farsi, like omitting short vowels, were evident. Instruction for Farsi learners should focus on specific grapheme errors such as "nj," "ć," "dž," and "đ," as well as consonant clusters and short vowel encoding in Croatian.

Eben Gering

and 7 more

Recent work indicates that feralisation is not a simple reversal of domestication, and therefore raises questions about the predictability of evolution across replicated feral populations. In the present study we compare genes and traits of two independently established feral populations of chickens (G. gallus) that inhabit archipelagos within the Pacific and Atlantic regions to test for evolutionary parallelism and/or divergence. We find that these two feral populations share close genetic similarities despite the lack of any current gene flow between them. Next, we used genome scans to contrast the targets of feralisation (selective sweeps) between the two independently feral populations from Bermuda and Hawaii. Three sweep loci (each identified by multiple detection methods) were shared between feral populations, and this overlap is inconsistent with a null model in which selection targets are randomly distributed throughout the genome. In the case of the Bermudian population, many of the genes present within the selective sweeps were either not annotated or of unknown function. Of the nine genes that were identifiable, five were related to behaviour, with the remaining genes involved in bone metabolism, eye development, and the immune system. Our findings suggest that a subset of feralisation loci (i.e. genomic targets of recent selection in feral populations) are shared across independently-established populations, raising the possibility that feralisation involves some degree of parallelism or convergence. A clearer understanding of whether these reflect selection for similar functional traits (‘feralisation syndromes’) will require elucidating genotype-phenotype relationships in any populations being compared.

Gonca BURAN

and 1 more

Objective To examine the effect of pregnancy pilates-assisted birth preparation training on urinary incontinence UI including during pregnancy, and the postpartum period and birth outcomes. Design The randomized controlled experimental study Setting Gynecology and Pregnancy Education Counseling Center Population Nulliparous pregnant women (n=126) at 28-30 weeks of gestation Method The was carried out between March and August 2022. Participants were divided into two groups by a simple random sampling method. Intervention was applied twice in a week, a total of eight weeks to pilates group. The control group was given routine obstetric and pregnancy care. A personal data form and the M-ISI were used as data collection tools. The data obtained were analyzed using the program SPSS 20. Main outcome measures A moderate-intensity prenatal pilates exercise program reduces the severity of UI symptoms during pregnancy and the early postpartum period. Results The mean weight gains of women who participated to the experimental group during pregnancy was significantly lower than the control group. While 80.6% of women who received pilates-assisted childbirth preparation training gave birth vaginally, this rate in the control group was 54.2%. The duration of labor mean score of pilates group was five hours and 43 minutes less than the duration of labor of the control group. After intervention, and postpartum period, the SUI severity of the experimental group was significantly lower than that of the control group. Conclusion Pilates-assisted childbirth preparation training reduced the severity of UI symptoms during pregnancy and the early postpartum. In addition, the decrease in weight gain during pregnancy and the increase in the vaginal birth rate contributed to the shortening of the duration of labor.

Raúl Araya-Donoso

and 4 more

The term psychopathology is composed of two terms: psyche, from the Greek psychè, meaning soul, "something more or less dematerialised that represents one of the vital functions of man". Pathology, on the other hand, is made up of two terms: "pato", which comes from the Greek and means suffering, and "logia", which comes from the Latin. Its meaning is commonly recognised as "word/speech", but its meaning is "sense" or "meaning". Thus, the term pathology is intended to give voice to human suffering by understanding what may be "morbid" mental processes in relation to some basic aspects: 1) Symptomatology 2) Classification and nosology 3) Causes 4) Mechanisms Symptoms must meet certain characteristics necessary to define whether the condition is transient or persistent. The characteristics to which the symptoms must respond are 1) Persistence 2) Frequency 3) distress 4) Distinction from "normality" 5) Specificity (symptoms that can be attributed to a specific disease) 6) Aspecificity (symptoms that may not be specific to one disease, but to more than one). In this case we use the term comorbidity. A set of symptoms defines a pathological syndrome that is to be classified, which is why we speak of nosology (nosos: "disease" and logos: "meaning"). The study of symptoms allows us to make a diagnosis and distinguish it from other disorders (differential diagnosis). In relation to their causes, we speak of etiology, another term derived from the Greek meaning "cause". It is important not to confuse etiology with pathogenesis, the mechanisms by which a disease develops. Unlike physical illness, where there is a clear boundary between normality and disorder, there is no such clear and sharp boundary in psychology. A given disorder is not necessarily psychopathological, but depends on its frequency and intensity. It is therefore necessary to take account of reference models: optimal models or elementary statistical principles, established a priori and present in a percentage of the population. It is essential to take into account the persistence of the disorder over time, the age of the person who comes to us and the sex. It is also necessary to take into account the context in which the person lives (family and social environment). Dysfunctional social factors can produce a cumulative risk score which, when it exceeds a certain threshold, will lead to a problem. This may be the case in families with conflict, instability, dysfunctional behaviour, but also with difficulties related to inclusion in the social network (e.g. children of one or both parents with disabilities, families where there is abuse).The term "developmental psychopathology" refers to a scientific discipline that originated in the United States. In Italy, the term is used in a broader sense, but it identifies a very precise field of study that is spreading in the rest of Europe and also in Italy. Developmental psychopathology is a scientific discipline whose aim is to clarify how the interaction between biological, psychological, social and environmental aspects can determine normal and abnormal development throughout life and, by moving precisely on the boundary of the interaction between normal and pathological, it provides, through this constant comparison, the theoretical framework for the prevention and intervention of psychopathological disorders.This scientific field has the merit of bringing together different disciplines, such as psychiatry, clinical psychology and psychopathology, and has succeeded in creating new scientific knowledge, as well as contributing to the expansion of our knowledge. Developmental psychopathology believes that there is a specific developmental path for each individual, from which it follows that each traumatic experience will have specific effects that depend on personal vulnerability, which cannot be predicted. It therefore emphasises the importance of assessing the individual, their uniqueness and their developmental path. One of the paradigms of this discipline is the relational perspective of adjustment, according to which if there are psychological disorders, there will also be relational disorders. The latter are not considered risk factors, but real precursors of individual psychopathology. Theoretically, this research is based on Bowlby's studies. For the moment, it is important to know that it is the conceptual pillar through which developmental psychopathology points out that relational problems cannot be identified only as problems of the child, but must always be considered as problems of the child and his or her environment, which does not provide the necessary adjustment experience to adapt to the context. Developmental psychopathology succeeds in providing a very broad and articulate view of psychopathological disorders, such as autism spectrum disorders, which represent the dysfunction of the relational system par excellence, but emphasises that children with the same diagnosis may show enormous differences among themselves, just as children with different diagnoses may show very similar profiles.

Alex George

and 5 more

Objective: To delineate the natural history of splenic complications other than the loss of splenic function in children with sickle cell disease (SCD), we performed a retrospective chart review of patients with SCD treated at the Texas Children’s Hospital. Methods: We determined the dates of diagnoses of splenic complications, the number of ASSC events, and hydroxyurea treatment in patients with SCD. We also examined the association of hydroxyurea therapy with the onset and severity of ASSC. Results: The cumulative prevalence of splenic complications was 24.7% for splenomegaly, 24.2% for ASSC, 9.6% for hypersplenism, and 5.6% for splenectomy. The cumulative prevalence of all splenic complications was highest in patients with hemoglobin Sβ 0 (69.2%), intermediate in hemoglobin SS (33.3%), low in hemoglobin SC (9.0%), and non-existent in hemoglobin Sβ +. The overall event-rate of ASSC was 8.3 per hundred patient-years. The event-rate was 28.4 in the hemoglobin Sβ 0, 10.9 in hemoglobin SS, and 3.5 in hemoglobin SC Patients with hemoglobin SS and hemoglobin Sβ 0 on hydroxyurea therapy had a significantly higher occurrence of ASSC than those who were not, with event-rates of 14.2 and 3.1, respectively. The event-rate was also higher for children who started hydroxyurea before age 2 years than for those who started after this age (19.8 and 9.2 respectively). Conclusions: The prevalence and severity of splenic problems vary widely between different sickle cell genotypes, with hemoglobin Sβ 0 having the most severe complications. Hydroxyurea therapy is strongly associated with incidence of ASSC, particularly when initiated before two years of age.

Pablo Lohmann

and 2 more

A breath of fresh air: Does spontaneous breathing and early repair in neonates with very mild congenital diaphragmatic hernia lead to earlier discharge? Dear Editor:We read with great interest the article by Kipfmueller et al. that investigated the feasibility and outcomes of a spontaneous breathing approach (SBA) versus immediate intubation in neonates with prenatally diagnosed very mild CDH and found that it appears to be feasible and beneficial1. The authors present an approach that is quite novel - spontaneous breathing and enteral feeding in the pre-surgical repair phase. We compliment the authors for their attempt to address an issue very relevant to the acute management of CDH. Nonetheless, we feel compelled to highlight some aspects that should be considered for adequate interpretation of their findings.The study’s sample size is quite small (n=24), but the fact that the investigators found statistical significance for numerous associations despite such a small sample size demonstrates the strength of the relationships.  It is a common misconception that statistical significance due to chance (i.e., Type I error) is more likely when the sample size is small, although low power due to the small sample size is actually difficult to overcome2. However, when evaluating Table 1, after matching on observed-to-expected lung-to-head-ratio (o/e LHR), liver position, gestational age at delivery, birth weight, and defect size, we note that prerepair characteristics such as early feeding, Oxygenation Index (OI) and FiO2, and Apgar at 10min are still significantly imbalanced between the SBA and standard treatment groups, which raises concerns about potential confounding. For this reason, we recommend the authors complement the unadjusted analyses they report with multivariable regression analyses that compare SBA versus standard treatment after controlling for Apgar 10, OI and FiO2, although the study sample size of n=24 would typically be considered too small for this kind of multivariable regression analysis. Per the authors, 39 patients met their prenatal eligibility criteria. A better and more meaningful comparison of outcomes would be to compare the 8 patients that underwent SBA versus the remaining 31 patient that met their predetermined ’eligibility criteria’ and did not undergo planed SBA. Using this approach would diminish the potential differences in cohort caused by severity of hernia defect, given the fact that some patients in the standard treatment group required patch repair. In the study, the authors incorporated the post natally determined CDH defect size into the matching process; we would advise against using defect size for matching as it cannot be replicated prospectively.The authors utilized the Mann-Whitney U test and Fisher’s exact test to compare the SBA versus standard treatment groups in terms of quantitative and categorical variables, respectively.  These methods ignore the dependence structure in the data resulting from matching. Although this type of oversight is common, we would recommend analyzing the data differently. Utilizing mixed-effects linear models and generalized estimating equations for quantitative and categorical outcomes, respectively, would appropriately accommodate the clustering of study patients due to matching.We were impressed by the decision to initiate enteral feeding prior to surgery and wonder if this approach could be a gut priming strategy favoring outcomes beyond the need for parenteral nutrition3. However, while novel and potentially beneficial, this strategy carries with it risks and will need to be investigated further before others will choose to adopt such a practice.Overall, the authors tackle an important subject and their findings raise questions on whether routine intubation is beneficial for infants with mild CDH. As SBA infants were compared to those with more severe hernias, the observed differences noted between groups are likely a reflection of the severity of lung hypoplasia and not a result of the intervention. We encourage the authors to further explore this strategy with a larger multicenter study to draw meaningful conclusions from the study results.Clinicians should be cautious of implementing guideline changes based on retrospective studies, as prospective studies do not always validate inferences derived from retrospectives studies, such as permissive hypercapnia to prevent bronchopulmonary dysplasia in extremely low birth weight infants (ELBW)4. Centers that perform early repair could consider an SBA approach for a well-defined cohort of infants with mild CDH, as it appears this can decrease the duration of ventilation and length of hospital stay. However, this precision-based medicine approach would be best evaluated by a prospective study to assess the benefits and risks of implementing this strategy.1. Kipfmueller F, Leyens J, Pugnaloni F, et al. Spontaneous breathing in selected neonates with very mild congenital diaphragmatic hernia.Pediatr Pulmonol. 2024;59(3):617-624.2. Jones SR, Carley S, Harrison M. An introduction to power and sample size estimation. Emerg Med J. 2003;20(5):453-458.3. Ratsika A, Codagnone MC, O’Mahony S, Stanton C, Cryan JF. Priming for Life: Early Life Nutrition and the Microbiota-Gut-Brain Axis.Nutrients. 2021;13(2):423.4. Thome UH, Genzel-Boroviczeny O, Bohnhorst B, et al. Neurodevelopmental outcomes of extremely low birthweight infants randomised to different PCO(2) targets: the PHELBI follow-up study.Arch Dis Child Fetal Neonatal Ed. 2017;102(5):F376-F382.The authors have disclosed no conflicts of interest.

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Karma Norbu

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Introduction: Scrub typhus is a neglected life threatening acute febrile illness caused by bacteria Orientia tsutsugamushi and it is a vector-borne zoonotic disease. In 2009, scrub typhus outbreak at Gedu has awakened Bhutan on the awareness and testing of the disease.Information and data of the study highlights the need for in depth surveillance, awareness among prescribers and initiate preventive measures in the country. Methods: We used retrospective descriptive study through review of laboratory registers across three health centres in Zhemgang district, south central Bhutan. The laboratories registers have been transcribed into CSV file using Microsoft excel. Variables of interest were collected from the registers and then analysed using open statistical software R, (R Core Team (2020). R: A language and environment for statistical computing. R Foundation for Statistical Computing, Vienna, Austria.) And use of mStats package, (MyoMinnOo (2020). mStats: Epidemiological DataAnalysis. R package version 3.4.0.) Results: Of the total 922 tests prescribed for suspected scrub typhus in the three health centers in Zhemgang, only 8.2 % (n=76) were tested positive. Of these, Panbang Hospital had highest reported positive for scrub typhus with 56.6 %( n=43) followed by Yebilaptsa Hospital 35.5 %( n=27) and Zhemgang Hospital with 7.9 %( n=6). The female gender is comparably more affected as opposed to male with 57.9% (n=44) of the positive cases being female. The prevalence of scrub typhus seems to be affected by the seasonal variation as the months of Spring, Summer and Autumn together accounts for 98.7%(n=75) of total positive cases. The year 2019 noted significant scrub typhus cases accounting to 89.5 %(n=68) of the total positive cases over the two years. Conclusions:The overall tests tested positive of the scrub typhus infection within two years was 8.2%.

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