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Introduction: Early-onset neonatal sepsis (EONS) significantly impacts neonatal morbidity and mortality, with maternal bacteremia during the peripartum period being a potential risk factor. This study aims to explore the association between peripartum maternal bacteremia and EONS., Methods: A retrospective cohort study at the Women's Wellness and Research Center in Doha, Qatar (2015-2019) compared women with and without bacteremia, based on blood cultures taken from up to seven days before to 48 h after delivery, examining the association with EONS., Results: Among the 536 maternal blood cultures analyzed, 102 (19.0%) were positive. The most prevalent organisms were Group B streptococcus (GBS) (39.2%), followed by Escherichia coli (14.7%) and anaerobes (10.8%). Neonates from bacteremic mothers had lower birth weights (2913 ± 86 g vs. 3140 ± 745 g; MD 227.63 g; 95% CI 61.72 - 393.55; p = 0.007), required more resuscitation (27.5% vs. 13.2%; OR 2.48; 95% CI 1.48 - 4.17; p < 0.001), and received antibiotics for ≥ 7 days more frequently (41.2% vs. 16.6%; OR 3.51; 95% CI 2.20 - 5.62; p < 0.001) compared to those from non-bacteremic mothers. Maternal Gram-positive (GP) organisms were more commonly isolated in term gestation (67.9%) compared to Gram-negative (GN) (22.2%) and anaerobic bacteremias (9.9%). During intrapartum, GP bacteremia was predominant (67.1%) vs. GN (21.4%) and Anaerobes (11.4%), with GN bacteremia being more common in postpartum samples. Culture-proven EONS occurred in 0.75% of the cohort, affecting 3.9% of infants from bacteremic mothers vs. none in controls (OR 2.34; 95% CI 1.27 - 4.31; p < 0.001). Culture-negative EONS appeared in 14.7% of infants from bacteremic mothers vs. 7.8% in controls (OR 2.02; 95% CI, 1.05 - 3.88; p = 0.03). Among 40 cases of maternal GBS bacteremia, culture-proven GBS EONS occurred in 3 neonates (7.5%), all from mothers with negative GBS screening, compared to none in the control group. A strong association was found between EONS and maternal bacteremia due to any organism (aOR 2.34; 95% CI, 1.24 - 4.41; p = 0.009), GP bacteremia (aOR 3.66; 95% CI, 1.82 - 7.34; p < 0.001), or GBS (aOR 5.74; 95% CI, 2.57 - 12.81; p < 0.001). Bacteremia due to GN and Anaerobic organisms were not associated with EONS. Chorioamnionitis and antepartum fever were independent predictors for EONS associated with significant bacterial isolates., Conclusion: This study underscores the significant impact of maternal GP bacteremia, particularly from GBS, on EONS. The strong association highlights the need for vigilant monitoring and interventions in pregnancies complicated by bacteremia to reduce adverse neonatal outcomes., (© 2024. The Author(s).)

Introduction: The present study evaluated the psychometric properties of the Arabic translation of the Mukbang Addiction Scale (MAS) among Arabic-speaking adults from the general population. Specifically, it aimed to assess the factorial structure through a confirmatory factor analysis, determine the composite reliability through Cronbach alpha and McDonald's omega scores, assess gender invariance, and evaluate the convergent validity by examining its correlation to eating addiction and psychological distress., Methods: A total of 370 individuals with a mean age of 21.94 ± 2.29 years participated in this study, which was conducted using an online platform. The participants were surveyed on demographic information, mukbang addiction, food addiction, and psychological distress. Translation was conducted using the forward and backward technique., Results: The findings demonstrated excellent internal consistency of the Arabic MAS (McDonald's omega coefficient = 0.93). Confirmatory factor analyses validated the one-factor structure of the scale, while establishing measurement invariance across sex at the configural, metric, and scalar levels. No sex differences were observed in the Mukbang addiction levels. Lastly, the MAS scores were significantly and positively correlated with food addiction and psychological distress, supporting their convergent validity., Conclusion: The current research provides evidence supporting the reliability and validity of the Arabic version of the MAS as a self-report method for assessing addictive Mukbang watching. While further validations are needed to corroborate the present findings, this measure can be effectively utilized across different fields, including schools, mental health centers, and researchers aiming to understand this global phenomenon. Mukbang refers to individuals or hosts consuming large quantities of food while interacting with their audiences through recorded video or a live stream. The Mukbang phenomenon has gained substantial popularity among young individuals over the past years, rising concerns about its potential impact on their eating habits and health, especially when overconsumed. Overconsumption of mukbang content, or Mukbang addiction, aligns with the core features of addiction, including compulsive engagement, tolerance, and withdrawal symptoms, making it comparable to other addictive behaviors. Mukbang addiction can lead to detrimental effects on mental and physical health, including neglect of balanced nutrition, disordered eating habits, obesity, feelings of guilt, shame, poor self-esteem, distorted self-images, body dissatisfaction, heightened anxiety or depression, and social isolation. Given these significant impacts, valid and reliable tools are crucial to enable an accurate assessment of Mukbang addiction. This study proposes to translate, adapt and examine the psychometric properties of the Mukbang Addiction Scale (MAS) in a sample of Arabic-speaking individuals from the general population. Findings showed that the six MAS items loaded on a single factor with strong internal consistency and good convergent validity, preliminarily indicating its potential validity and reliability for assessing addictive mukbang-watching among Arabic-speaking individuals., (© 2024. The Author(s).)

Background: The most common cause of revision arthroplasty is prosthetic joint infection (PJI). Chronic PJI is commonly treated with two-stage exchange arthroplasty involving the placement of antibiotic-laden cement spacers (ACS) in the first stage, often containing nephrotoxic antibiotics. These patients often have significant comorbidity burdens and have higher rates of acute kidney injury (AKI). This systematic review aims to assess the current literature to identify (1) AKI incidence, (2) associated risk factors, and (3) antibiotic concentration thresholds in ACS that increase AKI risk following first-stage revision arthroplasty., Methods: An electronic search was performed of the PubMed database of all studies involving patients undergoing ACS placement for chronic PJI. Studies assessing AKI rates and risk factors were screened by two authors independently. Data synthesis was performed when possible. Significant heterogeneity prevented meta-analysis., Results: Eight observational studies consisting of 540 knee PJIs and 943 hip PJIs met inclusion criteria. There were 309 (21%) cases involving AKI. The most commonly reported risk factors included perfusion-related factors (lower preoperative hemoglobin, transfusion requirement, or hypovolemia), older age, increased comorbidity burden, and nonsteroidal anti-inflammatory drug consumption. Only two studies found increased risk with greater ACS antibiotic concentration (> 4 g vancomycin and > 4.8 g tobramycin per spacer in one study, > 3.6 g of vancomycin per batch or > 3.6 g of aminoglycosides per batch in the other); however, these were reported from univariate analyses not accounting for other potential risk factors., Discussion: Patients undergoing ACS placement for chronic PJI are at an increased risk for AKI. Understanding the risk factors may lead to better multidisciplinary care and safer outcomes for chronic PJI patients., (© 2023. The Author(s).)

Background and Objectives: Children with medical complexity have been disproportionately impacted by the COVID-19 pandemic and the associated changes in healthcare delivery. The primary objective of this study was to gain a thorough understanding of the lived experiences of family caregivers of children with medical complexity during the pandemic., Methods: We conducted semi-structured interviews with family caregivers of children with medical complexity from a tertiary pediatric hospital. Interview questions focused on the aspects of caregiving for children with medical complexity, impact on caregiver mental and physical well-being, changes to daily life secondary to the pandemic, and experiences receiving care in the healthcare system. Interviews were conducted until thematic saturation was achieved. Interviews were audio recorded, deidentified, transcribed verbatim, coded and analyzed using content analysis., Results: Twelve semi-structured interviews were conducted. The interviews revealed three major themes and several associated subthemes: (1) experiences with the healthcare system amid the pandemic (lack of access to healthcare services and increased hospital restrictions, negative clinical interactions and communication breakdowns, virtual care use); (2) common challenges during the pandemic (financial strain, balancing multiple roles, inadequate homecare nursing); and (3) the pandemic's impact on family caregiver well-being (mental toll, physical toll)., Conclusions: Family caregivers of children with medical complexity experienced mental and physical burden due to the intense nature of their caregiving responsibilities that were exacerbated during the pandemic. Our results highlight key priorities for the development of effective interventions to support family caregivers and their children., (© 2023. The Author(s).)

Background: Universal screening for neonatal hyperbilirubinemia risk assessment is recommended by the American Academy of Pediatrics to reduce related morbidity. In Bangladesh and in many low- and middle-income countries, there is no screening for neonatal hyperbilirubinemia. Furthermore, neonatal hyperbilirubinemia may not be recognized as a medically significant condition by caregivers and community members. We aimed to evaluate the acceptability and operational feasibility of community health worker (CHW)-led, home-based, non-invasive neonatal hyperbilirubinemia screening using a transcutaneous bilimeter in Shakhipur, a rural subdistrict in Bangladesh., Methods: We employed a two-step process. In the formative phase, we conducted eight focus group discussions with parents and grandparents of infants and eight key informant interviews with public and private healthcare providers and managers to explore their current knowledge, perceptions, practices, and challenges regarding identification and management of neonatal hyperbilirubinemia. Next, we piloted a prenatal sensitization intervention and home-based screening by CHWs using transcutaneous bilimeters and evaluated the acceptability and operational feasibility of this approach through focus group discussions and key informant interviews with parents, grandparents and CHWs., Results: Formative findings identified misconceptions regarding neonatal hyperbilirubinemia causes and health risks among caregivers in rural Bangladesh. CHWs were comfortable with adoption, maintenance and use of the device in routine home visits. Transcutaneous bilimeter-based screening was also widely accepted by caregivers and family members due to its noninvasive technique and immediate display of findings at home. Prenatal sensitization of caregivers and family members helped to create a supportive environment in the family and empowered mothers as primary caregivers., Conclusion: Adopting household neonatal hyperbilirubinemia screening in the postnatal period by CHWs using a transcutaneous bilimeter is an acceptable approach by both CHWs and families and may increase rates of screening to prevent morbidity and mortality., (© 2023. The Author(s).)

Background: This study was conducted with the intension of providing a more detailed view about the dynamics of COVID-19 pandemic. To this aim, characteristics, implemented public health measures, and health outcome of COVID-19 patients during five consecutive waves of the disease were assessed., Methods: This study was a population-based cross-sectional analysis of data on adult patients who were diagnosed with COVID-19 during five waves of the disease in Iran. Chi-squared test, One-way ANOVA, and Logistic Regression analysis were applied. A detailed literature review on implemented public health policies was performed by studying published documents and official websites responsible for conveying information about COVID-19., Results: Data on 328,410 adult patients was analyzed. Main findings indicated that the probability of dying with COVID-19 has increased as the pandemic wore on, showing its highest odd during the third wave (odds ratio: 1.34, CI: 1.283-1.395) and has gradually decreased during the next two waves. The same pattern was observed in the proportion of patients requiring ICU admission (P < 0.001). First wave presented mainly with respiratory symptoms, gastrointestinal complaints were added during the second wave, neurological manifestations with peripheral involvement replaced the gastrointestinal complaints during the third wave, and central nervous system manifestations were added during the fourth and fifth waves. A significant difference in mean age of patients was revealed between the five waves (P < 0.001). Moreover, results showed a significant difference between men and women infected with COVID-19, with men having higher rates of the disease at the beginning. However, as the pandemic progressed the proportion of women gradually increased, and ultimately more women were diagnosed with COVID-19 during the fifth wave. Our observations pointed to the probability that complete lockdowns were the key measures that helped to mitigate the virus spread during the first twenty months of the pandemic in the country., Conclusion: A changing pattern in demographic characteristics, clinical manifestations, and severity of the disease has been revealed as the pandemic unfolded. Reviewing COVID-19-related public health interventions highlighted the importance of immunization and early implementation of restrictive measures as effective strategies for reducing the acute burden of the disease., (© 2022. The Author(s).)

Background: It remains crucial to understand socio-demographic determinants of COVID-19 infection to improve access to care and recovery rates from the disease. This study aimed to investigate the urban and sub-urban disparities associated with COVID-19 in patients visiting healthcare facilities in the province of Tehran, Iran., Methods: Data from 234 418 patients who were diagnosed with COVID-19 infection from March 2020 to March 2021 in the province of Tehran were used in this analysis. Descriptive statistics were used to describe the characteristics of the study population. Chi-Squared test was applied to examine the association of study variables with residing area. Independent samples t-test was performed to compare mean age of patients in urban and sub-urban areas. Multiple Logistic Regression model was applied to examine the association of study variables with disease outcome., Results: Overall, most patients resided in the urban settings (73%). Mean age of patients was significantly lower in sub-urban areas compared to their counterparts in urban settings (49 ± 23.1 years versus 53 ± 21.1 years, P < 0.001). Positive PCR test results were more common in urban areas (48.5% versus 41.3%, P < 0.001). Yet, sub-urban settings had higher rates of positive chest CT scan reports (62.8% versus 53.4%, P < 0.001). After accounting for age and sex covariates, residing in urban areas was associated with higher likelihood of being admitted to an ICU (OR = 1.27, CI: 1.240-1.305). Yet, a greater vulnerability to fatal outcome of COVID-19 infection was shown in patients living in sub-urban areas (OR = 1.13, CI: 1.105-1.175)., Conclusions: This study revealed a clear disparity in the health outcome of patients infected with COVID-19 between urban and sub-urban areas., (© 2022. The Author(s).)

Background: Studies in the literature have found mixed results on the effect of microcredit on health outcomes. Of the five previous experimental studies that included microcredit and a health intervention, three reported no significant changes in health status or behaviors. The purpose of this study was to test for marginal and interactive effects of increased microcredit and provision of basic health services., Methods: This study had a 4-celled experimental design in 128 villages in rural Bangladesh. For villages in one cell, an additional microcredit worker was assigned. For those in a second cell, a health assistant visited households each month, provided simple medicines and announced a satellite clinic held monthly in each village. For a third cell, both interventions were combined, and villages in a fourth cell served as control. A baseline survey was completed and a follow-up survey was done three years later. Outcome measures were food security, contraceptive use, having a trained birth attendant at last birth, and measles immunization., Results: Comparison of follow-up with baseline levels of the four outcome measures (for 3787 households (96% completeness) and 3687 women (94% completeness)) showed significant improvement in food security in all study arms and a significant increase in trained birth attendant at last birth in the health services villages. Due to confusion within Grameen Bank about which workers would provide the additional microcredit work, that intervention was poorly implemented so in multivariate analyses, the data for that intervention arm were grouped with data from the control arm. Logistic regression with values of the outcomes at follow-up as dependent variable and study arm and women's schooling as covariates showed no significant effects of either separate or grouped study arms., Conclusion: Two of the three health behaviors showed no significant changes over time but having a trained birth attendant at last delivery did increase significantly in the health services arm. Therefore, community health education can sometimes be effective in promoting healthy behaviors., Trial Registration: This was a field trial rather than a clinical trial, so trial registration was unnecessary., (© 2022. The Author(s).)

Background Overview and Rationale: We co-developed a multi-component virtual care solution (TtLIVE) for the home mechanical ventilation (HMV) population using the aTouchAway™ platform (Aetonix). The TtLIVE intervention includes (1) virtual home visits; (2) customizable care plans; (3) clinical workflows that incorporate reminders, completion of symptom profiles, and tele-monitoring; and (4) digitally secure communication via messaging, audio, and video calls; (5) Resource library including print and audiovisual material., Objectives and Brief Methods: Our primary objective is to evaluate the TtLIVE intervention compared to a usual care control group using an eight-center, pragmatic, parallel-group single-blind (outcome assessors) randomized controlled trial. Eligible patients are children and adults newly transitioning to HMV in Ontario, Canada. Our target sample size is 440 participants (220 each arm). Our co-primary outcomes are a number of emergency department (ED) visits in the 12 months after randomization and change in family caregiver (FC) reported Pearlin Mastery Scale score from baseline to 12 months. Secondary outcomes also measured in the 12 months post randomization include healthcare utilization measured using a hybrid Ambulatory Home Care Record (AHCR-hybrid), FC burden using the Zarit Burden Interview, and health-related quality of life using the EQ-5D. In addition, we will conduct a cost-utility analysis over a 1-year time horizon and measure process outcomes including healthcare provider time using the Care Coordination Measurement Tool. We will use qualitative interviews in a subset of study participants to understand acceptability, barriers, and facilitators to the TtLIVE intervention. We will administer the Family Experiences with Care Coordination (FECC) to interview participants. We will use Poisson regression for a number of ED visits at 12 months. We will use linear regression for the Pearlin Mastery scale score at 12 months. We will adjust for the baseline score to estimate the effect of the intervention on the primary outcomes. Analysis of secondary outcomes will employ regression, causal, and linear mixed modeling. Primary analysis will follow intention-to-treat principles. We have Research Ethics Board approval from SickKids, Children's Hospital Eastern Ontario, McMaster Children's Hospital, Children's Hospital-London Health Sciences, Sunnybrook Hospital, London Health Sciences, West Park Healthcare Centre, and Ottawa Hospital., Discussion: This pragmatic randomized controlled single-blind trial will determine the effectiveness and cost-effectiveness of the TtLIVE virtual care solution compared to usual care while providing important data on patient and family experience, as well as process measures such as healthcare provider time to deliver the intervention., Trial Registration: ClinicalTrials.gov NCT04180722 . Registered on November 27, 2019., (© 2022. The Author(s).)

Follicular lymphoma (FL) is a B-cell non-Hodgkin lymphoma of germinal center (GC) origin with a distinctive tumor microenvironment (TME) and a unique spectrum of mutations. Despite the important therapeutic advances, FL is still incurable. During B-cell development, the GC reaction is a complex multistep process in which epigenetic regulators dynamically induce or suppress transcriptional programs. In FL, epigenetic gene mutations perturb the regulation of these programs, changing GC B-cell function and skewing differentiation towards tumor cells and altering the microenvironment interactions. FL pathogenesis and malignant transformation are promoted by epigenetic reprogramming of GC B cells that alters the immunological synapse and niche. Despite the extensive characterization of FL epigenetic signature and TME, the functional consequences of epigenetic dysregulation on TME and niche plasticity need to be better characterized. In this review, first we describe the most frequent epigenomic alterations in FL (KMT2D, CREBBP and EZH2) that affect the immunological niche, and their potential consequences on the informational transfer between tumor B cells and their microenvironment. Then, we discuss the latest progress to harness epigenetic targets for inhibiting the FL microenvironment. Finally, we highlight unexplored research areas and outstanding questions that should be considered for a successful long-term treatment of FL., (© 2022. The Author(s).)

Background: Idiopathic pulmonary fibrosis (IPF) is one of the common types of interstitial lung disease having high prevalence and mortality worldwide. As a result of patient-centred hindering factors of adherence to centre-based pulmonary rehabilitation (PR), home-based PR is an alternate mode of rehabilitating individuals with IPF. This systematic review will evaluate the effectiveness of unsupervised home-based PR on functional capacity and health-related quality of life (HRQoL) in individuals with IPF., Methods: Clinically stable, high resolution computed tomography and physician diagnosed IPF participants having modified Medical Research Council score below 5 will be considered for the systematic review. Studies involving home-based PR as an intervention to treat individuals with IPF will be considered. Randomised controlled trials and quasi-randomised studies (with two groups followed up) are eligible to be included. Outcomes of our interest are functional capacity (6-min walk distance, shuttle walk test and incremental shuttle walk test) and secondary outcome measure would include assessment of quality of life and adverse effects of intervention. Electronic databases such as SCOPUS, Medline (PubMed and Web of Science), PEDRo and CINAHL will be searched using database specific terms. Additionally, forward and backward citations of included studies will be searched to identify potential records. Two review authors, independently, will conduct the screening, data extraction using a customised standard tool, and critical appraisal using Cochrane Risk of Bias 2 tool of included studies. If data permits, meta-analysis will be conducted. In case of substantial heterogeneity, we will do a narrative synthesis. Subgroup analysis will be undertaken based on various contextual and interventional factors., Discussion: This review will provide comprehensive evidence on the effectiveness of unsupervised home-based PR to physiotherapists, policy makers and researchers who are interested in IPF management. Findings from this review may guide the development and evaluation of more robust evidence based home-based PR that aimed to improve functional capacity among people with IPF., Systematic Review Registration: PROSPERO CRD42020213883., (© 2021. The Author(s).)

Background: The mosquito-borne arboviral disease dengue has become a global public health concern. However, very few studies have reported atypical clinical features of dengue among children. Because an understanding of various spectrums of presentation of dengue is necessary for timely diagnosis and management, we aimed to document the typical and atypical clinical features along with predictors of severity among children with dengue during the largest outbreak in Bangladesh in 2019., Methods: We conducted a cross-sectional study between August 15 and September 30, 2019. in eight tertiary level hospitals in Dhaka city. Children (aged < 15 years) with serologically confirmed dengue were conveniently selected for data collection through a structured questionnaire. Descriptive, inferential statistics, and multivariable logistic regression were used to analyze data., Results: Among the 190 children (mean age 8.8 years, and male-female ratio 1.22:1) included in the analysis, respectively 71.1 and 28.9% children had non-severe and severe dengue. All children had fever with an average temperature of 103.3 ± 1.2 F (SD). Gastrointestinal symptoms were the most common associated feature, including mostly vomiting (80.4%), decreased appetite (79.5%), constipation (72.7%), and abdominal pain (64.9%). Mouth sore, a less reported feature besides constipation, was present in 28.3% of children. Atypical clinical features were mostly neurological, with confusion (21.3%) being the predominant symptom. Frequent laboratory abnormalities were thrombocytopenia (87.2%), leucopenia (40.4%), and increased hematocrit (13.4%). Age (AOR 0.86, 95%CI 0.75-0.98, p = 0.023), mouth sore (AOR 2.69, 95%CI 1.06-6.96, p = 0.038) and a decreased platelet count (< 50,000/mm 3 ) with increased hematocrit (> 20%) (AOR 4.94, 95%CI 1.48-17.31, p = 0.01) were significant predictors of severity., Conclusions: Dengue in children was characterized by a high severity, predominance of gastrointestinal symptoms, and atypical neurological presentations. Younger age, mouth sores, and a decreased platelet with increased hematocrit were significant predictors of severity. Our findings would contribute to the clinical management of dengue in children., (© 2021. The Author(s).)

Objective: Ketamine has been shown to decrease sedative requirements in intensive care unit (ICU). Randomized trials are limited on patient-centered outcomes. We designed this pilot trial to evaluate the feasibility of a large randomized controlled trial (RCT) testing the effect of ketamine as an adjunct analgosedative compared with standard of care alone as a control group (CG) in critically ill patients with mechanical ventilation (MV). We also provided preliminary evidence on clinically relevant outcomes to plan a larger trial., Material and Methods: Pilot, active-controlled, open-label RCT was conducted at medical, surgical, and transplant ICUs at a large tertiary and quaternary care medical institution (King Faisal Specialist Hospital and Research Center, Saudi Arabia). The study included adult patients who were intubated within 24 h, expected to require MV for the next calendar day, and had institutional pain and sedation protocol initiated. Patients were randomized in a 1:1 ratio to adjunct ketamine infusion 1-2 μg/kg/min for 48 h or CG alone., Results: Of 437 patients screened from September 2019 through November 2020, 83 (18.9%) patients were included (43 in CG and 40 in ketamine) and 352 (80.5%) were excluded. Average enrollment rate was 3-4 patients/month. Consent and protocol adherence rates were adequate (89.24% and 76%, respectively). Demographics were balanced between groups. Median MV duration was 7 (interquartile range [IQR] 3-9.25 days) in ketamine and 5 (IQR 2-8 days) in CG. Median VFDs was 19 (IQR 0-24.75 days) in ketamine and 19 (IQR 0-24 days) in the CG (p = 0.70). More patients attained goal Richmond Agitation-Sedation Scale at 24 and 48 h in ketamine (67.5% and 73.5%, respectively) compared with CG (52.4% and 66.7%, respectively). Sedatives and vasopressors cumulative use, and hemodynamic changes were similar. ICU length-of-stay was 12.5 (IQR 6-21.2 days) in ketamine, compared with 12 (IQR 5.5-23 days) in CG. No serious adverse events were observed in either group., Conclusions: Ketamine as an adjunct analgosedative agent appeared to be feasible and safe with no negative impact on outcomes, including hemodynamics. This pilot RCT identified areas of improvement in study protocol before conducting a large, adequately powered, multicenter RCT which is likely justified to investigate ketamine association with patient-centered outcomes further. Trial registration ClinicalTrials.gov: NCT04075006. Registered on 30 August 2019. Current controlled trials: ISRCTN14730035. Registered on 3 February 2020., (© 2021. The Author(s).)

Background: Sleep disturbances are common in individuals with post traumatic stress disorder (PTSD). However, little is known about how daily variation in sleep characteristics is related to PTSD. This study examined the night-to-night and weekday versus weekend variation in sleep duration, sleep quality, trouble falling asleep, and difficulty staying asleep in individuals with and without PTSD., Methods: Participants (N = 157; 80 with PTSD, 77 without PTSD) completed daily self-reports of their nighttime sleep characteristics for 15 consecutive days. Linear mixed models were used to examine the associations between the 7 days of the week and weekday versus weekend variation in sleep characteristics and PTSD., Results: Individuals with PTSD reported shorter sleep duration, lower sleep quality, more trouble falling asleep, and more difficulty staying asleep than individuals without PTSD. The pattern of change across the week and between weekdays and weekends was different between those with and without PTSD for sleep quality and trouble falling asleep. Among those with PTSD, sleep duration, sleep quality, and trouble falling asleep differed across the 7 days of the week and showed differences between weekdays and weekends. For those without PTSD, only sleep duration differed across the 7 days of the week and showed differences between weekdays and weekends. Neither group showed 7 days of the week nor weekday versus weekend differences in difficulty staying asleep., Conclusions: On average those with PTSD had shorter sleep duration, poorer sleep quality, and greater trouble falling and staying asleep. In particular, the day of week variation in sleep quality and trouble falling asleep specifically distinguishes those with PTSD from those without PTSD. Our findings suggest that clinical care might be improved by assessments of sleep patterns and disturbances across at least a week, including weekdays and weekends. Future studies should explore the mechanisms related to the patterns of sleep disturbance among those with PTSD.

Background: To identify key information regarding potential treatment differences in refugees and the host population, we aimed to investigate patterns (trajectories) of antidepressant use during 3 years before and after a suicide attempt in refugees, compared with Swedish-born. Association of the identified trajectory groups with individual characteristics were also investigated., Methods: All 20-64-years-old refugees and Swedish-born individuals having specialised healthcare for suicide attempt during 2009-2015 (n = 62,442, 5.6% refugees) were followed 3 years before and after the index attempt. Trajectories of annual defined daily doses (DDDs) of antidepressants were analysed using group-based trajectory models. Associations between the identified trajectory groups and different covariates were estimated by chi 2 -tests and multinomial logistic regression., Results: Among the four identified trajectory groups, antidepressant use was constantly low (≤15 DDDs) for 64.9% of refugees. A 'low increasing' group comprised 5.9% of refugees (60-260 annual DDDs before and 510-685 DDDs after index attempt). Two other trajectory groups had constant use at medium (110-190 DDDs) and high (630-765 DDDs) levels (22.5 and 6.6% of refugees, respectively). Method of suicide attempt and any use of psychotropic drugs during the year before index attempt discriminated between refugees' trajectory groups. The patterns and composition of the trajectory groups and their association, discriminated with different covariates, were fairly similar among refugees and Swedish-born, with the exception of previous hypnotic and sedative drug use being more important in refugees., Conclusions: Despite previous reports on refugees being undertreated regarding psychiatric healthcare, no major differences in antidepressant treatment between refugees and Swedish-born suicide attempters were found.

Background: Defining socio-demographic factors, clinical presentations and underlying diseases associated with COVID-19 severity could be helpful in its management. This study aimed to further clarify the determinants and clinical risk factors of the disease severity in patients infected with COVID-19., Methods: A multi-centre descriptive study on all patients who have been diagnosed with COVID-19 in the province of Tehran from March 2020 up to Dec 2020 was conducted. Data on socio-demographic characteristics, clinical presentations, comorbidities, and the health outcomes of 205,654 patients were examined. Characteristics of the study population were described. To assess the association of study variables with the disease severity, the Chi-Squared test and Multiple Logistic Regression model were applied., Results: The mean age of the study population was 52.8 years and 93,612 (45.5%) were women. About half of the patients have presented with low levels of blood oxygen saturation. The ICU admission rate was 17.8% and the overall mortality rate was 10.0%. Older age, male sex, comorbidities including hypertension, cancer, chronic respiratory diseases other than asthma, chronic liver diseases, chronic kidney diseases, chronic neurological disorders, and HIV/AIDS infection were risk markers of poor health outcome. Clinical presentations related with worse prognosis included fever, difficulty breathing, impaired consciousness, and cutaneous manifestations., Conclusion: These results might alert physicians to pay attention to determinants and risk factors associated with poor prognosis in patients with COVID-19. In addition, our findings aid decision makers to emphasise on vulnerable groups in the public health strategies that aim at preventing the spread of the disease and its mortalities.

Background: Whipple's disease is a chronic infectious disease that primarily affects the small intestine, but several organs can simultaneously be involved. The disease is caused by a gram-positive bacterium called Tropheryma whipplei. The disease is difficult to suspect because it is rare with unspecific and long-term symptoms; it can be lethal if not properly treated., Case Presentation: We here present three patients who presented with a plethora of symptoms, mainly long-standing seronegative arthritis and gastrointestinal symptoms in the form of diarrhea with blood, weight loss, fever, and lymphadenopathy. They were after extensive investigations diagnosed with Whipple's disease, in two of them as long as 8 years after the first occurrence of joint manifestations. The diagnosis was made by PCR targeting the T. whipplei 16S rRNA gene from small bowel specimen in all three patients, and, besides from histopathologic findings from the duodenum and distal ileum in one and mesenteric lymph nodes in another patient., Conclusions: This report aims to raise awareness of a very rare disease that presents with a combination of symptoms mimicking other and significantly more common diseases.

Background: One of the most important concerns in every healthcare system is the elimination of disparities in health service utilization and achievement of health equity. This study aimed to investigate the disparities in cervical cancer screening participation in Iran., Methods: A cross-sectional study was conducted using data from the National Non-Communicable Risk Factors Survey in 2016 (STEPs 2016). Data on cervical cancer screening in addition to demographic and socio-economic factors from 15,975 women aged 18 and above were analyzed. The distribution of surveyed women with regard to cervical cancer screening practice was described. Chi square and logistic regression were used to assess the association of demographic and socio-economic factors with cervical cancer screening participation., Results: Overall, 52.1% of women aged 30-59 years, had undergone cervical cancer screening at least once in their lifetime. Participation rate in cervical cancer screening programs varied between provinces; ranging from 7.6% in Sistan and Baluchestan to 61.2% in Isfahan. Single marital status, illiteracy, being employed, and having no insurance coverage were associated with lower participation. Age and area of residence were insignificant predictors for participating in cervical cancer screening program. Analysis of the cervical cancer uptake rates across the socio-economic levels revealed that the service is less utilised by high income groups., Conclusions: Participation in cervical cancer screening program in Iran is not optimal and could be improved. With regard to the distribution of cervical cancer screening practice, social and geographical disparities indicate the need for further research and more comprehensive strategies in order to reduce them.

Background: A noticeable interest in ketamine infusion for sedation management has developed among critical care physicians for critically ill patients. The 2018 Pain, Agitation/sedation, Delirium, Immobility, and Sleep disruption guideline suggested low-dose ketamine infusion as an adjunct to opioid therapy to reduce opioid requirements in post-surgical patients in the intensive care unit (ICU). This was, however, rated as conditional due to the very low quality of evidence. Ketamine has favorable characteristics, making it an especially viable alternative for patients with respiratory and hemodynamic instability. The Analgo-sedative adjuncT keTAmine Infusion iN Mechanically vENTilated ICU patients (ATTAINMENT) trial aims to assess the effect and safety of adjunct low-dose continuous infusion of ketamine as an analgo-sedative compared to standard of care in critically ill patients on mechanical ventilation (MV) for ≥ 24 h., Methods/design: This trial is a prospective, randomized, active controlled, open-label, pilot, feasibility study of adult ICU patients (> 14 years old) on MV. The study will take place in the adult ICUs in the King Faisal Specialist Hospital and Research Center (KFSH&RC), Riyadh, Saudi Arabia, and will enroll 80 patients. Patients will be randomized post-intubation into two groups: the intervention group will receive an adjunct low-dose continuous infusion of ketamine plus standard of care. Ketamine will be administered over a period of 48 h at a fixed infusion rate of 2 μg/kg/min (0.12 mg/kg/h) in the first 24 h followed by 1 μg/kg/min (0.06 mg/kg/h) in the second 24 h. The control group will receive standard of care in the ICU (propofol and/or fentanyl and/or midazolam) according to the KFSH&RC sedation and analgesia protocol as clinically appropriate. The primary outcome is MV duration until ICU discharge, death, extubation, or 28 days post-randomization, whichever comes first., Discussion: The first patient was enrolled on 1 September 2019. As of 10 October 2019, a total of 16 patients had been enrolled. We expect to complete the recruitment by 31 December 2020. The findings of this pilot trial will likely justify further investigation for the role of adjunct low-dose ketamine infusion as an analgo-sedative agent in a larger, multicenter, randomized controlled trial., Trial Registration: ClinicalTrials.gov: NCT04075006. Registered on 30 August 2019. Current controlled trials: ISRCTN14730035. Registered on 3 February 2020.

Background: The Appraisal of Guidelines for Research & Evaluation (AGREE) II has been widely used to evaluate the quality of clinical practice guidelines (CPGs). While the relationship between the overall assessment of CPGs and scores of six domains were reported in previous studies, the relationship between items constituting these domains and the overall assessment has not been analyzed. This study aims to investigate the relationship between the score of each item and the overall assessment and identify items that could influence the overall assessment., Methods: All Japanese CPGs developed using the evidence-based medicine method and published from 2011 to 2015 were used. They were independently evaluated by three appraisers using AGREE II. The evaluation results were analyzed using regression analysis to evaluate the influence of 6 domains and 23 items on the overall assessment., Results: A total of 206 CPGs were obtained. All domains and all items except one were significantly correlated to the overall assessment. Regression analysis revealed that Domain 3 (Rigour of Development), Domain 4 (Clarity of Presentation), Domain 5 (Applicability), and Domain 6 (Editorial Independence) had influence on the overall assessment. Additionally, four items of AGREE II, clear selection of evidence (Item 8), specific/unambiguous recommendations (Item 15), advice/tools for implementing recommendations (Item 19), and conflicts of interest (Item 22), significantly influenced the overall assessment and explained 72.1% of the variance., Conclusions: These four items may highlight the areas for improvement in developing CPGs.

Background: Pneumoperitoneum poses an important diagnostic sign determining the urgency of management of patients in an emergency department. Chilaiditi sign is a rare radiologic finding of large intestines transposition between the diaphragm and the liver. If the patient becomes symptomatic, then the condition is called Chilaiditi syndrome., Case Presentation: We present a rare case of a 49-year-old Egyptian man who presented to our emergency department complaining of cough and vague abdominal discomfort who was found to have Chilaiditi syndrome diagnosed radiologically by computed tomography scan. He was conservatively managed rather than undergoing invasive non-warranted diagnostic and therapeutic testing that may have resulted in increased morbidity., Conclusions: A review of the current literature on Chilaiditi syndrome is provided with a focus on increasing the familiarity of health care professionals with the conditions and stressing the importance of a physical examination in evaluating patients with what appears to be air under the diaphragm.

Background: Increased consumption of omega-3 (ω-3) fatty acids found in cold-water fish and fish oil has been reported to protect against obesity. A potential mechanism may be through reduction in adipocyte differentiation. Stearidonic acid (SDA), a plant-based ω-3 fatty acid, has been targeted as a potential surrogate for fish-based fatty acids; however, its role in adipocyte differentiation is unknown. This study was designed to evaluate the effects of SDA on adipocyte differentiation in 3T3-L1 cells., Methods: 3T3-L1 preadipocytes were differentiated in the presence of SDA or vehicle-control. Cell viability assay was conducted to determine potential toxicity of SDA. Lipid accumulation was measured by Oil Red O staining and triglyceride (TG) quantification in differentiated 3T3-L1 adipocytes. Adipocyte differentiation was evaluated by adipogenic transcription factors and lipid accumulation gene expression by quantitative real-time polymerase chain reaction (qRT-PCR). Fatty acid analysis was conducted by liquid chromatography-mass spectrometry/mass spectrometry (LC-MS/MS)., Results: 3T3-L1 cells treated with SDA were viable at concentrations used for all studies. SDA treatment reduced lipid accumulation in 3T3-L1 adipocytes. This anti-adipogenic effect by SDA was a result of down-regulation of mRNA levels of the adipogenic transcription factors CCAAT/enhancer-binding proteins alpha and beta (C/EBPα, C/EBPβ), peroxisome proliferator-activated receptor gamma (PPARγ), and sterol-regulatory element binding protein-1c (SREBP-1c). SDA treatment resulted in decreased expression of the lipid accumulation genes adipocyte fatty-acid binding protein (AP2), fatty acid synthase (FAS), stearoyl-CoA desaturase (SCD-1), lipoprotein lipase (LPL), glucose transporter 4 (GLUT4) and phosphoenolpyruvate carboxykinase (PEPCK). The transcriptional activity of PPARγ was found to be decreased with SDA treatment. SDA treatment led to significant EPA enrichment in 3T3-L1 adipocytes compared to vehicle-control., Conclusion: These results demonstrated that SDA can suppress adipocyte differentiation and lipid accumulation in 3T3-L1 cells through down-regulation of adipogenic transcription factors and genes associated with lipid accumulation. This study suggests the use of SDA as a dietary treatment for obesity.

Background: Phytotherapeutics exhibit diverse pharmacological effects that are based on the combined action of a mixture of phytoconstituents. In this study, Prunus domestica gum-loaded, stabilized gold and silver nanoparticles (Au/Ag-NPs) were evaluated for their prospective anticancer, antibacterial, urease-inhibition, anti-inflammatory, and analgesic properties., Methods: Au/Ag-NPs were biosynthesized and characterized with UV-Vis, FTIR, SEM, EDX, and XRD techniques. The effect of gum and metal ion concentration, reaction temperature, and time on the synthetic stability of nanoparticles was studied along with their post-synthetic stability against varying pH and salt concentrations, long-term storage and extremes of temperature. Nanoparticles were tested for anticancer (HeLa cervical cancer cells), antibacterial (Staphylococcus aureus, Escherichia coli, and Pseudomonas aeruginosa), urease inhibition (jack-bean urease), anti-inflammatory (carrageenan-induced paw edema), and antinociceptive (abdominal constriction response) activities., Results: The nanoparticles were mostly spherical with an average particle size between 7 and 30 nm (Au-NPs) and 5-30 nm (Ag-NPs). Au/Ag-NPs maintained their colloidal stability and nanoscale characteristics against variations in physicochemical factors. Au/Ag-NPs have potent anticancer potential (IC 50  = 2.14 ± 0.15 μg/mL and 3.45 ± 0.23 μg/mL). Au/Ag-NPs selectively suppressed the growth of S. aureus (10.5 ± 0.6 mm, 19.7 ± 0.4 mm), E. coli (10 ± 0.4 mm, 14.4 ± 0.7 mm), and P. aeruginosa (8.2 ± 0.3 mm, 13.1 ± 0.2 mm), as well as showed preferential inhibition against jack-bean urease (19.2 ± 0.86%, 21.5 ± 1.17%). At doses of 40 and 80 mg/kg, Au-NPs significantly ameliorated the increase in paw edema during the 1st h (P < 0.05, P < 0.01) and 2-5 h (P < 0.001) of carrageenan-induced inflammation compared to the 200 and 400 mg/kg doses of P. domestica gum (P < 0.05, P < 0.001). At similar doses, Au-NPs also significantly abolished (P < 0.01) the tonic visceral, chemically-induced nociception, which was comparable to that of P. domestica gum (200 mg/kg; P < 0.05, 400 mg/kg; P < 0.01).

Background: Obesity is associated with vascular inflammation, fibrosis and reduced high-density lipoproteins (HDL)-cholesterol. We aimed to investigate whether adenoviral gene transfer with human apolipoprotein (apo) A-I (Ad.A-I), the main apo of HDL, could exert immunomodulatory effects and counteract vascular inflammation and fibrosis in ob/ob mice., Methods: Ad.A-I transfer was performed in 8 weeks (w) old ob/ob mice, which were sacrificed 7 w later. The aorta was excised for mRNA analysis and the spleen for splenocyte isolation for subsequent flow cytometry and co-culture with murine fibroblasts. HDL was added to mononuclear cells (MNC) and fibroblasts to assess their impact on adhesion capacity and collagen deposition, respectively., Results: Ad.A-I led to a 1.8-fold (p < 0.05) increase in HDL-cholesterol versus control ob/ob mice at the day of sacrifice, which was paralleled by a decrease in aortic TNF-α and VCAM-1 mRNA expression. Pre-culture of MNC with HDL decreased their adhesion to TNF-α-activated HAEC. Ad.A-I exerted immunomodulatory effects as evidenced by a downregulation of aortic NOD2 and NLRP3 mRNA expression and by a 12 %, 6.9 %, and 15 % decrease of the induced proliferation/activity of total splenic MNC, CD4+, and CD8+ cells in ob/ob Ad.A-I versus control ob/ob mice, respectively (p < 0.05). Ad.A-I further reduced aortic collagen I and III mRNA expression by 62 % and 66 %, respectively (p < 0.0005), and abrogated the potential of ob/ob splenocytes to induce the collagen content in murine fibroblasts upon co-culture. Finally, HDL decreased the TGF-ß1-induced collagen deposition of murine fibroblasts in vitro., Conclusions: Apo A-I transfer counteracts vascular inflammation and fibrosis in ob/ob mice.

Background: Landmark studies in adult-onset type 1 diabetes (T1D) populations indicate that improved glycaemic control through use of intensive insulin therapy is strongly associated with reduced risk for the development of diabetes-related complications and mortality in later years. However, it is unclear whether these associations can be extrapolated to childhood-onset T1D, given the influence of other important biological and psychosocial determinants of glycaemic control, particularly during adolescence. The aims of the review are (1) to investigate the impact of early glycaemic control (within the first 2 years after diagnosis) on subsequent glycaemic trends and risk of complications during the life course of childhood-onset T1D and (2) to identify the predictors of early glycaemic control in children and young people (0-25 years)., Methods: The methods used in this study are systematic identification, review and mapping of quantitative (intervention and observational) and qualitative literature; assessing the effect and predictors of early glycaemic control in T1D (diagnosed ≤18 years) on risk or prevalence of later complications. An iterated search strategy, with no language or period restrictions, was applied to identify studies from six electronic databases. This will be supplemented by hand-searching (reference lists and contacting authors of studies meeting the inclusion criteria). Studies assessing glycaemic control within the first 2 years of diagnosis in children (at baseline) will be quality-assessed against predefined criteria and mapped descriptively to future health outcomes. Extracted data will be analysed and synthesised using narrative and forest plots or harvest plots for quantitative evidence and thematic analyses for qualitative studies. To get a deeper understanding of the predictors of early glycaemic control in reducing complications in childhood and adult life, we will integrate qualitative and quantitative evidence using mixed methods or parallel synthesis approach., Discussion: These linked reviews will be the first to systematically investigate the effects of early glycaemic control and integrate both the quantitative and qualitative evidence on predictors of early glycaemic control in childhood-onset T1D in reducing future diabetes complications. This will help identify and map current research and inform development of effective future interventions., Systematic Review Registration: PROSPERO CRD42015024546.

Background: Epidemiological evidence indicates yet unknown epigenetic mechanisms underlying a propensity for overweight and type 2 diabetes. We analyzed the extent of methylation at lysine 4 and lysine 9 of histone H3 in primary human adipocytes from 43 subjects using modification-specific antibodies., Results: The level of lysine 9 dimethylation was stable, while adipocytes from type 2 diabetic and non-diabetic overweight subjects exhibited about 40% lower levels of lysine 4 dimethylation compared with cells from normal-weight subjects. In contrast, trimethylation at lysine 4 was 40% higher in adipocytes from overweight diabetic subjects compared with normal-weight and overweight non-diabetic subjects. There was no association between level of modification and age of subjects., Conclusions: The findings define genome-wide molecular modifications of histones in adipocytes that are directly associated with overweight and diabetes, and thus suggest a molecular basis for existing epidemiological evidence of epigenetic inheritance.

Background: In vivo models of uremia are important tools to study numerous aspects of acute and chronic kidney disease. Mouse models are pivotal because most genetically engineered animal models are mice, which allow dissecting the impact of selected target genes in renal failure. Adenine-based protocols to induce renal failure are available in rats, but have not been adapted in mice due to their reluctance to consume adenine. In the current paper we developed a novel method for induction of renal failure through dietary delivery of adenine mixed in a casein-based diet., Results: After an induction phase, a stable model of renal impairment was obtained (target urea range 80-100 mg/dL), mimicking several aspects of chronic kidney disease - mineral and bone disorder including secondary hyperparathyroidism, bone abnormalities and pathological elevation of FGF23. No deaths occurred and the level of uremia was adaptable through adjustments of the adenine content, providing significant advantages compared to existing models. In an 8-week proof-of-concept study, renal histology showed mainly a tubulointerstitial damage with infiltrating leukocytes, interstitial edema and widening of the Bownman's space. Fibrosis was present in most animals as defined by histology and gene expression changes of fibrosis markers. Parathyroid cell proliferation was markedly increased but without signs of glandular hypertrophy. Skeletal histology showed increased trabecular bone and bone marrow adiposity whereas bone biomarkers (CTX and PINP) suggested higher bone formation, but surprisingly, lower bone resorption and perturbations in mineral metabolism., Conclusions: We present a novel, non-surgical method for induction of renal failure in mice. This is an important complement to existing uremic models for pathophysiological studies in acute and chronic kidney disease, especially in terms of tubulointerstitial lesions.

Background: Epidemiological data on malaria in Bangladesh are sparse, particularly on severe and fatal malaria. This hampers the allocation of healthcare provision in this resource-poor setting. Over 85% of the estimated 150,000-250,000 annual malaria cases in Bangladesh occur in Chittagong Division with 80% in the Chittagong Hill Tracts (CHT). Chittagong Medical College Hospital (CMCH) is the major tertiary referral hospital for severe malaria in Chittagong Division., Methods: Malaria screening data from 22,785 inpatients in CMCH from 1999-2011 were analysed to investigate the patterns of referral, temporal trends and geographical distribution of severe malaria in Chittagong Division, Bangladesh., Results: From 1999 till 2011, 2,394 malaria cases were admitted, of which 96% harboured Plasmodium falciparum and 4% Plasmodium vivax. Infection was commonest in males (67%) between 15 and 34 years of age. Seasonality of malaria incidence was marked with a single peak in P. falciparum transmission from June to August coinciding with peak rainfall, whereas P. vivax showed an additional peak in February-March possibly representing relapse infections. Since 2007 there has been a substantial decrease in the absolute number of admitted malaria cases. Case fatality in severe malaria was 18% from 2008-2011, remaining steady during this period.A travel history obtained in 226 malaria patients revealed only 33% had been to the CHT in the preceding three weeks. Of all admitted malaria patients, only 9% lived in the CHT, and none in the more remote malaria endemic regions near the Indian border., Conclusions: The overall decline in admitted malaria cases to CMCH suggests recent control measures are successful. However, there are no reliable data on the incidence of severe malaria in the CHT, the most endemic area of Bangladesh, and most of these patients do not reach tertiary health facilities. Improvement of early treatment and simple supportive care for severe malaria in remote areas and implementation of a referral system for cases requiring additional supportive care could be important contributors to further reducing malaria-attributable disease and death in Bangladesh.

Background: There has been an increasing availability and accessibility of modern health services in rural Bangladesh over the past decades. However, previous studies on the socioeconomic differentials in the utilization of these services were based on a limited number of factors, focusing either on preventive or on curative modern health services. These studies failed to collect data from remote rural areas of the different regions to examine the socioeconomic differentials in health-seeking behavior., Methods: Data from 3,498 randomly selected currently married women from three strata of households within 128 purposively chosen remote villages in three divisions of Bangladesh were collected in 2006. This study used bivariate and multivariate logistic analyses to examine both curative and preventive health-seeking behaviors in seven areas of maternal and child health care: antenatal care, postnatal care, child delivery care, mother's receipt of Vitamin A postpartum, newborn baby care, care during recent child fever/cough episodes, and maternal coverageby tetanus toxoid (TT)., Results: A principal finding was that a household's relative poverty status, as reflected by wealth quintiles, was a major determinant in health-seeking behavior. Mothers in the highest wealth quintile were significantly more likely to use modern trained providers for antenatal care, birth attendance, post natal care and child health care than those in the poorest quintile (chi2, p < 0.01). The differentials were less pronounced for other factors examined, such as education, age, and the relative decision-making power of a woman, in both bivariate and multivariate analyses., Conclusion: Within rural areas of Bangladesh, where overall poverty is greater and access to health care more difficult, wealth differentials in utilization remain pronounced. Those programs with high international visibility and dedicated funding (e.g., Immunization and Vitamin A delivery) have higher overall prevalence and a more equitable distribution of beneficiaries than the use of modern trained providers for basic essential health care services. Implications of these findings and recommendations are provided.