Background: H1-antihistamines (AHs) are widely used for the treatment of allergic diseases, being one of the most commonly prescribed classes of medications in Pediatrics. Newer-generation AHs are associated with fewer adverse effects compared to first-generation. However, their relative harms in the pediatric population still need scrutiny. Methods: We performed a systematic review of randomized controlled trials (RCTs) which included comparisons of safety parameters between an orally administered newer-generation AH with another AH (first- or second- generation), montelukast or placebo in children aged≤12 years. We searched MEDLINE and CENTRAL, independently extracted data on study population, interventions, adverse events (AEs) and treatment discontinuations, and assessed the methodological quality of the included RCTs using the Cochrane’s risk of bias tool. Results: Fourty-five RCTs published between 1989 and 2017 met eligibility criteria. The majority of RCTs included school-aged children with allergic rhinitis and had a follow-up period of up to a month. Four RCTs reported serious AEs in patients receiving a newer-generation AH, but only two patients experienced a possibly drug-related serious AE. The occurrence of AEs, drug-related AEs and treatment discontinuations due to AEs varied between RCTs. Most AEs reported were of mild intensity. Indirect evidence indicates that cetirizine is more sedating than the other newer-generation AHs. Conclusion: Our findings confirm that newer-generation AHs have a favorable safety and tolerability profile. However, we could not draw firm conclusions regarding the comparative safety profile of the newer-generation AHs due to the paucity of head-to-head RCTs, variation in definitions and reporting of AEs, and short follow-up duration.

Background: Lack of time has consistently been reported as a major barrier to effective research evidence-uptake into clinical practice. There has been no research to our knowledge that explores time as a barrier within the Transtheoretical model of Stages of Change (SoC), to better understand the processes of physiotherapists’ uptake of clinical practice guidelines (CPG). This paper explores the concept of lack of time as a barrier for CPG uptake for physiotherapists at different SoC. Methods: A 6-step process is presented to determine the best-fit SoC for 31 physiotherapy interviewees. This process used an amalgamation of interview findings and socio-demographic data, which was layered onto the SoC and previously identified time-barriers to CPG uptake (few staff; high workload; access to CPGs; evidence-based practice as priority in clinical practice; “time is money” attitude; and knowledge on the use of CPGs). Results: The analysis process highlighted the complexities of assigning individuals to a SoC. A model of time management for better CPG uptake is proposed which is a novel approach to assist evidence implementalists and clinicians alike to determine how to progress through the SoC and barriers to improve CPG uptake. Conclusions: To the authors’ knowledge, this is the first attempt at exploring the construct of (lack of) time for CPG-uptake in relation to the physiotherapists’ readiness to behaviour change. This study shows that ‘lack of time’ is a euphemism for quite different barriers, which map to different stages of readiness to embrace current best evidence into physiotherapy practice. By understanding what is meant by ‘lack of time’, it may indicate specific support required by physiotherapists at different stages of changing these behaviours.

Allergic bronchopulmonary aspergillosis (ABPA) is a pulmonary disease caused by Aspergillus induced hypersensitivity that occurs in immunocompetent but susceptible patients with asthma and/or cystic fibrosis (CF). In children, ABPA remains mostly undiagnosed, resulting in one of the most common causes of poorly controlled asthma and highly significant morbidity in children with CF. Currently, no specific diagnostic criteria of ABPA for children are available. Corticosteroids and itraconazole are the mainstays of therapy, althoughthere is a lack of randomized clinical trials regarding their usefulness for ABPA in children. Several monoclonal antibodies, such asomalizumab and mepolizumab, may be potential therapies for refractory ABPA in pediatric patients; however, further data are required to clarify the optimal dose and duration of therapy as a routine treatment approach.

Dear Editor,Thank you for the opportunity to respond to Dr Sahu’s letter1. We would like to thank Dr Sahu and his team for their valuable points and ourselves recognise and acknowledge the gaps in our early commentary2 which reflected on the early practice at our hospital, with an aim to help fellow obstetricians with the management of COVID-19 at the start of the outbreak. Since then, more literature has been published providing us with greater knowledge regarding this new infection. Guidance from the Royal College of Obstetricians and Gynaecologists (RCOG)3 and International Society of Ultrasound in Obstetrics and Gynaecology (ISUOG)4 amongst others help us streamline management of COVID-19 in pregnant patients.Both guidelines concur that radiographic investigations should be performed in pregnant patients – protecting the fetus by using a radiation shield over the gravid uterus. Chest CT has high sensitivity up to 97% for diagnosis of COVID-19 and may be considered as primary tool for COVID-19 detection.Both guidelines recommend the use of antenatal corticosteroids (ANC) for the usual indications but cautions use in critically ill women with COVID-19 infection as it may worsen their clinical condition. Importantly, urgent deliveries should not be delayed for the administration of ANC.Li et al5 compared clinical characteristics, maternal and neonatal outcomes of pregnant women with and without COVID-19. They found that COVID-19 infection generally causes mild respiratory symptoms in pregnant women, with no deaths or severe respiratory complications requiring critical care. They observed a higher rate of preterm deliveries in confirmed cases (33.3%) compared to control groups (¬5%). This study included two patients who had vaginal deliveries prior to COVID-19 diagnosis. Their newborns did not show any respiratory symptoms.New reports of SARS-COV-2 IgM in infants6 at birth suggest possibility of vertical transmission although COVID-19 infection in newborns is more commonly likely due to neonatal transmission.During breastfeeding, the main risk for infants lies in their close contact with mothers and transmission of infective respiratory droplets. Infected mothers wishing to breastfeed should do so with precautions such as wearing surgical masks, practising good hand hygiene and thorough cleaning of equipment after use. While the decision for separation of mother and baby has serious consequences on bonding and mental health, we continue to advise separation of baby from mothers infected with COVID-19 due to risk of neonatal transmission.Current data suggests that the adverse effects of COVID-19 in pregnancy are less severe than those of SARS-CoV and MERS-CoV. All presently reported patients were diagnosed in the third trimester and the potential effects of COVID-19 infections in the first and second trimesters remain to be investigated.As Dr Sahu mentioned, comparative studies are scarce. Establishment of international registries will improve our understanding of COVID-19 in pregnancy. Meanwhile, we shall continue to support one another and work together in the fight against this pandemic.We would like to thank the all departments from the Division of Obstetrics and Gynaecology, Infectious Diseases Department and all staff in KK Womens’ and Children’s Hospital for leading the COVID-19 fight locally.Monica Shi Qi Chua1, Jill Cheng Sim Lee2, Suzanna Sulaiman1, Hak Koon Tan31Department of Obstetrics and Gynaecology,2Department of Urogynaecology,3Division of Obstetrics and GynaecologyKK Women’s and Children’s Hospital, Singapore

Rendu Osler's disease is a genetic disease characterized by mucocutaneous and visceral telangiectasias. Rendu Osler's disease was discovered during hypoxemia during an outbreak of SARS-Cov2.This was a 36-year-old woman with exertional dyspnea and severe hypoxemia revealing pulmonary arteriovenous malformations on chest CT scan.

Background and purpose: Increasing evidence has shown that human cholestasis is closely related to hepatic macrophage accumulation and activation. Research has indicated that peroxisome proliferator-activated receptor-g (PPARg) activation exerts liver protection in cholestatic liver disease (CLD), particularly by ameliorating inflammation and fibrosis, thus limiting disease progression. However, existing PPARg agonists, such as troglitazone and rosiglitazone, have significant side effects that impede their clinical application in the treatment of CLD. In this study, we found that tectorigenin (TEC) can alleviate intrahepatic cholestasis in mice by activating PPARg. Experimental approach: Wild-type mice received intragastric administration of a-naphthylisothiocyanate (ANIT) or were fed a diet containing 0.1% 3,5-diethoxycarbonyl-1,4-dihydrocollidine (DDC) to establish an experimental intrahepatic cholestasis model and TEC intervention simultaneously, followed by determination of intrahepatic cholestasis and the involved mechanisms. In addition, PPARg deficient mice were administered ANIT and/or TEC to determine whether TEC exerts its liver protection effect by activating PPARg. Key results: Our results demonstrated that TEC intervention alleviated intrahepatic cholestasis by inhibiting hepatic macrophage recruitment and activation as well as promoting the expression of bile transporters through activating PPARg. Furthermore, our results show that TEC increased bile salt export pump (Bsep) expression through enhanced PPARg binding to the Bsep promoter. We also demonstrated that PPARg deficiency blocked the hepatocyte protective effect of TEC during cholestasis. Conclusions and implications: In conclusion, TEC reduced hepatic macrophage recruitment and activation, and enhanced bile acid export by activating PPARg. Taken together, our results suggest that TEC is a potential drug for the prevention of CLD.

The WHO Unity Studies initiative engaged low- and middle-income countries in the implementation of standardized SARS-CoV-2 sero-epidemiological investigation protocols and timely sharing of comparable results for evidence-based action. To gain a deeper understanding of the methodological challenges faced when conducting seroprevalence studies in the Africa region, we conducted unstructured interviews with key study teams in five countries. We discuss the challenges identified: participant recruitment and retention, sample frame, sample and data management, data analysis and presentation to policy makers. Potential solutions to aid future implementation include preparedness actions such as the development of new tools, robust planning and practice.

Staircase testing is a standard method for evaluating the fatigue strength of components. However, staircase testing assumes a normal distribution, while components can display bimodal behavior due to flaws in material, or issues during the manufacturing process. Three unique step loading data sets on different production crankshafts provide evidence that step loading reliably identifies material or manufacturing issues, that lower a component’s fatigue strength. Staircase testing has an 87% or greater chance of overestimating the component’s fatigue strength, which in turn overestimates the component’s expected reliability. For example, a component with a 99.9% reliability, based on staircase testing would only have a 74% reliability based on step loading. If a component contains an undetectable manufacturing defect, staircase testing has a 99% chance of overestimating the component’s fatigue strength. Step loading reliably improves the estimation of a component’s fatigue strength distribution while providing insights into a component’s defect tolerance.

DNA damage occurs throughout life from a variety of sources, and it is imperative to repair damage in a timely manner to maintain genome stability. Thus, DNA repair mechanisms are a fundamental part of life. Nucleotide Excision Repair (NER) plays an important role in the removal of bulky DNA adducts, such as cyclobutane pyrimidine dimers (CPDs) from ultraviolet (UV) light or DNA crosslinking damage from platinum-based chemotherapeutics, such as cisplatin. A main component for the NER pathway is transcription factor IIH (TFIIH), a multifunctional, 10-subunit protein complex with crucial roles in both transcription and NER. In transcription, TFIIH is a component of the pre-initiation complex (PIC) and is important for promoter opening and the phosphorylation of RNA Polymerase II (RNA Pol II). During repair, TFIIH is important for DNA unwinding, recruitment of downstream repair factors, and verification of the bulky lesion. Several different disease states can arise from mutations within subunits of the TFIIH complex. Most strikingly are Xeroderma Pigmentosum (XP), XP combined with Cockayne Syndrome (CS), and Trichothiodystrophy (TTD). Here, we summarize the recruitment and functions of TFIIH in the two NER subpathways, global genomic (GG-NER) and transcription-coupled NER (TC-NER). We will also discuss how TFIIH’s roles in the two subpathways lead to different genetic disorders.

Aims: to test the hypothesis that a semi-supervised home physical exercise program improves the functional mobility and quality of life (QOL) of elderly in the community. Methods: This trial was conducted with elderly people (88% female), aged 60 years or older, sedentary and without cognitive decline. Elderly were randomly assigned to an intervention group - IG (home physical exercise and sleep hygiene) and a control group - CG (sleep hygiene). Were applied the International Questionnaire on Physical Activity; mental state mini-exam and the Timed Up and Go test (TUG) before and after the 12-week intervention period. Results: The IG showed an improvement in functional mobility, with a mean reduction in TUG execution time (p <0.01) and improvement in the QOL, (p <0.01) in WHOQOL-OLD. Conclusion: Semi-supervised physical home exercise is effective in improving the functional mobility and the QOL of sedentary elderly in the community. Trial Registration: Registro Brasileiro de Ensaios Clínicos (REBEC) Identifier: RBR-3cqzfy Keywords: Elderly; exercise; functional mobility; quality of life; community; physical activity; home exercise.

There are no proven safe and effective therapies for children who develop life-threatening complications of SARS-CoV-2. Convalescent plasma (CP) has demonstrated potential benefit in adults with SARS-CoV-2 but has theoretical risks. We report on the first use of CP in children with life-threatening COVID-19, providing data on four pediatric patients with acute respiratory distress syndrome. We measured donor antibody levels and recipient antibody response prior to and following CP infusion. Infusion of CP was not associated with antibody-dependent enhancement (ADE) and did not suppress endogenous antibody response. We found CP was safe and possibly efficacious. Randomized pediatric trials are needed.

The effects of various heat treatments on the microstructure and mechanical properties of laser beam powder bed fused AlSi10Mg were investigated. Specimens were solutionized at three different temperatures of 425, 475 and 525 °C followed by natural aging (T4) prior to microstructural and mechanical characterization. In addition, the effect of aging was studied by artificially aging (i.e., T7) some of the solutionized specimens at 165 °C. Solutionizing at all temperatures was observed to fully dissolve the additive manufacturing (AM) induced dendritic microstructure, leaving bulky Si and needle-shaped β-AlFeSi precipitates in the grain interiors and boundaries. Tensile results revealed that T4 specimens exhibited more ductility, while T7 specimens showed substantially higher strengths with slightly reduced ductility. Interestingly, no significant effect of heat treatment on strain-life fatigue behavior was observed. Fractography found the Si-particles to be responsible for tensile fracture, while AM volumetric defects were the main initiators of fatigue cracks.

Langerhans Cell Histiocytosis (LCH) is characterized by activating variants of the MAPK pathway. Inhibition of the MAPK pathway with trametinib (MEK inhibitor) has been shown to induce responses in LCH patients. Two adolescent males with LCH driven by BRAF p.N486_P490del have received trametinib for >1 year with no reactivation in one and partial response in another (including stable lung disease). A third male with neonatal LCH and MAP2K1 p.K57_G61del had a complete response to trametinib with no active disease after 22 months. All patients continue on trametinib monotherapy with tolerable skin and CPK toxicity.

A document by Duygu AYHAN BASER. Click on the document to view its contents.

Objectives. Fifteen potentially low value practices in adult orthopaedic trauma care were previously identified in a scoping review. The aim of this study was to synthesize the evidence on these practices. Methods. We searched four databases for systematic reviews, randomized controlled trials (RCTs), cohort studies and case series that assessed the effectiveness of selected practices. Methodological quality was evaluated using the Measurement Tool to Assess Systematic Reviews version 2 (AMSTAR-2) for systematic reviews and the Critical Appraisal Checklist for Case Series. We evaluated risk of bias with the Cochrane revised tool for RCTs and the risk of bias in non-randomized studies of interventions tool for observational studies. We summarized findings with measures of frequency and association for primary outcomes. Results. Of the 30,670 records screened, 70 studies were retained. We identified high-level evidence of lack of effectiveness or harm for routine initial imaging of ankle injury, orthosis for A0-A3 thoracolumbar burst fracture in patients < 60 years of age, cast or splint immobilization for suspected scaphoid fracture negative on MRI or confirmed fifth metacarpal neck fracture, and routine follow-up imaging for distal radius and ankles fractures. However, evidence was mostly based on studies of low methodological quality or high risk of bias. Conclusion. In this review, we identified clinical practices in orthopedic injury care which are not supported by current evidence and whose use may be questioned. In future research we should measure their frequency, assess practice variations and evaluate root causes to identify practices that could be targeted for de-implementation.

Background: Outcome of children with bladder-prostate rhabdomyosarcoma has improved with multimodal therapies, including surgery and/or radiotherapy for local treatment. Our aim was to report the long-term urological complications after a conservative approach combining conservative surgery and brachytherapy. Patients and methods: Eighty-six patients, free of disease, were retrospectively reviewed. Symptoms related to urinary tract obstruction, incontinence, infection and lithiasis were reported and graded according to CTCAE classification. Only symptomatic patients underwent urodynamic studies. Risk factors for complications were analyzed. Results: There were 76 males and 10 females. The median follow-up was 6.3 years (18 months-24 years). Complications occurred after a median follow up 5 years (0-21). Twenty-two patients had long-term urological complications. Urinary tract obstruction was found in 15 patients, urinary incontinence in 14 patients. Recurrent urinary tract infection and urinary lithiasis were found in 5 patients respectively. Beyond symptom, 3 etiologies were identified: bladder dysfunction in 15 patients, urethral stenosis in 6 and uretero-vesical junction stenosis in 5. Posterior bladder wall dissection used in large prostatic tumors, operation at age less than 2 years and partial prostatectomy were identified as risk factors for these complications. Conclusion: The conservative surgical approach combined with brachytherapy for BPRMS leads to long-term urological complications in 22% of patients free of their disease. Optimizing brachytherapy doses for young children and establishing a clear and long term follow-up protocol, could help to reduce these complications.

Background This meta-analysis aims to evaluate the utility of speckle tracking echocardiography (STE) as a tool to evaluate for cardiac sarcoidosis (CS) early in its course. Electrocardiography and echocardiography have limited sensitivity in this role, while advanced imaging modalities such as cardiac magnetic resonance (CMR) and 18F-Fluorodeoxyglucose–Positron Emission Tomography (FDG-PET) are limited by cost and availability. Methods We compiled English language articles that reported left ventricular global longitudinal strain (LVGLS) or global circumferential strain (GCS) in patients with confirmed extra-cardiac sarcoidosis versus healthy controls. Studies that exclusively included patients with probable or definite CS were excluded. Continuous data were pooled as a standard mean difference (SMD) between the sarcoidosis group and controls. A random effect model was adopted in all analyses. Heterogeneity was assessed using Q and I2 statistics. Results Nine studies with 967 patients were included in our analysis. LVGLS was significantly lower in the extra-cardiac sarcoidosis group as compared to controls, SMD -3.98, 95% confidence interval (CI): -5.32, -2.64, p< 0.001, also was significantly lower in patients who suffered Major Cardiac Events(MCE), -3.89, 95% CI -6.14, -1.64, p< 0.001 . GCS was significantly lower in the extra-cardiac sarcoidosis group as compared to controls, SMD: -3.33, 95% CI -4.71, -1.95, p< 0.001 Conclusion LVGLS and GCS were significantly lower in extra-cardiac sarcoidosis patients despite not exhibiting any cardiac symptoms. LVGLS correlates with MCEs in CS. Further studies are required to investigate the role of STE in the early screening of CS.

Herpes Simplex Encephalitis is the most common cause of infectious encephalitis. Our case is of a 75-year-old woman who presented with dysuria and altered mental status. Our case addresses the difficulties in diagnosis and highlights the importance of early recognition of HSE and its associated neurological sequelae.