Diagnostic stewardship : the impact of rapid diagnostic testing for paediatric respiratory presentations in the emergency setting : a systematic review

Antimicrobial resistance is a growing public health crisis, propelled by inappropriate antibiotic prescription, in particular the over-prescription of antibiotics, prolonged duration of antibiotic therapy and the overuse of broad-spectrum antibiotics. The paediatric population, in particular, those presenting to emergency settings with respiratory symptoms, have been associated with a high rate of antibiotic prescription rates. Further research has now shown that many of these antibiotic prescriptions may have been avoided, with more targeted diagnostic methods to identify underlying aetiologies. The purpose of this systematic review was to assess the impact of rapid diagnostic testing, for paediatric respiratory presentations in the emergency setting, on antibiotic prescription rates. To review the relevant history, a comprehensive search of Medline, EMBASE and Cochrane Database of Systematic Reviews was performed. Eighteen studies were included in the review, and these studies assessed a variety of rapid diagnostic testing tools and outcome measures. Overall, rapid diagnostic testing was found to be an effective method of diagnostic antibiotic stewardship with great promise in improving antibiotic prescribing behaviours. Further studies are required to evaluate the use of rapid diagnostic testing with other methods of antibiotics stewardship, including clinical decisions aids and to increase the specificity of interventions following diagnosis to further reduce rates of antibiotic prescriptio

Biophysical characteristics of tears in children

Purpose : The tear film forms an important part of our visual system and is essential for the functioning of the ocular surface. A stable tear film is required for preventing the most common ocular surface disease - dry-eye. Most of the studies on tears are conducted using samples from adult subjects and only few reports are available on tears of infants and children while it is known that infants and children have more stable tear film than adults. It is likely that nature of tears is different in children because dry-eye mainly occurs in adults. This study aimed at characterizing the biophysical characteristics of the tear film of children to look into tear film stability

Formaldehyde as an alternative to antibiotics for treatment of refractory impetigo and other infectious skin diseases

Introduction: Antibiotic-resistant strains of bacteria are an increasing problem in hospitals and in the community. This has resulted in bacterial infections such as impetigo becoming difficult to treat. Alternative treatment options are needed. Areas covered: In this paper, a past study that assessed the health burden of scabies in North Queensland is described and from it, the potential for formaldehyde as an alternative antimicrobial treatment is discussed. In doing so, antibiotic resistance, impetigo, permethrin, and formaldehyde are introduced and the current understanding and limitations of the effects of formaldehyde on humans are outlined. The limited cases of formaldehyde resistance in bacteria are also discussed. Expert opinion: Formaldehyde is currently used as a preservative in cosmetics and medicinal creams due to its antibacterial activity. It, therefore, has the potential to be used as an alternative antibacterial treatment for infections with antibiotic-resistant bacteria. The harmful side effects of airborne formaldehyde and exposure in allergic individuals have been extensively studied. Significantly less research has been conducted on formaldehyde skin contact in healthy individuals. If formaldehyde is safe for topical use in humans, it has the potential to assist with combating antibiotic resistance

The in vitro antibacterial effect of permethrin and formaldehyde on Staphylococcus aureus

Antibiotic‐resistant strains of bacteria such as methicillin‐resistant Staphylococcus aureus are a threat to human health, and effective treatment options against them are needed. This study aimed to determine whether the insecticide permethrin was capable of inhibiting the growth of S. aureus or if some other component of a permethrin cream was responsible for a decrease in scabies associated bacterial infection previously observed. Ten S. aureus strains were grown in the presence of permethrin and formaldehyde both alone and in combination with percent inhibition determined by viable counts. Also, a time‐kill assay was conducted on S. aureus exposed to the same conditions. Finally, the morphology of S. aureus grown in the presence of permethrin was examined by scanning electron microscopy. Bacterial inhibition by permethrin ranged from 0% to 41% whereas inhibition by formaldehyde was 100%. The time‐kill curves of permethrin exposed cells were very similar to the positive growth control while the formaldehyde and combination exposure showed complete inhibition even at the 0‐hr time point. The scanning electron micrographs of permethrin grown S. aureus showed healthy cocci cells with no sign of cell damage. Our results show that permethrin is not capable of inhibiting the growth of bacteria enough for it to be termed bactericidal. Formaldehyde is a known antiseptic and therefore was responsible for the antibacterial effect observed after the use of permethrin cream

Biophysical characteristics of the tear film in school-aged children

Purpose : The ocular surface and tear film in children are not as well characterised as in adults. Biophysical properties of tears are associated with their ability to spread on the ocular surface and reduce surface tension to form a stable tear film. The aim of this study was to investigate biophysical properties of tears in school-aged children and examine the relationship with age. Methods : Unstimulated tears were collected from 21 healthy children (age 6-14 years, 71% female) using glass capillary tubes. For each participant, tears were spread on the surface of an artificial tear solution reflecting the salt composition of tears and maintained at the physiological pH (7.4) and temperature (35°C) in a Langmuir trough. The tear film was compressed and expanded with two barriers and surface pressure was continually recorded with a pressure sensor to give pressure-area profiles. Pressure-area profiles were qualitatively compared between all participant tear samples. Maximum surface pressure at the highest compression for each participant sample was determined from profiles. Associations between maximum surface pressure and age were examined using Pearson correlation, and male and female samples were compared using Mann-Whitney U test. Profiles were also compared with a representative historical adult tear sample (35 y, female, normal ocular surface). Results : Pressure-area profiles of tear films of all participants indicated features of a stable, highly compressible liquid film with continuous increase in pressure without any collapse of the film. Profiles of child participants were similar and comparable to the profile of the historical adult sample. Group mean maximum surface pressure at the highest compression for child participants was 33 ± 3.5 mN/m. There were no significant relationships between maximum surface pressure and age (p=0.8) or sex (p=0.7). Conclusions : Biophysical characteristics of tears in school-aged children are comparable with adult tears and are not affected by age or sex. Many components including lipids and proteins contribute to the surface pressure of tears. Surface pressure of adult tears is known to be higher than surface pressure of lipid component alone because of additional contribution from proteins. Future investigations will examine the contribution of different components in children’s tears to overall tear stability

Comprehensive Biostatistical Analysis of CpG Island Methylator Phenotype in Colorectal Cancer Using a Large Population-Based Sample

The CpG island methylator phenotype (CIMP) is a distinct phenotype associated with microsatellite instability (MSI) and BRAF mutation in colon cancer. Recent investigations have selected 5 promoters (CACNA1G, IGF2, NEUROG1, RUNX3 and SOCS1) as surrogate markers for CIMP-high. However, no study has comprehensively evaluated an expanded set of methylation markers (including these 5 markers) using a large number of tumors, or deciphered the complex clinical and molecular associations with CIMP-high determined by the validated marker panel. METHOLODOLOGY/PRINCIPAL FINDINGS: DNA methylation at 16 CpG islands [the above 5 plus CDKN2A (p16), CHFR, CRABP1, HIC1, IGFBP3, MGMT, MINT1, MINT31, MLH1, p14 (CDKN2A/ARF) and WRN] was quantified in 904 colorectal cancers by real-time PCR (MethyLight). In unsupervised hierarchical clustering analysis, the 5 markers (CACNA1G, IGF2, NEUROG1, RUNX3 and SOCS1), CDKN2A, CRABP1, MINT31, MLH1, p14 and WRN were generally clustered with each other and with MSI and BRAF mutation. KRAS mutation was not clustered with any methylation marker, suggesting its association with a random methylation pattern in CIMP-low tumors. Utilizing the validated CIMP marker panel (including the 5 markers), multivariate logistic regression demonstrated that CIMP-high was independently associated with older age, proximal location, poor differentiation, MSI-high, BRAF mutation, and inversely with LINE-1 hypomethylation and beta-catenin (CTNNB1) activation. Mucinous feature, signet ring cells, and p53-negativity were associated with CIMP-high in only univariate analysis. In stratified analyses, the relations of CIMP-high with poor differentiation, KRAS mutation and LINE-1 hypomethylation significantly differed according to MSI status.Our study provides valuable data for standardization of the use of CIMP-high-specific methylation markers. CIMP-high is independently associated with clinical and key molecular features in colorectal cancer. Our data also suggest that KRAS mutation is related with a random CpG island methylation pattern which may lead to CIMP-low tumors

World Health Organization cardiovascular disease risk charts: revised models to estimate risk in 21 global regions

BACKGROUND: To help adapt cardiovascular disease risk prediction approaches to low-income and middle-income countries, WHO has convened an effort to develop, evaluate, and illustrate revised risk models. Here, we report the derivation, validation, and illustration of the revised WHO cardiovascular disease risk prediction charts that have been adapted to the circumstances of 21 global regions. METHODS: In this model revision initiative, we derived 10-year risk prediction models for fatal and non-fatal cardiovascular disease (ie, myocardial infarction and stroke) using individual participant data from the Emerging Risk Factors Collaboration. Models included information on age, smoking status, systolic blood pressure, history of diabetes, and total cholesterol. For derivation, we included participants aged 40-80 years without a known baseline history of cardiovascular disease, who were followed up until the first myocardial infarction, fatal coronary heart disease, or stroke event. We recalibrated models using age-specific and sex-specific incidences and risk factor values available from 21 global regions. For external validation, we analysed individual participant data from studies distinct from those used in model derivation. We illustrated models by analysing data on a further 123 743 individuals from surveys in 79 countries collected with the WHO STEPwise Approach to Surveillance. FINDINGS: Our risk model derivation involved 376 177 individuals from 85 cohorts, and 19 333 incident cardiovascular events recorded during 10 years of follow-up. The derived risk prediction models discriminated well in external validation cohorts (19 cohorts, 1 096 061 individuals, 25 950 cardiovascular disease events), with Harrell's C indices ranging from 0·685 (95% CI 0·629-0·741) to 0·833 (0·783-0·882). For a given risk factor profile, we found substantial variation across global regions in the estimated 10-year predicted risk. For example, estimated cardiovascular disease risk for a 60-year-old male smoker without diabetes and with systolic blood pressure of 140 mm Hg and total cholesterol of 5 mmol/L ranged from 11% in Andean Latin America to 30% in central Asia. When applied to data from 79 countries (mostly low-income and middle-income countries), the proportion of individuals aged 40-64 years estimated to be at greater than 20% risk ranged from less than 1% in Uganda to more than 16% in Egypt. INTERPRETATION: We have derived, calibrated, and validated new WHO risk prediction models to estimate cardiovascular disease risk in 21 Global Burden of Disease regions. The widespread use of these models could enhance the accuracy, practicability, and sustainability of efforts to reduce the burden of cardiovascular disease worldwide. FUNDING: World Health Organization, British Heart Foundation (BHF), BHF Cambridge Centre for Research Excellence, UK Medical Research Council, and National Institute for Health Research

Mortality and pulmonary complications in patients undergoing surgery with perioperative SARS-CoV-2 infection: an international cohort study

Background: The impact of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) on postoperative recovery needs to be understood to inform clinical decision making during and after the COVID-19 pandemic. This study reports 30-day mortality and pulmonary complication rates in patients with perioperative SARS-CoV-2 infection. Methods: This international, multicentre, cohort study at 235 hospitals in 24 countries included all patients undergoing surgery who had SARS-CoV-2 infection confirmed within 7 days before or 30 days after surgery. The primary outcome measure was 30-day postoperative mortality and was assessed in all enrolled patients. The main secondary outcome measure was pulmonary complications, defined as pneumonia, acute respiratory distress syndrome, or unexpected postoperative ventilation. Findings: This analysis includes 1128 patients who had surgery between Jan 1 and March 31, 2020, of whom 835 (74·0%) had emergency surgery and 280 (24·8%) had elective surgery. SARS-CoV-2 infection was confirmed preoperatively in 294 (26·1%) patients. 30-day mortality was 23·8% (268 of 1128). Pulmonary complications occurred in 577 (51·2%) of 1128 patients; 30-day mortality in these patients was 38·0% (219 of 577), accounting for 81·7% (219 of 268) of all deaths. In adjusted analyses, 30-day mortality was associated with male sex (odds ratio 1·75 [95% CI 1·28–2·40], p\textless0·0001), age 70 years or older versus younger than 70 years (2·30 [1·65–3·22], p\textless0·0001), American Society of Anesthesiologists grades 3–5 versus grades 1–2 (2·35 [1·57–3·53], p\textless0·0001), malignant versus benign or obstetric diagnosis (1·55 [1·01–2·39], p=0·046), emergency versus elective surgery (1·67 [1·06–2·63], p=0·026), and major versus minor surgery (1·52 [1·01–2·31], p=0·047). Interpretation: Postoperative pulmonary complications occur in half of patients with perioperative SARS-CoV-2 infection and are associated with high mortality. Thresholds for surgery during the COVID-19 pandemic should be higher than during normal practice, particularly in men aged 70 years and older. Consideration should be given for postponing non-urgent procedures and promoting non-operative treatment to delay or avoid the need for surgery. Funding: National Institute for Health Research (NIHR), Association of Coloproctology of Great Britain and Ireland, Bowel and Cancer Research, Bowel Disease Research Foundation, Association of Upper Gastrointestinal Surgeons, British Association of Surgical Oncology, British Gynaecological Cancer Society, European Society of Coloproctology, NIHR Academy, Sarcoma UK, Vascular Society for Great Britain and Ireland, and Yorkshire Cancer Research