Impact of acute otitis media clinical practice guidelines on antibiotic and analgesic prescriptions: a systematic review

BACKGROUND: Clinical practice guidelines focusing on judicious use of antibiotics for childhood acute otitis media (AOM) have been introduced in many countries around the world. OBJECTIVE: To systematically review the effects of these guidelines on the prescription of antibiotics and analgesics for children with AOM. METHODS: Systematic searches of PubMed, Embase and Cochrane Library from inception to 6 June 2017 using broad search terms. Studies specifically aimed at evaluating the effects of introduction of national AOM practice guidelines on type of antibiotic and/or analgesic prescriptions were included, irrespective of design, setting or language. The Risk Of Bias In Non-randomized Studies of Interventions tool was used to assess risk of bias. RESULTS: Of 411 unique records retrieved, seven studies conducted in six different countries (France, Italy, Spain, Sweden, UK and USA (twice)) compared data before and after guideline introduction. All studies had an observational design, using longitudinal data of children aged under 15 years (n=200-4.6 million) from either routine care, insurance databases or electronic surveys. Risk of bias of all studies was judged serious to critical.Of the five studies reporting on antibiotic prescription rates, three showed a decline of 5%-12% up to 3 years after guideline introduction and two found no or negligible effect. In one US study, the initial 9% decline decreased to 5% after 4-6 years. The recommended first choice antibiotic was prescribed more frequently (9%-58% increase) after guideline introduction in four out of five studies reporting on this outcome. Analgesic prescription rates for AOM were reported in one US study and increased from 14% to 24% after guideline introduction. CONCLUSION: Based upon what is published, the effects of introduction of national clinical practice guidelines on antibiotic and analgesic prescribing for children with AOM seem modest at the most. REGISTRATION: PROSPERO: CRD42016050976

Anaerobic animals from an ancient, anoxic ecological niche

Tiny marine animals that complete their life cycle in the total absence of light and oxygen are reported by Roberto Danovaro and colleagues in this issue of BMC Biology. These fascinating animals are new members of the phylum Loricifera and possess mitochondria that in electron micrographs look very much like hydrogenosomes, the H2-producing mitochondria found among several unicellular eukaryotic lineages. The discovery of metazoan life in a permanently anoxic and sulphidic environment provides a glimpse of what a good part of Earth's past ecology might have been like in 'Canfield oceans', before the rise of deep marine oxygen levels and the appearance of the first large animals in the fossil record roughly 550-600 million years ago. The findings underscore the evolutionary significance of anaerobic deep sea environments and the anaerobic lifestyle among mitochondrion-bearing cells. They also testify that a fuller understanding of eukaryotic and metazoan evolution will come from the study of modern anoxic and hypoxic habitats

Decreased endothelin receptor B expression in large primary uveal melanomas is associated with early clinical metastasis and short survival

The most devastating aspect of cancer is the metastasis of tumour cells to organs distant from the original tumour site. The major problem facing oncologists treating uveal melanoma, the most common cancer of the eye, is metastatic disease. To lower mortality, it is necessary to increase our understanding of the molecular genetic alterations involved in this process. Using suppression subtractive hybridisation, we have analysed differential gene expression between four primary tumours from patients who have developed clinical metastasis and four primary tumours from patients with no evidence of metastasis to date. We have identified endothelin receptor type B as differentially expressed between these tumours and confirmed this observation using comparative multiplex RT–PCR. In a further 33 tumours, reduced endothelin receptor type B expression correlated with death from metastatic disease. Reduced expression also correlated with other known prognostic indicators, including the presence of epithelioid cells, chromosome 3 allelic imbalance and chromosome 8q allelic imbalance. Endothelin receptor type B expression was also reduced in four out of four primary small cell lung carcinomas compared to normal bronchial epithelium. We also show that the observed down-regulation of endothelin receptor type B in uveal melanoma was not due to gene deletion. Our findings suggest a role for endothelin receptor type B in the metastasis of uveal melanoma and, potentially, in the metastasis of other neural crest tumours

Defective CFTR Expression and Function Are Detectable in Blood Monocytes: Development of a New Blood Test for Cystic Fibrosis

BACKGROUND: Evaluation of cystic fibrosis transmembrane conductance regulator (CFTR) functional activity to assess new therapies and define diagnosis of cystic fibrosis (CF) is cumbersome. It is known that leukocytes express detectable levels of CFTR but the molecule has not been characterized in these cells. In this study we aim at setting up and validating a blood test to evaluate CFTR expression and function in leukocytes. DESCRIPTION: Western blot, PCR, immunofluorescence and cell membrane depolarization analysis by single-cell fluorescence imaging, using the potential-sensitive DiSBAC(2)(3) probe were utilized. Expression of PKA phosphorylated, cell membrane-localized CFTR was detected in non-CF monocytes, being undetectable or present in truncated form in monocytes derived from CF patients presenting with nonsense mutations. CFTR agonist administration induced membrane depolarization in monocytes isolated from non-CF donors (31 subjects) and, to a lesser extent, obligate CFTR heterozygous carriers (HTZ: 15 subjects), but it failed in monocytes from CF patients (44 subjects). We propose an index, which values in CF patients are significantly (p<0.001) lower than in the other two groups. Nasal Potential Difference, measured in selected subjects had concordant results with monocytes assay (Kappa statistic 0.93, 95%CI: 0.80-1.00). RESULTS AND SIGNIFICANCE: CFTR is detectable and is functional in human monocytes. We also showed that CFTR-associated activity can be evaluated in 5 ml of peripheral blood and devise an index potentially applicable for diagnostic purposes and both basic and translational research: from drug development to evaluation of functional outcomes in clinical trials

High Diversity of Cryptosporidium Subgenotypes Identified in Malaysian HIV/AIDS Individuals Targeting gp60 Gene

BACKGROUND: Currently, there is a lack of vital information in the genetic makeup of Cryptosporidium especially in developing countries. The present study aimed at determining the genotypes and subgenotypes of Cryptosporidium in hospitalized Malaysian human immunodeficiency virus (HIV) positive patients. METHODOLOGY/PRINCIPAL FINDINGS: In this study, 346 faecal samples collected from Malaysian HIV positive patients were genetically analysed via PCR targeting the 60 kDa glycoprotein (gp60) gene. Eighteen (5.2% of 346) isolates were determined as Cryptosporidium positive with 72.2% (of 18) identified as Cryptosporidium parvum whilst 27.7% as Cryptosporidium hominis. Further gp60 analysis revealed C. parvum belonging to subgenotypes IIaA13G1R1 (2 isolates), IIaA13G2R1 (2 isolates), IIaA14G2R1 (3 isolates), IIaA15G2R1 (5 isolates) and IIdA15G1R1 (1 isolate). C. hominis was represented by subgenotypes IaA14R1 (2 isolates), IaA18R1 (1 isolate) and IbA10G2R2 (2 isolates). CONCLUSIONS/SIGNIFICANCE: These findings highlighted the presence of high diversity of Cryptosporidium subgenotypes among Malaysian HIV infected individuals. The predominance of the C. parvum subgenotypes signified the possibility of zoonotic as well as anthroponotic transmissions of cryptosporidiosis in HIV infected individuals

Anxiety and Depression in Adults with Autism Spectrum Disorder: A Systematic Review and Meta-analysis

Adults with autism spectrum disorder (ASD) are thought to be at disproportionate risk of developing mental health comorbidities, with anxiety and depression being considered most prominent amongst these. Yet, no systematic review has been carried out to date to examine rates of both anxiety and depression focusing specifically on adults with ASD. This systematic review and meta-analysis examined the rates of anxiety and depression in adults with ASD and the impact of factors such as assessment methods and presence of comorbid intellectual disability (ID) diagnosis on estimated prevalence rates. Electronic database searches for studies published between January 2000 and September 2017 identified a total of 35 studies, including 30 studies measuring anxiety (n = 26 070; mean age = 30.9, s.d. = 6.2 years) and 29 studies measuring depression (n = 26 117; mean age = 31.1, s.d. = 6.8 years). The pooled estimation of current and lifetime prevalence for adults with ASD were 27% and 42% for any anxiety disorder, and 23% and 37% for depressive disorder. Further analyses revealed that the use of questionnaire measures and the presence of ID may significantly influence estimates of prevalence. The current literature suffers from a high degree of heterogeneity in study method and an overreliance on clinical samples. These results highlight the importance of community-based studies and the identification and inclusion of well-characterized samples to reduce heterogeneity and bias in estimates of prevalence for comorbidity in adults with ASD and other populations with complex psychiatric presentations

On transmissible load formulations in topology optimization

Transmissible loads are external loads defined by their line of action, with actual points of load application chosen as part of the topology optimization process. Although for problems where the optimal structure is a funicular, transmissible loads can be viewed as surface loads, in other cases such loads are free to be applied to internal parts of the structure. There are two main transmissible load formulations described in the literature: a rigid bar (constrained displacement) formulation or, less commonly, a migrating load (equilibrium) formulation. Here, we employ a simple Mohr’s circle analysis to show that the rigid bar formulation will only produce correct structural forms in certain specific circumstances. Numerical examples are used to demonstrate (and explain) the incorrect topologies produced when the rigid bar formulation is applied in other situations. A new analytical solution is also presented for a uniformly loaded cantilever structure. Finally, we invoke duality principles to elucidate the source of the discrepancy between the two formulations, considering both discrete truss and continuum topology optimization formulations