Assessing potential sources of clustering in individually randomised trials

Recent reviews have shown that while clustering is extremely common in individually randomised trials (for example, clustering within centre, therapist, or surgeon), it is rarely accounted for in the trial analysis. Our aim is to develop a general framework for assessing whether potential sources of clustering must be accounted for in the trial analysis to obtain valid type I error rates (non-ignorable clustering), with a particular focus on individually randomised trials

Comparing the Effects of the Induction of Anesthesia with Etomidate to the Induction of Anesthesia with Midazolam on the Incidence of In-Hospital Mortality: A Scoping Review

Purpose/Background The induction of anesthesia using hypnotic sedatives, such as etomidate and midazolam, is common practice. Etomidate and midazolam are commonly employed in the induction of anesthesia in the septic patient population, each with its unique advantages and drawbacks. This scoping review aims to synthesize evidence on the effects of anesthetic induction with etomidate versus midazolam in adult septic patients, focusing on the incidence of mortality and associated adverse effects during hospitalization. The purpose is to establish a standard of care for anesthetic induction in this population. Methods A literature review was conducted from September 2022 to March 2023 utilizing CINAHL Complete, SCOPUS, Access Medicine, Cochrane Library, and PubMed databases. Over 100 articles were found utilizing our keywords, which included induction agent, etomidate, midazolam, critical illness, sepsis, septic shock, severe sepsis, mortality, and hospital length of stay. Of these, 25 articles met the author’s inclusion criteria and underwent Rapid Critical Appraisal (RCA) to assess the quality and validity of the studies. This appraisal yielded ten articles that were further synthesized and classified by their level of evidence table. Results Ten studies were examined to assess the effects of etomidate and midazolam on septic patients. The results showed that when etomidate is used to induce anesthesia in septic patients, it can lead to increased in-hospital mortality rates and longer ICU and hospital lengths of stay. Additionally, six studies found that etomidate can cause adrenal gland suppression. On the other hand, midazolam was associated with lower mortality rates when used to induce anesthesia in septic patients. However, there is insufficient data concerning its ability to produce profound anesthesia in septic patients without causing undesirable hemodynamic changes. Based on the available data, midazolam is considered to be the safer option for inducing anesthesia in septic patients. Implications for Nursing Practice The results of the scoping review support that etomidate usage is linked to longer stays in the ICU and hospital and higher hospital-wide mortality compared to midazolam. These findings indicate that the use of midazolam to induce anesthesia in septic patients is preferred but not without risks to patients. Anesthesia personnel should be educated when utilizing midazolam, blood pressure should be monitored closely, and timely intervention should be conducted to prevent hemodynamic changes. The results of this scoping review highlight the need for a standard of care to be established on what medications to use during the induction of anesthesia in septic patients. Further research is needed to guide nurse anesthesia practice for improved septic patient outcomes

Electoral Volatility, Political Sophistication, Trust and Efficacy

In this article we investigate voter volatility and analyze the causes and motives of switching vote intentions. We test two main sets of variables linked to volatility in literature; political sophistication and ‘political (dis)satisfaction’. Results show that voters with low levels of political efficacy tend to switch more often, both within a campaign and between elections. In the analysis we differentiate between campaign volatility and inter-election volatility and by doing so show that the dynamics of a campaign have a profound impact on volatility. The campaign period is when the lowly sophisticated switch their vote intention. Those with higher levels of interest in politics have switched their intention before the campaign has started. The data for this analysis are from the three wave PartiRep Belgian Election Study (2009)

MRI in multiple myeloma : a pictorial review of diagnostic and post-treatment findings

Magnetic resonance imaging (MRI) is increasingly being used in the diagnostic work-up of patients with multiple myeloma. Since 2014, MRI findings are included in the new diagnostic criteria proposed by the International Myeloma Working Group. Patients with smouldering myeloma presenting with more than one unequivocal focal lesion in the bone marrow on MRI are considered having symptomatic myeloma requiring treatment, regardless of the presence of lytic bone lesions. However, bone marrow evaluation with MRI offers more than only morphological information regarding the detection of focal lesions in patients with MM. The overall performance of MRI is enhanced by applying dynamic contrast-enhanced MRI and diffusion weighted imaging sequences, providing additional functional information on bone marrow vascularization and cellularity. This pictorial review provides an overview of the most important imaging findings in patients with monoclonal gammopathy of undetermined significance, smouldering myeloma and multiple myeloma, by performing a 'total' MRI investigation with implications for the diagnosis, staging and response assessment. Main message aEuro cent Conventional MRI diagnoses multiple myeloma by assessing the infiltration pattern. aEuro cent Dynamic contrast-enhanced MRI diagnoses multiple myeloma by assessing vascularization and perfusion. aEuro cent Diffusion weighted imaging evaluates bone marrow composition and cellularity in multiple myeloma. aEuro cent Combined morphological and functional MRI provides optimal bone marrow assessment for staging. aEuro cent Combined morphological and functional MRI is of considerable value in treatment follow-up

FISH as an effective diagnostic tool for the management of challenging melanocytic lesions

<p>Abstract</p> <p>Background</p> <p>The accuracy of melanoma diagnosis continues to challenge the pathology community, even today with sophisticated histopathologic techniques. Melanocytic lesions exhibit significant morphological heterogeneity. While the majority of biopsies can be classified as benign (nevus) or malignant (melanoma) using well-established histopathologic criteria, there exists a cohort for which the prediction of clinical behaviour and invasive or metastatic potential is difficult if not impossible to ascertain on the basis of morphological features alone. Multiple studies have shown that there is significant disagreement between pathologists and even expert dermatopathologists in the diagnosis of this subgroup of difficult melanocytic lesions.</p> <p>Methods</p> <p>A four probe FISH assay was utilized to analyse a cohort of 500 samples including 157 nevus, 176 dysplastic nevus and 167 melanoma specimens.</p> <p>Results</p> <p>Review of the lesions determined the assay identified genetic abnormalities in a total of 83.8% of melanomas, and 1.9% of nevus without atypia, while genetic abnormalities were identified in 6.3%, 6.7%, and 10.3% of nevus identified with mild, moderate and severe atypia, respectively.</p> <p>Conclusions</p> <p>Based on this study, inheritable genetic damage/instability identified by FISH testing is a hallmark of a progressive malignant process, and a valuable diagnostic tool for the identification of high risk lesions.</p

Life History of Female Preferences for Male Faces: A Comparison of Pubescent Girls, Nonpregnant and Pregnant Young Women, and Middle-aged Women

Although scientific interest in facial attractiveness has developed substantially in recent years, few studies have contributed to our understanding of the ontogeny of facial preferences. In this study, attractiveness of 30 male faces was evaluated by four female groups: girls at puberty, nonpregnant and pregnant young women, and middle-aged women. The main findings are as follows: (1) Preference for sexy-looking faces was strongest in young, nonpregnant women. (2) Biologically more mature girls displayed more adultlike preferences. (3) The intragroup consistency for postmenopausal women was relatively low. (4) In terms of the preference pattern, pregnant women were more similar to perimenopausal women than they were to their nonpregnant peers. (5) Preference for youthful appearance decreased with the age of the women. I argue that the life history of female preferences for male faces is, to a large extent, hormone-driven and underpinned by a set of evolutionary adaptations

Demographic and Psychological Predictors of Parent–Adolescent Communication About Sex: A Representative Statewide Analysis

Sexual communication is a principal means of transmitting sexual values, beliefs, expectations, and knowledge between parents and children. Although this area has received considerable research attention, more studies with representative samples are needed to assure that findings are reflective of populations of interest. A representative statewide sample of households with adolescents (N = 907) from a large and diverse state in the United States was employed to examine the content and extent of sexual communication between parents and their adolescents, and the influence of selected primary demographic (age and gender), socio-demographic (Hispanic ethnicity, education, and religious attendance), and psychological (self-reported comfort, knowledge, and sexual communication difficulties) factors on the number of topics discussed. More than two-thirds of the parents reported experiencing some type of sexual communication difficulty, such as developmental concerns and embarrassment. Hierarchical regression results indicated that self-reported comfort, knowledge, and sexual communication difficulties strongly predicted the number of topics discussed, beyond the effect of demographic variables. These findings reinforce the notion that sexual communication between parents and adolescents can be universally challenging, and parents of both genders, all ages, and all socio-demographic characteristics might benefit from education and support

Generation of angiostatin-like fragments from plasminogen by prostate-specific antigen

Angiostatin, a potent inhibitor of angiogenesis, tumour growth and metastasis, is a biologically active fragment of plasminogen, containing the kringle domains 1–4. It is generated from plasminogen by limited proteolysis. We show that prostate-specific antigen (PSA), a serine proteinase secreted by human prostate and human prostate cancer cells, is able to convert Lys-plasminogen to biologically active angiostatin-like fragments, containing kringles 1–4, by limited proteolysis of peptide bond Glu439–Ala440 in vitro. In an in vitro morphogenesis assay, the purified angiostatin-like fragments inhibited proliferation and tubular formation of human umbilical vein endothelial cells with the same efficacy as angiostatin. This finding might help to understand growth characteristics of prostate cancer, which usually has low microvessel density and slow proliferation. © 1999 Cancer Research Campaig

Klebsiella pneumoniae Multiresistance Plasmid pMET1: Similarity with the Yersinia pestis Plasmid pCRY and Integrative Conjugative Elements

Dissemination of antimicrobial resistance genes has become an important public health and biodefense threat. Plasmids are important contributors to the rapid acquisition of antibiotic resistance by pathogenic bacteria.The nucleotide sequence of the Klebsiella pneumoniae multiresistance plasmid pMET1 comprises 41,723 bp and includes Tn1331.2, a transposon that carries the bla(TEM-1) gene and a perfect duplication of a 3-kbp region including the aac(6')-Ib, aadA1, and bla(OXA-9) genes. The replication region of pMET1 has been identified. Replication is independent of DNA polymerase I, and the replication region is highly related to that of the cryptic Yersinia pestis 91001 plasmid pCRY. The potential partition region has the general organization known as the parFG locus. The self-transmissible pMET1 plasmid includes a type IV secretion system consisting of proteins that make up the mating pair formation complex (Mpf) and the DNA transfer (Dtr) system. The Mpf is highly related to those in the plasmid pCRY, the mobilizable high-pathogenicity island from E. coli ECOR31 (HPI(ECOR31)), which has been proposed to be an integrative conjugative element (ICE) progenitor of high-pathogenicity islands in other Enterobacteriaceae including Yersinia species, and ICE(Kp1), an ICE found in a K. pneumoniae strain causing primary liver abscess. The Dtr MobB and MobC proteins are highly related to those of pCRY, but the endonuclease is related to that of plasmid pK245 and has no significant homology with the protein of similar function in pCRY. The region upstream of mobB includes the putative oriT and shares 90% identity with the same region in the HPI(ECOR31).The comparative analyses of pMET1 with pCRY, HPI(ECOR31), and ICE(Kp1 )show a very active rate of genetic exchanges between Enterobacteriaceae including Yersinia species, which represents a high public health and biodefense threat due to transfer of multiple resistance genes to pathogenic Yersinia strains

The Role of the RN in an Interprofessional Primary Health Care Team

OBJECTIVE OF THE PROJECT To understand the role of RN as a member of the interprofessional health care team in primary care and its effect on patient care outcomes, cost and effectiveness and provider satisfaction