Overstating the evidence - double counting in meta-analysis and related problems

Background: The problem of missing studies in meta-analysis has received much attention. Less attention has been paid to the more serious problem of double counting of evidence. Methods: Various problems in overstating the precision of results from meta-analyses are described and illustrated with examples, including papers from leading medical journals. These problems include, but are not limited to, simple double-counting of the same studies, double counting of some aspects of the studies, inappropriate imputation of results, and assigning spurious precision to individual studies. Results: Some suggestions are made as to how the quality and reliability of meta-analysis can be improved. It is proposed that the key to quality in meta-analysis lies in the results being transparent and checkable. Conclusions: Existing quality check lists for meta-analysis do little to encourage an appropriate attitude to combining evidence and to statistical analysis. Journals and other relevant organisations should encourage authors to make data available and make methods explicit. They should also act promptly to withdraw meta-analyses when mistakes are found

A Comparative Computer Simulation of Dendritic Morphology

Computational modeling of neuronal morphology is a powerful tool for understanding developmental processes and structure-function relationships. We present a multifaceted approach based on stochastic sampling of morphological measures from digital reconstructions of real cells. We examined how dendritic elongation, branching, and taper are controlled by three morphometric determinants: Branch Order, Radius, and Path Distance from the soma. Virtual dendrites were simulated starting from 3,715 neuronal trees reconstructed in 16 different laboratories, including morphological classes as diverse as spinal motoneurons and dentate granule cells. Several emergent morphometrics were used to compare real and virtual trees. Relating model parameters to Branch Order best constrained the number of terminations for most morphological classes, except pyramidal cell apical trees, which were better described by a dependence on Path Distance. In contrast, bifurcation asymmetry was best constrained by Radius for apical, but Path Distance for basal trees. All determinants showed similar performance in capturing total surface area, while surface area asymmetry was best determined by Path Distance. Grouping by other characteristics, such as size, asymmetry, arborizations, or animal species, showed smaller differences than observed between apical and basal, pointing to the biological importance of this separation. Hybrid models using combinations of the determinants confirmed these trends and allowed a detailed characterization of morphological relations. The differential findings between morphological groups suggest different underlying developmental mechanisms. By comparing the effects of several morphometric determinants on the simulation of different neuronal classes, this approach sheds light on possible growth mechanism variations responsible for the observed neuronal diversity

Antimicrobial-impregnated central venous catheters for preventing neonatal bloodstream infection: the PREVAIL RCT

BACKGROUND: Clinical trials show that antimicrobial-impregnated central venous catheters reduce catheter-related bloodstream infection in adults and children receiving intensive care, but there is insufficient evidence for use in newborn babies. OBJECTIVES: The objectives were (1) to determine clinical effectiveness by conducting a randomised controlled trial comparing antimicrobial-impregnated peripherally inserted central venous catheters with standard peripherally inserted central venous catheters for reducing bloodstream or cerebrospinal fluid infections (referred to as bloodstream infections); (2) to conduct an economic evaluation of the costs, cost-effectiveness and value of conducting additional research; and (3) to conduct a generalisability analysis of trial findings to neonatal care in the NHS. DESIGN: Three separate studies were undertaken, each addressing one of the three objectives. (1) This was a multicentre, open-label, pragmatic randomised controlled trial; (2) an analysis was undertaken of hospital care costs, lifetime cost-effectiveness and value of information from an NHS perspective; and (3) this was a retrospective cohort study of bloodstream infection rates in neonatal units in England. SETTING: The randomised controlled trial was conducted in 18 neonatal intensive care units in England. PARTICIPANTS: Participants were babies who required a peripherally inserted central venous catheter (of 1 French gauge in size). INTERVENTIONS: The interventions were an antimicrobial-impregnated peripherally inserted central venous catheter (coated with rifampicin-miconazole) or a standard peripherally inserted central venous catheter, allocated randomly (1 : 1) using web randomisation. MAIN OUTCOME MEASURE: Study 1 - time to first bloodstream infection, sampled between 24 hours after randomisation and 48 hours after peripherally inserted central venous catheter removal. Study 2 - cost-effectiveness of the antimicrobial-impregnated peripherally inserted central venous catheter compared with the standard peripherally inserted central venous catheters. Study 3 - risk-adjusted bloodstream rates in the trial compared with those in neonatal units in England. For study 3, the data used were as follows: (1) case report forms and linked death registrations; (2) case report forms and linked death registrations linked to administrative health records with 6-month follow-up; and (3) neonatal health records linked to infection surveillance data. RESULTS: Study 1, clinical effectiveness - 861 babies were randomised (antimicrobial-impregnated peripherally inserted central venous catheter, n = 430; standard peripherally inserted central venous catheter, n = 431). Bloodstream infections occurred in 46 babies (10.7%) randomised to antimicrobial-impregnated peripherally inserted central venous catheters and in 44 (10.2%) babies randomised to standard peripherally inserted central venous catheters. No difference in time to bloodstream infection was detected (hazard ratio 1.11, 95% confidence interval 0.73 to 1.67; p = 0.63). Secondary outcomes of rifampicin resistance in positive blood/cerebrospinal fluid cultures, mortality, clinical outcomes at neonatal unit discharge and time to peripherally inserted central venous catheter removal were similar in both groups. Rifampicin resistance in positive peripherally inserted central venous catheter tip cultures was higher in the antimicrobial-impregnated peripherally inserted central venous catheter group (relative risk 3.51, 95% confidence interval 1.16 to 10.57; p = 0.02) than in the standard peripherally inserted central venous catheter group. Adverse events were similar in both groups. Study 2, economic evaluation - the mean cost of babies' hospital care was £83,473. Antimicrobial-impregnated peripherally inserted central venous catheters were not cost-effective. Given the increased price, compared with standard peripherally inserted central venous catheters, the minimum reduction in risk of bloodstream infection for antimicrobial-impregnated peripherally inserted central venous catheters to be cost-effective was 3% and 15% for babies born at 23-27 and 28-32 weeks' gestation, respectively. Study 3, generalisability analysis - risk-adjusted bloodstream infection rates per 1000 peripherally inserted central venous catheter days were similar among babies in the trial and in all neonatal units. Of all bloodstream infections in babies receiving intensive or high-dependency care in neonatal units, 46% occurred during peripherally inserted central venous catheter days. LIMITATIONS: The trial was open label as antimicrobial-impregnated and standard peripherally inserted central venous catheters are different colours. There was insufficient power to determine differences in rifampicin resistance. CONCLUSIONS: No evidence of benefit or harm was found of peripherally inserted central venous catheters impregnated with rifampicin-miconazole during neonatal care. Interventions with small effects on bloodstream infections could be cost-effective over a child's life course. Findings were generalisable to neonatal units in England. Future research should focus on other types of antimicrobial impregnation of peripherally inserted central venous catheters and alternative approaches for preventing bloodstream infections in neonatal care. TRIAL REGISTRATION: Current Controlled Trials ISRCTN81931394. FUNDING: This project was funded by the National Institute for Health Research Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 24, No. 57. See the NIHR Journals Library website for further project information

Free abdominal fluid without obvious solid organ injury upon CT imaging: an actual problem or simply over-diagnosing?

Whereas a non-operative approach for hemodynamically stable patients with free intraabdominal fluid in the presence of solid organ injury is generally accepted, the presence of free fluid in the abdomen without evidence of solid organ injury not only presents a challenge for the treating emergency physician but also for the surgeon in charge. Despite recent advances in imaging modalities, with multi-detector computed tomography (CT) (with or without contrast agent) usually the imaging method of choice, diagnosis and interpretation of the results remains difficult. While some studies conclude that CT is highly accurate and relatively specific at diagnosing mesenteric and hollow viscus injury, others studies deem CT to be unreliable. These differences may in part be due to the experience and the interpretation of the radiologist and/or the treating physician or surgeon

Quality of life among parents of preterm infants: a scoping review

Purpose: To synthesize the body of knowledge on the factors influencing the QoL of mothers and fathers of preterm infants. Methods: A scoping review was performed. Publications indexed in PubMed®, Web of Science™, CINAHL® and PsycINFO® were searched, targeting studies presenting original empirical data that examined parental perception on QoL after a preterm delivery. Eligibility and data extraction were conducted by two independent researchers. The main quantitative findings were synthesized and qualitative data were explored by content analysis. Results: The studies, 11 quantitative and 1 mixed methods, were derived mainly from the USA (n = 6). Heterogeneity across the studies was observed regarding the operationalization of QoL and the use of units of analysis (mothers, parents, families and caregivers). In a context where 40 out of 45 covariates were analysed by only one or two studies, results suggested that parental QoL after a preterm delivery is influenced by factors related with mother’s characteristics, family issues and health care environment rather than infants’ variables. Factors regarding fathers’ characteristics and structural levels were not addressed. Conclusions: Standardizing the operationalization of the QoL when analysing mothers and fathers of preterm infants calls for a structured questionnaire adapted to their specific needs. Further research should include both mothers and fathers, invest in mixed methods approaches and be performed in different countries and settings for allowing integration and comparison of findings.This work was supported by FEDER funding from the Operational Programme Factors of Competitiveness—COMPETE and by national funding from the Foundation for Science and Technology—FCT (Portuguese Ministry of Science, Technology and Higher Education) under the project “Parenting roles and knowledge in Neonatal Intensive Care Units” (FCOMP-01-0124-FEDER-019902; Ref. FCT PTDC/CS-ECS/120750/2010) and the Unidade de Investigação em Epidemiologia—Instituto de Saúde Pública da Universidade do Porto (EPIUnit) (POCI-01-0145-FEDER-006862; Ref. UID/DTP/04750/2013); the grants PD/BD/105830/2014 (to MA), SFRH/BPD/103562/2014 (to EA), co-funded by the FCT and the POPH/FSE Program and the FCT Investigator contract IF/01674/2015 (to SS)

The Role of Methylation in the Intrinsic Dynamics of B- and Z-DNA

Methylation of cytosine at the 5-carbon position (5mC) is observed in both prokaryotes and eukaryotes. In humans, DNA methylation at CpG sites plays an important role in gene regulation and has been implicated in development, gene silencing, and cancer. In addition, the CpG dinucleotide is a known hot spot for pathologic mutations genome-wide. CpG tracts may adopt left-handed Z-DNA conformations, which have also been implicated in gene regulation and genomic instability. Methylation facilitates this B-Z transition but the underlying mechanism remains unclear. Herein, four structural models of the dinucleotide d(GC)5 repeat sequence in B-, methylated B-, Z-, and methylated Z-DNA forms were constructed and an aggregate 100 nanoseconds of molecular dynamics simulations in explicit solvent under physiological conditions was performed for each model. Both unmethylated and methylated B-DNA were found to be more flexible than Z-DNA. However, methylation significantly destabilized the BII, relative to the BI, state through the Gp5mC steps. In addition, methylation decreased the free energy difference between B- and Z-DNA. Comparisons of α/γ backbone torsional angles showed that torsional states changed marginally upon methylation for B-DNA, and Z-DNA. Methylation-induced conformational changes and lower energy differences may contribute to the transition to Z-DNA by methylated, over unmethylated, B-DNA and may be a contributing factor to biological function

Shiga Toxin Binding to Glycolipids and Glycans

Background: Immunologically distinct forms of Shiga toxin (Stx1 and Stx2) display different potencies and disease outcomes, likely due to differences in host cell binding. The glycolipid globotriaosylceramide (Gb3) has been reported to be the receptor for both toxins. While there is considerable data to suggest that Gb3 can bind Stx1, binding of Stx2 to Gb3 is variable. Methodology: We used isothermal titration calorimetry (ITC) and enzyme-linked immunosorbent assay (ELISA) to examine binding of Stx1 and Stx2 to various glycans, glycosphingolipids, and glycosphingolipid mixtures in the presence or absence of membrane components, phosphatidylcholine, and cholesterol. We have also assessed the ability of glycolipids mixtures to neutralize Stx-mediated inhibition of protein synthesis in Vero kidney cells. Results: By ITC, Stx1 bound both Pk (the trisaccharide on Gb3) and P (the tetrasaccharide on globotetraosylceramide, Gb4), while Stx2 did not bind to either glycan. Binding to neutral glycolipids individually and in combination was assessed by ELISA. Stx1 bound to glycolipids Gb3 and Gb4, and Gb3 mixed with other neural glycolipids, while Stx2 only bound to Gb3 mixtures. In the presence of phosphatidylcholine and cholesterol, both Stx1 and Stx2 bound well to Gb3 or Gb4 alone or mixed with other neutral glycolipids. Pre-incubation with Gb3 in the presence of phosphatidylcholine and cholesterol neutralized Stx1, but not Stx2 toxicity to Vero cells

Transmission-Blocking Vaccines: Focus on Anti-Vector Vaccines against Tick-Borne Diseases

Tick-borne diseases are a potential threat that account for significant morbidity and mortality in human population worldwide. Vaccines are not available to treat several of the tick-borne diseases. With the emergence and resurgence of several tick-borne diseases, emphasis on the development of transmission-blocking vaccines remains increasing. In this review, we provide a snap shot on some of the potential candidates for the development of anti-vector vaccines (a form of transmission-blocking vaccines) against wide range of hard and soft ticks that include Ixodes, Haemaphysalis, Dermacentor, Amblyomma, Rhipicephalus and Ornithodoros species

Nurse-patient interaction and communication: a systematic literature review

Aim: The purpose of this review is to describe the use and definitions of the concepts of nurse-patient interaction and nurse-patient communication in nursing literature. Furthermore, empirical findings of nurse-patient communication research will be presented, and applied theories will be shown. Method: An integrative literature search was executed. The total number of relevant citations found was 97. The search results were reviewed, and key points were extracted in a standardized form. Extracts were then qualitatively summarized according to relevant aspects and categories for the review. Results: The relation of interaction and communication is not clearly defined in nursing literature. Often the terms are used interchangeably or synonymously, and a clear theoretical definition is avoided or rather implicit. Symbolic interactionism and classic sender-receiver models were by far the most referred to models. Compared to the use of theories of adjacent sciences, the use of original nursing theories related to communication is rather infrequent. The articles that try to clarify the relation of both concepts see communication as a special or subtype of interaction. Conclusion: The included citations all conclude that communication skills can be learned to a certain degree. Involvement of patients and their role in communication often is neglected by authors. Considering the mutual nature of communication, patients’ share in conversation should be taken more into consideration than it has been until now. Nursing science has to integrate its own theories of nursing care with theories of communication and interaction from other scientific disciplines like sociology