Selecting and implementing overview methods: implications from five exemplar overviews

This is the final version of the article. Available from BioMed Central via the DOI in this record.Background Overviews of systematic reviews are an increasingly popular method of evidence synthesis; there is a lack of clear guidance for completing overviews and a number of methodological challenges. At the UK Cochrane Symposium 2016, methodological challenges of five overviews were explored. Using data from these five overviews, practical implications to support methodological decision making of authors writing protocols for future overviews are proposed. Methods Methods, and their justification, from the five exemplar overviews were tabulated and compared with areas of debate identified within current literature. Key methodological challenges and implications for development of overview protocols were generated and synthesised into a list, discussed and refined until there was consensus. Results Methodological features of three Cochrane overviews, one overview of diagnostic test accuracy and one mixed methods overview have been summarised. Methods of selection of reviews and data extraction were similar. Either the AMSTAR or ROBIS tool was used to assess quality of included reviews. The GRADE approach was most commonly used to assess quality of evidence within the reviews. Eight key methodological challenges were identified from the exemplar overviews. There was good agreement between our findings and emerging areas of debate within a recent published synthesis. Implications for development of protocols for future overviews were identified. Conclusions Overviews are a relatively new methodological innovation, and there are currently substantial variations in the methodological approaches used within different overviews. There are considerable methodological challenges for which optimal solutions are not necessarily yet known. Lessons learnt from five exemplar overviews highlight a number of methodological decisions which may be beneficial to consider during the development of an overview protocol.The overview conducted by Pollock [19] was supported by a project grant from the Chief Scientist Office of the Scottish Government. The overview conducted by McClurg [21] was supported by a project grant by the Physiotherapy Research Foundation. The overview by Hunt [22] was supported as part of doctoral programme funding by the National Institute for Health Research (NIHR) Collaboration for Leadership in Applied Health Research and Care South West Peninsula (PenCLAHRC). The overview conducted by Estcourt [20] was supported by an NIHR Cochrane Programme Grant for the Safe and Appropriate Use of Blood Components. The overview conducted by Brunton [23] was commissioned by the Department of Health as part of an ongoing programme of work on health policy research synthesis. Alex Pollock is employed by the Nursing, Midwifery and Allied Health Professions (NMAHP) Research Unit, which is supported by the Chief Scientist Office of the Scottish Government. Pauline Campbell is supported by the Chief Nurses Office of the Scottish Government

MMS observations of electron-scale filamentary currents in the reconnection exhaust and near the X line

© 2016. American Geophysical Union. All Rights Reserved.We report Magnetospheric Multiscale observations of macroscopic and electron-scale current layers in asymmetric reconnection. By intercomparing plasma, magnetic, and electric field data at multiple crossings of a reconnecting magnetopause on 22 October 2015, when the average interspacecraft separation was ~10km, we demonstrate that the ion and electron moments are sufficiently accurate to provide reliable current density measurements at 30ms cadence. These measurements, which resolve current layers narrower than the interspacecraft separation, reveal electron-scale filamentary Hall currents and electron vorticity within the reconnection exhaust far downstream of the X line and even in the magnetosheath. Slightly downstream of the X line, intense (up to 3μA/m2) electron currents, a super-Alfvénic outflowing electron jet, and nongyrotropic crescent shape electron distributions were observed deep inside the ion-scale magnetopause current sheet and embedded in the ion diffusion region. These characteristics are similar to those attributed to the electron dissipation/diffusion region around the X line

Event-related potential studies of post-traumatic stress disorder: a critical review and synthesis

Despite the sparseness of the currently available data, there is accumulating evidence of information processing impairment in post-traumatic stress disorder (PTSD). Studies of event-related potentials (ERPs) are the main tool in real time examination of information processing. In this paper, we sought to critically review the ERP evidence of information processing abnormalities in patients with PTSD. We also examined the evidence supporting the existence of a relationship between ERP abnormalities and symptom profiles or severity in PTSD patients. An extensive Medline search was performed. Keywords included PTSD or post-traumatic stress disorder, electrophysiology or EEG, electrophysiology, P50, P100, N100, P2, P200, P3, P300, sensory gating, CNV (contingent negative variation) and MMN (mismatch negativity). We limited the review to ERP adult human studies with control groups which were reported in the English language. After applying our inclusion-exclusion review criteria, 36 studies were included. Subjects exposed to wide ranges of military and civilian traumas were studied in these reports. Presented stimuli were both auditory and visual. The most widely studied components included P300, P50 gating, N100 and P200. Most of the studies reported increased P300 response to trauma-related stimuli in PTSD patients. A smaller group of studies reported dampening of responses or no change in responses to trauma-related and/or unrelated stimuli. P50 studies were strongly suggestive of impaired gating in patients with PTSD. In conclusion, the majority of reports support evidence of information processing abnormalities in patients with PTSD diagnosis. The predominance of evidence suggests presence of mid-latency and late ERP components differences in PTSD patients in comparison to healthy controls. Heterogeneity of assessment methods used contributes to difficulties in reaching firm conclusions regarding the nature of these differences. We suggest that future ERP-PTSD studies utilize standardized assessment scales that provide detailed information regarding the symptom clusters and the degree of symptom severity. This would allow assessment of electrophysiological indices-clinical symptoms relationships. Based on the available data, we suggest that ERP abnormalities in PTSD are possibly affected by the level of illness severity. If supported by future research, ERP studies may be used for both initial assessment and treatment follow-up

Communication between family carers and health professionals about end-of-life care for older people in the acute hospital setting: a qualitative study

This paper focuses on communication between hospital staff and family carers of patients dying on acute hospital wards, with an emphasis on the family carers’ perspective. The age at which people in the UK die is increasing and many continue to die in the acute hospital setting. Concerns have been expressed about poor quality end of life care in hospitals, in particular regarding communication between staff and relatives. This research aimed to understand the factors and processes which affect the quality of care provided to frail older people who are dying in hospital and their family carers

Using an online survey of healthcare-seeking behaviour to estimate the magnitude and severity of the 2009 H1N1v influenza epidemic in England

Background : During the 2009 H1N1v influenza epidemic, the total number of symptomatic cases was estimated by combining influenza-like illness (ILI) consultations, virological surveillance and assumptions about healthcare-seeking behaviour. Changes in healthcare-seeking behaviour due to changing scientific information, media coverage and public anxiety, were not included in case estimates. The purpose of the study was to improve estimates of the number of symptomatic H1N1v cases and the case fatality rate (CFR) in England by quantifying healthcare-seeking behaviour using an internet-based survey carried out during the course of the 2009 H1N1v influenza epidemic. Methods : We used an online survey that ran continuously from July 2009 to March 2010 to estimate the proportion of ILI cases that sought healthcare during the 2009 H1N1v influenza epidemic. We used dynamic age- and gender-dependent measures of healthcare-seeking behaviour to re-interpret consultation numbers and estimate the true number of cases of symptomatic ILI in 2009 and the case fatality rate (CFR). Results : There were significant differences between age groups in healthcare usage. From the start to the end of the epidemic, the percentage of individuals with influenza-like symptoms who sought medical attention decreased from 43% to 32% (p < 0.0001). Adjusting official numbers accordingly, we estimate that there were 1.1 million symptomatic cases in England, over 320,000 (40%) more cases than previously estimated and that the autumn epidemic wave was 45% bigger than previously thought. Combining symptomatic case numbers with reported deaths leads to a reduced overall CFR estimate of 17 deaths per 100,000 cases, with the largest reduction in adults. Conclusions : Active surveillance of healthcare-seeking behaviour, which can be achieved using novel data collection methods, is vital for providing accurate real-time estimates of epidemic size and disease severity. The differences in healthcare-seeking between different population groups and changes over time have significant implications for estimates of total case numbers and the case fatality rate

Consistency and accuracy of diagnostic cancer codes generated by automated registration: comparison with manual registration

BACKGROUND: Automated procedures are increasingly used in cancer registration, and it is important that the data produced are systematically checked for consistency and accuracy. We evaluated an automated procedure for cancer registration adopted by the Lombardy Cancer Registry in 1997, comparing automatically-generated diagnostic codes with those produced manually over one year (1997). METHODS: The automatically generated cancer cases were produced by Open Registry algorithms. For manual registration, trained staff consulted clinical records, pathology reports and death certificates. The social security code, present and checked in both databases in all cases, was used to match the files in the automatic and manual databases. The cancer cases generated by the two methods were compared by manual revision. RESULTS: The automated procedure generated 5027 cases: 2959 (59%) were accepted automatically and 2068 (41%) were flagged for manual checking. Among the cases accepted automatically, discrepancies in data items (surname, first name, sex and date of birth) constituted 8.5% of cases, and discrepancies in the first three digits of the ICD-9 code constituted 1.6%. Among flagged cases, cancers of female genital tract, hematopoietic system, metastatic and ill-defined sites, and oropharynx predominated. The usual reasons were use of specific vs. generic codes, presence of multiple primaries, and use of extranodal vs. nodal codes for lymphomas. The percentage of automatically accepted cases ranged from 83% for breast and thyroid cancers to 13% for metastatic and ill-defined cancer sites. CONCLUSION: Since 59% of cases were accepted automatically and contained relatively few, mostly trivial discrepancies, the automatic procedure is efficient for routine case generation effectively cutting the workload required for routine case checking by this amount. Among cases not accepted automatically, discrepancies were mainly due to variations in coding practice

Validation of the Organizational Culture Assessment Instrument

Organizational culture is a commonly studied area in industrial/organizational psychology due to its important role in workplace behaviour, cognitions, and outcomes. Jung et al.'s [1] review of the psychometric properties of organizational culture measurement instruments noted many instruments have limited validation data despite frequent use in both theoretical and applied situations. The Organizational Culture Assessment Instrument (OCAI) has had conflicting data regarding its psychometric properties, particularly regarding its factor structure. Our study examined the factor structure and criterion validity of the OCAI using robust analysis methods on data gathered from 328 (females = 226, males = 102) Australian employees. Confirmatory factor analysis supported a four factor structure of the OCAI for both ideal and current organizational culture perspectives. Current organizational culture data demonstrated expected reciprocally-opposed relationships between three of the four OCAI factors and the outcome variable of job satisfaction but ideal culture data did not, thus indicating possible weak criterion validity when the OCAI is used to assess ideal culture. Based on the mixed evidence regarding the measure's properties, further examination of the factor structure and broad validity of the measure is encouraged

Breastfeeding, Maternal Education and Cognitive Function: A Prospective Study in Twins

The effect of breastfeeding on cognitive abilities is examined in the offspring of highly educated women and compared to the effects in women with low or middle educational attainment. All offspring consisted of 12-year old mono- or dizygotic twins and this made it possible to study the effect of breastfeeding on mean cognition scores as well as the moderating effects of breastfeeding on the heritability of variation in cognition. Information on breastfeeding and cognitive ability was available for 6,569 children. Breastfeeding status was prospectively assessed in the first years after birth of the children. Maternal education is positively associated with performance on a standardized test for cognitive ability in offspring. A significant effect of breastfeeding on cognition was also observed. The effect was similar for offspring with mothers with a high, middle, and low educational level. Breast-fed children of highly educated mothers score on average 7.6 point higher on a standardized test of cognitive abilities (CITO test; range 500–550; effects size = .936) than formula-fed children of mothers with a low education. Individual differences in cognition scores are largely accounted for by additive genetic factors (80%) and breastfeeding does not modify the effect of genetic factors in any of the three strata of maternal education. Heritability was slightly lower in children with a mother with a middle-level education

Epigenetic re-wiring of breast cancer by pharmacological targeting of C-terminal binding protein

The C-terminal binding protein (CtBP) is an NADH-dependent dimeric family of nuclear proteins that scaffold interactions between transcriptional regulators and chromatin-modifying complexes. Its association with poor survival in several cancers implicates CtBP as a promising target for pharmacological intervention. We employed computer-assisted drug design to search for CtBP inhibitors, using quantitative structure-activity relationship (QSAR) modeling and docking. Functional screening of these drugs identified 4 compounds with low toxicity and high water solubility. Micro molar concentrations of these CtBP inhibitors produces significant de-repression of epigenetically silenced pro-epithelial genes, preferentially in the triple-negative breast cancer cell line MDA-MB-231. This epigenetic reprogramming occurs through eviction of CtBP from gene promoters; disrupted recruitment of chromatin-modifying protein complexes containing LSD1, and HDAC1; and re-wiring of activating histone marks at targeted genes. In functional assays, CtBP inhibition disrupts CtBP dimerization, decreases cell migration, abolishes cellular invasion, and improves DNA repair. Combinatorial use of CtBP inhibitors with the LSD1 inhibitor pargyline has synergistic influence. Finally, integrated correlation of gene expression in breast cancer patients with nuclear levels of CtBP1 and LSD1, reveals new potential therapeutic vulnerabilities. These findings implicate a broad role for this class of compounds in strategies for epigenetically targeted therapeutic intervention

Utilisation of an operative difficulty grading scale for laparoscopic cholecystectomy

Background A reliable system for grading operative difficulty of laparoscopic cholecystectomy would standardise description of findings and reporting of outcomes. The aim of this study was to validate a difficulty grading system (Nassar scale), testing its applicability and consistency in two large prospective datasets. Methods Patient and disease-related variables and 30-day outcomes were identified in two prospective cholecystectomy databases: the multi-centre prospective cohort of 8820 patients from the recent CholeS Study and the single-surgeon series containing 4089 patients. Operative data and patient outcomes were correlated with Nassar operative difficultly scale, using Kendall’s tau for dichotomous variables, or Jonckheere–Terpstra tests for continuous variables. A ROC curve analysis was performed, to quantify the predictive accuracy of the scale for each outcome, with continuous outcomes dichotomised, prior to analysis. Results A higher operative difficulty grade was consistently associated with worse outcomes for the patients in both the reference and CholeS cohorts. The median length of stay increased from 0 to 4 days, and the 30-day complication rate from 7.6 to 24.4% as the difficulty grade increased from 1 to 4/5 (both p < 0.001). In the CholeS cohort, a higher difficulty grade was found to be most strongly associated with conversion to open and 30-day mortality (AUROC = 0.903, 0.822, respectively). On multivariable analysis, the Nassar operative difficultly scale was found to be a significant independent predictor of operative duration, conversion to open surgery, 30-day complications and 30-day reintervention (all p < 0.001). Conclusion We have shown that an operative difficulty scale can standardise the description of operative findings by multiple grades of surgeons to facilitate audit, training assessment and research. It provides a tool for reporting operative findings, disease severity and technical difficulty and can be utilised in future research to reliably compare outcomes according to case mix and intra-operative difficulty