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Introduction Deprescribing, the systematic process of stopping or altering inappropriate medicines, has been suggested as a safe, effective and appropriate process to optimise prescribing for older adults (1). There is still a lack of understanding of how best to implement sustainable deprescribing in long-term care (LTC). Aim Design a theory-driven implementation strategy, based on consensus from healthcare professionals (HCPs), to facilitate their engagement with deprescribing for frail older adults in LTC. Methods This study consisted of three phases and was designed in conjunction with HCPs working in LTC. Firstly, barriers and enablers to deprescribing in LTC previously identified by the research team were mapped to behaviour change techniques (BCTs) (2). Secondly, a Delphi survey of HCPs (General Practitioners (GPs), Pharmacists, nurses, geriatricians and psychiatrists of old age) was conducted to select feasible BCTs to support deprescribing. HCPs were purposively sampled and recruited via email, divided into HCPs working in Ireland and internationally. Experts were identified from existing professional relationships, engagement with LTC or deprescribing research. Using the results from the Delphi process, the literature on deprescribing interventions and research team knowledge, the BCTs which could form components of an intervention in LTC were shortlisted based on was acceptability, effectiveness, affordability, safety and equity (APEASE). Finally, a roundtable discussion was held with a purposeful, convenience sample of GPs, Pharmacists and nurses working in LTC in Ireland, to prioritise the previously identified barriers/enablers and operationalise the proposed deprescribing strategies created from feasible BCTs and identify the most important strategy to facilitate deprescribing. Results Overall, 34 BCTs were mapped to previously identified barriers/enablers to deprescribing in LTC. For the Delphi survey, 33 HCPs were invited, 20 agreed and it was completed by 16 participants. The Delphi consisted of two rounds. Participants reached consensus that 26 of the BCTs could feasibly be implemented in LTC. Following the APEASE assessment, 21 BCTs were considered eligible for operationalisation. The roundtable discussion, consisting of eight HCPs, identified that lack of resources (time, staffing, technology), was the most important barrier to address. The agreed implementation strategy to enhance engagement with deprescribing processes was an education session prior to a multidisciplinary team (MDT) meeting, led by a nurse from the LTC setting. This was designed from 11 BCTs, including action planning, social support and environmental restructuring addressing the predominant barrier. Incorporating the MDT reduces the burden which would exist if the responsibility was placed on one HCP. Meeting at the LTC site addresses the insufficient technology, as patient information is available. Conclusion This study describes an implementation strategy design process following principles of behavioural and implementation science. Engaging targeted end users throughout the process allows for the creation of a strategy which is intended to address the main perceived barrier to deprescribing of insufficient resources. A limitation of this study is the specificity of the intervention for Irish LTC context, which may have different staffing and organisational structures compared to international healthcare systems. References 1. Ibrahim K, Cox NJ, Stevenson JM, Lim S, Fraser SDS, Roberts HC. A systematic review of the evidence for deprescribing interventions among older people living with frailty. BMC Geriatrics. 2021 Apr 17;21(1):258. 2. Michie S, Atkins L, West R. The Behaviour Change Wheel: A Guide to Designing Interventions [Internet]. 1st ed. Silverback Publishing; 2014 [cited 2022 Jan 11]. Available from: https://books.google.ie/books/about/The_behaviour_change_wheel_a_guide_to_de.html?id=1TGIrgEACAAJ&source=kp_book_description&redir_esc=y

Background Multimorbidity and polypharmacy often result in numerous interactions with different Healthcare Professionals (HCPs) and many transitions of care. Keeping up-to-date medications list in people taking medicines and/or carers can reduce medication errors at care transitions. The HSE National Quality Improvement team is working on a national medication safety campaign which encourages people to keep lists. However, there is limited information about perceptions of Patient-Held Medication Lists (PHML) in clinical practice. The aim of this study was to examine attitudes to PHML among people taking/managing multiple medicines, HCPs; and how lists are used in practice. Methods Purposive sampling was employed and recruitment through relevant organisations, social media and snowballing methods. Semi-structured telephone interviews were conducted with 39 people; HCPs (N=21), patients/caregivers (N=18). Interviews were transcribed and thematically analysed with behavioural frameworks - the Consolidated Framework for Implementation Research (CFIR) and Theoretical Domains Framework (TDF). Results Three core themes were identified: Attitudes to PHML; Function and preferred features of PHML and Barriers and facilitators to future use of PHML. All participants thought keeping medication lists had benefits for both people and HCPs (e.g. empowering, improving adherence). All who were taking medicines used lists and found them useful in particular situations (e.g. emergencies). However, HCPs and patient/caregiver groups expressed concerns about their accuracy. It was felt that some individuals may have difficulties keeping an accurate PHML (e.g. older adults, on multiple/changing medications). The participants also differed on the level of detail that should be included in PHMLs. Most patients favoured simple lists but HCPs reported the lack of detailed information in PHML may be an issue. Conclusion Common concerns about the accuracy of PHML and diverging opinions on list content need to be addressed. Health promotion strategies which focus on promotion of lists by key HCPs and provide people with a variety of list options could increase the wider implementation of PHMLs.

Background Deprescribing is associated with positive health outcomes for older adults in long-term care, however deprescribing is not universally implemented. This study aims to identify the most prevalent Potentially Inappropriate Medication (PIM) used among frail older adults resident in Irish Long-Term Care Facilities (LTCFs), as identified by the Screening Tool of Older Persons Prescriptions in Frail adults with limited life expectancy version 2 (STOPPFrail V2), to form the basis of a deprescribing intervention. Methods A retrospective chart review was conducted in two publicly-funded LTCFs in the South/Southwest of Ireland (‘Site 1’ and ‘Site 2’). Eligible participants were those: (i) ≥65 years, (ii) resident in Site 1 or 2, (iii) eligible as per the STOPPFrail v2 criteria by the site’s medical officer, and (iv) receiving regular prescribed medication. Data collected included age, gender, drug, dose, frequency, regular/pro re nata and indication/relevant diagnoses. Descriptive and associative statistics were calculated. STOPPFrail was used to identify PIMs. Polypharmacy (taking ≥ 5 medications) and excessive polypharmacy (taking ≥10 medications) were calculated on the percentage of STOPPFrail eligible patients. Results Of the 103 residents screened, 89 were eligible and included in the analysis (86%). The prevalence of frailty for residents aged ≥65 was 93.7% (n=89), polypharmacy 95.5% (n=85) and excessive polypharmacy 64% (n=57). The mean number of regular medications (standard deviation) was 10.8 (±3.8), total medications 17.7 (±5) and diagnoses 5.5 (±2.5). A significant relationship existed between the number of PIMs and the number of medicines prescribed (ρ 0.525, p Conclusion Medication and PIM usage was high among LTCF residents, with inappropriate polypharmacy of concern. Potential deprescribing interventions include documenting indications for medications, incorporating routine blood pressure measurements and drug-specific guidelines to support deprescribing PIMs, reducing drug-related morbidity and medication burden.

Aims To define the burden of wound complications in patients with infra-inguinal bypass surgery. Methods A retrospective review of 50 consecutive patients from January 2012 to July 2017. Data collected included patient demographics, operative details, length of stay (LOS) and postoperative complications. Results The average age was 64 years (range 25-88 years) and 10 had a body mass index (BMI) ≥25 kg/m2. Pre-operative methicillin-resistant Staphylococcus aureus (MRSA) screening was performed in 17 patients (n=4 positive). Surgical antimicrobial prophylaxis (SAP) continued longer than 24 hours in 25. Surgical site infection (SSI) was the most common complication (n=10) and associated with female gender (p= 0.039), high BMI (p=0.017), shorter preoperative (p=0.039) and longer postoperative LOS (p=0.022). Three of 46 patients and four of 38 had graft occlusion at 30 days and one year respectively. Conclusion Pre-operative co-morbidity (e.g., BMI reduction), and MRSA screening optimization and SAP are areas identified for improvement.

Additional file 2. The four patient pathways specified by NAMP and the practice changes recommended. Word document (table format) describing the four patient pathways.

List of BCTs and functions used at the organisational level targeting behaviours ‘supporting the implementation of fall risk assessment clinics’. Table outlining the activities undertaken within each component of the implementation strategy, the BCT coded to that activity and the intervention function(s) it served. (PDF 358 kb)

Table S1. Coding frame: barriers and enablers. (DOCX 38Â kb)

Outline of Fall Risk Assessment Clinics. Figure depicting the organisation and main features of fall risk assessment clinics being supported by the implementations strategy. (PDF 172 kb)

Standards for Reporting Qualitative Research (SRQR) Checklist. (PDF 328 kb)

Documents collated and analysed. Table of the documents collated and analysed in the study. (PDF 189 kb)

Recent trends in cellular handsets demand SAW resonators with increased performance. Most importantly, improvements in both the resonators' quality factor (Q) and temperature coefficient of frequency (TCF) are needed. The TC-SAW concept employing buried Cu electrodes in SiO 2 /128°Y-LiNbO 3 has attracted considerable practical interest in this view, with the requirement that the spurious transverse modes in the structure are suppressed. Thus, practical TC-SAW resonators employ a specific geometry ensuring a piston mode of operation. Here we present a theoretical and experimental parametric study of the piston geometry as function of the resonance frequency and aperture. The extracted scaling rules are subsequently used in the design of RF filters.

Driven by the need for high data-rates and improved cell coverage, mobile phone filters are required to process increasingly high RF power levels. The simultaneous demand for smaller filter footprints makes designing a filter for high-power performance a challenge. We report a method for simulating the self-heating effects of high input powers on a surface acoustic wave (SAW) filter. We also report gain compression measurements and infrared microscopy to validate the model.

This study examined embedded performance validity indicators (PVI) based on the number of impaired scores in an evaluation and the overall test battery mean (OTBM). Adult participants (N = 175) reporting traumatic brain injury were grouped using eight PVI. Participants who passed all PVI (n = 67) demonstrated fewer impaired scores and higher OTBM than those who failed two or more PVI (n = 66). Impairment was defined at three levels: T scores < 40, 35, and 30. With specificity ≥.90, sensitivity ranged from .51 to .71 for number of impaired scores and .74 for OTBM.

ATRX is a SWI/SNF chromatin remodeler proposed to govern genomic stability through the regulation of repetitive sequences, such as rDNA, retrotransposons, and pericentromeric and telomeric repeats. However, few direct ATRX target genes have been identified and high-throughput genomic approaches are currently lacking for ATRX. Here we present a comprehensive ChIP-sequencing study of ATRX in multiple human cell lines, in which we identify the 3′ exons of zinc finger genes (ZNFs) as a new class of ATRX targets. These 3′ exonic regions encode the zinc finger motifs, which can range from 1–40 copies per ZNF gene and share large stretches of sequence similarity. These regions often contain an atypical chromatin signature: they are transcriptionally active, contain high levels of H3K36me3, and are paradoxically enriched in H3K9me3. We find that these ZNF 3′ exons are co-occupied by SETDB1, TRIM28, and ZNF274, which form a complex with ATRX. CRISPR/Cas9-mediated loss-of-function studies demonstrate (i) a reduction of H3K9me3 at the ZNF 3′ exons in the absence of ATRX and ZNF274 and, (ii) H3K9me3 levels at atypical chromatin regions are particularly sensitive to ATRX loss compared to other H3K9me3-occupied regions. As a consequence of ATRX or ZNF274 depletion, cells with reduced levels of H3K9me3 show increased levels of DNA damage, suggesting that ATRX binds to the 3′ exons of ZNFs to maintain their genomic stability through preservation of H3K9me3.

Secondary sources of information included in documentary analysis. Description of data: details of documents used in documentary analysis during stage 1 (DOCX 24Â kb)

Topic guide stage 1. Description of data: topic guide used during semi-structured interviews in stage 1. (DOCX 22Â kb)

Sample matrix. Description of data: an example of the matrix approach that will be used to integrate qualitative and quantitative data. (DOCX 11Â kb)

BCT groups and corresponding BCTs and definitions. (DOCX 16Â kb)

Mapping of behaviour change techniques (BCTs) to key domains for inclusion in an intervention targeting immunoglobulin testing behaviour of general practitioners. (DOCX 20Â kb)

Case selection. Description of data: rationale for case selection. (DOCX 12Â kb)

Topic Guide using TDF framework. (DOCX 19Â kb)

Objective: The International Mission on Prognosis and Analysis of Clinical Trials and Corticoid Randomisation After Significant Head injury prognostic models predict outcome after traumatic brain injury but have not been compared in large datasets. The objective of this is study is to validate externally and compare the International Mission on Prognosis and Analysis of Clinical Trials and Corticoid Randomisation after Significant Head injury prognostic models for prediction of outcome after moderate or severe traumatic brain injury. Design: External validation study. Patients: We considered five new datasets with a total of 9,036 patients, comprising three randomized trials and two observational series, containing prospectively collected individual traumatic brain injury patient data. Measurements and Main Results: Outcomes were mortality and unfavorable outcome, based on the Glasgow Outcome Score at 6 months after injury. To assess performance, we studied the discrimination of the models (by area under the receiver operating characteristic curves), and calibration (by comparison of the mean observed to predicted outcomes and calibration slopes). The highest discrimination was found in the Trauma Audit and Research Network trauma registry (area under the receiver operating characteristic curves between 0.83 and 0.87), and the lowest discrimination in the Pharmos trial (area under the receiver operating characteristic curves between 0.65 and 0.71). Although differences in predictor effects between development and validation populations were found (calibration slopes varying between 0.58 and 1.53), the differences in discrimination were largely explained by differences in case mix in the validation studies. Calibration was good, the fraction of observed outcomes generally agreed well with the mean predicted outcome. No meaningful differences were noted in performance between the International Mission on Prognosis and Analysis of Clinical Trials and Corticoid Randomisation After Significant Head injury models. More complex models discriminated slightly better than simpler variants. Conclusions: Since both the International Mission on Prognosis and Analysis of Clinical Trials and the Corticoid Randomisation After Significant Head injury prognostic models show good generalizability to more recent data, they are valid instruments to quantify prognosis in traumatic brain injury. (Crit Care Med 2012; 40: 1609-1617)

The Glasgow Outcome Scale (GOS) is firmly established as the primary outcome measure for use in Phase III trials of interventions in traumatic brain injury (TBI). However, the GOS has been criticized for its lack of sensitivity to detect small but clinically relevant changes in outcome. The Glasgow Outcome Scale-Extended (GOSE) potentially addresses this criticism, and in this study we estimate the efficiency gain associated with using the GOSE in place of the GOS in ordinal analysis of 6-month outcome. The study uses both simulation and the reanalysis of existing data from two completed TBI studies, one an observational cohort study and the other a randomized controlled trial. As expected, the results show that using an ordinal technique to analyze the GOS gives a substantial gain in efficiency relative to the conventional analysis, which collapses the GOS onto a binary scale (favorable versus unfavorable outcome). We also found that using the GOSE gave a modest but consistent increase in efficiency relative to the GOS in both studies, corresponding to a reduction in the required sample size of the order of 3-5%. We recommend that the GOSE be used in place of the GOS as the primary outcome measure in trials of TBI, with an appropriate ordinal approach being taken to the statistical analysis.

Picture Completion (PC) indices from the Wechsler Adult Intelligence Scale, Third Edition, were investigated as performance validity indicators (PVIs) in a sample referred for independent neuropsychological examination. Participants from an archival database were included in the study if they were between the ages of 18 and 65 and were administered at least two PVIs. Effort measure performance yielded groups that passed all or failed one measure (Pass; n= 95) and failed two or more PVIs (Fail-2; n= 61). The Pass group performed better on PC than the Fail-2 group. PC cut scores were compared in differentiating Pass and Fail-2 groups. PC raw score of ≤12 showed the best classification accuracy in this sample correctly classifying 91% of Pass and 41% of Fail-2 cases. Overall, PC indices show good specificity and low sensitivity for exclusive use as PVIs, demonstrating promise for use as adjunctive embedded measures. Language: en

Background Clinical trials in traumatic brain injury have a disappointing track record, with a long history of ‘negative’ Phase III trials. One contributor to this lack of success is almost certainly the low efficiency of the conventional approach to the analysis, which discards information by dichotomizing an ordinal outcome scale. Purpose Our goal was to evaluate the potential efficiency gains, which can be achieved by using techniques, which extract additional information from ordinal outcome data — the proportional odds model and the sliding dichotomy. In addition, we evaluated the additional efficiency gains, which can be achieved through covariate adjustment. Methods The study was based on simulations, which were built around a database of patient-level data extracted from eight Phase III trials and three observational studies in traumatic brain injury. Two different putative treatment effects were explored, one which followed the proportional odds model, and the other which assumed that the effect of the intervention was to reduce the risk of death without changing the distribution of outcomes within survivors. The results are expressed as efficiency gains, reported as the percentage reduction in sample size that can be used with the ordinal analyses without loss of statistical power relative to the conventional binary analysis. Results The simulation results show substantial efficiency gains. Use of the sliding dichotomy allows sample sizes to be reduced by up to 40% without loss of statistical power. The proportional odds model gives modest additional gains over and above the gains achieved by use of the sliding dichotomy. Limitations As with any simulation study, it is difficult to know how far the findings may be extrapolated beyond the actual situations that were modeled. Conclusions Both ordinal techniques offer substantial efficiency gains relative to the conventional binary analysis. The choice between the two techniques involves subtle value judgments. In the situations examined, the proportional odds model gave efficiency gains over and above the sliding dichotomy, but arguably, the sliding dichotomy is more intuitive and clinically appealing. Clinical Trials 2010; 7: 44—57. http://ctj.sagepub.com

Substantial heterogeneity exists among patients who suffer from traumatic brain injury (TBI). Strict enrollment criteria may diminish heterogeneity in randomized controlled trials (RCTs), but will also decrease recruitment and may affect the outcome distribution. The aim of this study was to investigate the influences of commonly used enrollment criteria for RCTs in TBI on potential recruitment and on outcome distribution. We used individual patient data from the International Mission on Prognosis and Analysis of Clinical Trials in TBI (IMPACT) database, including six therapeutic phase III RCTs (n-5816) and three surveys (n-2217) in TBI. The primary outcome was the Glasgow Outcome Scale (GOS) at 6 months after injury, which we dichotomized as favorable/unfavorable. We investigated the influences of commonly used enrollment criteria on recruitment and outcome distribution: time window between injury and admission to study hospital = 1 reactive pupil; motor score > 1; Glasgow Coma Scale

The purpose of this study was to evaluate the accuracy of model surgery prediction after orthognathic surgery and to identify possible errors associated with the prediction process. The study included 46 patients who had undergone orthognathic surgical procedures; 22 in Group A who had had a Le Fort I osteotomy; and 24 in Group B who had had a Le Fort I osteotomy and mandibular setback surgery. The immediate postoperative and preoperative lateral cephalograms were analysed to calculate surgical changes; these were compared with those obtained from model surgery prediction and a statistical analysis was undertaken. The maxilla was more under-advanced and over-impacted anteriorly than predicted by model surgery. The amount of mandibular setback was more than that predicted by model surgery. None of the differences between prediction planning and actual surgical changes was statistically significant at p

Summary Background Major depressive disorder severely impairs the quality of life of patients with medical disorders such as cancer, but evidence to guide its management is scarce. We aimed to assess the efficacy and cost of a nurse-delivered complex intervention that was designed to treat major depressive disorder in patients who have cancer. Methods We did a randomised trial in a regional cancer centre in Scotland, UK. 200 outpatients who had cancer with a prognosis of greater than 6 months and major depressive disorder (identified by screening) were eligible and agreed to take part. Their mean age was 56·6 (SD 11·9) years, and 141 (71%) were women. We randomly assigned 99 of these participants to usual care, and 101 to usual care plus the intervention, with minimisation for sex, age, diagnosis, and extent of disease. The intervention was delivered by a cancer nurse at the centre over an average of seven sessions. The primary outcome was the difference in mean score on the self-reported Symptom Checklist-20 depression scale (range 0 to 4) at 3 months after randomisation. Analysis was by intention to treat. This trial is registered as ISRCTN84767225. Findings Primary outcome data were missing for four patients. For 196 patients for whom we had data at 3 months, the adjusted difference in mean Symptom Checklist-20 depression score, between those who received the intervention and those who did not, was 0·34 (95% CI 0·13–0·55). This treatment effect was sustained at 6 and 12 months. The intervention also improved anxiety and fatigue but not pain or physical functioning. It cost an additional £5278 (US$10 556) per quality-adjusted life-year gained. Interpretation The intervention—Depression Care for People with Cancer—offers a model for the management of major depressive disorder in patients with cancer and other medical disorders who are attending specialist medical services that is feasible, acceptable, and potentially cost effective. Funding Cancer Research UK.

The Glasgow Outcome Scale (GOS) is the primary endpoint for efficacy analysis of clinical trials in traumatic brain injury (TBI). Accurate and consistent assessment of outcome after TBI is essential to the evaluation of treatment results, particularly in the context of multicenter studies and trials. The inconsistent measurement or interobserver variation on GOS outcome, or for that matter, on any outcome scales, may adversely affect the sensitivity to detect treatment effects in clinical trial. The objective of this study is to examine effects of nondifferential misclassification of the widely used five-category GOS outcome scale and in particular to assess the impact of this misclassification on detecting a treatment effect and statistical power. We followed two approaches. First, outcome differences were analyzed before and after correction for misclassification using a dataset of 860 patients with severe brain injury randomly sampled from two TBI trials with known differences in outcome. Second, the effects of misclassification on outcome distribution and statistical power were analyzed in simulation studies on a hypothetical 800-patient dataset. Three potential patterns of nondifferential misclassification (random, upward and downward) on the dichotomous GOS outcome were analyzed, and the power of finding treatments differences was investigated in detail. All three patterns of misclassification reduce the power of detecting the true treatment effect and therefore lead to a reduced estimation of the true efficacy. The magnitude of such influence not only depends on the size of the misclassification, but also on the magnitude of the treatment effect. In conclusion, nondifferential misclassification directly reduces the power of finding the true treatment effect. An awareness of this procedural error and methods to reduce misclassification should be incorporated in TBI clinical trials.

Computerized tomography (CT) scanning provides an objective assessment of the structural damage to the brain following traumatic brain injury (TBI). We aimed to describe and quantify the relationship between CT characteristics and 6-month outcome, assessed by the Glasgow Outcome Scale (GOS). Individual patient data from the IMPACT database were available on CT classification (N = 5209), status of basal cisterns ( N = 3861), shift ( N = 4698), traumatic subarachnoid hemorrhage (tSAH) ( N = 7407), and intracranial lesions ( N = 7613). We used binary logistic and proportional odds regression for prognostic analyses. The CT classification was strongly related to outcome, with worst outcome for patients with diffuse injuries in CT class III (swelling; OR 2.50; CI 2.09-3.0) or CT class IV (shift; OR 3.03; CI 2.12-4.35). The prognosis in patients with mass lesions was better for patients with an epidural hematoma (OR 0.64; CI 0.56-0.72) and poorer for an acute subdural hematoma (OR 2.14; CI 1.87-2.45). Partial obliteration of the basal cisterns (OR 2.45; CI 1.88-3.20), tSAH (OR 2.64; CI 2.42-2.89), or midline shift (1-5 mm-OR 1.36; CI 1.09-1.68);5 mm-OR 2.20; CI 1.64-2.96) were strongly related to poorer outcome. Discrepancies were found between the scoring of basal cisterns/shift and the CT classification, indicating observer variation. These were less marked in studies that had used a central review process. Multivariable analysis indicated that individual CT characteristics added substantially to the prognostic value of the CT classification alone. We conclude that both the CT classification and individual CT characteristics are important predictors of outcome in TBI. For clinical trials, a central review process is advocated to minimize observer variability in CT assessment.

We aimed to describe and quantify the relationship between cause of injury and final outcome following traumatic brain injury (TBI). Individual patient data (N = 8708) from eight therapeutic Phase III randomized clinical trials in moderate or severe TBI, and three TBI surveys were used to investigate the relationship between cause of injury and outcome, as assessed by the Glasgow Outcome Scale (GOS) at 6 months. Proportional odds methodology was applied to quantify the strength of the association and expressed as an odds ratio in a meta-analysis. Heterogeneity across studies was assessed and associations with other predictive factors explored. In a univariate analysis, a strong association between the cause of injury and long-term outcome in moderate to severe TBI patients was observed, with consistent results across the studies. Road traffic accidents (OR 0.66, 95% CI 0.60-0.73), assaults (OR 0.66, 95% CI 0.52-0.84), and injuries sustained during sporting or recreational activities (OR 0.45, 95% CI 0.28-0.71) were all associated with better outcomes than the reference category of falls. Falls were found to be associated with an older age and with a higher incidence of mass lesions. Following adjustment for age in the analysis, the relationship between cause of injury and outcome was lost.

Abnormalities in laboratory parameters are frequent following traumatic brain injury (TBI), but few studies have investigated their predictive value. We aimed to describe and quantify the relation between laboratory parameters that are routinely determined on admission and final outcome following TBI. Individual patient data were available in the IMPACT database from six Phase III randomized controlled trials and one observational study in TBI. We studied glucose (N = 4834), sodium ( N = 5270), pH ( N = 3398), hemoglobin (Hb, N = 3875), platelet count ( N = 1629), and prothrombin time (PT; N = 840) for their associations with outcome at 6 months (Glasgow Outcome Scale [GOS]). We used logistic regression models with linear, quadratic, and restricted cubic spline functions. The strength of the associations was expressed as an unadjusted odds ratio, calculated over the shift in outcome between the 25th and 75th percentiles. Proportional odds methodology was further applied to quantify the strength of the associations across the full range of the GOS. All parameters were consistently associated with outcome in a continuous relationship: glucose and prothrombin time showed a positive linear relation to outcome (i.e., increasing values associated with poorer outcome) and Hb, platelets, and pH an inverse linear relation (i.e., low values associated with poorer outcome). Sodium demonstrated a U-shaped relation to outcome, with low levels being more strongly related to poorer outcome. Effects were strongest for increasing levels of glucose (odds ratio 1.7; 95% CI 1.54-1.83) and decreasing levels of Hb (odds ratio 0.7; CI 0.60-0.78). Higher glucose values were associated with increasing age, but on adjusted analysis, the strength of the association with outcome remained. Whether treatment of abnormal values may improve outcome needs further rigorous study.

The univariate prognostic analysis of the IMPACT database on traumatic brain injury (TBI) poses the formidable challenge of how best to summarize a highly complex set of data in a way which is accessible without being overly simplistic. In this paper, we describe and illustrate the battery of statistical methods that have been used. Boxplots, histograms, tabulations, and splines were used for initial data checking and in identifying appropriate transformations for more formal statistical modeling. Imputation techniques were used to minimize the problems associated with the analysis of incomplete data due to missing values. The associations between covariates and outcome (Glasgow Outcome Scale [GOS] assessed at 6 months) were expressed as odds ratios with supporting confidence intervals when the GOS was collapsed to a dichotomous scale. This was extended to use common odds ratios from proportional odds models to express associations over the full range of the GOS. Forest plots were used to illustrate the consistency of results from study to study within the IMPACT database. The overall prognostic strength of the prognostic factors was expressed as the proportion of variance explained (Nagelkerke's R(2) statistic). Many of our approaches are based on simple graphical displays of the data, but, where appropriate, we have also used methods that although established in the statistical literature are relatively novel in their application to TBI.