Test-retest reliability of graph theory measures of structural brain connectivity

The human connectome has recently become a popular research topic in neuroscience, and many new algorithms have been applied to analyze brain networks. In particular, network topology measures from graph theory have been adapted to analyze network efficiency and 'small-world' properties. While there has been a surge in the number of papers examining connectivity through graph theory, questions remain about its test-retest reliability (TRT). In particular, the reproducibility of structural connectivity measures has not been assessed. We examined the TRT of global connectivity measures generated from graph theory analyses of 17 young adults who underwent two high-angular resolution diffusion (HARDI) scans approximately 3 months apart. Of the measures assessed, modularity had the highest TRT, and it was stable across a range of sparsities (a thresholding parameter used to define which network edges are retained). These reliability measures underline the need to develop network descriptors that are robust to acquisition parameters.

Nursing physical assessment for patient safety in general wards: Reaching consensus on core skills

Aims and objectives To determine consensus across acute care specialty areas on core physical assessment skills necessary for early recognition of changes in patient status in general wards. Background Current approaches to physical assessment are inconsistent and have not evolved to meet increased patient and system demands. New models of nursing assessment are needed in general wards that ensure a proactive and patient safety approach. Design A modified Delphi study. Methods Focus group interviews with 150 acute care registered nurses (RNs) at a large tertiary referral hospital generated a framework of core skills that were developed into a web-based survey. We then sought consensus with a panel of 35 senior acute care RNs following a classical Delphi approach over three rounds. Consensus was predefined as at least 80% agreement for each skill across specialty areas. Results Content analysis of focus group transcripts identified 40 discrete core physical assessment skills. In the Delphi rounds, 16 of these were consensus validated as core skills and were conceptually aligned with the primary survey: (Airway) Assess airway patency; (Breathing) Measure respiratory rate, Evaluate work of breathing, Measure oxygen saturation; (Circulation) Palpate pulse rate and rhythm, Measure blood pressure by auscultation, Assess urine output; (Disability) Assess level of consciousness, Evaluate speech, Assess for pain; (Exposure) Measure body temperature, Inspect skin integrity, Inspect and palpate skin for signs of pressure injury, Observe any wounds, dressings, drains and invasive lines, Observe ability to transfer and mobilise, Assess bowel movements. Conclusions Among a large and diverse group of experienced acute care RNs consensus was achieved on a structured core physical assessment to detect early changes in patient status. Relevance to clinical practice Although further research is needed to refine the model, clinical application should promote systematic assessment and clinical reasoning at the bedside.

Patient preferences for receiving remote communication support for lifestyle physical activity behaviour change: The perspective of patients with musculoskeletal disorders from three hospital services

This study examined patients’ preference ratings for receiving support via remote communication to increase their lifestyle physical activity. Methods People with musculoskeletal disorders ( n=221 of 296 eligible) accessing one of three clinics provided preference ratings for “how much” they wanted to receive physical activity support via five potential communication modalities. The five ratings were generated on a horizontal analogue rating scale (0 represented “not at all”; 10 represented “very much”). Results Most (n=155, 70%) desired referral to a physical activity promoting intervention. “Print and post” communications had the highest median preference rating (7/10), followed by email and telephone (both 5/10), text messaging (1/10), and private Internet-based social network messages (0/10). Desire to be referred was associated with higher preference for printed materials (coefficient = 2.739, p<0.001), telephone calls (coefficient = 3.000, p<0.001), and email (coefficient = 2.059, p=0.02). Older age was associated with lower preference for email (coefficient = −0.100, p<0.001), texting (coefficient = −0.096, p<0.001), and social network messages (coefficient = −0.065, p<0.001). Conclusion Patients desiring support to be physically active indicated preferences for interventions with communication via print, email, or telephone calls.

Nonlinear measures of respiration: Respiratory irregularity and increased chaos of respiration in patients with panic disorder

Background. Respiratory irregularity has been previously reported in patients with panic disorder using time domain measures. However, the respiratory signal is not entirely linear and a few previous studies used approximate entropy (APEN), a measure of regularity of time series. We have been studying APEN and other nonlinear measures including a measure of chaos, the largest Lyapunov exponent (LLE) of heart rate time series, in some detail. In this study, we used these measures of respiration to compare normal controls (n = 18) and patients with panic disorder (n = 22) in addition to the traditional time domain measures of respiratory rate and tidal volume. Methods: Respiratory signal was obtained by the Respitrace system using a thoracic and an abdominal belt, which was digitized at 500 Hz. Later, the time series were constructed at 4 Hz, as the highest frequency in this signal is limited to 0.5 Hz. We used 256 s of data (1,024 points) during supine and standing postures under normal breathing and controlled breathing at 12 breaths/min. Results: APEN was significantly higher in patients in standing posture during normal as well as controlled breathing (p = 0.002 and 0.02, respectively). LLE was also significantly higher in standing posture during normal breathing (p = 0.009). Similarly, the time domain measures of standard deviations and the coefficient of variation (COV) of tidal volume (TV) were significantly higher in the patient group (p = 0.02 and 0.004, respectively). The frequency of sighs was also higher in the patient group in standing posture (p = 0.02). In standing posture, LLE (p < 0.05) as well as APEN (p < 0.01) contributed significantly toward the separation of the two groups over and beyond the linear measure, i.e. the COV of TV. Conclusion: These findings support the previously described respiratory irregularity in patients with panic disorder and also illustrate the utility of nonlinear measures such as APEN and LLE as additional measures toward a better understanding of the abnormalities of respiratory physiology in similar patient populations as the correlation between LLE, APEN and some of the time domain measures only explained up to 50-60% of the variation. Copyright (C) 2002 S. Karger AG, Basel.

Nonlinear measures of QT interval series: novel indices of cardiac repolarization lability: MEDqthr and LLEqthr

In this study, we investigated nonlinear measures of chaos of QT interval time series in 28 normal control subjects, 36 patients with panic disorder and 18 patients with major depression in supine and standing postures. We obtained the minimum embedding dimension (MED) and the largest Lyapunov exponent (LLE) of instantaneous heart rate (HR) and QT interval series. MED quantifies the system's complexity and LLE predictability. There was a significantly lower MED and a significantly increased LLE of QT interval time series in patients. Most importantly, nonlinear indices of QT/HR time series, MEDqthr (MED of QT/HR) and LLEqthr (LLE of QT/HR), were highly significantly different between controls and both patient groups in either posture. Results remained the same even after adjusting for age. The increased LLE of QT interval time, series in patients with anxiety and depression is in line with our previous findings of higher QTvi (QT variability index, a log ratio of QT variability corrected for mean QT squared divided by heart rate variability corrected for mean heart rate squared) in these patients, using linear techniques. Increased LLEqthr (LLE of QT/HR) may be a more sensitive tool to study cardiac repolarization and a valuable addition to the time domain measures such as QTvi. This is especially important in light of the finding that LLEqthr correlated poorly and nonsignificantly with QTvi. These findings suggest an increase in relative cardiac sympathetic activity and a decrease in certain aspects of cardiac vagal function in patients with anxiety as well as depression. The lack of correlation between QTvi and LLEqthr suggests that this nonlinear index is a valuable addition to the linear measures. These findings may also help to explain the higher incidence of cardiovascular mortality in patients with anxiety and depressive disorders. (C) 2002 Elsevier Science Ireland Ltd. All rights reserved.

Impact of depressive symptoms on subjective well-being: the importance of patient-reported outcomes in schizophrenia

Objective: The subjective experience of psychotic patients toward treatment is a key factor in medication adherence, quality of life, and clinical outcome. The aim of this study was to assess the subjective well-being in patients with schizophrenia and to examine its relationship with the presence and severity of depressive symptoms. Methods: A multicenter, cross-sectional study was conducted with clinically stable outpatients diagnosed with schizophrenia. The Subjective Well-Being under Neuroleptic Scale - short version (SWN-K) and the Calgary Depression Scale for Schizophrenia (CDSS) were used to gather information on well-being and the presence and severity of depressive symptoms, respectively. Spearman's rank correlation was used to assess the associations between the SWN-K total score, its five subscales, and the CDSS total score. Discriminative validity was evaluated against that criterion by analysing the area under the curve (AUC). Results: Ninety-seven patients were included in the study. Mean age was 35 years (standard deviation = 10) and 72% were male. Both the total SWN-K scale and its five subscales correlated inversely and significantly with the CDSS total score (P < 0.0001). The highest correlation was observed for the total SWN-K (Spearman's rank order correlation [ rho] = -0.59), being the other correlations: mental functioning (-0.47), social integration (-0.46), emotional regulation (-0.51), physical functioning (-0.48), and self-control (-0.41). A total of 33 patients (34%) were classified as depressed. Total SWN-K showed the highest AUC when discriminating between depressive severity levels (0.84), followed by emotional regulation (0.80), social integration (0.78), physical functioning and self-control (0.77), and mental functioning (0.73). Total SWN-K and its five subscales showed a significant linear trend against CDSS severity levels (P < 0.001). Conclusion: The presence of moderate to severe depressive symptoms was relatively high, and correlated inversely with patients' subjective well-being. Routine assessment of patient-reported measures in patients with schizophrenia might reduce potential discrepancy between patient and physician assessment, increase therapeutic alliance, and improve outcome.

Avaliação da presença de mutações de resistência no gene da NS5B e do prognóstico da infecção pelo HCV através da IL-28B em pacientes monoinfectados com HCV no RJ

Estima-se que a prevalência global da população mundial com hepatite C é de 3%. Pouco se sabe sobre a resposta ao tratamento com respeito à resistência viral. Algumas mutações no fragmento de 109 aminoácidos da NS5B são associadas com resistência ao interferon (IFN) e ribavirina (RBV). Estudos moleculares e clínicos identificaram fatores associados com o hospedeiro e vírus relacionados associada com a resposta ao tratamento, tal como o gene que codifica a IL-28B. Este estudo foi dividido em duas fases, cujos objetivos foram caracterizar a frequência de mutações que conferem resistência ao HCV e avaliar a relevância das mutações em pacientes Respondedores (R) ou Não Respondedores (NR) ao tratamento e caracterizar geneticamente as populações sobre polimorfismos genéticos nos SNPs da IL-28B em relação ao prognóstico da resposta ao tratamento. As amostras dos pacientes foram submetidas a testes de genotipagem e carga viral. As sequências geradas foram comparadas no BLAST e no banco de dados Los Alamos HCV. Realizamos o alinhamento das sequências homólogas e as mutações identificadas. Com base no genótipo e carga viral determinamos a classificação dos pacientes de acordo com a resposta à terapia. O DNA genômico foi isolado a partir de sangue periférico para a realização da tipagem de SNPs de IL-28B. A metodologia utilizada foi de PCR em tempo real utilizando sondas TaqMan SNP específico. A análise dos dados foi realizada utilizando GraphPad Prism com qui-quadrado, risco relativo (RR), Odds Ratio (OR) e intervalo de confiança de 95%, com um nível de significância de P <0,05. Foi encontrado na primeira fase deste estudo uma taxa significativa mutações associadas ao tratamento nas amostras estudadas. A prevalência de mutações associadas à resistência ao IFN e RBV bem como a novos medicamentos antivirais localizados no fragmento de 109 aminoácidos da NS5B foi examinado em 69 indivíduos infectados naïve no Rio de Janeiro, Brasil. Na segunda fase, as mutações foram clinicamente relevantes. Desde então, procuramos observar as diferenças entre melhor ou pior prognóstico de acordo com a imunogenética que mostrou diferenciação entre os grupos R e NR ao tratamento em relação ao prognóstico da resposta terapêutica. Quando as diferenças entre as sequências da NS5B e a resposta ao tratamento foram consideradas verificou-se que associada a mutação R254K, estava a C316N que poderia conduzir a uma não resposta à terapia no genótipo 1b. Os nossos dados também suportaram forte associação de IL-28B rs12979860, com elevada probabilidade de resposta à terapia de IFN + RBV. Nossos dados evidenciam a presença de pacientes virgens de tratamento que abrigam mutações de resistência previamente descritas na literatura. A análise dos fatores preditores de resposta virológica mostrou que a predição de boa resposta ou não ao tratamento e ainda da progressão da doença é dependente de uma importante interação entre a genética viral e a do hospedeiro. Fato este importante para que no momento de avaliação de diagnóstico e conduta terapêutica, o médico possa tomar medidas apropriadas para o tratamento de cada paciente individualmente independentemente do genótipo do HCV em questão.

Generating Options for Active Risk Control (GO-ARC): introducing a novel technique.

BACKGROUND: After investing significant amounts of time and money in conducting formal risk assessments, such as root cause analysis (RCA) or failure mode and effects analysis (FMEA), healthcare workers are left to their own devices in generating high-quality risk control options. They often experience difficulty in doing so, and tend toward an overreliance on administrative controls (the weakest category in the hierarchy of risk controls). This has important implications for patient safety and the cost effectiveness of risk management operations. This paper describes a before and after pilot study of the Generating Options for Active Risk Control (GO-ARC) technique, a novel tool to improve the quality of the risk control options generation process. OUTCOME MEASURES: The quantity, quality (using the three-tiered hierarchy of risk controls), variety, and novelty of risk controls generated. RESULTS: Use of the GO-ARC technique was associated with improvement on all measures. CONCLUSIONS: While this pilot study has some notable limitations, it appears that the GO-ARC technique improved the risk control options generation process. Further research is needed to confirm this finding. It is also important to note that improved risk control options are a necessary, but not sufficient, step toward the implementation of more robust risk controls.

Patient-based outcome assessment instruments in acupuncture research.

BACKGROUND: Outcome assessment can support the therapeutic process by providing a way to track symptoms and functionality over time, providing insights to clinicians and patients, as well as offering a common language to discuss patient behavior/functioning. OBJECTIVES: In this article, we examine the patient-based outcome assessment (PBOA) instruments that have been used to determine outcomes in acupuncture clinical research and highlight measures that are feasible, practical, economical, reliable, valid, and responsive to clinical change. The aims of this review were to assess and identify the commonly available PBOA measures, describe a framework for identifying appropriate sets of measures, and address the challenges associated with these measures and acupuncture. Instruments were evaluated in terms of feasibility, practicality, economy, reliability, validity, and responsiveness to clinical change. METHODS: This study was a systematic review. A total of 582 abstracts were reviewed using PubMed (from inception through April 2009). RESULTS: A total of 582 citations were identified. After screening of title/abstract, 212 articles were excluded. From the remaining 370 citations, 258 manuscripts identified explicit PBOA; 112 abstracts did not include any PBOA. The five most common PBOA instruments identified were the Visual Analog Scale, Symptom Diary, Numerical Pain Rating Scales, SF-36, and depression scales such as the Beck Depression Inventory. CONCLUSIONS: The way a questionnaire or scale is administered can have an effect on the outcome. Also, developing and validating outcome measures can be costly and difficult. Therefore, reviewing the literature on existing measures before creating or modifying PBOA instruments can significantly reduce the burden of developing a new measure.

An active learning approach for rapid characterization of endothelial cells in human tumors.

Currently, no available pathological or molecular measures of tumor angiogenesis predict response to antiangiogenic therapies used in clinical practice. Recognizing that tumor endothelial cells (EC) and EC activation and survival signaling are the direct targets of these therapies, we sought to develop an automated platform for quantifying activity of critical signaling pathways and other biological events in EC of patient tumors by histopathology. Computer image analysis of EC in highly heterogeneous human tumors by a statistical classifier trained using examples selected by human experts performed poorly due to subjectivity and selection bias. We hypothesized that the analysis can be optimized by a more active process to aid experts in identifying informative training examples. To test this hypothesis, we incorporated a novel active learning (AL) algorithm into FARSIGHT image analysis software that aids the expert by seeking out informative examples for the operator to label. The resulting FARSIGHT-AL system identified EC with specificity and sensitivity consistently greater than 0.9 and outperformed traditional supervised classification algorithms. The system modeled individual operator preferences and generated reproducible results. Using the results of EC classification, we also quantified proliferation (Ki67) and activity in important signal transduction pathways (MAP kinase, STAT3) in immunostained human clear cell renal cell carcinoma and other tumors. FARSIGHT-AL enables characterization of EC in conventionally preserved human tumors in a more automated process suitable for testing and validating in clinical trials. The results of our study support a unique opportunity for quantifying angiogenesis in a manner that can now be tested for its ability to identify novel predictive and response biomarkers.

Development and usability testing of a Web-based decision aid for families of patients receiving prolonged mechanical ventilation.

BACKGROUND: Web-based decision aids are increasingly important in medical research and clinical care. However, few have been studied in an intensive care unit setting. The objectives of this study were to develop a Web-based decision aid for family members of patients receiving prolonged mechanical ventilation and to evaluate its usability and acceptability. METHODS: Using an iterative process involving 48 critical illness survivors, family surrogate decision makers, and intensivists, we developed a Web-based decision aid addressing goals of care preferences for surrogate decision makers of patients with prolonged mechanical ventilation that could be either administered by study staff or completed independently by family members (Development Phase). After piloting the decision aid among 13 surrogate decision makers and seven intensivists, we assessed the decision aid's usability in the Evaluation Phase among a cohort of 30 surrogate decision makers using the Systems Usability Scale (SUS). Acceptability was assessed using measures of satisfaction and preference for electronic Collaborative Decision Support (eCODES) versus the original printed decision aid. RESULTS: The final decision aid, termed 'electronic Collaborative Decision Support', provides a framework for shared decision making, elicits relevant values and preferences, incorporates clinical data to personalize prognostic estimates generated from the ProVent prediction model, generates a printable document summarizing the user's interaction with the decision aid, and can digitally archive each user session. Usability was excellent (mean SUS, 80 ± 10) overall, but lower among those 56 years and older (73 ± 7) versus those who were younger (84 ± 9); p = 0.03. A total of 93% of users reported a preference for electronic versus printed versions. CONCLUSIONS: The Web-based decision aid for ICU surrogate decision makers can facilitate highly individualized information sharing with excellent usability and acceptability. Decision aids that employ an electronic format such as eCODES represent a strategy that could enhance patient-clinician collaboration and decision making quality in intensive care.

Nursing resources and patient outcomes in intensive care: a systematic review of the literature

Objectives: To evaluate the empirical evidence linking nursing resources to patient outcomes in intensive care settings as a framework for future research in this area. Background: Concerns about patient safely and the quality of care are driving research on the clinical and cost-effectiveness of health care interventions, including the deployment of human resources. This is particularly important in intensive care where a large proportion of the health care budget is consumed and where nursing staff is the main item of expenditure. Recommendations about staffing levels have been trade but may not be evidence based and may not always be achieved in practice. Methods: We searched systematically for studies of the impact of nursing resources (e.g. nurse-patient ratios, nurses' level of education, training and experience) on patient Outcomes, including mortality and adverse events, in adult intensive care. Abstracts of articles were reviewed and retrieved if they investigated the relationship between nursing resources and patient Outcomes. Characteristics of the studies were tabulated and the quality of the Studies assessed. Results: Of the 15 studies included in this review, two reported it statistical relationship between nursing resources and both mortality and adverse events, one reported ail association to mortality only, seven studies reported that they Could not reject the null hypothesis of no relationship to mortality and 10 studies (out of 10 that tested the hypothesis) reported a relationship to adverse events. The main explanatory mechanisms were the lack of time for nurses to perform preventative measures, or for patient surveillance. The nurses' role in pain control was noted by One author. Studies were mainly observational and retrospective and varied in scope from 1 to 52 units. Recommendations for future research include developing the mechanisms linking nursing resources to patient Outcomes, and designing large multi-centre prospective Studies that link patient's exposure to nursing care oil a shift-by-shift basis over time. (C) 2007 Elsevier Ltd. All rights reserved.

The impact of the nursing workforce on patient outcomes in intensive care

Introduction: Evidence from studies conducted mainly in the US and mainland Europe suggests that characteristics of the workforce, such as nurse patient ratios and workload (measured in a number of different ways) may be linked to variations in patient outcomes across health care settings (Carmel and Rowan 2001). Few studies have tested this relationship in the UK thus questions remain about whether we are justified in extrapolating evidence from studies conducted in very different health care systems. Objectives: To investigate whether characteristics of the nursing workforce affect patient mortality UK Intensive Care Units. Data: Patient data came from the case mix programme, Intensive Care National Audit and Research Centre (ICNARC), while information about the units came from a survey of all ICUs in England (Audit Comission 1998). The merged data set contained information on 43,859 patients in 69 units across England. ICNARC also supplied a risk adjustment variable to control for patient characteristics that are often the most important determinants of survival. Methods: Multivariate multilevel logistic regression. Findings: Higher numbers of direct care nurses and lower scores on measures of workload(proportion of occupied beds at the time the patient was admitted and mean daily transfers into the unit) were associated with lower mortality rates. Furthermore, the effect of the number of direct care nurses was greatest on the life chances of the patients who were most at risk of dying. Implications: This study has wide implications for workforce policy and planning because it shows that the size of the nursing workforce is associated with mortality (West et al 2006). Few studies have demonstrated this relationship in the UK. This study has a number of strengths and weaknesses and further research is required to determine whether this relationship between the nursing workforce and patient outcomes is causal.

Effect of tailored practice and patient care plans on secondary prevention of heart disease in general practice: cluster randomised controlled trial

Objective: To test the effectiveness of a complex intervention designed, within a theoretical framework, to improve outcomes for patients with coronary heart disease. Design: Cluster randomised controlled multicentre trial. Setting: General practices in Northern Ireland and the Republic of Ireland, regions with different healthcare systems. Participants: 903 patients with established coronary heart disease registered with one of 48 practices. Intervention: Tailored care plans for practices (practice based training in prescribing and behaviour change, administrative support, quarterly newsletter), and tailored care plans for patients (motivational interviewing, goal identification, and target setting for lifestyle change) with reviews every four months at the practices. Control practices provided usual care. Main outcome measures: The proportion of patients at 18 month follow-up above target levels for blood pressure and total cholesterol concentration, and those admitted to hospital, and changes in physical and mental health status (SF-12). Results: At baseline the numbers (proportions) of patients above the recommended limits were: systolic blood pressure greater than 140 mm Hg (305/899; 33.9%, 95% confidence interval 30.8% to 33.9%), diastolic blood pressure greater than 90 mm Hg (111/901; 12.3%, 10.2% to 14.5%), and total cholesterol concentration greater than 5 mmol/l (188/860; 20.8%, 19.1% to 24.6%). At the 18 month follow-up there were no significant differences between intervention and control groups in the numbers (proportions) of patients above the recommended limits: systolic blood pressure, intervention 98/360 (27.2%) v control, 133/405 (32.8%), odds ratio 1.51 (95% confidence interval 0.99 to 2.30; P=0.06); diastolic blood pressure, intervention 32/360 (8.9%) v control, 40/405 (9.9%), 1.40 (0.75 to 2.64; P=0.29); and total cholesterol concentration, intervention 52/342 (15.2%) v control, 64/391 (16.4%), 1.13 (0.63 to 2.03; P=0.65). The number of patients admitted to hospital over the 18 month study period significantly decreased in the intervention group compared with the control group: 107/415 (25.8%) v 148/435 (34.0%), 1.56 (1.53 to 2.60; P=0.03). Conclusions: Admissions to hospital were significantly reduced after an intensive 18 month intervention to improve outcomes for patients with coronary heart disease, but no other clinical benefits were shown, possibly because of a ceiling effect related to improved management of the disease. Trial registration: Current Controlled Trials ISRCTN24081411.

A method to reconstruct patient-specific proximal femur surface models from planar pre-operative radiographs

Three-dimensional reconstruction from volumetric medical images (e.g. CT, MRI) is a well-established technology used in patient-specific modelling. However, there are many cases where only 2D (planar) images may be available, e.g. if radiation dose must be limited or if retrospective data is being used from periods when 3D data was not available. This study aims to address such cases by proposing an automated method to create 3D surface models from planar radiographs. The method consists of (i) contour extraction from the radiograph using an Active Contour (Snake) algorithm, (ii) selection of a closest matching 3D model from a library of generic models, and (iii) warping the selected generic model to improve correlation with the extracted contour.

This method proved to be fully automated, rapid and robust on a given set of radiographs. Measured mean surface distance error values were low when comparing models reconstructed from matching pairs of CT scans and planar X-rays (2.57–3.74 mm) and within ranges of similar studies. Benefits of the method are that it requires a single radiographic image to perform the surface reconstruction task and it is fully automated. Mechanical simulations of loaded bone with different levels of reconstruction accuracy showed that an error in predicted strain fields grows proportionally to the error level in geometric precision. In conclusion, models generated by the proposed technique are deemed acceptable to perform realistic patient-specific simulations when 3D data sources are unavailable.