European surveillance of infections in cancer patients - ESIC

Major advances in cancer therapy result from development of multidrug chemotherapy regimens. Besides death from tumor progression, infections are currently one of the major causes of mortality and morbidity. Because of the risk of complications and mortality, the treatment for febrile neutropenia is admission to hospital and administration of broad-spectrum antibiotics. Response rates of initial antimicrobial treatment vary considerably (40-92%). Due to the heterogeneity of populations in randomized studies, comparison of efficacy and identification of risk factors is limited. This is the main reason why the European Society of Biomodulation and Chemotherapy (ESBiC) is conducting a surveillance study that concentrates more on the evaluation of risk factors than on the therapeutic outcome of prospective randomized antimicrobial regimens: European Surveillance of Infections in Cancer Patients (ESIC). The present contribution is to determine which cancer patients are at low risk for fever, and can benefit from first-line treatment with treatment options such as monotherapy as well as on an outpatient basis

Assessment of non-invasive ICP during CSF infusion test: an approach with transcranial Doppler.

BACKGROUND: This study aimed to compare four non-invasive intracranial pressure (nICP) methods in a prospective cohort of hydrocephalus patients whose cerebrospinal fluid dynamics was investigated using infusion tests involving controllable test-rise of ICP. METHOD: Cerebral blood flow velocity (FV), ICP and non-invasive arterial blood pressure (ABP) were recorded in 53 patients diagnosed for hydrocephalus. Non-invasive ICP methods were based on: (1) interaction between FV and ABP using black-box model (nICP_BB); (2) diastolic FV (nICP_FVd); (3) critical closing pressure (nICP_CrCP); (4) transcranial Doppler-derived pulsatility index (nICP_PI). Correlation between rise in ICP (∆ICP) and ∆nICP and averaged correlations for changes in time between ICP and nICP during infusion test were investigated. RESULTS: From baseline to plateau, all nICP estimators increased significantly. Correlations between ∆ICP and ∆nICP were better represented by nICP_PI and nICP_BB: 0.45 and 0.30 (p < 0.05). nICP_FVd and nICP_CrCP presented non-significant correlations: -0.17 (p = 0.21), 0.21 (p = 0.13). For changes in ICP during individual infusion test nICP_PI, nICP_BB and nICP_FVd presented similar correlations with ICP: 0.39 ± 0.40, 0.39 ± 0.43 and 0.35 ± 0.41 respectively. However, nICP_CrCP presented a weaker correlation (R = 0.29 ± 0.24). CONCLUSIONS: Out of the four methods, nICP_PI was the one with best performance for predicting changes in ∆ICP during infusion test, followed by nICP_BB. Unreliable correlations were shown by nICP_FVd and nICP_CrCP. Changes of ICP observed during the test were expressed by nICP values with only moderate correlations.DC is supported by a Cambridge Commonwealth, European & International Trust Scholarship, University of Cambridge. JD is supported by a Woolf Fisher Trust Scholarship. XL is supported by a Gates Cambridge Trust Scholarship. BCTC is supported by CNPQ (Research Project 203792/2014-9). DC and MC are partially supported by NIHR Brain Injury Healthcare Technology Co-operative, Cambridge, UK.This is the final version of the article. It was first available from Springer via http://dx.doi.org/10.1007/s00701-015-2661-

Options for early breast cancer follow-up in primary and secondary care : a systematic review

Background Both incidence of breast cancer and survival have increased in recent years and there is a need to review follow up strategies. This study aims to assess the evidence for benefits of follow-up in different settings for women who have had treatment for early breast cancer. Method A systematic review to identify key criteria for follow up and then address research questions. Key criteria were: 1) Risk of second breast cancer over time - incidence compared to general population. 2) Incidence and method of detection of local recurrence and second ipsi and contra-lateral breast cancer. 3) Level 1–4 evidence of the benefits of hospital or alternative setting follow-up for survival and well-being. Data sources to identify criteria were MEDLINE, EMBASE, AMED, CINAHL, PSYCHINFO, ZETOC, Health Management Information Consortium, Science Direct. For the systematic review to address research questions searches were performed using MEDLINE (2011). Studies included were population studies using cancer registry data for incidence of new cancers, cohort studies with long term follow up for recurrence and detection of new primaries and RCTs not restricted to special populations for trials of alternative follow up and lifestyle interventions. Results Women who have had breast cancer have an increased risk of a second primary breast cancer for at least 20 years compared to the general population. Mammographically detected local recurrences or those detected by women themselves gave better survival than those detected by clinical examination. Follow up in alternative settings to the specialist clinic is acceptable to women but trials are underpowered for survival. Conclusions Long term support, surveillance mammography and fast access to medical treatment at point of need may be better than hospital based surveillance limited to five years but further large, randomised controlled trials are needed

Fe XVII X-ray Line Ratios for Accurate Astrophysical Plasma Diagnostics

New laboratory measurements using an Electron Beam Ion Trap (EBIT) and an x-ray microcalorimeter are presented for the n=3 to n=2 Fe XVII emission lines in the 15 {\AA} to 17 {\AA} range, along with new theoretical predictions for a variety of electron energy distributions. This work improves upon our earlier work on these lines by providing measurements at more electron impact energies (seven values from 846 to 1185 eV), performing an in situ determination of the x-ray window transmission, taking steps to minimize the ion impurity concentrations, correcting the electron energies for space charge shifts, and estimating the residual electron energy uncertainties. The results for the 3C/3D and 3s/3C line ratios are generally in agreement with the closest theory to within 10%, and in agreement with previous measurements from an independent group to within 20%. Better consistency between the two experimental groups is obtained at the lowest electron energies by using theory to interpolate, taking into account the significantly different electron energy distributions. Evidence for resonance collision effects in the spectra is discussed. Renormalized values for the absolute cross sections of the 3C and 3D lines are obtained by combining previously published results, and shown to be in agreement with the predictions of converged R-matrix theory. This work establishes consistency between results from independent laboratories and improves the reliability of these lines for astrophysical diagnostics. Factors that should be taken into account for accurate diagnostics are discussed, including electron energy distribution, polarization, absorption/scattering, and line blends.Comment: 29 pages, including 7 figure

An Association Between ICP-Derived Data and Outcome in TBI Patients: The Role of Sample Size.

BACKGROUND: Many demographic and physiological variables have been associated with TBI outcomes. However, with small sample sizes, making spurious inferences is possible. This paper explores the effect of sample sizes on statistical relationships between patient variables (both physiological and demographic) and outcome. METHODS: Data from head-injured patients with monitored arterial blood pressure, intracranial pressure (ICP) and outcome assessed at 6 months were included in this retrospective analysis. A univariate logistic regression analysis was performed to obtain the odds ratio for unfavorable outcome. Three different dichotomizations between favorable and unfavorable outcomes were considered. A bootstrap method was implemented to estimate the minimum sample sizes needed to obtain reliable association between physiological and demographic variables with outcome. RESULTS: In a univariate analysis with dichotomized outcome, samples sizes should be generally larger than 100 for reproducible results. Pressure reactivity index, ICP, and ICP slow waves offered the strongest relationship with outcome. Relatively small sample sizes may overestimate effect sizes or even produce conflicting results. CONCLUSION: Low power tests, generally achieved with small sample sizes, may produce misleading conclusions, especially when they are based only on p values and the dichotomized criteria of rejecting/not-rejecting the null hypothesis. We recommend reporting confidence intervals and effect sizes in a more complete and contextualized data analysis.National Institute of Health Research (Cambridge Centre) and NIHR Health Technology Co-operative, CNPQ Scholarship (Research Project 203792/2014-9), Woolf Fisher Trust Scholarship, Cambridge Commonwealth European and International Trust Scholarship, Gates Cambridge Trust ScholarshipThis is the author accepted manuscript. It is currently under an indefinite embargo pending publication by Springer

Randomly Broken Nuclei and Disordered Systems

Similarities between models of fragmenting nuclei and disordered systems in condensed matter suggest corresponding methods. Several theoretical models of fragmentation investigated in this fashion show marked differences, indicating possible new methods for distinguishing models using yield data. Applying nuclear methods to disordered systems also yields interesting results.Comment: 10 pages, 4 figure

Autonomic Impairment in Severe Traumatic Brain Injury: A Multimodal Neuromonitoring Study

Objectives: Autonomic impairment after acute traumatic brain injury has been associated independently with both increased morbidity and mortality. Links between autonomic impairment and increased intracranial pressure or impaired cerebral autoregulation have been described as well. However, relationships between autonomic impairment, intracranial pressure, impaired cerebral autoregulation, and outcome remain poorly explored. Using continuous measurements of heart rate variability and baroreflex sensitivity we aimed to test whether autonomic markers are associated with functional outcome and mortality independently of intracranial variables. Further, we aimed to evaluate the relationships between autonomic functions, intracranial pressure, and cerebral autoregulation. Design: Retrospective analysis of a prospective database. Setting: Neurocritical care unit in a university hospital. Subjects: Sedated patients with severe traumatic brain injury. Measurements and Main Results: Waveforms of intracranial pressure and arterial blood pressure, baseline Glasgow Coma Scale and 6 months Glasgow Outcome Scale were recorded. Baroreflex sensitivity was assessed every 10 seconds using a modified cross-correlational method. Frequency domain analyses of heart rate variability were performed automatically every 10 seconds from a moving 300 seconds of the monitoring time window. Mean values of baroreflex sensitivity, heart rate variability, intracranial pressure, arterial blood pressure, cerebral perfusion pressure, and impaired cerebral autoregulation over the entire monitoring period were calculated for each patient. Two hundred and sixty-two patients with a median age of 36 years entered the analysis. The median admission Glasgow Coma Scale was 6, the median Glasgow Outcome Scale was 3, and the mortality at 6 months was 23%. Baroreflex sensitivity (adjusted odds ratio, 0.9; p = 0.02) and relative power of a high frequency band of heart rate variability (adjusted odds ratio, 1.05; p 60 yr). The relative power of high frequency correlated significantly with intracranial pressure and cerebral perfusion pressure, but not with pressure reactivity index. The relative power of low frequency correlated significantly with pressure reactivity index. Conclusions: Autonomic impairment, as measured by heart rate variability and baroreflex sensitivity, is significantly associated with increased mortality after traumatic brain injury. These effects, though partially interlinked, seem to be independent of age, trauma severity, intracranial pressure, or autoregulatory status, and thus represent a discrete phenomenon in the pathophysiology of traumatic brain injury. Continuous measurements of heart rate variability and baroreflex sensitivity in the neuromonitoring setting of severe traumatic brain injury may carry novel pathophysiological and predictive information.Peter Hutchinson is supported by a National Institute for Health Research (NIHR) Research Professorship and the Cambridge NIHR Biomedical Research Center

Effects of short-term treatment with atorvastatin in smokers with asthma - a randomized controlled trial

&lt;b&gt;Background&lt;/b&gt; The immune modulating properties of statins may benefit smokers with asthma. We tested the hypothesis that short-term treatment with atorvastatin improves lung function or indices of asthma control in smokers with asthma.&lt;p&gt;&lt;/p&gt; &lt;b&gt;Methods&lt;/b&gt; Seventy one smokers with mild to moderate asthma were recruited to a randomized double-blind parallel group trial comparing treatment with atorvastatin (40 mg per day) versus placebo for 4 weeks. After 4 weeks treatment inhaled beclometasone (400 ug per day) was added to both treatment arms for a further 4 weeks. The primary outcome was morning peak expiratory flow after 4 weeks treatment. Secondary outcome measures included indices of asthma control and airway inflammation.&lt;p&gt;&lt;/p&gt; &lt;b&gt;Results&lt;/b&gt; At 4 weeks, there was no improvement in the atorvastatin group compared to the placebo group in morning peak expiratory flow [-10.67 L/min, 95% CI -38.70 to 17.37, p=0.449], but there was an improvement with atorvastatin in asthma quality of life score [0.52, 95% CI 0.17 to 0.87 p=0.005]. There was no significant improvement with atorvastatin and inhaled beclometasone compared to inhaled beclometasone alone in outcome measures at 8 weeks.&lt;p&gt;&lt;/p&gt; &lt;b&gt;Conclusions&lt;/b&gt; Short-term treatment with atorvastatin does not alter lung function but may improve asthma quality of life in smokers with mild to moderate asthma. Clinicaltrials.gov identifier: NCT0046382

Cerebrovascular Pressure Reactivity Monitoring Using Wavelet Analysis in Traumatic Brain Injury Patients: A Retrospective Study

Background After traumatic brain injury (TBI), the ability of cerebral vessels to appropriately react to changes in arterial blood pressure (pressure reactivity) is impaired, leaving patients vulnerable to cerebral hypo- or hyper-perfusion. Although, the traditional pressure reactivity index (PRx) has demonstrated that impaired pressure reactivity associates with poor patient outcome, PRx is sometimes erratic and may not be reliable in various clinical circumstances. Here, we introduce a more robust wavelet transform based pressure reactivity index (wPRx) and compare its performance with the widely used traditional PRx across three areas: its stability and reliability in time, its ability to give an optimal cerebral perfusion pressure (CPPopt) recommendation and its relationship with patient outcome. Methods and Findings 515 TBI patients admitted in Addenbrooke’s Hospital, UK (March 23rd, 2003- December 9th, 2014), with continuous monitoring of arterial blood pressure (ABP) and intracranial pressure (ICP) were retrospectively analyzed to calculate the traditional PRx and a novel wavelet transform based wPRx. wPRx was calculated by taking the cosine of the wavelet transform phase-shift between ABP and ICP. A time trend of CPPopt was calculated using an automated curve fitting method that determined the CPP at which the pressure reactivity (PRx or wPRx) was most efficient (CPPopt_PRx and CPPopt_wPRx, respectively). There was a significantly positive relationship between PRx and wPRx (r = 0.73) and wavelet wPRx was more reliable in time (ratio of between-hour variance to total variance, wPRx 0.957± 0.0032 vs PRx and 0.949 ± 0.047 for PRx, p=0.002). The 2-hour interval standard deviation of wPRx (0.19± 0.07) was smaller than that of PRx (0.30 ± 0.13, p<0.001). wPRx performed better in distinguishing between mortality and survival (AUROC for wPRx was 0.73 vs 0.66 for PRx, p = 0.003). The mean difference between the patients’ CPP and their CPPopt was related to outcome for both calculation methods. There was a good relationship between the two CPPopts (r=0.814, p<0.001). CPPopt_wPRx was more stable than CPPopt_PRx (within patient standard deviation 7.05 ± 3.78 vs 8.45 ± 2.90; p<0.001). Key limitations include that this study is a retrospective analysis and only compared wPRx with PRx in the cohort of TBI patients. Prospective validation is required prior to better assess clinical utility of this approach. Conclusions Wavelet based pressure reactivity index (wPRx) offers several advantages to the traditional PRx: it is more stable in time, it yields a more consistent optimal CPP recommendation, and importantly, it has a stronger relationship with patient outcome. The clinical utility of wPRx should be explored in prospective studies of critically injured neurological patients.XL is a recipient of Gates Cambridge Scholarship (University of Cambridge, https://www.gatescambridge.org/). JD is funded by Woolf Fisher Scholarship (the Woolf Fisher Trust, NZ, http://www.woolffishertrust.co.nz/). DC is supported by a Cambridge Commonwealth, European & International Trust Scholarship (University of Cambridge,https://www.cambridgetrust.org/). PJH is supported by a National Institute for Health Research (NIHR) Professorship and the NIHR Cambridge Bran Repair Centre

Effects of pneumoperitoneum and Trendelenburg position on intracranial pressure assessed using different non-invasive methods

$\textbf{Background:}$ The laparoscopic approach is becoming increasingly frequent for many different surgical procedures. However, the combination of pneumoperitoneum and Trendelenburg positioning associated with this approach may increase the patient's risk for elevated intracranial pressure (ICP). Given that the gold standard for the measurement of ICP is invasive, little is known about the effect of these common procedures on ICP. $\textbf{Methods:}$ We prospectively studied 40 patients without any history of cerebral disease who were undergoing laparoscopic procedures. Three different methods were used for non-invasive estimation of ICP: ultrasonography of the optic nerve sheath diameter (ONSD); transcranial Doppler-based (TCD) pulsatility index (ICP$_{\text{PI}}$); and a method based on the diastolic component of the TCD cerebral blood flow velocity (ICP$_{\text{FVd}}$). The ONSD and TCD were measured immediately after induction of general anaesthesia, after pneumoperitoneum insufflation, after Trendelenburg positioning, and again at the end of the procedure. $\textbf{Results:}$ The ONSD, ICP$_{\text{FVd}}$, and ICP$_{\text{PI}}$ increased significantly after the combination of pneumoperitoneum insufflation and Trendelenburg positioning. The ICP$_{\text{FVd}}$ showed an area under the curve of 0.80 [95% confidence interval (CI) 0.70-0.90] to distinguish the stage associated with the application of pneumoperitoneum and Trendelenburg position; ONSD and ICP$_{\text{PI}}$ showed an area under the curve of 0.75 (95% CI 0.65-0.86) and 0.70 (95% CI 0.58-0.81), respectively. $\textbf{Conclusions:}$ The concomitance of pneumoperitoneum and the Trendelenburg position can increase ICP as estimated with non-invasive methods. In high-risk patients undergoing laparoscopic procedures, non-invasive ICP monitoring through a combination of ONSD ultrasonography and TCD-derived ICP$_{\text{FVd}}$ could be a valid option to assess the risk of increased ICP.Cambridge Commonwealth European and International Trust Scholarship (D.C.); Woolf Fisher Trust Scholarship (J.D.); Gates Cambridge Trust Scholarship (X.L.); CNPQ Scholarship (Research Project 203792/2014-9 to B.C.); NIHR Brain Injury Healthcare Technology Co-operative, Cambridge (M.C. and D.C.)