Accuracy of the "traffic light" clinical decision rule for serious bacterial infections in young children with fever: A retrospective cohort study

Objectives To determine the accuracy of a clinical decision rule (the traffic light system developed by the National Institute for Health and Clinical Excellence (NICE)) for detecting three common serious bacterial infections (urinary tract infection, pneumonia, and bacteraemia) in young febrile children. Design Retrospective analysis of data from a two year prospective cohort study Setting A paediatric emergency department. Participants 15 781 cases of children under 5 years of age presenting with a febrile illness. Main outcome measures Clinical features were used to categorise each febrile episodes as low, intermediate, or high probability of serious bacterial infection (green, amber, and red zones of the traffic light system); these results were checked (using standard radiological and microbiological tests) for each of the infections of interest and for any serious bacterial infection. Results After combination of the intermediate and high risk categories, the NICE traffic light system had a test sensitivity of 85.8% (95% confidence interval 83.6% to 87.7%) and specificity of 28.5% (27.8% to 29.3%) for the detection of any serious bacterial infection. Of the 1140 cases of serious bacterial infection, 157 (13.8%) were test negative (in the green zone), and, of these, 108 (68.8%) were urinary tract infections. Adding urine analysis (leucocyte esterase or nitrite positive), reported in 3653 (23.1%) episodes, to the traffic light system improved the test performance: sensitivity 92.1% (89.3% to 94.1%), specificity 22.3% (20.9% to 23.8%), and relative positive likelihood ratio 1.10 (1.06 to 1.14). Conclusion The NICE traffic light system failed to identify a substantial proportion of serious bacterial infections, particularly urinary tract infections. The addition of urine analysis significantly improved test sensitivity, making the traffic light system a more useful triage tool for the detection of serious bacterial infections in young febrile children

Serum levels of phosphorus, parathyroid hormone, and calcium and risks of death and cardiovascular disease in individuals with chronic kidney disease a systematic review and meta-analysis

Context: Clinical practice guidelines on the management of mineral and bone disorders due to chronic kidney disease recommend specific treatment target levels for serum phosphorus, parathyroid hormone, and calcium. Objective: To assess the quality of evidence for the association between levels of serum phosphorus, parathyroid hormone, and calcium and risks of death, cardiovascular mortality, and nonfatal cardiovascular events in individuals with chronic kidney disease. Data Sources: The databases of MEDLINE (1948 to December 2010) and EMBASE (1947 to December 2010) were searched without language restriction. Hand searches also were conducted of the reference lists of primary studies, review articles, and clinical guidelines along with full-text review of any citation that appeared relevant. Study Selection: Of 8380 citations identified in the original search, 47 cohort studies (N=327 644 patients) met the inclusion criteria. Data Extraction: The characteristics of study design, participants, exposures, and covariates together with the outcomes of all-cause mortality, cardiovascular mortality, and nonfatal cardiovascular events at different levels of serum phosphorus, parathyroid hormone, and calcium were analyzed within studies. Data were summarized across studies (when possible) using random-effects meta-regression. Data Synthesis: The risk of death increased 18% for every 1-mg/dL increase in serum phosphorus (relative risk [RR], 1.18 [95% confidence interval {CI}, 1.12-1.25]). There was no significant association between all-cause mortality and serum level of parathyroid hormone (RR per 100-pg/mL increase, 1.01 [95% CI, 1.00-1.02]) or serum level of calcium (RR per 1-mg/dL increase, 1.08 [95% CI, 1.00-1.16]). Data for the association between serum level of phosphorus, parathyroid hormone, and calcium and cardiovascular death were each available in only 1 adequately adjusted cohort study. Lack of adjustment for confounding variables was not a major limitation of the available studies. Conclusions: The evidentiary basis for a strong, consistent, and independent association between serum levels of calcium and parathyroid hormone and the risk of death and cardiovascular events in chronic kidney disease is poor. There appears to be an association between higher serum levels of phosphorus and mortality in this population. ©2011 American Medical Association. All rights reserved

Cardiac testing for coronary artery disease in potential kidney transplant recipients.

Patients with chronic kidney disease (CKD) are at increased risk of coronary artery disease (CAD) and adverse cardiac events. Screening for CAD is therefore an important part of preoperative evaluation for kidney transplant candidates. There is significant interest in the role of non-invasive cardiac investigations and their ability to identify patients at high risk of CAD.  We investigated the accuracy of non-invasive cardiac screening tests compared with coronary angiography to detect CAD in patients who are potential kidney transplant recipients. MEDLINE and EMBASE searches (inception to November 2010) were performed to identify studies that assessed the diagnostic accuracy of non-invasive screening tests, using coronary angiography as the reference standard. We also conducted citation tracking via Web of Science and handsearched reference lists of identified primary studies and review articles.   We included in this review all diagnostic cross sectional, cohort and randomised studies of test accuracy that compared the results of any cardiac test with coronary angiography (the reference standard) relating to patients considered as potential candidates for kidney transplantation or kidney-pancreas transplantation at the time diagnostic tests were performed.  We used a hierarchical modelling strategy to produce summary receiver operating characteristic (SROC) curves, and pooled estimates of sensitivity and specificity. Sensitivity analyses to determine test accuracy were performed if only studies that had full verification or applied a threshold of ≥ 70% stenosis on coronary angiography for the diagnosis of significant CAD were included. The following screening investigations included in the meta-analysis were: dobutamine stress echocardiography (DSE) (13 studies), myocardial perfusion scintigraphy (MPS) (nine studies), echocardiography (three studies), exercise stress electrocardiography (two studies), resting electrocardiography (three studies), and one study each of electron beam computed tomography (EBCT), exercise ventriculography, carotid intimal media thickness (CIMT) and digital subtraction fluorography (DSF). Sufficient studies were present to allow hierarchical summary receiver operating characteristic (HSROC) analysis for DSE and MPS. When including all available studies, both DSE and MPS had moderate sensitivity and specificity in detecting coronary artery stenosis in patients who are kidney transplant candidates [DSE (13 studies) - pooled sensitivity 0.79 (95% CI 0.67 to 0.88), pooled specificity 0.89 (95% CI 0.81 to 0.94); MPS (nine studies) - pooled sensitivity 0.74 (95% CI 0.54 to 0.87), pooled specificity 0.70 (95% CI 0.51 to 0.84)]. When limiting to studies which defined coronary artery stenosis using a reference threshold of ≥ 70% stenosis on coronary angiography, there was little change in these pooled estimates of accuracy [DSE (9 studies) - pooled sensitivity 0.76 (95% CI 0.60 to 0.87), specificity 0.88 (95% CI 0.78 to 0.94); MPS (7 studies) - pooled sensitivity 0.67 (95% CI 0.48 to 0.82), pooled specificity 0.77 (95% CI 0.61 to 0.88)]. There was evidence that DSE had improved accuracy over MPS (P = 0.02) when all studies were included in the analysis, but this was not significant when we excluded studies which did not avoid partial verification or use a reference standard threshold of ≥70% stenosis (P = 0.09).   DSE may perform better than MPS but additional studies directly comparing these cardiac screening tests are needed. Absence of significant CAD may not necessarily correlate with cardiac-event free survival following transplantation. Further research should focus on assessing the ability of functional tests to predict postoperative outcome

Advances in structure elucidation of small molecules using mass spectrometry

The structural elucidation of small molecules using mass spectrometry plays an important role in modern life sciences and bioanalytical approaches. This review covers different soft and hard ionization techniques and figures of merit for modern mass spectrometers, such as mass resolving power, mass accuracy, isotopic abundance accuracy, accurate mass multiple-stage MS(n) capability, as well as hybrid mass spectrometric and orthogonal chromatographic approaches. The latter part discusses mass spectral data handling strategies, which includes background and noise subtraction, adduct formation and detection, charge state determination, accurate mass measurements, elemental composition determinations, and complex data-dependent setups with ion maps and ion trees. The importance of mass spectral library search algorithms for tandem mass spectra and multiple-stage MS(n) mass spectra as well as mass spectral tree libraries that combine multiple-stage mass spectra are outlined. The successive chapter discusses mass spectral fragmentation pathways, biotransformation reactions and drug metabolism studies, the mass spectral simulation and generation of in silico mass spectra, expert systems for mass spectral interpretation, and the use of computational chemistry to explain gas-phase phenomena. A single chapter discusses data handling for hyphenated approaches including mass spectral deconvolution for clean mass spectra, cheminformatics approaches and structure retention relationships, and retention index predictions for gas and liquid chromatography. The last section reviews the current state of electronic data sharing of mass spectra and discusses the importance of software development for the advancement of structure elucidation of small molecules

Day-to-day variability in spot urine protein-creatinine ratio measurements

Background: Accurate measurement of proteinuria is important in the diagnosis and management of chronic kidney disease (CKD). The reference standard test, 24-hour urinary protein excretion, is inconvenient and vulnerable to collection errors. Spot urine protein-creatinine ratio (PCR) is a convenient alternative and is in widespread use. However, day-to-day variability in PCR measurements has not been evaluated. Study Design: Prospective cohort study of day-to-day variability in spot urine PCR measurement. Setting & Participants: Clinically stable outpatients with CKD (n = 145) attending a university hospital CKD clinic in Australia between July 2007 and April 2010. Index Test: Spot urine PCR. Outcomes: Spot PCR variability was assessed and repeatability limits were determined using fractional polynomials. Measurements: Spot PCRs were measured from urine samples collected at 9:00 am on consecutive days and 24-hour urinary protein excretion was collected concurrently. Results: Paired results were analyzed from 145 patients: median age, 56 years; 59% men; and median 24-hour urinary protein excretion, 0.7 (range, 0.06-35.7) g/d. Day-to-day variability was substantial and increased in absolute terms, but decreased in relative terms with increasing baseline PCR. For patients with a low baseline PCR (20 mg/mmol [177 mg/g]), a change greater than ±160% (repeatability limits, 0-52 mg/mmol [0-460 mg/g]) is required to indicate a real change in proteinuria status with 95% certainty, whereas for those with a high baseline PCR (200 mg/mmol [1,768 mg/g]), a change of ±50% (decrease to 300 mg/mmol [>2,652 mg/g]) represents significant change. Limitations: These study results need to be replicated in other ethnic groups. Conclusions: Changes in PCR observed in patients with CKD, ranging from complete resolution to doubling of PCR values, could be due to inherent biological variation and may not indicate a change in disease status. This should be borne in mind when using PCR in the diagnosis and management of CKD. © 2012 National Kidney Foundation, Inc

Effect of comorbidity on relative survival following hospitalisation for fall-related hip fracture in older people

© 2012 ACOTA. Aim: To assess the effect of comorbidity on relative survival after hip fracture. Methods: Relative survival analysis was undertaken in 16838 fall-related hip fracture hospitalisations in New South Wales, Australia. Comorbidity was measured on the basis of additional diagnosis codes on the same hospital separation as the hip fracture using the Charlson Comorbidity Index (CCI). Interval-specific relative survival and relative excess risk of death were calculated. Results: Comorbidity was more frequently documented in men than women across the age groups. Survival decreased with increasing age and increasing comorbidity, but the relative impact of comorbidity was greater in the younger-old age group (65-74 years). The excess mortality in men was not accounted for by age or comorbidities. Conclusions: This study demonstrates an association between increasing comorbidity and death particularly in the first 3 months post hip fracture. It also highlights a relative excess risk of death in men after hip fracture after adjusting for age and comorbidity

Risk of bias in randomized trials of pharmacological interventions in children and adults

Objective To determine whether randomized controlled trials of pharmacologic interventions in children are more likely to be biased than similar trials in adults. Study design Trials involving only children and published in MEDLINE between January 2008 and October 2009 (n = 100) were randomly selected and matched, by drug class and therapeutic area, with a similar trial completed in adults. The Cochrane risk of bias tool was used to compare the pediatric and adult trials. Results The characteristics of adult and pediatric trials included were similar, except that adult studies were more likely to be conducted in Europe and published in specialty journals. Two-thirds of all trials were single center, and 62% had 100 or fewer participants. Many trials had an unclear risk of bias for allocation concealment (65% adult, 52% pediatric). More pediatric trials had a low risk of bias for random sequence generation (59% pediatric, 41% adult, P =.002) and blinding of outcome assessment (63% pediatric, 48% adult, P =.04) than adult trials; however, a sensitivity analysis of trials published since 2008 (and so matched by year of publication) did not confirm this finding, suggesting year of publication was an important confounder. Conclusions When randomized controlled trials are matched for drug class and therapeutic area, trials involving children display a similar risk of bias. Differences in the risk of bias between pediatric and adult trials are not caused by differences in the capacity of researchers to conduct and report trials of high quality. Copyright © 2014 Elsevier Inc. All rights reserved

A comparison of doctors', parents' and children's reports of health states and health-related quality of life in children with chronic conditions

Background Health-related quality of life is an important outcome. Self-report is the gold standard, but in the paediatric setting we often rely on proxy reporting. Our understanding of the differences between self- and proxy reports and the factors that influence them is limited. These differences can impact on treatment choices and the patient-doctor relationship. Objective To evaluate differences between children's, parents' and doctors' perceptions of health states and health-related quality of life in children with chronic illness and explore factors which explain these differences. Methods Consecutive families attending eligible clinics at a tertiary paediatric centre were invited to complete the Health Utilities Index (HUI) 23 questionnaire. Percentage agreement and kappas were calculated as a measure of the agreement between pairs. Chi-squared tests or Fisher's exact test, if appropriate, were performed to determine if there was an association between level of agreement and participant variables. Results Data were collected for 130 parent-doctor pairs, 59 child-parent pairs and 59 child-doctor pairs. Overall health-related quality of life scores did not differ between responders, but there was poorer agreement for subjective domains. Doctor-child agreement was lower than parent-child agreement. Children with a diagnosis of cerebral palsy or chronic neurological condition were more likely to have lower inter-rater agreement for both subjective and objective domains. On the HUI2, agreement was lower for parent-child pairs when the father was the respondent. For child-doctor pairs, an increased frequency of patient-doctor visits and doctors' seniority were predictors of poorer agreement on the HUI3 and HUI2 respectively. Conclusions We identified factors associated with level of agreement for self- and proxy reporting on the HUI23. Parent-child agreement was higher than doctor-child agreement. Patients with significant pain or emotional distress and patients with a diagnosis of severe cerebral palsy or chronic neurological conditions were more susceptible to under-reporting of subjective aspects of well-being by doctors and parents and may benefit from formal assessment of health-related quality of life in the clinical setting. © 2011 Blackwell Publishing Ltd