Clinical prediction rules in Staphylococcus aureus bacteremia demonstrate the usefulness of reporting likelihood ratios in infectious diseases.

Infectious diseases specialists often use diagnostic tests to assess the probability of a disease based on knowledge of the diagnostic properties. It has become standard for published studies on diagnostic tests to report sensitivity, specificity and predictive values. Likelihood ratios are often omitted. We compared published clinical prediction rules in Staphylococcus aureus bacteremia to illustrate the importance of likelihood ratios. We performed a narrative review comparing published clinical prediction rules used for excluding endocarditis in S. aureus bacteremia. Of nine published clinical prediction rules, only three studies reported likelihood ratios. Many studies concluded that the clinical prediction rule could safely exclude endocarditis based on high sensitivity and high negative predictive value. Of the studies with similar high sensitivity and high negative predictive value, calculated negative likelihood ratios were able to differentiate and identify the best clinical prediction rule for excluding endocarditis. Compared to sensitivity, specificity and predictive values, likelihood ratios can be more directly used to interpret diagnostic test results to assist in ruling in or ruling out a disease. Therefore, a new standard should be set to include likelihood ratios in reporting of diagnostic tests in infectious diseases research.

Refinement of the symptom screening in pediatrics tool (SSPedi).

BACKGROUND: Objective was to evaluate and refine a new instrument for paediatric cancer symptom screening named the Symptom Screening in Pediatrics Tool (SSPedi). METHODS: Respondents were children 8-18 years of age undergoing active cancer treatment and parents of eligible children. Respondents completed SSPedi once and then responded to semi-structured questions. They rated how easy or difficult SSPedi was to complete. For items containing two concepts, we asked respondents whether concepts should remain together or be separated into two questions. We also asked about each item's importance and whether items were missing. Cognitive probing was conducted in children to evaluate their understanding of items and the response scale. After each group of 10 children and 10 parents, responses were reviewed to determine whether modifications were required. Recruitment ceased with the first group of 10 children in which modifications were not required. RESULTS: Thirty children and 20 parents were required to achieve a final version of SSPedi. Fifteen items remain in the final version; the score ranges from 0 to 60. CONCLUSIONS: Using opinions of children with cancer and parents of paediatric cancer patients, we successfully developed a symptom screening tool that is easy to complete, is understandable and demonstrates content validity.

Do quality of life or physical function at diagnosis predict short-term outcomes during intensive chemotherapy in AML?

BACKGROUND: Intensive chemotherapy (IC) used to treat acute myeloid leukemia (AML) is associated with toxicity, particularly in older adults. Emerging data suggest that baseline quality of life (QOL) and physical function may predict outcomes in oncology, although data in AML are limited. We investigated the association between baseline QOL and physical function with short-term treatment outcomes in adults and elderly AML patients. MATERIALS AND METHODS: We conducted a prospective, longitudinal study of adults (age 18+) AML patients undergoing IC. Before starting IC, patients completed the European Organisation for the Research and Treatment of Cancer (EORTC) 30-item questionnaire (QLQ-C30) and Functional Assessment of Cancer Therapy Fatigue subscale (FACT-Fatigue) in addition to physical function tests (grip strength, timed chair stands, 2-min walk test). Outcomes included 60-day mortality, intensive care unit (ICU) admission and achievement of complete remission (CR). Logistic regression was carried out to evaluate each outcome. RESULTS: Of the 239 patients (median age 57.5 years), 56.7% were male and median Charlson comorbidity score was 0. Sixty-day mortality, ICU admission and CR occurred in 9 (3.7%), 15 (6.3%) and 167 (69.9%) patients, respectively. Using univariate regression, neither QOL nor physical function at presentation was predictive of 60-day mortality (all P > 0.05), whereas ICU admission (P < 0.001) and remission status at 30 days (P = 0.007) were. Fatigue (P = 0.004) and role functioning (P = 0.003) were predictors of ICU admission; QOL and physical function were not. A higher Charlson score predicted ICU admission (P = 0.01) and remission status (P = 0.002). The cytogenetic risk group was associated with achievement of CR (P = 0.02); QOL and physical function were not (all P > 0.05). Findings were similar when patients age 60+ were examined. Relationships between fatigue and role functioning with ICU admission deserve further exploration. CONCLUSIONS: Baseline QOL and physical function tests in this prospective study were not associated with short-term mortality, ICU admission or achievement of CR after the first cycle of chemotherapy.

Plantar flexion, dorsiflexion, range of movement and hindfoot deviation are important determinants of foot function in children.

PURPOSE: Paediatric foot surgery is often performed to restore anatomical shape or range of movement (ROM). The purpose of this study was to determine how foot morphology and ROM are associated with foot function in children aged five to 16 years of age. METHODS: Participants included 89 patients with foot disorders and 58 healthy controls. In addition to measuring children's foot alignment and ankle ROM, children and parents completed the Oxford Ankle and Foot Questionnaire (OxAFQ). RESULTS: Mean age was 10.3 years for patients and 10.6 years for controls; 53 of 89 patients had clubfoot. All foot measurements and scores on the OxAFQ significantly differed (p < 0.001) between patients and controls. Patients and their parents significantly differed on the physical (p = 0.03) and emotional (p = 0.02) domains of the OxAFQ, with parents' ratings being lower than their children. Moderate correlations (r = 0.54 to 0.059; p < 0.001) were found between physical domain (reported by parents on the OxAFQ) and dorsiflexion-knee flexed, and foot- arc-of-movement. Moderate correlations were found between physical domain (reported by children on OxAFQ) and foot-arc-of-movement (r = 0.56; p < 0.001). Patients in the surgical group showed moderate correlations (r = 0.57;, p < 0.001) between physical domain (reported by children on OxAFQ) and plantar flexion, and foot arc-of-movement. The control group and the patients in non-surgical subgroup showed no significant correlations. CONCLUSION: Plantar flexion, arc of ankle ROM and hindfoot alignment impact foot function in children with foot deformities. Parents report significantly lower scores on the OxAFQ when judging foot functioning. LEVEL OF EVIDENCE: Level II. Prognostic Studies.

Long-term recovery of quality of life and physical function over three years in adult survivors of acute myeloid leukemia after intensive chemotherapy.

We previously described impairments in quality of life (QOL) and physical function among acute myeloid leukemia (AML) survivors between diagnosis and 1 year. The aim of the current study is to describe and compare to normative data QOL and physical function recovery over 3 years from diagnosis and treatment with intensive chemotherapy (IC). At assessments done at baseline (pre-IC) and at 11 time points over 3 years, QOL, fatigue, and 3 physical performance measures (PPMs; grip strength, 6-min walk test (6MWT), and timed chair stands) were collected. Long-term recovery was defined by reaching scores within the minimum clinically important difference of normative data. Global QOL recovery was seen in 79% at 1 year, 75% at 2 years, and 86% at 3 years. At 3 years, the QLQ-C30 subscales with the greatest recovery were physical and emotional functioning. For FACT-fatigue, recovery was seen in 68% at 1 year and 77% at 3 years. Recovery on PPMs was poorer on average, with only 17% on the 6MWT and 42% in grip strength returning to normal at 3 years. The vast majority of AML survivors after IC achieve recovery in QOL and fatigue by three years. However, recovery in physical performance remained blunted.

Serial controlled N-of-1 trials of topical vitamin E as prophylaxis for chemotherapy-induced oral mucositis in paediatric patients.

The objectives were (1) to determine whether in children undergoing doxorubicin-containing chemotherapy, topical vitamin E decreases an objective measurement of oral mucositis compared to placebo, and (2) to assess the feasibility of an innovative trial design in paediatric cancer, combining N-of-1 trials using Bayesian meta-analysis. We conducted a series of N-of-1, double-blinded, randomised controlled trials in children > or = 6 years of age receiving repeated cycles of identical doxorubicin-containing chemotherapy. Each study cycle was followed by topical vitamin E (800 mg) or placebo. We enroled 16 children and 45 post chemotherapy cycles were randomised to vitamin E (N=22) or placebo (N=23). There was no difference in objective mucositis scores with a mean score of 0.2 with vitamin E and 0.3 with placebo. Topical vitamin E does not reduce doxorubicin-induced oral mucositis in children. The use of N-of-1 studies and Bayesian meta-analysis may facilitate the study of some therapies in paediatric oncology.

A phase II exercise randomized controlled trial for patients with acute myeloid leukemia undergoing induction chemotherapy.

Curative treatment for acute myeloid leukemia (AML) involves induction chemotherapy (IC) which is associated with bed rest and toxicities, leading to worsening quality of life (QOL), fatigue, and fitness. Exercise during IC may ameliorate declines but has not been rigorously tested. We examined the efficacy of supervised exercise during IC on QOL, fatigue, and fitness. Eighty-three inpatients age 18-80 scheduled to receive IC for newly diagnosed or relapsed AML were randomized 2:1 (exercise intervention:control group). Study measures were completed at baseline, post-IC, and following the first cycle of consolidation. The intervention consisted of a supervised mixed-modality, moderate-intensity exercise program (4-5 days per week, 30-60min per session) throughout admission. Recruitment was good (56%), retention excellent (96%), and adherence was 54%. Global QOL improved similarly in both groups from baseline to post-IC (between-group difference 3.0 points, p=0.62). Fatigue improved in the exercise group from baseline to post-IC (potentially clinically important between-group difference of 3.6 points, p=0.23). Aerobic fitness, lower body strength, and grip strength improved in the exercise group (between-group differences p=0.005, p<0.001, p=0.03, respectively). Supervised exercise for patients with AML undergoing IC is feasible, safe, and appears effective at improving fitness and possibly fatigue. A larger trial is warranted.

Denitrification by extremely halophilic bacteria.

Extremely halophilic bacteria were isolated from widely separated sites by anaerobic enrichment in the presence of nitrate. The anaerobic growth of several of these isolates was accompanied by the production of nitrate, nitrous oxide, and dinitrogen. These results are a direct confirmation of the existence of extremely halophilic denitrifying bacteria, and suggest that such bacteria may be common inhabitants of hypersaline environments.

Polar lipid composition of a new halobacterium.

Investigations of the polar lipid composition of a new aerobic, extremely halophilic aracheabacterium capable of nitrate reduction have shown that this organism contains two previously unknown phospholycolipids derived from diphytanyl glycerol diethers. Comparison of the lipid pattern from this new isolate with other known strains indicate that this organism is novel. On the basis of the unique polar lipid pattern it can be concluded that this organism represents a new taxon, at least at the species level.

Dangerous advances in measurements from digital subtraction angiography: when is a millimeter not a millimeter?

Aneurysms need accurate millimeters (mm). Direct millimeters were lost with digital subtraction angiography (DSA) years ago, with measurements in pixels. Advances in DSA can now give inherent millimeters. The Cerecyte aneurysm coiling trial's angiographic core lab assesses images from compact disc (CD). External fiducials for millimeter calibration are required. Of 25 cases with two 10 mm fiducials, near and far from the intensifier, the midline mean is between 9 "mm" to 15 "mm". Yet 10 mm must be 10 mm. This variance is potentially dangerous. Proprietary software seems to prohibit calibration transfer via CD to another vendor's system.

A Bayesian meta-analysis of prophylactic granulocyte colony-stimulating factor and granulocyte-macrophage colony-stimulating factor in children with cancer.

The purpose of this analysis was to examine the efficacy of prophylactic hematopoietic colony-stimulating factors (CSFs) in pediatric cancer and to describe how a Bayesian meta-analysis can be conducted and then modified to incorporate information not readily included in a frequentist meta-analysis. Three Bayesian models were developed. The simplest model used the same data as a published frequentist meta-analysis. The second model included data that could not easily be incorporated into the frequentist meta-analysis, including data from different courses of chemotherapy and continuous outcomes that did not report variance estimates. The third model examined the effect of CSF type (granulocyte CSF vs. granulocyte-macrophage CSF). Compared with the frequentist model, the Bayesian model with the most data suggested a greater benefit of CSFs, with a 3.2-day reduction in duration of parenteral antibiotics (95% credible interval: -7.1, 0.7) in the expanded Bayesian model compared with a 0.8-day (95% confidence interval: -2.3, 0.7) reduction in the frequentist model. Bayesian meta-analysis also suggested that, compared with granulocyte-macrophage CSF, granulocyte CSF was associated with a 4.8-day decrease in the duration of parenteral antibiotics. Bayesian meta-analysis can readily include information not easily incorporated in a frequentist meta-analysis. Some treatment effect estimates were larger by a clinically important amount when additional data contributed to the pooled estimate.

The formation of bilirubin and p-nitrophenyl glucuronides by rabbit liver.

1. Glucuronide formation of bilirubin and p-nitrophenol in vitro with excess of UDP-glucuronic acid by UDP-glucuronyltransferase from livers of young and adult rabbits was studied. 2. The development of UDP-glucuronyltransferase for the two substrates followed a markedly different pattern during maturation of young rabbits, p-nitrophenol-conjugation ability being much higher at birth than that for bilirubin. 3. Mg(2+) increased bilirubin conjugation, but inhibited p-nitrophenyl glucuronide formation. 4. p-Nitrophenol acted as a potent non-competitive inhibitor for bilirubin conjugation but bilirubin did not affect p-nitrophenyl glucuronidation. 5. The enzyme for bilirubin conjugation was inactivated at pH9 during treatment with snake venom, whereas in the same preparation the activity of the corresponding enzyme for p-nitrophenol was enhanced. In addition, some solubilization of the latter enzyme could be achieved by this method. 6. The possibility of the existence of more than one enzyme system for the formation of O-glucuronides is discussed.

Halobacterium saccharovorum sp. nov., a carbohydrate-metabolizing, extremely halophilic bacterium.

The previously described extremely halophilic bacterium, strain M6, metabolizes a variety of carbohydrates with the production of acid. In addition, the organism produces nitrite (but no gas) from nitrate, is motile, and grows most rapidly at about 50 degrees C. These characteristics distinguish it from all previously described halophilic bacteria in the genus Halobacterium. It is suggested that it be designated as a new species, Halobacterium saccharovorum.

The enzymes associated with denitrification.

NASA: The enzymes involved in the reduction of nitrogenous oxides are thought to be intermediates in denitrification processes. This review examines the roles of nitrate reductase, nitrite reductases, nitric oxide reductase, mechanisms of N-N bond formation, and nitrous oxide reductases.^ieng

The growth of Paracoccus halodenitrificans in a defined medium.

A synthetic medium, consisting of inorganic salts and any of a number of carbon sources, supported the aerobic growth of Paracoccus halodenitrificans when supplemented with thiamine. The same medium plus an appropriate nitrogenous oxide supported anaerobic growth when additionally supplemented with methionine. The observation that vitamin B12 or betaine replaced methionine suggested that P. halodenitrificans had a defect in the cobalamin-dependent pathway for methionine biosynthesis, as well as the inability to synthesize betaine when growing anaerobically.

The metabolism of carbohydrates by extremely halophilic bacteria: the identification of lactobionic acid as a product of lactose metabolism by Halobacterium saccharovorum.

Nongrowing cells of Halobacterium saccharovorum oxidized lactose to a product identified as lactobionic acid by thin-layer, paper, and column chromatography, and by identification of the galactose and gluconic acid produced from it after acid hydrolysis. Growing cells oxidized lactose to a product that was identical with lactobionate except that it did not serve as a substrate for galactose oxidase. While the identity of this compound has not been established, it is suggested that the product is lactobionic acid in which the galactose moeity is in the furanose form. Neither lactobionate nor the product produced by growing cells was further metabolized, suggesting that lactose oxidation is not coupled to growth.

Mortality among fire fighters in metropolitan Toronto.

Fire fighters are exposed to substances which are recognized or suspected causal agents in cancer or heart disease. The purpose of this study was to determine whether or not fire fighters experience increased risk for any specific cause of death. A retrospective cohort study was conducted, with 5,995 subjects recruited from all six fire departments within Metropolitan Toronto. The mortality experience of the cohort was ascertained through computerized record linkage and compared to that of the male Ontario population specific to cause, age, and calendar period from 1950 through 1989. Average duration of follow-up was 21 years, and there were 777 deaths among the 5,414 males included in the analysis, giving an all-cause standardized mortality ratio of 95 (95% confidence interval: 88-102). Three specific causes of death exhibit statistically significant excesses (brain tumors, "other" malignant neoplasms, and aortic aneurysms). There are also slight increases in risk for some other sites of cancer, and for various diseases of the respiratory, circulatory, and digestive systems. This study is consistent with others in demonstrating that fire fighters experience increased risk of death from cancer of the brain, and in suggesting increased risk for various other causes of death.