Pointed Wings, Low Wingloading and Calm Air Reduce Migratory Flight Costs in Songbirds

Migratory bird, bat and insect species tend to have more pointed wings than non-migrants. Pointed wings and low wingloading, or body mass divided by wing area, are thought to reduce energy consumption during long-distance flight, but these hypotheses have never been directly tested. Furthermore, it is not clear how the atmospheric conditions migrants encounter while aloft affect their energy use; without such information, we cannot accurately predict migratory species' response(s) to climate change. Here, we measured the heart rates of 15 free-flying Swainson's Thrushes (Catharus ustulatus) during migratory flight. Heart rate, and therefore rate of energy expenditure, was positively associated with individual variation in wingtip roundedness and wingloading throughout the flights. During the cruise phase of the flights, heart rate was also positively associated with wind speed but not wind direction, and negatively but not significantly associated with large-scale atmospheric stability. High winds and low atmospheric stability are both indicative of the presence of turbulent eddies, suggesting that birds may be using more energy when atmospheric turbulence is high. We therefore suggest that pointed wingtips, low wingloading and avoidance of high winds and turbulence reduce flight costs for small birds during migration, and that climate change may have the strongest effects on migrants' in-flight energy use if it affects the frequency and/or severity of high winds and atmospheric instability

Variation of health-related quality of life assessed by caregivers and patients affected by severe childhood infections.

BACKGROUND: The agreement between self-reported and proxy measures of health status in ill children is not well established. This study aimed to quantify the variation in health-related quality of life (HRQOL) derived from young patients and their carers using different instruments. METHODS: A hospital-based cross-sectional survey was conducted between August 2010 and March 2011. Children with meningitis, bacteremia, pneumonia, acute otitis media, hearing loss, chronic lung disease, epilepsy, mild mental retardation, severe mental retardation, and mental retardation combined with epilepsy, aged between five to 14 years in seven tertiary hospitals were selected for participation in this study. The Health Utilities Index Mark 2 (HUI2), and Mark 3 (HUI3), and the EuroQoL Descriptive System (EQ-5D) and Visual Analogue Scale (EQ-VAS) were applied to both paediatric patients (self-assessment) and caregivers (proxy-assessment). RESULTS: The EQ-5D scores were lowest for acute conditions such as meningitis, bacteremia, and pneumonia, whereas the HUI3 scores were lowest for most chronic conditions such as hearing loss and severe mental retardation. Comparing patient and proxy scores (n = 74), the EQ-5D exhibited high correlation (r = 0.77) while in the HUI2 and HUI3 patient and caregiver scores were moderately correlated (r = 0.58 and 0.67 respectively). The mean difference between self and proxy-assessment using the HUI2, HUI3, EQ-5D and EQ-VAS scores were 0.03, 0.05, -0.03 and -0.02, respectively. In hearing-impaired and chronic lung patients the self-rated HRQOL differed significantly from their caregivers. CONCLUSIONS: The use of caregivers as proxies for measuring HRQOL in young patients affected by pneumococcal infection and its sequelae should be employed with caution. Given the high correlation between instruments, each of the HRQOL instruments appears acceptable apart from the EQ-VAS which exhibited low correlation with the others

Development of the Thalassaemia Adult Life Index (ThALI)

Abstract: Background: Beta Thalassaemia Major (βTM) is a chronic genetic illness whereby the challenges faced by patients exposes them to increased risk of psychosocial issues. Despite this, a disease-specific tool to measure the impact of this illness on adult patients has yet to be developed. Methods: In collaboration with βTM adult patients, this study aimed to develop a comprehensive, disease-specific, easy to use psychometrically sound tool to measure the impact of chelation and transfusion dependent βTM in a cross-cultural patient group in England.The Thalassaemia Life Index (ThALI) was developed in two stages – item generation and pre-testing and item reduction – in collaboration with service users. Recruited adult patients shaped the design of the instrument including its statements and subscales. Standard item reduction techniques were used to develop the instrument. Results: The final version of the ThALI encompasses 35 statements and five sub-scales - general physical health, coping, body image, appearance and confidence, social relationships and autonomy. This endorses the multidimensionality of quality of life (QoL). The factor structure of the ThALI is highly stable and its internal consistency is high (alpha = 0.87 for the overall scale; 0.83–0.94 for its subscales). The ThALI has sound scaling assumptions, acceptability and score variability. Content validity was confirmed by experts and service user interviewees. The loadings for the items retained were adequate and the item discriminant validity sound. Conclusions: The ThALI covers the impact of βTM in adult patients. Preliminary testing shows its multidimensionality to be reliable and valid. The national authentication of the tool with patients treated in Centres of Excellence will aim to provide further evidence regarding the ThALI’s psychometric properties. Once authenticated, the ThALI may be utilised in research and in clinical settings to assess the effects of new therapies and/or interventions from the patients’ perspective to inform practice and/or to identify areas of concern

Phase I study of dose-escalated paclitaxel, ifosfamide, and cisplatin (PIC) combination chemotherapy in advanced solid tumours

Based on the already known in vitro synergy between paclitaxel (taxol), cisplatin and oxazophosphorine cytostatics and the broad spectrum of activity of the above drugs we sought to evaluate the paclitaxel (taxol)-ifosfamide-cisplatin (PIC) combination in the outpatient setting in individuals with a variety of advanced solid tumours. Cohorts of patients were entered into six successive dose levels (DLs) with drug doses ranging as follows: paclitaxel 135–215 mg m−2day 1 – (1 h infusion), ifosfamide 4.5–6.0 g m−2(total dose) – divided over days 1 and 2, and cisplatin 80–100 mg m−2(total) – divided over days 1 and 2. Granulocyte colony-stimulating factor was given from day 5 to 14. Forty-two patients were entered. Eighteen patients had 2–8 cycles of prior chemotherapy with no taxanes or ifosfamide (cisplatin was allowed). The regimen was tolerated with outpatient administration in 36/42 patients. Toxicities included: grade 4 neutropenia for ≤ 5 days in 27% of cycles; 5 episodes of febrile neutropenia in three patients at DL-III, -V and -VI. Grade 3/4 thrombocytopenia and cumulative grade 3 anaemia were seen in 7% and 13% of cycles respectively. Three cases of severe grade 3 neuromotor/sensory neuropathy were recorded at DL-II, -III, and -V, all after cycle 3. The maximum tolerated dose was not formally reached at DL-V, but because of progressive anaemia and asthenia/fatigue, it was decided to test a new DL-VI with doses of paclitaxel 200 mg m−2, ifosfamide 5.0 g m−2and cisplatin 100 mg m−2; this appeared to be tolerable and is recommended for further phase II testing. The response rate was 47.5% (complete response + partial response: 20/42). The PIC regimen appears to be feasible and safe in the outpatient setting. Care should be paid to neurotoxicity. Phase II studies are starting in non-small-cell lung cancer, ovarian cancer and head and neck cancer at DL-VI. © 2000 Cancer Research Campaig

Predicting microbiologically defined infection in febrile neutropenic episodes in children : global individual participant data multivariable meta-analysis

BACKGROUND: Risk-stratified management of fever with neutropenia (FN), allows intensive management of high-risk cases and early discharge of low-risk cases. No single, internationally validated, prediction model of the risk of adverse outcomes exists for children and young people. An individual patient data (IPD) meta-analysis was undertaken to devise one. METHODS: The 'Predicting Infectious Complications in Children with Cancer' (PICNICC) collaboration was formed by parent representatives, international clinical and methodological experts. Univariable and multivariable analyses, using random effects logistic regression, were undertaken to derive and internally validate a risk-prediction model for outcomes of episodes of FN based on clinical and laboratory data at presentation. RESULTS: Data came from 22 different study groups from 15 countries, of 5127 episodes of FN in 3504 patients. There were 1070 episodes in 616 patients from seven studies available for multivariable analysis. Univariable analyses showed associations with microbiologically defined infection (MDI) in many items, including higher temperature, lower white cell counts and acute myeloid leukaemia, but not age. Patients with osteosarcoma/Ewings sarcoma and those with more severe mucositis were associated with a decreased risk of MDI. The predictive model included: malignancy type, temperature, clinically 'severely unwell', haemoglobin, white cell count and absolute monocyte count. It showed moderate discrimination (AUROC 0.723, 95% confidence interval 0.711-0.759) and good calibration (calibration slope 0.95). The model was robust to bootstrap and cross-validation sensitivity analyses. CONCLUSIONS: This new prediction model for risk of MDI appears accurate. It requires prospective studies assessing implementation to assist clinicians and parents/patients in individualised decision making

Consensus Paper—ICIS Expert Meeting Basel 2009 treatment milestones in immune thrombocytopenia

The rarity of severe complications of this disease in children makes randomized clinical trials in immune thrombocytopenia (ITP) unfeasible. Therefore, the current management recommendations for ITP are largely dependent on clinical expertise and observations. As part of its discussions during the Intercontinental Cooperative ITP Study Group Expert Meeting in Basel, the Management working group recommended that the decision to treat an ITP patient be individualized and based mainly on bleeding symptoms and not on the actual platelet count number and should be supported by bleeding scores using a validated assessment tool. The group stressed the need to develop a uniform validated bleeding score system and to explore new measures to evaluate bleeding risk in thrombocytopenic patients—the role of rituximab as a splenectomy-sparing agent in resistant disease was also discussed. Given the apparently high recurrence rate to rituximab therapy in children and the drug's possible toxicity, the group felt that until more data are available, a conservative approach may be considered, reserving rituximab for patients who failed splenectomy. More studies of the effectiveness and side effects of drugs to treat refractory patients, such as TPO mimetics, cyclosporine, mycophenolate mofetil, and cytotoxic agents are required, as are long-term data on post-splenectomy complications. In the patient with either acute or chronic ITP, using a more personalized approach to treatment based on bleeding symptoms rather than platelet count should result in less toxicity and empower both physicians and families to focus on quality-of-life

Updated Systematic Review and Meta-Analysis of the Performance of Risk Prediction Rules in Children and Young People with Febrile Neutropenia

Introduction: Febrile neutropenia is a common and potentially life-threatening complication of treatment for childhood cancer, which has increasingly been subject to targeted treatment based on clinical risk stratification. Our previous meta-analysis demonstrated 16 rules had been described and 2 of them subject to validation in more than one study. We aimed to advance our knowledge of evidence on the discriminatory ability and predictive accuracy of such risk stratification clinical decision rules (CDR) for children and young people with cancer by updating our systematic review. Methods: The review was conducted in accordance with Centre for Reviews and Dissemination methods, searching multiple electronic databases, using two independent reviewers, formal critical appraisal with QUADAS and meta-analysis with random effects models where appropriate. It was registered with PROSPERO: CRD42011001685. Results: We found 9 new publications describing a further 7 new CDR, and validations of 7 rules. Six CDR have now been subject to testing across more than two data sets. Most validations demonstrated the rule to be less efficient than when initially proposed; geographical differences appeared to be one explanation for this. Conclusion: The use of clinical decision rules will require local validation before widespread use. Considerable uncertainty remains over the most effective rule to use in each population, and an ongoing individual-patient-data meta-analysis should develop and test a more reliable CDR to improve stratification and optimise therapy. Despite current challenges, we believe it will be possible to define an internationally effective CDR to harmonise the treatment of children with febrile neutropenia