Validity, reliability and responsiveness of the EORTC QLQ-C30 and the EORTC QLQ-LC13 in Australians with early stage non-small cell lung cancer, CHERE Working Paper 2007/13

Aim: To assess the validity, reliability and responsiveness of two questionnaires, the QLQ-C30 and LC-13, as measures of health-related quality of life (HRQOL) in an Australian sample of people with early stage non-small cell lung cancer. Background: These two questionnaires are complementary components of the European Organisation for Research and Treatment of Cancer?s (EORTC?s) modular approach to measuring HRQOL: the QLQ-C30 is the core questionnaire, containing 30 items relevant to all cancers; the QLQ-LC13 contains 13 items specific to lung cancer. Methods: These two complementary questionnaires were assessed with data obtained from 183 participants of a randomised control trial investigating the use of Positron Emission Tomography in the management of stage I or II non-small cell lung cancer. A cohort of 173 participants, were treated by surgery and then followed for two years. Participants completed HRQOL questionnaires before the PET scan, before and after surgery, one month after surgery, and then four monthly for two years. Construct validity was tested with confirmatory factor analysis and correlation analysis was used to test for convergent/divergent validity. Discriminant validity was tested by assessing the sensitivity of the scales to the effects of moving from early to late stage disease, asymptomatic to mildly symptomatic, and to the effects of age, gender and number of comorbitities. Mean differences (standardized response means (SRM)) and effect sizes were estimated for: patients with Stage 1/11 and metastatic disease; ECOG score 0 and ECOG score 1; older and younger patients; men and women; patients with no comorbidities and those with 1 or more comorbidities. Reliability was assessed in terms of internal consistency and test-retest reliability. Responsiveness to the effects of major thoracic surgery, adjuvant radiotherapy, and disease recurrence was assessed by estimating mean differences (standardized response meansSRM?s and effect sizes for patients who underwent surgery, radiotherapy and whose disease recurred, respectively. Results: The factor structure reported previously was replicated in this sample, confirming the questionnaires? construct validity. Most scales demonstrated good to excellent internal consistency (Cronbach?s alpha range: 0.86 ? 0.94); the exceptions were the cognitive function (0.68) and nausea/vomiting scales (0.67). Test-retest reliability was generally good (intraclass correlation (ICC) range: 0.70 ? 0.81); the exceptions were the pain and nausea/vomiting scales (ICC 0.56 and 0.42). Most scales were sensitive to the large effect of moving from early to later stage disease with (SRM range: 21.3 ? 54.0; effect size range:1.14 ? 1.97 (except for emotional functioning: 13.7; 0.60)). The scales were also sensitive to small effects, detecting small to moderate differences for age (large for social functioning) and comorbidities, and small differences for moving from asymptomatic to mildly symptomatic disease, and for age. Responsiveness was also confirmed with most scales responsive to the large expected effects of surgery and disease progression ( SRM range: 21.6 ? 41.4; effect size range: 0.94 ? 1.89 (emotional functioning: 5.5; 0.19)). Conclusions: The QLQ-C30 and QLQ-LC13, when used together, provide a valid, reliable and responsive measure of HRQOL in Australians with early stage non-small cell lung cancer.Questionnaires, validity, reliability, responsiveness, QOL, lung cancer

Genes required for free phage production are essential for pseudomonas aeruginosa chronic lung infections

The opportunistic pathogen Pseudomonas aeruginosa causes chronic lung infection in patients with cystic fibrosis. The Liverpool Epidemic Strain LESB58 is highly resistant to antibiotics, transmissible, and associated with increased morbidity and mortality. Its genome contains 6 prophages and 5 genomic islands. We constructed a polymerase chain reaction (PCR)-based signature-tagged mutagenesis library of 9216 LESB58 mutants and screened the mutants in a rat model of chronic lung infection. A total of 162 mutants were identified as defective for in vivo maintenance, with 11 signature-tagged mutagenesis mutants having insertions in prophage and genomic island genes. Many of these mutants showed both diminished virulence and reduced phage production. Transcription profiling by quantitative PCR and RNA-Seq suggested that disruption of these prophages had a widespread trans-acting effect on the transcriptome. This study demonstrates that temperate phages play a pivotal role in the establishment of infection through modulation of bacterial host gene expression

Comparative genomics of isolates of a pseudomonas aeruginosa epidemic strain associated with chronic lung infections of cystic fibrosis patients

Pseudomonas aeruginosa is the main cause of fatal chronic lung infections among individuals suffering from cystic fibrosis (CF). During the past 15 years, particularly aggressive strains transmitted among CF patients have been identified, initially in Europe and more recently in Canada. The aim of this study was to generate high-quality genome sequences for 7 isolates of the Liverpool epidemic strain (LES) from the United Kingdom and Canada representing different virulence characteristics in order to: (1) associate comparative genomics results with virulence factor variability and (2) identify genomic and/or phenotypic divergence between the two geographical locations. We performed phenotypic characterization of pyoverdine, pyocyanin, motility, biofilm formation, and proteolytic activity. We also assessed the degree of virulence using the Dictyostelium discoideum amoeba model. Comparative genomics analysis revealed at least one large deletion (40-50 kb) in 6 out of the 7 isolates compared to the reference genome of LESB58. These deletions correspond to prophages, which are known to increase the competitiveness of LESB58 in chronic lung infection. We also identified 308 non-synonymous polymorphisms, of which 28 were associated with virulence determinants and 52 with regulatory proteins. At the phenotypic level, isolates showed extensive variability in production of pyocyanin, pyoverdine, proteases and biofilm as well as in swimming motility, while being predominantly avirulent in the amoeba model. Isolates from the two continents were phylogenetically and phenotypically undistinguishable. Most regulatory mutations were isolate-specific and 29% of them were predicted to have high functional impact. Therefore, polymorphism in regulatory genes is likely to be an important basis for phenotypic diversity among LES isolates, which in turn might contribute to this strain's adaptability to varying conditions in the CF lung

Hypoglycaemia in severe malaria, clinical associations and relationship to quinine dosage

<p>Abstract</p> <p>Background</p> <p>Hypoglycaemia is an independent risk factor for death in severe malaria and a recognized adverse treatment effect of parenteral quinine. In 2006 our hospital changed quinine treatment policy from 15 mg/kg loading (plus 10 mg/kg 12-hourly) to 20 mg/kg loading (plus 10 mg/kg 8-hourly) to comply with new WHO guidelines. This presented us with the opportunity to examine whether there was any dose relationship of quinine and hypoglycaemia occurrence.</p> <p>Methods</p> <p>Retrospective case notes review of all children admitted to hospital with severe falciparum malaria between April 2002 - July 2009, before and after the introduction of the new WHO quinine regimen. Four-hourly bedside glucose levels were measured until intravenous quinine was discontinued. Clinical events immediately preceding or concurrent with each episode of hypoglycaemia (glucose < = 3.0 mmol/l) were recorded.</p> <p>Results</p> <p>954 children received the old quinine regime and 283 received the new regime. We found no evidence of an increased prevalence of hypoglycaemia (< = 3.0 mmol/L) on the new regime compared to former (15% vs. 15%); similar findings were noted for profound hypoglycaemia (< 2.2 mmols/L) 8% v 5%, P = 0.07. Episodes were co-incident with disease severity markers: coma (57%), circulatory failure (38%) and respiratory distress (21%) but less commonly with seizures (10%). Disruption of maintenance fluids and/or blood transfusion concurred with 42% of the hypoglycaemia episodes. Post admission hypoglycaemia increased odds of fatal outcome (24%) compared to euglycaemic counterparts (8%), odds ratio = 3.45 (95% confidence interval = 2.30-5.16) P < 0.01.</p> <p>Conclusion</p> <p>There was no evidence to indicate a dose relationship between quinine and occurrence of hypoglycaemia. Hypoglycaemia concurred with severity features, disruption of glucose infusion and transfusion. Careful glucose monitoring should be targeted to these complications where resources are limited.</p

Population pharmacokinetics of artesunate and amodiaquine in African children

<p>Abstract</p> <p>Background</p> <p>Pharmacokinetic (PK) data on amodiaquine (AQ) and artesunate (AS) are limited in children, an important risk group for malaria. The aim of this study was to evaluate the PK properties of a newly developed and registered fixed dose combination (FDC) of artesunate and amodiaquine.</p> <p>Methods</p> <p>A prospective population pharmacokinetic study of AS and AQ was conducted in children aged six months to five years. Participants were randomized to receive the new artesunate and amodiaquine FDC or the same drugs given in separate tablets. Children were divided into two groups of 70 (35 in each treatment arm) to evaluate the pharmacokinetic properties of AS and AQ, respectively. Population pharmacokinetic models for dihydroartemisinin (DHA) and desethylamodiaquine (DeAq), the principal pharmacologically active metabolites of AS and AQ, respectively, and total artemisinin anti-malarial activity, defined as the sum of the molar equivalent plasma concentrations of DHA and artesunate, were constructed using the non-linear mixed effects approach. Relative bioavailability between products was compared by estimating the ratios (and 95% CI) between the areas under the plasma concentration-time curves (AUC).</p> <p>Results</p> <p>The two regimens had similar PK properties in young children with acute malaria. The ratio of loose formulation to fixed co-formulation AUCs, was estimated as 1.043 (95% CI: 0.956 to 1.138) for DeAq. For DHA and total anti-malarial activity AUCs were estimated to be the same. Artesunate was rapidly absorbed, hydrolysed to DHA, and eliminated. Plasma concentrations were significantly higher following the first dose, when patients were acutely ill, than after subsequent doses when patients were usually afebrile and clinically improved. Amodiaquine was converted rapidly to DeAq, which was then eliminated with an estimated median (range) elimination half-life of 9 (7 to 12) days. Efficacy was similar in the two treatments groups, with cure rates of 0.946 (95% CI: 0.840–0.982) in the AS+AQ group and 0.892 (95% CI: 0.787 – 0.947) in the AS/AQ group. Four out of five patients with PCR confirmed recrudescences received AQ doses < 10 mg/kg. Both regimens were well tolerated. No child developed severe, post treatment neutropaenia (<1,000/μL). There was no evidence of AQ dose related hepatotoxicity, but one patient developed an asymptomatic rise in liver enzymes that was resolving by Day-28.</p> <p>Conclusion</p> <p>The bioavailability of the co-formulated AS-AQ FDC was similar to that of the separate tablets for desethylamodiaquine, DHA and the total anti-malarial activity. These data support the use this new AS-AQ FDC in children with acute uncomplicated falciparum malaria.</p

Clinical Supervision for mental health professionals

This article acknowledges an enduring debate about the nature of evidence and provides a context for the selective review of a literature on the outcomes of Clinical Supervision, a structured arrangement to support staff, which has been widely introduced into health service systems across the world. The literature revealed that many of the claims for the positive effects of CS have remained unsubstantiated. A contemporary pragmatic randomised controlled trial, summarised here, tested the relationships between Clinical Supervision, quality of care and patient outcomes, in mental health settings in Queensland, Australia. It confirmed that beneficial and sustainable CS outcomes accrued for Supervisors and Supervisees, as measured by a suite of research methods and instruments including The Manchester Clinical Supervision Scale©, and for patients in one private sector mental health facility. However, the effect Clinical Supervision had on nominated outcomes still remained difficult to demonstrate across a broad front. Plausible explanations are offered for this and a new framework for future outcomes-related research studies is suggested, in the continuing attempt to strengthen an empirical evidence base for Clinical Supervision

Thoracolumbar proprioception in individuals with and without low back pain: Intratester reliability, clinical applicability, and validity

Study Design: Repeated measures design of active spinal position sense in individuals with and without low back pain (LBP). Objectives: Reproducibility and validity evaluation of thoracolumbar proprioception measurement. Background: Proprioception studies in peripheral joints and the spine suggest that there may be proprioception deficits due to injury, pain, or degeneration. Kinesthetic retraining may be useful in rehabilitation of patients with LBP, but appropriate measures are required to objectively quantify spinal proprioception. Methods and Measures: Active-target reproduction in the sagittal, horizontal, and coronal planes was assessed (3 separate occasions for 18 asymptomatic volunteers and 2 occasions for 62 patients with LBP). Repositioning accuracy was expressed as absolute errors (AE) and variable errors (VE). Reliability was analyzed with intraclass correlation coefficient (ICC) and precision with standard error of measurement (SEM) and calculation of the smallest detectable difference (SDD) index. Repeated measures ANOVA and correlations were used for within-group comparisons and discriminant analysis for between-group comparisons. Results: Reproducibility was better for the asymptomatic group, with AE for flexion and rotation being the most reliable (ICC = 0.76-0.80, SEM = 0.91°-1.34°). SDDs were high for all tests, suggesting limited clinical applicability. Reproducibility for the same tests was poor-moderate (ICC = 0.31-0.64, SEM = 0.45°-3.90°) for the patient group. AE for right-side rotation could discriminate between subject groups with 83.3% specificity but only 54.8% sensitivity. Conclusions: Proprioception testing, with the methods employed, did not demonstrate good measurement properties in a sample of patients with recurrent LBP. Neither could it sufficiently discriminate between individuals with and without LBP. Possible reasons for these findings are discussed

Observing washing and dressing of stroke patients: nursing intervention compared with occupational therapists. What is the difference?

This study sought to compare the interventions of qualified nurses with those of occupational therapists during morning care with the same population of stroke patients. Nonparticipant structured observation was used to identify the activities and interventions carried out by each of the two groups in a naturalistic care setting. Approval for the study was granted by the local ethics committee. In order to allow comparison between pairs, staff–patient interactions during morning care (n=10) were observed by a single researcher, firstly, with an occupational therapist and within 3 days of this, with a nurse. Twenty observation sessions were recorded in total during which time the activities, contacts and interactions were coded and recorded at 20-second intervals on a standard proforma. Analysis was undertaken using the Statistical Package for Social Sciences (SPSS) for windows. The results showed that occupational therapists used 'prompting and instructing' commands more than nurses and used facilitation techniques significantly more (P=0·0283). 'Supervision' interactions were preferred by nurses with 42·1% of their time spent performing this activity compared with 25·1% for occupational therapists. These results are limited to the group under observation. It is suggested that the reasons for the observed differences in intervention styles used by occupational therapists and nurses may be attributed to the approach taken to the assessment and treatment of stroke patients. This difference might be attributed to a lack of preparation for specialist neurological/neurovascular practices of nurses working in the field of stroke rehabilitation