Design, construction and evaluation of systems to predict risk in obstetrics

We present a systematic, practical approach to developing risk prediction systems, suitable for use with large databases of medical information. An important part of this approach is a novel feature selection algorithm which uses the area under the receiver operating characteristic (ROC) curve to measure the expected discriminative power of different sets of predictor variables. We describe this algorithm and use it to select variables to predict risk of a specific adverse pregnancy outcome: failure to progress in labour. Neural network, logistic regression and hierarchical Bayesian risk prediction models are constructed, all of which achieve close to the limit of performance attainable on this prediction task. We show that better prediction performance requires more discriminative clinical information rather than improved modelling techniques. It is also shown that better diagnostic criteria in clinical records would greatly assist the development of systems to predict risk in pregnancy. We present a systematic, practical approach to developing risk prediction systems, suitable for use with large databases of medical information. An important part of this approach is a novel feature selection algorithm which uses the area under the receiver operating characteristic (ROC) curve to measure the expected discriminative power of different sets of predictor variables. We describe this algorithm and use it to select variables to predict risk of a specific adverse pregnancy outcome: failure to progress in labour. Neural network, logistic regression and hierarchical Bayesian risk prediction models are constructed, all of which achieve close to the limit of performance attainable on this prediction task. We show that better prediction performance requires more discriminative clinical information rather than improved modelling techniques. It is also shown that better diagnostic criteria in clinical records would greatly assist the development of systems to predict risk in pregnancy.

Standardising and assessing digital images for use in clinical trials : a practical, reproducible method that blinds the assessor to treatment allocation

With the increasing availability of high quality digital cameras that are easily operated by the non-professional photographer, the utility of using digital images to assess endpoints in clinical research of skin lesions has growing acceptance. However, rigorous protocols and description of experiences for digital image collection and assessment are not readily available, particularly for research conducted in remote settings. We describe the development and evaluation of a protocol for digital image collection by the non-professional photographer in a remote setting research trial, together with a novel methodology for assessment of clinical outcomes by an expert panel blinded to treatment allocation.

Using the WWW to teach undergraduate nurses clinical communication

On-line learning is increasingly being used in nursing education. Nevertheless, there is still insufficient evidence to demonstrate: whether students respond positively when this form of learning is used to teach relatively practical or clinical subjects; whether it is effective; and whether it is fair to students with less access to, or familiarity with, computers and the internet. In 2003, an on-line Unit on clinical communication was developed for Australian undergraduate nurses in partnership between an Australian School of Nursing and the a Department of Clinical Psychology. Students were overwhelmingly positive in their evaluation of the Unit although some regretted the lack of face-to-face contact with tutors and peers. The best aspects of the Unit included the content and structure being perceived as interesting, fun and informative, the relevance of the material for them as nurses, flexibility to work independently, promotion of critical thinking and gaining an understanding of client issues. Neither their evaluation nor their final grades were related to students’ age or whether they preferred on-line or traditional learning. Students who had readily available computer access, however, had better final grades. Also, students’ grades were correlated with how often they accessed the Unit.

Clinical use of diodes and micro-chambers to obtain accurate small field output factor measurements

There have been substantial advances in small field dosimetry techniques and technologies, over the last decade, which have dramatically improved the achievable accuracy of small field dose measurements. This educational note aims to help radiation oncology medical physicists to apply some of these advances in clinical practice. The evaluation of a set of small field output factors (total scatter factors) is used to exemplify a detailed measurement and simulation procedure and as a basis for discussing the possible effects of simplifying that procedure. Field output factors were measured with an unshielded diode and a micro-ionisation chamber, at the centre of a set of square fields defined by a micro-multileaf collimator. Nominal field sizes investigated ranged from 6×6 to 98×98 mm2. Diode measurements in fields smaller than 30 mm across were corrected using response factors calculated using Monte Carlo simulations of the full diode geometry and daisy-chained to match micro-chamber measurements at intermediate field sizes. Diode measurements in fields smaller than 15 mm across were repeated twelve times over three separate measurement sessions, to evaluate the to evaluate the reproducibility of the radiation field size and its correspondence with the nominal field size. The five readings that contributed to each measurement on each day varied by up to 0.26%, for the “very small” fields smaller than 15 mm, and 0.18% for the fields larger than 15 mm. The diode response factors calculated for the unshielded diode agreed with previously published results, within 1.6%. The measured dimensions of the very small fields differed by up to 0.3 mm, across the different measurement sessions, contributing an uncertainty of up to 1.2% to the very small field output factors. The overall uncertainties in the field output factors were 1.8% for the very small fields and 1.1% for the fields larger than 15 mm across. Recommended steps for acquiring small field output factor measurements for use in radiotherapy treatment planning system beam configuration data are provided.

The Lymphedema Evaluation in Gynecological cancer Study (LEGS): Design of a prospective, longitudinal, cohort study

Background The Lymphoedema Evaluation in Gynecological cancer Study (LEGS) was a longitudinal, observational, cohort study prospectively evaluating the incidence and risk factors of lower-limb lymphedema after treatment for gynecological cancer. Here we describe the study protocol and characteristics of the sample. Methods Women with a newly diagnosed gynecological cancer between June 1, 2008 and February 28, 2011, aged 18 years or older, and treated at one of six hospitals in Queensland, Australia, were eligible. Lymphedema was assessed by circumference measurements, bioimpedance spectroscopy, and self-reported swelling. LEGS incorporated a cohort of patients requiring surgery for benign gynecological conditions for comparison purposes. Data were collected prior to surgery and at regular intervals thereafter up to 2-years post-diagnosis. Results 546 women participated (408 cancer, 138 benign), with a 24-month retention rate of 78%. Clinical and treatment characteristics of participants were similar to the Queensland gynecological cancer population, except for a higher proportion of early-stage cervical cancers recruited to LEGS compared with Queensland proportions (89% versus 55%, respectively). Discussion Few imbalances were observed between participants with complete and incomplete follow-up data. The prospective design and collection of objective and patient-reported outcome data will allow comprehensive assessment of incidence and risk factors of lower-limb lymphedema.

Evaluation of a patient-specific finite-element model to simulate conservative treatment in adolescent idiopathic scoliosis

Study design Retrospective validation study. Objectives To propose a method to evaluate, from a clinical standpoint, the ability of a finite-element model (FEM) of the trunk to simulate orthotic correction of spinal deformity and to apply it to validate a previously described FEM. Summary of background data Several FEMs of the scoliotic spine have been described in the literature. These models can prove useful in understanding the mechanisms of scoliosis progression and in optimizing its treatment, but their validation has often been lacking or incomplete. Methods Three-dimensional (3D) geometries of 10 patients before and during conservative treatment were reconstructed from biplanar radiographs. The effect of bracing was simulated by modeling displacements induced by the brace pads. Simulated clinical indices (Cobb angle, T1–T12 and T4–T12 kyphosis, L1–L5 lordosis, apical vertebral rotation, torsion, rib hump) and vertebral orientations and positions were compared to those measured in the patients' 3D geometries. Results Errors in clinical indices were of the same order of magnitude as the uncertainties due to 3D reconstruction; for instance, Cobb angle was simulated with a root mean square error of 5.7°, and rib hump error was 5.6°. Vertebral orientation was simulated with a root mean square error of 4.8° and vertebral position with an error of 2.5 mm. Conclusions The methodology proposed here allowed in-depth evaluation of subject-specific simulations, confirming that FEMs of the trunk have the potential to accurately simulate brace action. These promising results provide a basis for ongoing 3D model development, toward the design of more efficient orthoses.

The Piper Fatigue Scale-Revised: Translation and psychometric evaluation in Spanish-speaking breast cancer survivors

Background Cancer-related fatigue (CRF) is the most common and distressing symptom reported by breast cancer survivors. The primary aim of this study was to translate and evaluate psychometrically for the first time a Spanish version of the Piper Fatigue Scale-Revised (S-PFS-R). Methods One hundred and eleven women with stage I–IIIA breast cancer who had completed their primary cancer therapy in the previous 6 months with the exception of hormone therapy completed the S-PFS-R, the Profile of Mood States (POMS) Fatigue (POMS-F) and Vigor subscales (POMS-V), and bilateral force handgrip testing. Data analysis included test–retest reliability, construct validity, criterion-related validity, and exploratory factor analyses. Results Test–retest reliability was satisfactory (r > 0.86), and all subscales showed moderate to high construct validity estimates [corrected item-subscale correlations (Pearson r = ≥ 0.65)]. The exploratory factor analysis revealed four dimensions with 75.5 % of the common variance explained. The S-PFS-R total score positively correlated with the POMS-F subscale (r = 0.50–0.78) and negatively with the POMS-V subscale (r = −0.13 to −0.44) confirming criterion-related validity. Negative correlations among force handgrip testing, subscales, and total scores were weak (r = −0.26 to −0.29). Conclusions The Spanish version of PFS-R shows satisfactory psychometric properties in a sample of breast cancer survivors. This is the first study to translate the PFS-R into Spanish and further testing is warranted.

Evaluation of immune responses to influenza vaccination in chronic obstructive pulmonary disease

Background: Given that viral infections are common triggers for exacerbations of Chronic Obstructive Pulmonary Disease (COPD), current clinical guidelines recommend that all patients receive annual influenza vaccinations. A detailed examination of the immune response to vaccination in COPD has not previously been undertaken, so this study aimed to compare immune responses to influenza vaccination between COPD patients and healthy subjects. Methods: Twenty one COPD patients and fourteen healthy subjects were recruited and cellular immune function was assessed pre- and post- vaccination with trivalent inactivated influenza vaccine. Results: One month after vaccination, H1N1 specific antibody titres were significantly lower in COPD patients than in healthy controls (p=0.02). Multivariate analysis demonstrated that post vaccination antibody titres were independently associated with COPD, but not with age or smoking status. Innate immune responses to the vaccine preparation did not differ between the two populations. Serum concentrations of IL-21, a cytokine that is important for B cell development and antibody synthesis, were also lower in COPD patients than in healthy subjects (p<0.01). In vitro functional differences were also observed, with fewer proliferating B cells expressing CD27 (p=0.04) and reduced T-cell IFN-γ synthesis (p<0.01) in COPD patients, relative to healthy subjects. Conclusions: In conclusion, COPD was associated with altered immune responses to influenza vaccination compared to healthy controls with reductions in both T-cell and B-cell function. These findings provide a foundation for future research aimed at optimising the effectiveness of influenza vaccination in COPD.

Comparator clinical trials of surrogate endpoints with albiglutide are in HARMONY

Introduction: Agonists of glucagon-like peptide-1 (GLP-1) receptors are used in the treatment of type 2 diabetes. Albiglutide is a new long acting GLP-1 receptor agonist being developed for once-weekly use. Areas covered: This evaluation is of 2 clinical trials in the HARMONY clinical trials series. HARMONY 3 compares albiglutide to sitagliptin and glimepiride in subjects with type 2 diabetes poorly controlled with metformin, and HARMONY 6 compares albiglutide to insulin lispro in subjects poorly controlled with slow/medium release preparations of insulin. Expert opinion: Both studies showed that albiglutide lowered HbA1c, and had advantages over its comparator drugs. However, questions remain about the safety of albiglutide. Albiglutide is not being used in subjects with a history of thyroid cancer, as it is not known whether this is a rare adverse effect with albiglutide. Also, the safety of albiglutide in subjects with type 2 diabetes and high cardiovascular risk is unknown.

Clinical pathways for chronic cough in children

Background Chronic cough (a cough lasting longer than four weeks) is a common problem internationally. Chronic cough has associated economic costs and is distressing to the child and to parents; ignoring cough may lead to delayed diagnosis and progression of serious underlying respiratory disease. Clinical guidelines have been shown to lead to efficient and effective patient care and can facilitate clinical decision making. Cough guidelines have been designed to facilitate the management of chronic cough. However, treatment recommendations vary, and specific clinical pathways for the treatment of chronic cough in children are important, as causes of and treatments for cough vary significantly from those in adults. Therefore, systematic evaluation of the use of evidence-based clinical pathways for the management of chronic cough in children would be beneficial for clinical practice and for patient care. Use of a management algorithm can improve clinical outcomes; such management guidelines can be found in the guidelines for cough provided by the American College of Chest Physicians (ACCP) and the British Thoracic Society (BTS). Objectives To evaluate the effectiveness of using a clinical pathway in the management of children with chronic cough. Search methods The Cochrane Register of Controlled Trials (CENTRAL), the Cochrane Airways Group Specialised Register, MEDLINE, EMBASE, review articles and reference lists of re levant articles were searched. The latest search was conducted in January 2014. Selection criteria All randomised controlled trials of parallel-group design comparing use versus non-use of a clinical pathway for treatment of chronic cough in children (< 18 years of age). Data collection and analysis Results of searches were reviewed against predetermined cr iteria for inclusion. Two review authors independently selected studies and performed data extraction in duplicate. Main results One study was included in the review. This multi-centre trial was based in five Australian hospitals and recruited 272 children with chronic cough. Children were randomly assigned to early (two weeks) or delayed (six weeks) referral to respiratory specialists who used a cough management pathway. When an intention-to-treat analysis was performed, clinical failure at six wee ks post randomisation (defined as < 75% improvement in cough score, or total resolution for fewer than three consecutive days) was significantly less in the early pathway arm compared with the control arm (odds ratio (OR) 0.35, 95% confidence interval (CI) 0.21 to 0.58). These results indicate that one additional child will be cured for e very five children treated via th e cough pathway (number needed to treat for an additional beneficial outcome (NNTB) = 5, 95% CI 3 to 9) at six weeks. Cough-specific parent-reported quality of life scores were significantly better in th e early-pathway group; the mean difference (MD) between groups was 0.60 (95% CI 0.19 to 1.01). Duration of cough post randomisation was significantly shorter in the intervention group (early-pathway arm) compared with the control group (delayed-pathway arm) (MD -2.70 weeks, 95% CI -4.26 to -1.14). Authors’ conclusions. Current evidence suggests that using a clinical algorithm for the management of children with ch r onic cough in h ospital outpatient settings is more effective than providing wait-list care. Futher high-quality randomised controlled trials are needed to perform ongoing evaluation of cough management pathways in general practitioner and other primary care settings.

Document timespan normalisation and understanding temporality for clinical records search

Previous qualitative research has highlighted that temporality plays an important role in relevance for clinical records search. In this study, an investigation is undertaken to determine the effect that the timespan of events within a patient record has on relevance in a retrieval scenario. In addition, based on the standard practise of document length normalisation, a document timespan normalisation model that specifically accounts for timespans is proposed. Initial analysis revealed that in general relevant patient records tended to cover a longer timespan of events than non-relevant patient records. However, an empirical evaluation using the TREC Medical Records track supports the opposite view that shorter documents (in terms of timespan) are better for retrieval. These findings highlight that the role of temporality in relevance is complex and how to effectively deal with temporality within a retrieval scenario remains an open question.

A 2-hour diagnostic protocol for possible cardiac chest pain in the emergency department: A randomized clinical trial

IMPORTANCE Patients with chest pain represent a high health care burden, but it may be possible to identify a patient group with a low short-term risk of adverse cardiac events who are suitable for early discharge. OBJECTIVE To compare the effectiveness of a rapid diagnostic pathway with a standard-care diagnostic pathway for the assessment of patients with possible cardiac chest pain in a usual clinical practice setting. DESIGN, SETTING, AND PARTICIPANTS A single-center, randomized parallel-group trial with blinded outcome assessments was conducted in an academic general and tertiary hospital. Participants included adults with acute chest pain consistent with acute coronary syndrome for whom the attending physician planned further observation and troponin testing. Patient recruitment occurred from October 11, 2010, to July 4, 2012, with a 30-day follow-up. INTERVENTIONS An experimental pathway using an accelerated diagnostic protocol (Thrombolysis in Myocardial Infarction score, 0; electrocardiography; and 0- and 2-hour troponin tests) or a standard-care pathway (troponin test on arrival at hospital, prolonged observation, and a second troponin test 6-12 hours after onset of pain) serving as the control. MAIN OUTCOMES AND MEASURES Discharge from the hospital within 6 hours without a major adverse cardiac event occurring within 30 days. RESULTS Fifty-two of 270 patients in the experimental group were successfully discharged within 6 hours compared with 30 of 272 patients in the control group (19.3% vs 11.0%; odds ratio, 1.92; 95% CI, 1.18-3.13; P = .008). It required 20 hours to discharge the same proportion of patients from the control group as achieved in the experimental group within 6 hours. In the experimental group, 35 additional patients (12.9%) were classified as low risk but admitted to an inpatient ward for cardiac investigation. None of the 35 patients received a diagnosis of acute coronary syndrome after inpatient evaluation. CONCLUSIONS AND RELEVANCE Using the accelerated diagnostic protocol in the experimental pathway almost doubled the proportion of patients with chest pain discharged early. Clinicians could discharge approximately 1 of 5 patients with chest pain to outpatient follow-up monitoring in less than 6 hours. This diagnostic strategy could be easily replicated in other centers because no extra resources are required.

Evaluation of a skin self examination attitude scale using an item response theory model approach

Introduction The Skin Self-Examination Attitude Scale (SSEAS) is a brief measure that allows for the assessment of attitudes in relation to skin self-examination. This study evaluated the psychometric properties of the SSEAS using Item Response Theory (IRT) methods in a large sample of men ≥ 50 years in Queensland, Australia. Methods A sample of 831 men (420 intervention and 411 control) completed a telephone assessment at the 13-month follow-up of a randomized-controlled trial of a video-based intervention to improve skin self-examination (SSE) behaviour. Descriptive statistics (mean, standard deviation, item–total correlations, and Cronbach’s alpha) were compiled and difficulty parameters were computed with Winsteps using the polytomous Rasch Rating Scale Model (RRSM). An item person (Wright) map of the SSEAS was examined for content coverage and item targeting. Results The SSEAS have good psychometric properties including good internal consistency (Cronbach’s alpha = 0.80), fit with the model and no evidence for differential item functioning (DIF) due to experimental trial grouping was detected. Conclusions The present study confirms the SSEA scale as a brief, useful and reliable tool for assessing attitudes towards skin self-examination in a population of men 50 years or older in Queensland, Australia. The 8-item scale shows unidimensionality, allowing levels of SSE attitude, and the item difficulties, to be ranked on a single continuous scale. In terms of clinical practice, it is very important to assess skin cancer self-examination attitude to identify people who may need a more extensive intervention to allow early detection of skin cancer.

Evaluation of the relationship between Chlamydia pecorum sequence types and disease using a species-specific multi-locus sequence typing scheme (MLST)

Chlamydia pecorum is globally associated with several ovine diseases including keratoconjunctivitis and polyarthritis. The exact relationship between the variety of C. pecorum strains reported and the diseases described in sheep remains unclear, challenging efforts to accurately diagnose and manage infected flocks. In the present study, we applied C. pecorum multi-locus sequence typing (MLST) to C. pecorum positive samples collected from sympatric flocks of Australian sheep presenting with conjunctivitis, conjunctivitis with polyarthritis, or polyarthritis only and with no clinical disease (NCD) in order to elucidate the exact relationships between the infecting strains and the range of diseases. Using Bayesian phylogenetic and cluster analyses on 62 C. pecorum positive ocular, vaginal and rectal swab samples from sheep presenting with a range of diseases and in a comparison to C. pecorum sequence types (STs) from other hosts, one ST (ST 23) was recognised as a globally distributed strain associated with ovine and bovine diseases such as polyarthritis and encephalomyelitis. A second ST (ST 69) presently only described in Australian animals, was detected in association with ovine as well as koala chlamydial infections. The majority of vaginal and rectal C. pecorum STs from animals with NCD and/or anatomical sites with no clinical signs of disease in diseased animals, clustered together in a separate group, by both analyses. Furthermore, 8/13 detected STs were novel. This study provides a platform for strain selection for further research into the pathogenic potential of C. pecorum in animals and highlights targets for potential strain-specific diagnostic test development.

Randomised clinical trial of a family-based lifestyle intervention for childhood obesity involving parents as the exclusive agents of change

Parent-centred interventions for childhood obesity aim to improve parents' skills and confidence in managing children's dietary and activity patterns, and in promoting a healthy lifestyle in their family. However, few studies assess changes in parenting over the course of treatment. This study describes the evaluation of a lifestyle-specific parenting program (Group Lifestyle Triple P) on multiple child and parent outcomes. One-hundred-and-one families with overweight and obese 4- to 11-year-old children participated in an intervention or waitlist control condition. The 12-week intervention was associated with significant reductions in child BMI z score and weight-related problem behaviour. At the end of the intervention, parents reported increased confidence in managing children's weight-related behaviour, and less frequent use of inconsistent or coercive parenting practices. All short-term intervention effects were maintained at one-year follow-up assessment, with additional improvements in child body size. The results support the efficacy of Group Lifestyle Triple P and suggest that parenting influences treatment outcomes. Further research is needed to evaluate the long-term effectiveness of the intervention and to elucidate the mechanisms of change. © 2010 Elsevier Ltd.