Use of condition-specific patient-reported outcome measures in clinical trials among patients with wrist osteoarthritis : a systematic review

Background. This paper aimed to identify condition-specific patient-reported outcome measures used in clinical trials among people with wrist osteoarthritis and summarise empirical peer-reviewed evidence supporting their reliability, validity, and responsiveness to change. Methods. A systematic review of randomised controlled trials among people with wrist osteoarthritis was undertaken. Studies reporting reliability, validity, or responsiveness were identified using a systematic reverse citation trail audit procedure. Psychometric properties of the instruments were examined against predefined criteria and summarised. Results. Thirteen clinical trials met inclusion criteria. The most common patient-reported outcome was the disabilities of the arm, shoulder, and hand questionnaire (DASH). The DASH, the Michigan Hand Outcomes Questionnaire (MHQ), the Patient Evaluation Measure (PEM), and the Patient-Reported Wrist Evaluation (PRWE) had evidence supporting their reliability, validity, and responsiveness. A post-hoc review of excluded studies revealed the AUSCAN Osteoarthritis Hand Index as another suitable instrument that had favourable reliability, validity, and responsiveness. Conclusions. The DASH, MHQ, and AUSCAN Osteoarthritis Hand Index instruments were supported by the most favourable empirical evidence for validity, reliability, and responsiveness. The PEM and PRWE also had favourable empirical evidence reported for these elements. Further psychometric testing of these instruments among people with wrist osteoarthritis is warranted.

Development and implementation of the Australian universities radiation therapy student clinical assessment form

Purpose: Prior to 2009, one of the problems faced by radiation therapists who supervised and assessed students on placement in Australian clinical centres, was that each of the six Australian universities where Radiation Therapy (RT) programmes were conducted used different clinical assessment and reporting criteria. This paper describes the development of a unified national clinical assessment and reporting form that was implemented nationally by all six universities in 2009. Methods: A four phase methodology was used to develop the new assessment form and user guide. Phase 1 included university consensus around domains of student practice and assessment, and alignment with national competency standards; Phase 2 was a national consensus workshop attended by radiation therapists involved in student supervision and assessment; Phase 3 was an action research re-iterative Delphi technique involving two rounds of a mail-out to gain further expert consensus; and stage 4 was national piloting of the developed assessment form. Results: The new assessment form includes five main domains of practice and 19 sub-domain criteria which students are assessed against during placement. Feedback from the pilot centre participants was positive, with the new form being assessed to be comprehensive and complemented by the accompanying user guide. Conclusion: The new assessment form has improved both the formative and summative assessment of students on placement, as well as enhancing the quality of feedback to students and the universities. The new national form has high acceptance from the Australian universities and has been subject to wide review by the profession.

Cervical auscultation in the diagnosis of oropharyngeal aspiration in children : a study protocol for a randomised controlled trial

Background Oropharyngeal aspiration (OPA) can lead to recurrent respiratory illnesses and chronic lung disease in children. Current clinical feeding evaluations performed by speech pathologists have poor reliability in detecting OPA when compared to radiological procedures such as the modified barium swallow (MBS). Improved ability to diagnose OPA accurately via clinical evaluation potentially reduces reliance on expensive, less readily available radiological procedures. Our study investigates the utility of adding cervical auscultation (CA), a technique of listening to swallowing sounds, in improving the diagnostic accuracy of a clinical evaluation for the detection of OPA. Methods We plan an open, unblinded, randomised controlled trial at a paediatric tertiary teaching hospital. Two hundred and sixteen children fulfilling the inclusion criteria will be randomised to one of the two clinical assessment techniques for the clinical detection of OPA: (1) clinical feeding evaluation only (CFE) group or (2) clinical feeding evaluation with cervical auscultation (CFE + CA) group. All children will then undergo an MBS to determine radiologically assessed OPA. The primary outcome is the presence or absence of OPA, as determined on MBS using the Penetration-Aspiration Scale. Our main objective is to determine the sensitivity, specificity, negative and positive predictive values of ‘CFE + CA’ versus ‘CFE’ only compared to MBS-identified OPA. Discussion Early detection and appropriate management of OPA is important to prevent chronic pulmonary disease and poor growth in children. As the reliability of CFE to detect OPA is low, a technique that can improve the diagnostic accuracy of the CFE will help minimise consequences to the paediatric respiratory system. Cervical auscultation is a technique that has previously been documented as a clinical adjunct to the CFE; however, no published RCTs addressing the reliability of this technique in children exist. Our study will be the first to establish the utility of CA in assessing and diagnosing OPA risk in young children.

Platinum-based chemotherapy in metastatic breast cancer : current status

Cisplatin and carboplatin are active in previously untreated patients with metastatic breast cancer (MBC) with mean response rates (RRs) of 50 and 32%, respectively. In pretreated patients the RR to cisplatin/carboplatin monotherapy declines markedly to <10%. Cisplatin and carboplatin have been combined with many other cytotoxics. In first-line setting high activity has been observed in combination with taxanes or vinorelbine (RRs consistently ∼60%). It appears that these newer combinations are superior to older regimens with etoposide (RRs 30 to 50%) or 5-fluorouracil (RRs 40 to 60%). Cisplatin-/carboplatin-based regimens with infusional 5-FU and epirubicin/paclitaxel/vinorelbine achieve high RRs of around 60 to 80%. However these regimens are difficult to administer in all patients because they require central venous access for continuous 5-FU infusion. In pretreated MBC the combinations of cisplatin-taxane/vinorelbine/gemcitabine or carboplatin-docetaxel/vinorelbine yield RRs of 40 to 50%, which are higher than those achieved with platinum-etoposide/5-FU. In locally advanced disease cisplatin-based regimens achieve very high RRs (>80%). This would suggest that in chemotherapy-naïve patients platinum-based therapy might have an important role to play. Additionally the synergy demonstrated between platinum compounds, taxanes and herceptin, in preclinical and clinical studies is of immense importance and the results of the two ongoing Breast Cancer International Research Group randomized phase III studies are eagerly awaited. These studies may help clarify the role of platinum compounds in the treatment of metastatic and possibly early breast cancer. © 2003 Elsevier Ltd. All rights reserved.

Exenatide extended-release; clinical trials, patient preference, and economic considerations

Type 2 diabetes remains an escalating world-wide problem, despite a range of treatments. The revelation that insulin secretion is under the control of a gut hormone, glucagon-like peptide 1 (GLP-1) led to a new paradigm in the management of type 2 diabetes, medicines that directly stimulate, or that prolong the actions of the endogenous GLP-1, at its receptors. Exenatide is an agonist at the GLP-1 receptors, and was initially developed as a subcutaneous twice daily medication, ExBID. The clinical trials with ExBID established a role for exenatide in the treatment of type 2 diabetes. Subsequently, once weekly exenatide (ExQW) was shown to have advantages over ExBID, and there is now more emphasis on the development of ExQW. ExQW alone reduces glycosylated haemoglobin (HbA1c) and body weight, and is well tolerated. ExQW has been compared to sitagliptin, pioglitazone and metformin, and shown to have a greater ability to reduce HbA1c than these other medicines. The only preparation of insulin, which ExQW has been compared to, is insulin glargine, and the ExQW has some favourable properties in this comparison, notably causing weight loss, compared to the gain with insulin glargine. ExQW has been compared to another GLP-1 receptor agonist, liraglutide, and ExQW is non-inferior to liraglutide in reducing HbA1c. The small amount of evidence available, shows that subjects with type 2 diabetes, prefer ExQW to ExBID, and that adherence was high to these in the clinical trial setting. Healthcare and economic modelling suggests that ExQW will reduce diabetic complications and be cost-effective, compared to other medications, with long term use. Little is known about whether subjects with type 2 diabetes prefer ExQW to other medicines, and whether adherence is good to ExQW in practice, and these important topics require further study.

Reversibility of liver failure secondary to metastatic breast cancer by vinorelbine and cisplatin chemotherapy

Purpose: The development of liver metastases from breast cancer is associated with a very poor prognosis, estimated at 4 months median survival. Since treatment with many chemotherapeutic agents is relatively contraindicated, we assessed the safety, tolerability and potential efficacy of combination chemotherapy with vinorelbine and cisplatin (ViP). Method: Pilot study in 11 patients with histologically confirmed breast carcinoma, radiological evidence of liver metastases and serum bilirubin greater than 1.5 times the upper limit of normal. Patients received up to six cycles of cisplatin (75 mg/m 2) every 21 days and vinorelbine (20 mg/m 2) on days 1 and 8 of every 21-day cycle. Measurement of liver lesions was performed on CT scan every 8 weeks into treatment. Results: The most frequently reported adverse event was myelosuppression. Other adverse effects included nausea, vomiting and mild neurotoxicity. Two patients died after one treatment with ViP, one of whom suffered an intracerebral haemorrhage that was possibly treatment-related. Improvement in liver function tests was observed in 10 patients, and mean time to normalization of bilirubin levels was 36 days. Partial responses were documented radiologically in 7 out of 11 patients treated. Median overall survival from trial entry was 6.5 months (range 11-364 days), with one patient alive 13 months from trial entry. Conclusion: Normalization of liver function is possible with ViP treatment of metastatic breast cancer, offering the potential to prolong survival. Phase II clinical trials of this regimen in this patient group should include measurement of quality of life in order to assess risk versus benefit.

Play and heal : randomized controlled trial of Ditto intervention efficacy on improving re-epithelialization in pediatric burns

BACKGROUND: The relationships between pain, stress and anxiety, and their effect on burn wound re-epithelialization have not been well explored to-date. The aim of this study was to investigate the effect of the Ditto (a hand-held electronic medical device providing procedural preparation and distraction) intervention on re-epithelialization rates in acute pediatric burns. METHODS/DESIGN: From August 2011 to August 2012, children (4-12 years) with an acute burn presenting to the Royal Children's Hospital, Brisbane, Australia fulfilled the study requirements and were randomized to [1] Ditto intervention or [2] standard practice. Burn re-epithelialization, pain intensity, anxiety and stress measures were obtained at every dressing change until complete wound re-epithelialization. RESULTS: One hundred and seventeen children were randomized and 75 children were analyzed (n=40 standard group; n=35 Ditto group). Inability to predict wound management resulted in 42 participants no longer meeting the eligibility criteria. Wounds in the Ditto intervention group re-epithelialized faster than the standard practice group (-2.14 days (CI: -4.38 to 0.10), p-value=0.061), and significantly faster when analyses were adjusted for mean burn depth (-2.26 days (CI: -4.48 to -0.04), p-value=0.046). Following procedural preparation at the first change of dressing, the Ditto group reported lower pain intensity scores (-0.64 (CI: -1.28, 0.01) p=0.052) and lower anxiety ratings (-1.79 (CI: -3.59, 0.01) p=0.051). At the second and third dressing removals average pain (FPS-R and FLACC) and anxiety scores (VAS-A) were at least one point lower when Ditto intervention was received. CONCLUSIONS: The Ditto procedural preparation and distraction device is a useful tool alongside pharmacological intervention to improve the rate of burn re-epithelialization and manage pain and anxiety during burn wound care procedures.

Comparison of three different dressings for partial thickness burns in children : study protocol for a randomised controlled trial

BACKGROUND: In the paediatric population, pain and distress associated with burn injuries during wound care procedures remain a constant challenge. Although silver dressings are the gold standard for burn care in Australasia, very few high-level trials have been conducted that compare silver dressings to determine which will provide the best level of care clinically. Therefore, for paediatric patients in particular, identifying silver dressings that are associated with lower levels of pain and rapid wound re-epithelialisation is imperative. This study will determine whether there is a difference in time to re-epithelialisation and pain and distress experienced during wound care procedures among Acticoat, Acticoat combined with Mepitel and Mepilex Ag dressings for acute, paediatric partial thickness burns. METHODS/DESIGN: Children aged 0 to 15 years with an acute partial thickness (superficial partial to deep partial thickness inclusive) burn injury and a burn total body surface area of

Determination of urinary thymidine glycol using affinity chromatography, HPLC and post-column reaction detection : a biomarker of oxidative DNA damage upon kidney transplantation

Reactive oxygen species are generated during ischaemia-reperfusion of tissue. Oxidation of thymidine by hydroxyl radicals (HO) leads to the formation of 5,6-dihydroxy-5,6-dihydrothymidine (thymidine glycol). Thymidine glycol is excreted in urine and can be used as biomarker of oxidative DNA damage. Time dependent changes in urinary excretion rates of thymidine glycol were determined in six patients after kidney transplantation and in six healthy controls. A new analytical method was developed involving affinity chromatography and subsequent reverse-phase high-performance liquid chromatography (RP-HPLC) with a post-column chemical reaction detector and endpoint fluorescence detection. The detection limit of this fluorimetric assay was 1.6 ng thymidine glycol per ml urine, which corresponds to about half of the physiological excretion level in healthy control persons. After kidney transplantation the urinary excretion rate of thymidine glycol increased gradually reaching a maximum around 48 h. The excretion rate remained elevated until the end of the observation period of 10 days. Severe proteinuria with an excretion rate of up to 7.2 g of total protein per mmol creatinine was also observed immediately after transplantation and declined within the first 24 h of allograft function (0.35 + 0.26 g/mmol creatinine). The protein excretion pattern, based on separation of urinary proteins on sodium dodecyl sulphate-polyacrylamide gel electrophorosis (SDS-PAGE), as well as excretion of individual biomarker proteins, indicated nonselective glomerular and tubular damage. The increased excretion of thymidine glycol after kidney transplantation may be explained by ischaemia-reperfusion induced oxidative DNA damage of the transplanted kidney.

Gliptins - do they increase cardiovascular risk or benefit?

INTRODUCTION: In 2008, the US FDA required all new glucose-lowering therapies to show cardiovascular safety, and this applies to the dipeptidyl peptidase-4 inhibitors ('gliptins'). AREAS COVERED: The cardiovascular safety trials of saxagliptin and alogliptin have recently been published and are the subject of this evaluation. EXPERT OPINION: The Saxagliptin Assessment of Vascular Outcomes Recorded in Patients with Diabetes Mellitus - Thrombolysis in Myocardial Infarction 53 trial and Examination of Cardiovascular Outcomes with Alogliptin versus Standard of Care were both multicentre, randomised, double-blind, placebo-controlled, Phase IV clinical trials. These trials showed that saxagliptin and alogliptin did not increase the primary end point, which was a composite of cardiovascular outcomes that did not include hospitalisations for heart failure. However, saxagliptin significantly increased hospitalisation for heart failure, which was a component of the secondary end point. The effect of alogliptin on hospitalisations for heart failure has not been reported. Neither agent improved cardiovascular outcomes. As there is no published evidence of improved outcomes with gliptins, it is unclear to us why these agents are so widely available for use. We suggest that the use of gliptins be restricted to Phase IV clinical trials until such time as cardiovascular safety and benefits/superiority are clearly established

Statistical methods for electromyography data and associated problems

This thesis proposes three novel models which extend the statistical methodology for motor unit number estimation, a clinical neurology technique. Motor unit number estimation is important in the treatment of degenerative muscular diseases and, potentially, spinal injury. Additionally, a recent and untested statistic to enable statistical model choice is found to be a practical alternative for larger datasets. The existing methods for dose finding in dual-agent clinical trials are found to be suitable only for designs of modest dimensions. The model choice case-study is the first of its kind containing interesting results using so-called unit information prior distributions.

Sharing of clinical data in a maternity setting: How do paper hand-held records and electronic health records compare for completeness?

Background Historically, the paper hand-held record (PHR) has been used for sharing information between hospital clinicians, general practitioners and pregnant women in a maternity shared-care environment. Recently in alignment with a National e-health agenda, an electronic health record (EHR) was introduced at an Australian tertiary maternity service to replace the PHR for collection and transfer of data. The aim of this study was to examine and compare the completeness of clinical data collected in a PHR and an EHR. Methods We undertook a comparative cohort design study to determine differences in completeness between data collected from maternity records in two phases. Phase 1 data were collected from the PHR and Phase 2 data from the EHR. Records were compared for completeness of best practice variables collected The primary outcome was the presence of best practice variables and the secondary outcomes were the differences in individual variables between the records. Results Ninety-four percent of paper medical charts were available in Phase 1 and 100% of records from an obstetric database in Phase 2. No PHR or EHR had a complete dataset of best practice variables. The variables with significant improvement in completeness of data documented in the EHR, compared with the PHR, were urine culture, glucose tolerance test, nuchal screening, morphology scans, folic acid advice, tobacco smoking, illicit drug assessment and domestic violence assessment (p = 0.001). Additionally the documentation of immunisations (pertussis, hepatitis B, varicella, fluvax) were markedly improved in the EHR (p = 0.001). The variables of blood pressure, proteinuria, blood group, antibody, rubella and syphilis status, showed no significant differences in completeness of recording. Conclusion This is the first paper to report on the comparison of clinical data collected on a PHR and EHR in a maternity shared-care setting. The use of an EHR demonstrated significant improvements to the collection of best practice variables. Additionally, the data in an EHR were more available to relevant clinical staff with the appropriate log-in and more easily retrieved than from the PHR. This study contributes to an under-researched area of determining data quality collected in patient records.

An immunodiagnostic assay for quantitation of specific ige to the major pollen allergen component, pas n 1, of the subtropical bahia grass

Background Pollens of the Panicoideae subfamily of grasses including Bahia (Paspalum notatum) are important allergen sources in subtropical regions of the world. An assay for specific IgE to the major molecular allergenic component, Pas n 1, of Bahia grass pollen (BaGP) would have immunodiagnostic utility for patients with pollen allergy in these regions. Methods Biotinylated Pas n 1 purified from BaGP was coated onto streptavidin ImmunoCAPs. Subjects were assessed by clinical history of allergic rhinitis and skin prick test (SPT) to aeroallergens. Serum total, BaGP-specific and Pas n 1-specific IgE were measured. Results: Pas n 1 IgE concentrations were highly correlated with BaGP SPT (r = 0.795, p < 0.0001) and BaGP IgE (r = 0.915, p < 0.0001). At 0.23 kU/l Pas n 1 IgE, the diagnostic sensitivity (92.4%) and specificity (93.1%) for the detection of BaGP allergy was high (area under receiver operator curve 0.960, p < 0.0001). The median concentrations of Pas n 1 IgE in non-Atopic subjects (0.01 kU/l, n = 67) and those with other allergies (0.02 kU/l, n = 59) showed no inter-group difference, whilst grass pollen-Allergic patients with allergic rhinitis showed elevated Pas n 1 IgE (6.71 kU/l, n = 182, p < 0.0001). The inter-Assay coefficient of variation for the BaGP-Allergic serum pool was 6.92%. Conclusions Pas n 1 IgE appears to account for most of the BaGP-specific IgE. This molecular component immunoassay for Pas n 1 IgE has potential utility to improve the sensitivity and accuracy of diagnosis of BaGP allergy for patients in subtropical regions.

Clinical factors associated with the humoral immune response to influenza vaccination in chronic obstructive pulmonary disease

Background and objective Individuals with chronic obstructive pulmonary disease (COPD) are at a high risk of developing significant complications from infection with the influenza virus. It is therefore vital to ensure that prophylaxis with the influenza vaccine is effective in COPD. The aim of this study was to assess the immunogenicity of the 2010 trivalent influenza vaccine in persons with COPD compared to healthy subjects without lung disease, and to examine clinical factors associated with the serological response to the vaccine. Methods In this observational study, 34 subjects (20 COPD, 14 healthy) received the 2010 influenza vaccine. Antibody titers at baseline and 28 days post-vaccination were measured using the hemagglutination inhibition assay (HAI) assay. Primary endpoints included seroconversion (≥4-fold increase in antibody titers from baseline) and the fold increase in antibody titer after vaccination. Results Persons with COPD mounted a significantly lower humoral immune response to the influenza vaccine compared to healthy participants. Seroconversion occurred in 90% of healthy participants, but only in 43% of COPD patients (P=0.036). Increasing age and previous influenza vaccination were associated with lower antibody responses. Antibody titers did not vary significantly with cigarette smoking, presence of other comorbid diseases, or COPD severity. Conclusion The humoral immune response to the 2010 influenza vaccine was lower in persons with COPD compared to non-COPD controls. The antibody response also declined with increasing age and in those with a history of prior vaccination.

A method for matching patients to advanced prostate cancer clinical trials

Objective: To illustrate a new method for simplifying patient recruitment for advanced prostate cancer clinical trials using natural language processing techniques. Background: The identification of eligible participants for clinical trials is a critical factor to increase patient recruitment rates and an important issue for discovery of new treatment interventions. The current practice of identifying eligible participants is highly constrained due to manual processing of disparate sources of unstructured patient data. Informatics-based approaches can simplify the complex task of evaluating patient’s eligibility for clinical trials. We show that an ontology-based approach can address the challenge of matching patients to suitable clinical trials. Methods: The free-text descriptions of clinical trial criteria as well as patient data were analysed. A set of common inclusion and exclusion criteria was identified through consultations with expert clinical trial coordinators. A research prototype was developed using Unstructured Information Management Architecture (UIMA) that identified SNOMED CT concepts in the patient data and clinical trial description. The SNOMED CT concepts model the standard clinical terminology that can be used to represent and evaluate patient’s inclusion/exclusion criteria for the clinical trial. Results: Our experimental research prototype describes a semi-automated method for filtering patient records using common clinical trial criteria. Our method simplified the patient recruitment process. The discussion with clinical trial coordinators showed that the efficiency in patient recruitment process measured in terms of information processing time could be improved by 25%. Conclusion: An UIMA-based approach can resolve complexities in patient recruitment for advanced prostate cancer clinical trials.