Upadacitinib in Rheumatoid Arthritis: A Benefit-Risk Assessment Across a Phase III Program.

Treating to a target of clinical remission or low disease activity is an important principle for managing rheumatoid arthritis (RA). Despite the availability of biologic disease-modifying antirheumatic drugs (bDMARDs), a substantial proportion of patients with RA do not achieve these treatment targets. Upadacitinib is a once-daily, oral Janus kinase (JAK) inhibitor with increased selectivity for JAK1 over JAK2, JAK3, and tyrosine kinase 2. The SELECT phase III upadacitinib clinical program comprised five pivotal trials of approximately 4400 patients with RA, including inadequate responders (IR) to conventional synthetic (cs)DMARDs or bDMARDs. This review aims to provide insights into the benefit-risk profile of upadacitinib in patients with RA. Upadacitinib 15 mg once daily, in combination with csDMARDs or as monotherapy, achieved all primary and ranked secondary endpoints in the five pivotal trials across csDMARD-naïve, csDMARD-IR, and bDMARD-IR populations. Upadacitinib 15 mg also demonstrated significantly higher rates of remission and low disease activity in all five pivotal trials, compared with placebo, methotrexate, or adalimumab. Labeled warnings of JAK inhibitors include serious infections, herpes zoster, malignancies, major cardiovascular events, and venous thromboembolic events. Short- and long-term integrated analyses showed that upadacitinib 15 mg was associated with increased risk of herpes zoster and creatine phosphokinase elevations compared with methotrexate and adalimumab but otherwise had comparable safety with these active comparators. This review suggests that upadacitinib 15 mg had a favorable benefit-risk profile. The safety of upadacitinib will continue to be monitored in long-term extensions and post-marketing studies.

Implementation of a novel stratified PAthway of CarE for common musculoskeletal (MSK) conditions in primary care: protocol for a multicentre pragmatic randomised controlled trial (the PACE MSK trial).

INTRODUCTION: Musculoskeletal (MSK) conditions constitute the highest burden of disease globally, with healthcare services often utilised inappropriately and overburdened. The aim of this trial is to evaluate the effectiveness of a novel clinical PAthway of CarE programme (PACE programme), where care is provided based on people's risk of poor outcome. METHODS AND ANALYSIS: Multicentre randomised controlled trial. 716 people with MSK conditions (low back pain, neck pain or knee osteoarthritis) will be recruited in primary care. They will be stratified for risk of a poor outcome (low risk/high risk) using the Short Form Örebro Musculoskeletal Pain Screening Questionnaire (SF-ÖMSPQ) then randomised to usual care (n=358) or the PACE programme (n=358). Participants at low risk in the PACE programme will receive up to 3 sessions of guideline based care from their primary healthcare professional (HCP) supported by a custom designed website (mypainhub.com). Those at high risk will be referred to an allied health MSK specialist who will conduct a comprehensive patient-centred assessment then liaise with the primary HCP to determine further care. Primary outcome (SF 12-item PCS) and secondary outcomes (eg, pain self-efficacy, psychological health) will be collected at baseline, 3, 6 and 12 months. Cost-effectiveness will be measured as cost per quality-adjusted life-year gained. Health economic analysis will include direct and indirect costs. Analyses will be conducted on an intention-to-treat basis. Primary and secondary outcomes will be analysed independently, using generalised linear models. Qualitative and mixed-methods studies embedded within the trial will evaluate patient experience, health professional practice and interprofessional collaboration. ETHICS AND DISSEMINATION: Ethics approval has been received from the following Human Research Ethics Committees: The University of Sydney (2018/926), The University of Queensland (2019000700/2018/926), University of Melbourne (1954239), Curtin University (HRE2019-0263) and Northern Sydney Local Health District (2019/ETH03632). Dissemination of findings will occur via peer-reviewed publications, conference presentations and social media. TRIAL REGISTRATION NUMBER: ACTRN12619000871145.

Clinician Assessment of Upper Limb Lymphedema: An Observational Study.

Background: Clinical management of lymphedema requires assessment, initially for detection, and then for determining treatment response and informing the treatment plan. It is unknown how the components of a lymphedema assessment are used in a clinical environment. Methods and Results: Experienced lymphedema therapists were observed assessing patients presenting with new or existing upper body lymphedema. Occupational and physiotherapists specializing in lymphedema management (n = 14) from public and private, rural and urban settings in Australia were visited at their work sites and observed with a minimum of two patients. In total, 37 upper limb assessments were observed. Reasons for attendance included: initial assessment with new swelling (n = 4); screening/detection for possible lymphedema (n = 3); bandaging as part of an intensive treatment program (n = 2); and review (n = 28). Clinicians were observed, in order of frequency, using (1) patient-reported outcomes, (2) palpation, (3) visual assessment, (4) assessment of limb size using circumference measurements, and (5) assessment of extracellular fluid using bioimpedance spectroscopy. Although clinicians selected similar assessments, differences were observed in the measurement protocols and informed reported. Objective assessment was commonly absent when the time available for an appointment was 30 minutes. Conclusions: While clinicians spent a significant portion of an appointment time assessing the limb, a standardized approach to the assessment of lymphedema was not observed. In the absence of a standardized assessment set, therapists have developed bespoke assessment routines.

Assessment of Upper Limb Lymphedema: A Qualitative Study Exploring Clinicians' Clinical Reasoning.

Background: A variety of objective and subjective assessments are available for clinical assessment of lymphedema. The aim of this study was to explore the clinical reasoning underpinning the assessment of upper limb lymphedema by experienced lymphedema clinicians. Methods and Results: Semistructured, individual, interviews were conducted with lymphedema therapists (n = 14) from a variety of treatment settings. These interviews were conducted after observations of these therapists assessing patients with lymphedema and focused on: (1) the therapists' rationale for the assessments selected, (2) how the data were analyzed, and (3) how the information was then used. Assessment selection was guided by the purpose of the visit, patient preference, resources, and time available. Subjective measures of visible and palpated tissue changes were used to target treatment, and objective measures of circumference and bioimpedance spectroscopy and patient report of symptoms informed treatment evaluation and disease progression. Objective data collected were primarily analyzed for interlimb difference and change between appointments. Conclusions: A range of clinical assessments were used in the evaluation of lymphedema to detect the presence of lymphedema, estimate the extent of soft tissue change, understand the patient experience of lymphedema, and evaluate treatment response. A primary determinant for the collection of objective measures was the appointment duration. Current methods of data analysis and reporting do not facilitate the review of change over time.

Best Evidence to Best Practice: Implementing an Innovative Model of Nutrition Care for Patients with Head and Neck Cancer Improves Outcomes.

Malnutrition is prevalent in patients with head and neck cancer (HNC), impacting outcomes. Despite publication of nutrition care evidence-based guidelines (EBGs), evidence-practice gaps exist. This study aimed to implement and evaluate the integration of a patient-centred, best-practice dietetic model of care into an HNC multidisciplinary team (MDT) to minimise the detrimental sequelae of malnutrition. A mixed-methods, pre-post study design was used to deliver key interventions underpinned by evidence-based implementation strategies to address identified barriers and facilitators to change at individual, team and system levels. A data audit of medical records established baseline adherence to EBGs and clinical parameters prior to implementation in a prospective cohort. Key interventions included a weekly Supportive Care-Led Pre-Treatment Clinic and a Nutrition Care Dashboard highlighting nutrition outcome data integrated into MDT meetings. Focus groups provided team-level evaluation of the new model of care. Economic analysis determined system-level impact. The baseline clinical audit (n = 98) revealed barriers including reactive nutrition care, lack of familiarity with EBGs or awareness of intensive nutrition care needs as well as infrastructure and dietetic resource limitations. Post-implementation data (n = 34) demonstrated improved process and clinical outcomes: pre-treatment dietitian assessment; use of a validated nutrition assessment tool before, during and after treatment. Patients receiving the new model of care were significantly more likely to complete prescribed radiotherapy and systemic therapy. Differences in mean percentage weight change were clinically relevant. At the system level, the new model of care avoided 3.92 unplanned admissions and related costs of $AUD121K per annum. Focus groups confirmed clear support at the multidisciplinary team level for continuing the new model of care. Implementing an evidence-based nutrition model of care in patients with HNC is feasible and can improve outcomes. Benefits of this model of care may be transferrable to other patient groups within cancer settings.

A phase III wait-listed randomised controlled trial of novel targeted inter-professional clinical education intervention to improve cancer patients' reported pain outcomes (The Cancer Pain Assessment (CPAS) Trial): study protocol.

BACKGROUND: Variations in care models contribute to cancer pain being under-recognised and under-treated in half of all patients with cancer. International and national cancer pain management guidelines are achievable with minimal investment but require practice changes. While much of the cancer pain research over the preceding decades has focused on management interventions, little attention has been given to achieving better adherence to recommended cancer pain guideline screening and assessment practices. This trial aims to reduce unrelieved cancer pain by improving cancer and palliative doctors' and nurses' ('clinicians') pain assessment capabilities through a targeted inter-professional clinical education intervention delivered to participants' mobile devices ('mHealth'). METHODS: A wait-listed, randomised control trial design. Cancer and/or palliative care physicians and nurses employed at one of the six participating sites across Australia will be eligible to participate in this trial and, on enrolment, will be allocated to the active or wait-listed arm. Participants allocated to the active arm will be invited to complete the mHealth cancer pain assessment intervention. In this trial, mHealth is defined as medical or public health practice supported by mobile devices (i.e. phones, patient monitoring devices, personal digital assistants and other wireless devices). This mHealth intervention integrates three evidence-based elements, namely: the COM-B theoretical framework; spaced learning pedagogy; and audit and feedback. This intervention will be delivered via the QStream online platform to participants' mobile devices over four weeks. The trial will determine if a tailored mHealth intervention, targeting clinicians' cancer pain assessment capabilities, is effective in reducing self-reported cancer pain scores, as measured by a Numerical Rating Scale (NRS). DISCUSSION: If this mHealth intervention is found to be effective, in addition to improving cancer pain assessment practices, it will provide a readily transferable evidence-based framework that could readily be applied to other evidence practice gaps and a scalable intervention that could be administered simultaneously to multiple clinicians across diverse geographical locations. Moreover, if found to be cost-effective, it will help transform clinical continuing professional development. In summary, this mHealth intervention will provide health services with an opportunity to offer an evidence-based, pedagogically robust, cost-effective, scalable training alternative. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry (ANZCTR), ACTRN12618001103257 . Registered on 3 July 2018.

Comparison of implementation strategies to influence adherence to the clinical pathway for screening, assessment and management of anxiety and depression in adult cancer patients (ADAPT CP): study protocol of a cluster randomised controlled trial.

BACKGROUND: Health service change is difficult to achieve. One strategy to facilitate such change is the clinical pathway, a guide for clinicians containing a defined set of evidence-based interventions for a specific condition. However, optimal strategies for implementing clinical pathways are not well understood. Building on a strong evidence-base, the Psycho-Oncology Co-operative Research Group (PoCoG) in Australia developed an evidence and consensus-based clinical pathway for screening, assessing and managing cancer-related anxiety and depression (ADAPT CP) and web-based resources to support it - staff training, patient education, cognitive-behavioural therapy and a management system (ADAPT Portal). The ADAPT Portal manages patient screening and prompts staff to follow the recommendations of the ADAPT CP. This study compares the clinical and cost effectiveness of two implementation strategies (varying in resource intensiveness), designed to encourage adherence to the ADAPT CP over a 12-month period. METHODS: This cluster randomised controlled trial will recruit 12 cancer service sites, stratified by size (large versus small), and randomised at site level to a standard (Core) versus supported (Enhanced) implementation strategy. After a 3-month period of site engagement, staff training and site tailoring of the ADAPT CP and Portal, each site will "Go-live", implementing the ADAPT CP for 12 months. During the implementation phase, all eligible patients will be introduced to the ADAPT CP as routine care. Patient participants will be registered on the ADAPT Portal to complete screening for anxiety and depression. Staff will be responsible for responding to prompts to follow the ADAPT CP. The primary outcome will be adherence to the ADAPT CP. Secondary outcomes include staff attitudes to and experiences of following the ADAPT CP, using the ADAPT Portal and being exposed to ADAPT implementation strategies, collected using quantitative and qualitative methods. Data will be collected at T0 (baseline, after site engagement), T1 (6 months post Go-live) and T2 (12 months post Go-live). DISCUSSION: This will be the first cluster randomised trial to establish optimal levels of implementation effort and associated costs to achieve successful uptake of a clinical pathway within cancer care. TRIAL REGISTRATION: The study was registered prospectively with the ANZCTR on 22/3/2017. Trial ID ACTRN12617000411347.

Protocol for a phase III pragmatic stepped wedge cluster randomised controlled trial comparing the effectiveness and cost-effectiveness of screening and guidelines with, versus without, implementation strategies for improving pain in adults with cancer attending outpatient oncology and palliative care services: the Stop Cancer PAIN trial.

BACKGROUND: Pain is a common and distressing symptom in people with cancer, but is under-recognised and under-treated. Australian guidelines for 'Cancer Pain Management in Adults' are available on the Cancer Council Australia Cancer Guideline Wiki. This study aims to evaluate the effectiveness and cost-effectiveness of a suite of guideline implementation strategies for improving pain outcomes in adults with cancer in oncology and palliative care outpatient settings. METHODS: The study will use a stepped-wedge cluster randomised controlled design, with oncology and palliative care outpatient services as the clusters. Patients will be eligible if they are adults with cancer and pain presenting to participating services during the study period. During an initial control arm, services will routinely screen patients for average and worst pain over the past 24 h using a 0-10 numerical rating scale (NRS) and have unfettered access to online guidelines. During the intervention arm, staff at each service will be encouraged to use: 1) a patient education booklet and self-management resource; 2) an online spaced learning cancer pain education module for clinicians from different disciplines; and 3) audit and feedback of service performance on key indices of cancer pain screening, assessment and management. Service-based clinical change champions will lead implementation of these strategies. The trial's primary outcome will be the probability that patients initially screened as having moderate-severe (≥5/10 NRS) worst pain experience a clinically important improvement one week later, defined as ≥ 30% reduction. Secondary outcomes will include patient empowerment and quality of life, carer experience, and cost-effectiveness. For the main analysis, linear mixed models will be used, accounting for clustering and the longitudinal design. Eighty-two patients per service at six services (N = 492) will provide > 90% power. A qualitative sub-study and analyses of structural and process factors will explore opportunities for further refinement and tailoring of the intervention. DISCUSSION: This pragmatic trial will inform implementation of guidelines across a range of oncology and palliative care outpatient service contexts. If found effective, the implementation strategies will be made freely available on the Wiki alongside the guidelines. TRIAL REGISTRATION: Registered 23/01/2015 on the Australian New Zealand Clinical Trials Registry ( ACTRN12615000064505 ).

Opioid errors in inpatient palliative care services: a retrospective review.

Opioids are a high-risk medicine frequently used to manage palliative patients' cancer-related pain and other symptoms. Despite the high volume of opioid use in inpatient palliative care services, and the potential for patient harm, few studies have focused on opioid errors in this population. OBJECTIVES: To (i) identify the number of opioid errors reported by inpatient palliative care services, (ii) identify reported opioid error characteristics and (iii) determine the impact of opioid errors on palliative patient outcomes. METHODS: A 24-month retrospective review of opioid errors reported in three inpatient palliative care services in one Australian state. RESULTS: Of the 55 opioid errors identified, 84% reached the patient. Most errors involved morphine (35%) or hydromorphone (29%). Opioid administration errors accounted for 76% of reported opioid errors, largely due to omitted dose (33%) or wrong dose (24%) errors. Patients were more likely to receive a lower dose of opioid than ordered as a direct result of an opioid error (57%), with errors adversely impacting pain and/or symptom management in 42% of patients. Half (53%) of the affected patients required additional treatment and/or care as a direct consequence of the opioid error. CONCLUSION: This retrospective review has provided valuable insights into the patterns and impact of opioid errors in inpatient palliative care services. Iatrogenic harm related to opioid underdosing errors contributed to palliative patients' unrelieved pain. Better understanding the factors that contribute to opioid errors and the role of safety culture in the palliative care service context warrants further investigation.

Enabler for Interdisciplinary eHealthcare: A Qualitative Study.

The complex relations between Health Technologies and clinical practices have been the focus of intensive research in recent years. This research represents a shift towards a holistic view where evaluation of health technologies is linked to organisational practices. In this paper, we address the gaps in existing literature regarding the holistic evaluation of e-health in clinical practice. We report the results from a qualitative study conducted to gain insight into e-health in practice within an interdisciplinary healthcare domain. Findings from this qualitative study, provides the foundation for the creation of a generic measurement model that allows for the comparative analysis of health technologies and assist in the decision-making of its stakeholders.

Can A Complex Online Intervention Improve Cancer Nurses' Pain Screening and Assessment Practices? Results from a Multicenter, Pre-post Test Pilot Study.

Unrelieved cancer pain has an adverse impact on quality of life. While routine screening and assessment forms the basis of effective cancer pain management, it is often poorly done, thus contributing to the burden of unrelieved cancer pain. The aim of this study was to test the impact of an online, complex, evidence-based educational intervention on cancer nurses' pain assessment capabilities and adherence to cancer pain screening and assessment guidelines. Specialist inpatient cancer nurses in five Australian acute care settings participated in an intervention combining an online spaced learning cancer pain assessment module with audit and feedback of pain assessment practices. Participants' self-perceived pain assessment competencies were measured at three time points. Prospective, consecutive chart audits were undertaken to appraise nurses' adherence with pain screening and assessment guidelines. The differences in documented pre-post pain assessment practices were benchmarked and fed back to all sites post intervention. Data were analyzed using inferential statistics. Participants who completed the intervention (n = 44) increased their pain assessment knowledge, assessment tool knowledge, and confidence undertaking a pain assessment (p < .001). The positive changes in nurses' pain assessment capabilities translated into a significant increasing linear trend in the proportion of documented pain assessments in patients' charts at the three time points (χ2 trend = 18.28, df = 1, p < .001). There is evidence that learning content delivered using a spaced learning format, augmented with pain assessment audit and feedback data, improves inpatient cancer nurses' self-perceived pain screening and assessment capabilities and strengthens cancer pain guideline adherence.

A Conceptual Measurement Model for eHealth Readiness: a Team Based Perspective.

Despite the shift towards collaborative healthcare and the increase in the use of eHealth technologies, there does not currently exist a model for the measurement of eHealth readiness in interdisciplinary healthcare teams. This research aims to address this gap in the literature through the development of a three phase methodology incorporating qualitative and quantitative methods. We propose a conceptual measurement model consisting of operationalized themes affecting readiness across four factors: (i) Organizational Capabilities, (ii) Team Capabilities, (iii) Patient Capabilities, and (iv) Technology Capabilities. The creation of this model will allow for the measurement of the readiness of interdisciplinary healthcare teams to use eHealth technologies to improve patient outcomes.

Impact of a novel online learning module on specialist palliative care nurses' pain assessment competencies and patients' reports of pain: Results from a quasi-experimental pilot study.

BACKGROUND: Pain is a complex multidimensional phenomenon moderated by consumer, provider and health system factors. Effective pain management cuts across professional boundaries, with failure to screen and assess contributing to the burden of unrelieved pain. AIM: To test the impact of an online pain assessment learning module on specialist palliative care nurses' pain assessment competencies, and to determine whether this education impacted positively on palliative care patients' reported pain ratings. DESIGN: A quasi-experimental pain assessment education pilot study utilising 'Qstream©', an online methodology to deliver 11 case-based pain assessment learning scenarios, developed by an interdisciplinary expert panel and delivered to participants' work emails over a 28-day period in mid-2012. The 'Self-Perceived Pain Assessment Competencies' survey and chart audit data, including patient-reported pain intensity ratings, were collected pre-intervention (T1) and post-intervention (T2) and analysed using inferential statistics to determine key outcomes. SETTING/PARTICIPANTS: Nurses working at two Australian inpatient specialist palliative care services in 2012. RESULTS: The results reported conform to the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) Guidelines. Participants who completed the education intervention ( n = 34) increased their pain assessment knowledge, assessment tool knowledge and confidence to undertake a pain assessment ( p < 0.001). Participants were more likely to document pain intensity scores in patients' medical records than non-participants (95% confidence interval = 7.3%-22.7%, p = 0.021). There was also a significant reduction in the mean patient-reported pain ratings between the admission and audit date at post-test of 1.5 (95% confidence interval = 0.7-2.3) units in pain score. CONCLUSION: This pilot confers confidence of the education interventions capacity to improve specialist palliative care nurses' pain assessment practices and to reduce patient-rated pain intensity scores.

Communities of practice - quality improvement or research in general practice.

BACKGROUND: A 'communities of practice' (CoP) approach has the potential to address quality improvement issues and facilitate research in general practice by engaging those most intimately involved in delivering services - the health professionals. OBJECTIVE: This article outlines the CoP approach and discusses some of the challenges involved in using this approach to raise standards in general practice and how these challenges might be addressed. DISCUSSION: General practitioner insight needs to be harnessed in order to develop solutions that are conceived in, and informed by, clinical practice. A CoP approach provides control to the practitioners over selection of the most relevant research question and outcome measure. However, the method is challenging as it requires a focus that is suitable, that motivates the participants, and effective management strategies and resources to support the CoP.

Addressing general practice workforce shortages: policy options.

There is an ongoing shortage of general practitioners in Australia, accompanied by a decline in the popularity of general practice as a career choice. Many factors influence the career choice of junior doctors and medical students, including role models, the quality of clinical attachments during training, remuneration, and flexibility of training and working hours. Evidence-based strategies that could increase the number of doctors choosing general practice as a career include longer and higher-quality general practice attachments during medical school and the early postgraduate years, and emphasising the positive aspects of general practice, such as flexibility. General practice would become a more attractive choice if remuneration was in line with hospital specialties.