Therapeutic approaches to disease modifying therapy for multiple sclerosis in adults: an Australian and New Zealand perspective: part 3 treatment practicalities and recommendations

In this third and final part of our review of multiple sclerosis (MS) treatment we look at the practical day-to-day management issues that are likely to influence individual treatment decisions. Whilst efficacy is clearly of considerable importance, tolerability and the potential for adverse effects often play a significant role in informing individual patient decisions. Here we review the issues surrounding switching between therapies, and the evidence to assist guiding the choice of therapy to change to and when to change. We review the current level of evidence with regards to the management of women in their child-bearing years with regards to recommendations about treatment during pregnancy and whilst breast feeding. We provide a summary of recommended pre- and post-treatment monitoring for the available therapies and review the evidence with regards to the value of testing for antibodies which are known to be neutralising for some therapies. We review the occurrence of adverse events, both the more common and troublesome effects and those that are less common but have potentially much more serious outcomes. Ways of mitigating these risks and managing the more troublesome adverse effects are also reviewed. Finally, we make specific recommendations with regards to the treatment of MS. It is an exciting time in the world of MS neurology and the prospects for further advances in coming years are high.

Schools, health literacy and public health: possibilities and challenges

Health literacy is a concept that can be widely embraced by schools. Schools throughout the world contribute to the achievement of public health goals in conjunction with their educational commitments. In this paper, the interface between a school's core business of education and public health goals is identified, and examples provided in the area of nutrition demonstrating how these links can operate at school level. The structure and function of the health promoting school is described and the author proposes that there is a very close connection between the health promoting school and the enabling factors necessary in achieving health literacy. Major findings in the literature that provide evidence of good practices in school health education and promotion initiatives are described. Also, those factors that make schools effective and which facilitate learning for students are identified. There is a substantial overlap between the successful components of a health promoting school and effective schools. This enables schools to potentially achieve all three levels of health literacy, including level 3—critical health literacy. However, there are three challenges that must be addressed to enable schools to achieve this level: the traditional structure and function of schools, teachers practices and skills, and time and resources. Strategies are proposed to address all three areas and to reduce the impediments to achieving the goals of health literacy and public health using the school as a setting.

Rationale and design of the national benchmarking and evidence-based national clinical guidelines for chronic heart failure management programs study

OBJECTIVES: The National Benchmarks and Evidence-Based National Clinical Guidelines for Heart Failure Management Programs Study is a national, multicenter study designed to determine the nature, range, and effect of interventions applied by chronic heart failure management programs (CHF-MPs) throughout Australia on patient outcomes. Its primary objective is to use these data to develop national benchmarks and evidence-based clinical guidelines and optimize their cost-effective application by reducing quality and outcome variability. DATA SOURCES/STUDY SETTING: Primary data will be collected from CHF-MP coordinators and CHF patients enrolled in these programs on a national basis. Secondary outcome data will be collected from a national morbidity record and from patients' medical records. STUDY DESIGN: Stage I of the study involves a prospective clinical audit of all CHF-MPs throughout Australia (n = 45) to determine the extent of variability in programs currently. Stage II is a prospective cross-sectional survey design enrolling 1,500 patients (average of 40 patients per program) to firstly determine the typical profile of patients being managed via a CHF-MP in Australia and, secondly, the subsequent morbidity and mortality during the 6-month follow-up. Outcome data will be subject to multivariate analysis to determine the key components of care in this regard. All study data will be then examined in the final stage of the study (III) to develop national benchmarks for the application and auditing of CHF-MPs in Australia. CONCLUSION: Variability in patient outcomes is a product of heterogeneity among CHF-MPs. The development of national benchmarks will minimize such heterogeneity and will provide a greater level of evidence for their cost-effective application.

Economic evaluation of Australian stroke services: a prospective, multicenter study comparing dedicated stroke units with other care modalities

Background and Purpose: Level I evidence from randomized controlled trials demonstrates that the model of hospital care influences stroke outcomes; however, the economic evaluation of such is limited. An economic appraisal of 3 acute stroke care models was facilitated through the Stroke Care Outcomes: Providing Effective Services (SCOPES) study in Melbourne, Australia. The aim was to describe resource use up to 28 weeks poststroke for each model and examine the cost-effectiveness of stroke care units (SCUs). Methods: A prospective, multicenter, cohort study design was used. Costs and outcomes of stroke patients receiving 100% treatment in 1 of 3 inpatient care models (SCUs, mobile service, conventional care) were compared. Health-sector resource use up to 28 weeks was measured in 1999. Outcomes were thorough adherence to a suite of important clinical processes and the number of severe inpatient complications. Results: The sample comprised 395 participants (mean age 73 [SD 14], 77% first-ever strokes, males 53%). When compared with conventional care (n=84), costs for mobile service (n=209) were significantly higher (P=0.024), but borderline for SCU (n=102, P=0.08; $AUD12 251; $AUD15 903; $AUD15 383 respectively). This was primarily explained by the greater use of specialist medical services. The incremental cost-effectiveness of SCUs over conventional care was $AUD9867 per patient achieving thorough adherence to clinical processes and $AUD16 372 per patient with severe complications avoided, based on costs to 28 weeks. Conclusions: Although acute SCU costs are generally higher, they are more cost-effective than either mobile service or conventional care.

Comparative accuracy of magnetic resonance imaging and ultrasonography in confirming clinically diagnosed patellar tendinopathy

Background: Diagnosis of patellar tendinopathy is based primarily on clinical examination; however, it is commonplace to image the patellar tendon for diagnosis confirmation, with the imaging modalities of choice being magnetic resonance imaging (MRI) and ultrasonography (US). The comparative accuracy of these modalities has not been established.

Hypothesis: Magnetic resonance imaging and US have good (>80%) accuracy and show substantial agreement in confirming clinically diagnosed patellar tendinopathy.

Study Design: Cohort study (diagnosis); Level of evidence, 2.

Methods: Magnetic resonance imaging and US (gray scale [GS-US] and color Doppler [CD-US]) features of 30 participants with clinically diagnosed patellar tendinopathy and 33 activity-matched, asymptomatic participants were prospectively compared. Accuracy, sensitivity, specificity, positive and negative predictive values, and the likelihood of positive and negative test results were determined for each technique.

Results: The accuracy of MRI, GS-US, and CD-US was 70%, 83%, and 83%, respectively (P = .04; MRI vs GS-US). The likelihood of positive MRI, GS-US, and CD-US was 3.1, 4.8, and 11.6, respectively. The MRI and GS-US had equivalent specificity (82% vs 82%; P = 1.00); however, the sensitivity of GS-US was greater than MRI (87% vs 57%; P = .01). Sensitivity (70% vs 87%; P = .06) and specificity (94% vs 82%; P = .10) did not differ between CD-US and GS-US.

Conclusions: Ultrasonography was more accurate than MRI in confirming clinically diagnosed patellar tendinopathy. GS-US and CD-US may represent the best combination for confirming clinically diagnosed patellar tendinopathy because GS-US had the greatest sensitivity, while a positive CD-US test result indicated a strong likelihood an individual was symptomatic.

The evidence that exercise during growth or adulthood reduces the risk of fragility fractures is weak

There has never been, and will never be, a randomized double-blind placebo-controlled trial demonstrating that exercise in youth, adulthood or old age reduces fragility or osteoporosis-related fractures in old age. The next level of evidence, a randomized, controlled but unblinded study with fractures as an end-point is feasible but has never been done. The basis for the belief that exercise reduces fractures is derived from lower levels of ‘evidence’, namely, retrospective and prospective observation cohort studies and case–control studies. These studies are at best hypothesis generating, never hypothesis testing. They are all subject to many systematic biases and should be interpreted with extreme scepticism. Surrogate measures of anti-fracture efficacy are the next level of evidence, such as the demonstration of a reduction in risk factors for falls, a reduction in falls, a reduction in fractures due to falls, an increase in peak bone size and mass, prevention of bone loss in midlife and restoration of bone mass and structure in old age.

Improving access to evidence-based acute stroke services: development and evaluation of a health systems model to address equity of access issues

Level 1 evidence for management of patients with stroke in a dedicated Stroke Care Unit (SCU) demonstrates improved outcomes by about 20%. It has been estimated that 21% of Australian hospitals provide an SCU and that these SCUs are mainly located in either metropolitan sites and/or in hospitals with more than 300 beds. To address equity issues related to access to SCUs, the National Stroke Foundation and the Australian Government undertook the National Stroke Units Program. One program outcome was the development of a conceptual model of acute stroke service delivery. The development process and initial evaluation of the model are described. Use of the model to increase capacity within the health care system to treat stroke is discussed.

Assessing advanced life support (ALS) competence: Victorian practices

Advanced life support (ALS) assessments are performed to assess nurses’ abilities to recognize cardiac arrest events, and appropriately manage patients according to resuscitation guidelines. Although there is evidence for conducting assessments after initial ALS education, there is little evidence to guide educators about ongoing assessments in terms of methods, format and frequency.

The aim of this study was to determine methods used by educators to assess ALS skills and knowledge for nurses in Victorian intensive care units. This descriptive study used telephone interviews to collect data. Data were analysed using content analysis. Twenty intensive care educators participated in this study. Thirteen educators (65%) were employed in public hospitals, and 7 educators (35%) worked in private hospitals across 12 Level 3 (60%) and 8 Level 2 (40%) intensive care units.

Results showed all educators used scenarios to assess ALS skills, with 12 educators (60%) including an additional theoretical test. There was variability in ALS assessment frequency, assessment timing in relation to initial/ongoing education, person performing the assessment, and the assessor/participant ratio. Nineteen educators (95%) reported ALS skill competency assessments occurred annually; 1 educator (5%) reported assessments occurred every 2 years. Assessments were conducted during a designated month (n = 10), numerous times throughout the year (n = 8), or on nurses’ employment anniversaries (n = 2). All educators reported many nurses avoided undertaking assessments.

Variability in ongoing ALS assessment methods was evident in Victorian intensive care units with some units applying evidence-based practices. Consideration should be given to the purposes and methods of conducting annual ALS assessments to ensure resources and strategies are directed appropriately. To encourage nurses to retain ALS skills and knowledge, regular practices are recommended as an alternative to assessments. However, further research is required to support this notion.

Better access to mental health : mapping the evidence supporting participation in meaningful occupations

Introduction: The purpose of this scoping and mapping project is to assess evidence for the use of focused psychological strategies (FPS) under the Better Access to Mental Health (BAMH) scheme to enable people with mental health problems to increase their functional performance and to participate in meaningful occupations. In particular, it aims to provide an accessible summary of evidence for practitioners who use FPS with their clients.

Methods: Evidence scoping and mapping is a relatively new technique, used to provide an overview of key findings in an area of practice. A five stage process of scoping and mapping was used in this project.

Results: A total of 81 studies which addressed the use of focused psychological strategies to promote functional performance and participation in meaningful occupations were found. Surprisingly, only three were published in occupational therapy journals with one further article being authored by occupational therapists. Three maps are provided showing this evidence by diagnosis, intervention and level of evidence.

Conclusion: Clinicians can say with some confidence that cognitive behavioural therapies are effective functional tools, particularly when working with people with depression or schizophrenia. They can also be confident that good quality evidence exists across a range of diagnoses, although there are many gaps where little to no research has been conducted. Suggestions for further research are provided which take into account the findings of these maps.

Do renal access coordinators make a difference? What is the evidence?

Background
Since the introduction of the renal access coordinator (RAC) role into Australia there have been only anecdotal examples of associated improvements in patient outcome and service delivery and scant published quantitative extant evidence exists.

Aim
To review the literature related to the impact of RACs on dialysis patient outcomes and associated service delivery, gauge the level of evidence available and identify gaps in the literature.

Method
A three stage Joanna Briggs Institute (JBI) systematic review process was used to collect and synthesise data. The review considered studies that explored and measured the RAC role in the adult haemodialysis context. All quantitative study designs were considered. Due to lack of homogeneity a narrative synthesis was undertaken.

Results
Five studies met the inclusion criteria for the review. All studies included multidisciplinary teams with variable emphasis on the RAC role. Four pre post intervention cohort studies measured incident and/or prevalent AVF, AVG and CVC rates in the haemodialysis population and the quality assurance report measured differences in patency rates between AVF and AVG and associated hospital length of stay. All discussed the role of central coordination as a contributor to the success of vascular access care.

Conclusion
The available reports do suggest an association between RACs and improved patient outcomes. These improved patient outcomes were apparent in an increase in incident and prevalent AVFs, and a decrease in the incidence and prevalence of CVCs. Both associations are correlated with a reduction in infection rates, length of hospital stay and healthcare costs
 

Protocol-directed sedation versus non-protocol-directed sedation to reduce duration of mechanical ventilation in mechanically ventilated intensive care patients (review)

Background : The sedation needs of critically ill patients have been recognized as a core component of critical care and meeting these is vital to assist recovery and ensure humane treatment. There is growing evidence to suggest that sedation requirements are not always optimally managed. Sub-optimal sedation incorporates both under- and over-sedation and has been linked to both short-term (e.g. length of stay) and long-term (e.g. psychological recovery) outcomes. Various strategies have been proposed to improve sedation management and address aspects of assessment as well as delivery of sedation.

Objectives : To assess the effects of protocol-directed sedation management on the duration of mechanical ventilation and other relevant patient outcomes in mechanically ventilated intensive care unit (ICU) patients. We looked at various outcomes and examined the role of bias in order to examine the level of evidence for this intervention.

Search methods : We searched the Cochrane Central Register of Controlled trials (CENTRAL) (2013; Issue 11), MEDLINE (OvidSP) (1990 to November 2013), EMBASE (OvidSP) (1990 to November 2013), CINAHL (BIREME host) (1990 to November 2013), Database of Abstracts of Reviews of Effects (DARE) (1990 to November 2013), LILACS (1990 to November 2013), Current Controlled Trials and US National Institutes of Health Clinical Research Studies (1990 to November 2013), and reference lists of articles. We re-ran the search in October 2014. We will deal with any studies of interest when we update the review.

Selection criteria : We included randomized controlled trials (RCTs) conducted in adult ICUs comparing management with and without protocol-directed sedation.

Data collection and analysis : Two authors screened the titles and abstracts and then the full-text reports identified from our electronic search. We assessed seven domains of potential risk of bias for the included studies. We examined the clinical, methodological and statistical heterogeneity and used the random-effects model for meta-analysis where we considered it appropriate. We calculated the mean difference (MD) for duration of mechanical ventilation and risk ratio (RR) for mortality across studies, with 95% confidence intervals (CI).

Main results : We identified two eligible studies with 633 participants. Both included studies compared the use of protocol-directed sedation, specifically protocols delivered by nurses, with usual care. We rated the risk of selection bias due to random sequence generation low for one study and unclear for one study. The risk of selection bias related to allocation concealment was low for both studies. We also assessed detection and attrition bias as low for both studies while we considered performance bias high due to the inability to blind participants and clinicians in both studies. Risk due to other sources of bias, such as potential for contamination between groups and reporting bias, was considered unclear. There was no clear evidence of differences in duration of mechanical ventilation (MD -5.74 hours, 95% CI -62.01 to 50.53, low quality evidence), ICU length of stay (MD -0.62 days, 95% CI -2.97 to 1.73) and hospital length of stay (MD -3.78 days, 95% CI -8.54 to 0.97) between people being managed with protocol-directed sedation versus usual care. Similarly, there was no clear evidence of difference in hospital mortality between the two groups (RR 0.96, 95% CI 0.71 to 1.31, low quality evidence). ICU mortality was only reported in one study preventing pooling of data. There was no clear evidence of difference in the incidence of tracheostomy (RR 0.77, 95% CI 0.31 to 1.89). The studies reported few adverse event outcomes; one study reported self extubation while the other study reported re-intubation; given this difference in outcomes, pooling of data was not possible. There was significant heterogeneity between studies for duration of mechanical ventilation (I2 = 86%, P value = 0.008), ICU length of stay (I2 = 82%, P value = 0.02) and incidence of tracheostomy (I2 = 76%, P value = 0.04), with one study finding a reduction in duration of mechanical ventilation and incidence of tracheostomy and the other study finding no difference.

Authors' conclusions : There is currently insufficient evidence to evaluate the effectiveness of protocol-directed sedation. Results from the two RCTs were conflicting, resulting in the quality of the body of evidence as a whole being assessed as low. Further studies, taking into account contextual and clinician characteristics in different ICU environments, are necessary to inform future practice. Methodological strategies to reduce the risk of bias need to be considered in future studies.

Do surgeons treat their patients like they would treat themselves?

Background - There is substantial unexplained geographical and surgeon-to-surgeon variation in rates of surgery. One would expect surgeons to treat patients and themselves similarly based on best evidence and accounting for patient preferences.

Questions/purposes - (1) Are surgeons more likely to recommend surgery when choosing for a patient than for themselves? (2) Are surgeons less confident in deciding for patients than for themselves?

Methods - Two hundred fifty-four (32%) of 790 Science of Variation Group (SOVG) members reviewed 21 fictional upper extremity cases (eg, distal radius fracture, De Quervain tendinopathy) for which surgery is optional answering two questions: (1) What treatment would you choose/recommend: operative or nonoperative? (2) On a scale from 0 to 10, how confident are you about this decision? Confidence is the degree that one believes that his or her decision is the right one (ie, most appropriate). Participants were orthopaedic, trauma, and plastic surgeons, all with an interest in treating upper extremity conditions. Half of the participants were randomized to choose for themselves if they had this injury or illness. The other half was randomized to make treatment recommendations for a patient of their age and gender. For the choice of operative or nonoperative, the overall recommendation for treatment was expressed as a surgery score per surgeon by dividing the number of cases they would operate on by the total number of cases (n = 21), where 100% is when every surgeon recommended surgery for every case. For confidence, we calculated the mean confidence for all 21 cases per surgeon; overall score ranges from 0 to 10 with a higher score indicating more confidence in the decision for treatment.

Results - Surgeons were more likely to recommend surgery for a patient (44.2% ± 14.0%) than they were to choose surgery for themselves (38.5% ± 15.4%) with a mean difference of 6% (95% confidence interval [CI], 2.1%–9.4%; p = 0.002). Surgeons were more confident in deciding for themselves than they were for a patient of similar age and gender (self: 7.9 ± 1.0, patient: 7.5 ± 1.2, mean difference: 0.35 [CI, 0.075–0.62], p = 0.012).

Conclusions - Surgeons are slightly more likely to recommend surgery for a patient than they are to choose surgery for themselves and they choose for themselves with a little more confidence. Different perspectives, preferences, circumstantial information, and cognitive biases might explain the observed differences. This emphasizes the importance of (1) understanding patients’ preferences and their considerations for treatment; (2) being aware that surgeons and patients might weigh various factors differently; (3) giving patients more autonomy by letting them balance risks and benefits themselves (ie, shared decision-making); and (4) assessing how dispassionate evidence-based decision aids help inform the patient and influences their decisional conflict.

Level of Evidence - Level III, diagnostic study.

Complete structure of an epithelial keratin dimer: implications for intermediate filament assembly

Keratins are cytoskeletal proteins that hierarchically arrange into filaments, starting with the dimer sub-unit. They are integral to the structural support of cells, in skin, hair and nails. In skin, keratin is thought to play a critical role in conferring the barrier properties and elasticity of skin. In general, the keratin dimer is broadly described by a tri-domain structure: a head, a central rod and a tail. As yet, no atomistic-scale picture of the entire dimer structure exists; this information is pivotal for establishing molecular-level connections between structure and function in intermediate filament proteins. The roles of the head and tail domains in facilitating keratin filament assembly and function remain as open questions. To address these, we report results of molecular dynamics simulations of the entire epithelial human K1/K10 keratin dimer. Our findings comprise: (1) the first three-dimensional structural models of the complete dimer unit, comprising of the head, rod and tail domains; (2) new insights into the chirality of the rod-domain twist gained from analysis of the full domain structure; (3) evidence for tri-subdomain partitioning in the head and tail domains; and, (4) identification of the residue characteristics that mediate non-covalent contact between the chains in the dimer. Our findings are immediately applicable to other epithelial keratins, such as K8/K18 and K5/K14, and to intermediate filament proteins in general.

Venn diagrams, Carroll Diagrams, tree sorts - activities

As early as Level 3 in VELS [Victorian Essential Learning Standards], the topics of Venn diagrams, Carroll Diagrams (which are identical to Karnaugh Maps) and Trees Sorts, are introduced as powerful visual organisers of categories. A selection of challenging tasks for these tools at various levels, including Level 9, are provided.