Assessment of the Methods Used to Develop Vitamin D and Calcium Recommendations-A Systematic Review of Bone Health Guidelines.

BACKGROUND: There are numerous guidelines developed for bone health. Yet, it is unclear whether the differences in guideline development methods explain the variability in the recommendations for vitamin D and calcium intake. The objective of this systematic review was to collate and compare recommendations for vitamin D and calcium across bone health guidelines, assess the methods used to form the recommendations, and explore which methodological factors were associated with these guideline recommendations. METHODS: We searched MEDLINE, EMBASE, CINAHL, and other databases indexing guidelines to identify records in English between 2009 and 2019. Guidelines or policy statements on bone health or osteoporosis prevention for generally healthy adults aged ≥40 years were eligible for inclusion. Two reviewers independently extracted recommendations on daily vitamin D and calcium intake, supplement use, serum 25 hydroxyvitamin D [25(OH)D] level, and sunlight exposure; assessed guideline development methods against 25 recommended criteria in the World Health Organization (WHO) handbook for guideline development; and, identified types identified types of evidence underpinning the recommendations. RESULTS: we included 47 eligible guidelines from 733 records: 74% of the guidelines provided vitamin D (200~600-4000 IU/day) and 70% provided calcium (600-1200 mg/day) recommendations, 96% and 88% recommended vitamin D and calcium supplements, respectively, and 70% recommended a specific 25(OH)D concentration. On average, each guideline met 10 (95% CI: 9-12) of the total of 25 methodological criteria for guideline development recommended by the WHO Handbook. There was uncertainty in the association between the methodological criteria and the proportion of guidelines that provided recommendations on daily vitamin D or calcium. Various types of evidence, including previous bone guidelines, nutrient reference reports, systematic reviews, observational studies, and perspectives/editorials were used to underpin the recommendations. CONCLUSIONS: There is considerable variability in vitamin D and calcium recommendations and in guideline development methods in bone health guidelines. Effort is required to strengthen the methodological rigor of guideline development and utilize the best available evidence to underpin nutrition recommendations in evidence-based guidelines on bone health.

Association of industry ties with outcomes of studies examining the effect of wholegrain foods on cardiovascular disease and mortality: systematic review and meta-analysis.

OBJECTIVE: To determine if observational studies examining the association of wholegrain foods with cardiovascular disease (CVD) with food industry sponsorship and/or authors with conflicts of interest (COI) with the food industry are more likely to have results and/or conclusions that are favourable to industry than those with no industry ties, and to determine whether studies with industry ties differ in their risk of bias compared with studies with no industry ties. DESIGN: Systematic review and meta-analysis of observational studies. DATA SOURCES: We searched eight databases from 1997 to 2017 and hand searched the reference lists of included studies. ELIGIBILITY CRITERIA FOR SELECTING STUDIES: Cohort and case-control studies that quantitatively examined the association of wholegrains or wholegrain foods with CVD outcomes in healthy adults or children. RESULTS: 21 of the 22 studies had a serious or critical risk of bias. Studies with industry ties more often had favourable results compared with those with no industry ties, but the Confidence Interval (CI) was wide, Risk Ratio (RR)=1.44 (95% CI 0.88 to 2.35). The same association was found for study conclusions. We did not find a difference in effect size (magnitude of RRs) between studies with industry ties, RR=0.77 (95% CI 0.58 to 1.01) and studies with no industry ties, RR=0.85 (95% CI 0.73 to 1.00) (p=0.50) I2 0%. These results were comparable for studies that measured the magnitude using Hazard Ratios (HR); industry ties HR=0.82 (95% CI 0.76 to 0.88) versus no industry ties HR=0.86 (95% CI 0.81 to 0.91) (p=0.34) I2 0%. CONCLUSIONS: We did not establish that the presence of food industry sponsorship or authors with a COI with the food industry was associated with results or conclusions that favour industry sponsors. The association of food industry sponsorship or authors with a COI with the food industry and favourable results or conclusions is uncertain. However, our analysis was hindered by the low level of COI disclosure in the included studies. Our findings support international reforms to improve the disclosure and management of COI in nutrition research. Without such disclosures, it will not be possible to determine if the results of nutrition research are free of food industry influences and potential biases. PROSPERO REGISTRATION NUMBER: CRD42017055841.

Economic evaluation of the NET intervention versus guideline dissemination for management of mild head injury in hospital emergency departments.

BACKGROUND: Evidence-based guidelines for the management of mild traumatic brain injury (mTBI) in the emergency department (ED) are now widely available, and yet, clinical practice remains inconsistent with the guidelines. The Neurotrauma Evidence Translation (NET) intervention was developed to increase the uptake of guideline recommendations and improve the management of minor head injury in Australian emergency departments (EDs). However, the adoption of this type of intervention typically entails an upfront investment that may or may not be fully offset by improvements in clinical practice, health outcomes and/or reductions in health service utilisation. The present study estimates the cost and cost-effectiveness of the NET intervention, as compared to the passive dissemination of the guideline, to evaluate whether any improvements in clinical practice or health outcomes due to the NET intervention can be obtained at an acceptable cost. METHODS AND FINDINGS: Study setting: The NET cluster randomised controlled trial [ACTRN12612001286831]. STUDY SAMPLE: Seventeen EDs were randomised to the control condition and 14 to the intervention. One thousand nine hundred forty-three patients were included in the analysis of clinical practice outcomes (NET sample). A total of 343 patients from 14 control and 10 intervention EDs participated in follow-up interviews and were included in the analysis of patient-reported health outcomes (NET-Plus sample). OUTCOME MEASURES: Appropriate post-traumatic amnesia (PTA) screening in the ED (primary outcome). Secondary clinical practice outcomes: provision of written information on discharge (INFO) and safe discharge (defined as CT scan appropriately provided plus PTA plus INFO). Secondary patient-reported, post-discharge health outcomes: anxiety (Hospital Anxiety and Depression Scale), post-concussive symptoms (Rivermead), and preference-based health-related quality of life (SF6D). METHODS: Trial-based economic evaluations from a health sector perspective, with time horizons set to coincide with the final follow-up for the NET sample (2 months post-intervention) and to 1-month post-discharge for the NET-Plus sample. RESULTS: Intervention and control groups were not significantly different in health service utilisation received in the ED/inpatient ward following the initial mTBI presentation (adjusted mean difference $23.86 per patient; 95%CI - $106, $153; p = 0.719) or over the longer follow-up in the NET-plus sample (adjusted mean difference $341.78 per patient; 95%CI - $58, $742; p = 0.094). Savings from lower health service utilisation are therefore unlikely to offset the significantly higher upfront cost of the intervention (mean difference $138.20 per patient; 95%CI $135, $141; p < 0.000). Estimates of the net effect of the intervention on total cost (intervention cost net of health service utilisation) suggest that the intervention entails significantly higher costs than the control condition (adjusted mean difference $169.89 per patient; 95%CI $43, $297, p = 0.009). This effect is larger in absolute magnitude over the longer follow-up in the NET-plus sample (adjusted mean difference $505.06; 95%CI $96, $915; p = 0.016), mostly due to additional health service utilisation. For the primary outcome, the NET intervention is more costly and more effective than passive dissemination; entailing an additional cost of $1246 per additional patient appropriately screened for PTA ($169.89/0.1363; Fieller's 95%CI $525, $2055). For NET to be considered cost-effective with 95% confidence, decision-makers would need to be willing to trade one quality-adjusted life year (QALY) for 25 additional patients appropriately screened for PTA. While these results reflect our best estimate of cost-effectiveness given the data, it is possible that a NET intervention that has been scaled and streamlined ready for wider roll-out may be more or less cost-effective than the NET intervention as delivered in the trial. CONCLUSIONS: While the NET intervention does improve the management of mTBI in the ED, it also entails a significant increase in cost and-as delivered in the trial-is unlikely to be cost-effective at currently accepted funding thresholds. There may be a scope for a scaled-up and streamlined NET intervention to achieve a better balance between costs and outcomes. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry ACTRN12612001286831 , date registered 12 December 2012.

Toward a comprehensive evidence map of overview of systematic review methods: paper 2-risk of bias assessment; synthesis, presentation and summary of the findings; and assessment of the certainty of the evidence.

BACKGROUND: Overviews of systematic reviews (SRs) attempt to systematically retrieve and summarise the results of multiple systematic reviews. This is the second of two papers from a study aiming to develop a comprehensive evidence map of the methods used in overviews. Our objectives were to (a) develop a framework of methods for conducting, interpreting and reporting overviews (stage I)-the Methods for Overviews of Reviews (MOoR) framework-and (b) to create an evidence map by mapping studies that have evaluated overview methods to the framework (stage II). In the first paper, we reported findings for the four initial steps of an overview (specification of purpose, objectives and scope; eligibility criteria; search methods; data extraction). In this paper, we report the remaining steps: assessing risk of bias; synthesis, presentation and summary of the findings; and assessing certainty of the evidence arising from the overview. METHODS: In stage I, we identified cross-sectional studies, guidance documents and commentaries that described methods proposed for, or used in, overviews. Based on these studies, we developed a framework of possible methods for overviews, categorised by the steps in conducting an overview. Multiple iterations of the framework were discussed and refined by all authors. In stage II, we identified studies evaluating methods and mapped these evaluations to the framework. RESULTS: Forty-two stage I studies described methods relevant to one or more of the latter steps of an overview. Six studies evaluating methods were included in stage II. These mapped to steps involving (i) the assessment of risk of bias (RoB) in SRs (two SRs and three primary studies, all reporting evaluation of RoB tools) and (ii) the synthesis, presentation and summary of the findings (one primary study evaluating methods for measuring overlap). CONCLUSION: Many methods have been described for use in the latter steps in conducting an overview; however, evaluation and guidance for applying these methods is sparse. The exception is RoB assessment, for which a multitude of tools exist-several with sufficient evaluation and guidance to recommend their use. Evaluation of other methods is required to provide a comprehensive evidence map.

Development and validation of SEER (Seeking, Engaging with and Evaluating Research): a measure of policymakers' capacity to engage with and use research.

BACKGROUND: Capacity building strategies are widely used to increase the use of research in policy development. However, a lack of well-validated measures for policy contexts has hampered efforts to identify priorities for capacity building and to evaluate the impact of strategies. We aimed to address this gap by developing SEER (Seeking, Engaging with and Evaluating Research), a self-report measure of individual policymakers' capacity to engage with and use research. METHODS: We used the SPIRIT Action Framework to identify pertinent domains and guide development of items for measuring each domain. Scales covered (1) individual capacity to use research (confidence in using research, value placed on research, individual perceptions of the value their organisation places on research, supporting tools and systems), (2) actions taken to engage with research and researchers, and (3) use of research to inform policy (extent and type of research use). A sample of policymakers engaged in health policy development provided data to examine scale reliability (internal consistency, test-retest) and validity (relation to measures of similar concepts, relation to a measure of intention to use research, internal structure of the individual capacity scales). RESULTS: Response rates were 55% (150/272 people, 12 agencies) for the validity and internal consistency analyses, and 54% (57/105 people, 9 agencies) for test-retest reliability. The individual capacity scales demonstrated adequate internal consistency reliability (alpha coefficients > 0.7, all four scales) and test-retest reliability (intra-class correlation coefficients > 0.7 for three scales and 0.59 for fourth scale). Scores on individual capacity scales converged as predicted with measures of similar concepts (moderate correlations of > 0.4), and confirmatory factor analysis provided evidence that the scales measured related but distinct concepts. Items in each of these four scales related as predicted to concepts in the measurement model derived from the SPIRIT Action Framework. Evidence about the reliability and validity of the research engagement actions and research use scales was equivocal. CONCLUSIONS: Initial testing of SEER suggests that the four individual capacity scales may be used in policy settings to examine current capacity and identify areas for capacity building. The relation between capacity, research engagement actions and research use requires further investigation.

Accelerometers for the Assessment of Concussion in Male Athletes: A Systematic Review and Meta-Analysis.

BACKGROUND: Concussion is common in the sporting arena and is often challenging to diagnose. The development of wearable head impact measurement systems has enabled measurement of head kinematics in contact sports. OBJECTIVES: The objective of this systematic review was to determine the characteristics of head kinematics measured by an accelerometer system among male athletes diagnosed with concussion. METHODS: A systematic search was conducted in July 2015. Inclusion criteria were English-language studies published after 1990 with a study population of male athletes, in any sport, where objectively measured biomechanical forces were reported in the setting of a concussive event. The random effects meta-analysis model was used to combine estimates of biomechanical force measurements in concussed athletes. RESULTS: Thirteen studies met the inclusion criteria, the majority of which were conducted with high school and college football teams in the US. Included studies measured a combination of linear and rotational acceleration. The meta-analysed mean peak linear head acceleration associated with a concussive episode was 98.68 g (95 % CI 82.36-115.00) and mean peak rotational head acceleration was 5776.60 rads/s2 (95 % CI 4583.53-6969.67). The estimates of the biomechanical forces were consistent across studies, with I 2 values of 0 % for both meta-analyses. CONCLUSIONS: Head impact monitoring through accelerometery has been shown to be useful with regard to characterising the kinematic load to the head associated with concussion. Future research with improved clinical outcome measures and head kinematic data may improve accuracy when evaluating concussion, and may assist with both interpretation of biomechanical data and the development and utilisation of implementation strategies for the technology.

The quality of reporting in cluster randomised crossover trials: proposal for reporting items and an assessment of reporting quality.

BACKGROUND: The cluster randomised crossover (CRXO) design is gaining popularity in trial settings where individual randomisation or parallel group cluster randomisation is not feasible or practical. Our aim is to stimulate discussion on the content of a reporting guideline for CRXO trials and to assess the reporting quality of published CRXO trials. METHODS: We undertook a systematic review of CRXO trials. Searches of MEDLINE, EMBASE, and CINAHL Plus as well as citation searches of CRXO methodological articles were conducted to December 2014. Reporting quality was assessed against both modified items from 2010 CONSORT and 2012 cluster trials extension and other proposed quality measures. RESULTS: Of the 3425 records identified through database searching, 83 trials met the inclusion criteria. Trials were infrequently identified as "cluster randomis(z)ed crossover" in title (n = 7, 8%) or abstract (n = 21, 25%), and a rationale for the design was infrequently provided (n = 20, 24%). Design parameters such as the number of clusters and number of periods were well reported. Discussion of carryover took place in only 17 trials (20%). Sample size methods were only reported in 58% (n = 48) of trials. A range of approaches were used to report baseline characteristics. The analysis method was not adequately reported in 23% (n = 19) of trials. The observed within-cluster within-period intracluster correlation and within-cluster between-period intracluster correlation for the primary outcome data were not reported in any trial. The potential for selection, performance, and detection bias could be evaluated in 30%, 81%, and 70% of trials, respectively. CONCLUSIONS: There is a clear need to improve the quality of reporting in CRXO trials. Given the unique features of a CRXO trial, it is important to develop a CONSORT extension. Consensus amongst trialists on the content of such a guideline is essential.

Implementing evidence-based recommended practices for the management of patients with mild traumatic brain injuries in Australian emergency care departments: study protocol for a cluster randomised controlled trial.

BACKGROUND: Mild head injuries commonly present to emergency departments. The challenges facing clinicians in emergency departments include identifying which patients have traumatic brain injury, and which patients can safely be sent home. Traumatic brain injuries may exist with subtle symptoms or signs, but can still lead to adverse outcomes. Despite the existence of several high quality clinical practice guidelines, internationally and in Australia, research shows inconsistent implementation of these recommendations. The aim of this trial is to test the effectiveness of a targeted, theory- and evidence-informed implementation intervention to increase the uptake of three key clinical recommendations regarding the emergency department management of adult patients (18 years of age or older) who present following mild head injuries (concussion), compared with passive dissemination of these recommendations. The primary objective is to establish whether the intervention is effective in increasing the percentage of patients for which appropriate post-traumatic amnesia screening is performed. METHODS/DESIGN: The design of this study is a cluster randomised trial. We aim to include 34 Australian 24-hour emergency departments, which will be randomised to an intervention or control group. Control group departments will receive a copy of the most recent Australian evidence-based clinical practice guideline on the acute management of patients with mild head injuries. The intervention group will receive an implementation intervention based on an analysis of influencing factors, which include local stakeholder meetings, identification of nursing and medical opinion leaders in each site, a train-the-trainer day and standardised education and interactive workshops delivered by the opinion leaders during a 3 month period of time. Clinical practice outcomes will be collected retrospectively from medical records by independent chart auditors over the 2 month period following intervention delivery (patient level outcomes). In consenting hospitals, eligible patients will be recruited for a follow-up telephone interview conducted by trained researchers. A cost-effectiveness analysis and process evaluation using mixed-methods will be conducted. Sample size calculations are based on including 30 patients on average per department. Outcome assessors will be blinded to group allocation. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry ACTRN12612001286831 (date registered 12 December 2012).

Economic evaluation of active implementation versus guideline dissemination for evidence-based care of acute low-back pain in a general practice setting.

INTRODUCTION: The development and publication of clinical practice guidelines for acute low-back pain has resulted in evidence-based recommendations that have the potential to improve the quality and safety of care for acute low-back pain. Development and dissemination of guidelines may not, however, be sufficient to produce improvements in clinical practice; further investment in active implementation of guideline recommendations may be required. Further research is required to quantify the trade-off between the additional upfront cost of active implementation of guideline recommendations for low-back pain and any resulting improvements in clinical practice. METHODS: Cost-effectiveness analysis alongside the IMPLEMENT trial from a health sector perspective to compare active implementation of guideline recommendations via the IMPLEMENT intervention (plus standard dissemination) against standard dissemination alone. RESULTS: The base-case analysis suggests that delivery of the IMPLEMENT intervention dominates standard dissemination (less costly and more effective), yielding savings of $135 per x-ray referral avoided (-$462.93/3.43). However, confidence intervals around point estimates for the primary outcome suggest that--irrespective of willingness to pay (WTP)--we cannot be at least 95% confident that the IMPLEMENT intervention differs in value from standard dissemination. CONCLUSIONS: Our findings demonstrate that moving beyond development and dissemination to active implementation entails a significant additional upfront investment that may not be offset by health gains and/or reductions in health service utilization of sufficient magnitude to render active implementation cost-effective.

Hand sanitisers for reducing illness absences in primary school children in New Zealand: a cluster randomised controlled trial study protocol.

BACKGROUND: New Zealand has relatively high rates of morbidity and mortality from infectious disease compared with other OECD countries, with infectious disease being more prevalent in children compared with others in the population. Consequences of infectious disease in children may have significant economic and social impact beyond the direct effects of the disease on the health of the child; including absence from school, transmission of infectious disease to other pupils, staff, and family members, and time off work for parents/guardians. Reduction of the transmission of infectious disease between children at schools could be an effective way of reducing the community incidence of infectious disease. Alcohol based no-rinse hand sanitisers provide an alternative hand cleaning technology, for which there is some evidence that they may be effective in achieving this. However, very few studies have investigated the effectiveness of hand sanitisers, and importantly, the potential wider economic implications of this intervention have not been established. AIMS: The primary objective of this trial is to establish if the provision of hand sanitisers in primary schools in the South Island of New Zealand, in addition to an education session on hand hygiene, reduces the incidence rate of absence episodes due to illness in children. In addition, the trial will establish the cost-effectiveness and conduct a cost-benefit analysis of the intervention in this setting. METHODS/DESIGN: A cluster randomised controlled trial will be undertaken to establish the effectiveness and cost-effectiveness of hand sanitisers. Sixty-eight primary schools will be recruited from three regions in the South Island of New Zealand. The schools will be randomised, within region, to receive hand sanitisers and an education session on hand hygiene, or an education session on hand hygiene alone. Fifty pupils from each school in years 1 to 6 (generally aged from 5 to 11 years) will be randomly selected for detailed follow-up about their illness absences, providing a total of 3400 pupils. In addition, absence information will be collected on all children from the school rolls. Investigators not involved in the running of the trial, outcome assessors, and the statistician will be blinded to the group allocation until the analysis is completed. TRIAL REGISTRATION: ACTRN12609000478213.

Exercise therapy, manual therapy, or both, for osteoarthritis of the hip or knee: a factorial randomised controlled trial protocol.

BACKGROUND: Non-pharmacological, non-surgical interventions are recommended as the first line of treatment for osteoarthritis (OA) of the hip and knee. There is evidence that exercise therapy is effective for reducing pain and improving function in patients with knee OA, some evidence that exercise therapy is effective for hip OA, and early indications that manual therapy may be efficacious for hip and knee OA. There is little evidence as to which approach is more effective, if benefits endure, or if providing these therapies is cost-effective for the management of this disorder. The MOA Trial (Management of OsteoArthritis) aims to test the effectiveness of two physiotherapy interventions for improving disability and pain in adults with hip or knee OA in New Zealand. Specifically, our primary objectives are to investigate whether:1. Exercise therapy versus no exercise therapy improves disability at 12 months;2. Manual physiotherapy versus no manual therapy improves disability at 12 months;3. Providing physiotherapy programmes in addition to usual care is more cost-effective than usual care alone in the management of osteoarthritis at 24 months. METHODS: This is a 2 x 2 factorial randomised controlled trial. We plan to recruit 224 participants with hip or knee OA. Eligible participants will be randomly allocated to receive either: (a) a supervised multi-modal exercise therapy programme; (b) an individualised manual therapy programme; (c) both exercise therapy and manual therapy; or, (d) no trial physiotherapy. All participants will continue to receive usual medical care. The outcome assessors, orthopaedic surgeons, general medical practitioners, and statistician will be blind to group allocation until the statistical analysis is completed. The trial is funded by Health Research Council of New Zealand Project Grants (Project numbers 07/199, 07/200). DISCUSSION: The MOA Trial will be the first to investigate the effectiveness and cost-effectiveness of providing physiotherapy programmes of this kind, for the management of pain and disability in adults with hip or knee OA. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry ref: ACTRN12608000130369.

Protocol for economic evaluation alongside the IMPLEMENT cluster randomised controlled trial.

BACKGROUND: The recent development and publication of evidence-based clinical practice guidelines (CPGs) for acute low back pain (LBP) has resulted in evidence-based recommendations that, if implemented, have the potential to improve the quality and safety of care for acute LBP. While a strategy has been specified for dissemination of the CPG for acute LBP in Australia, there is no accompanying plan for active implementation. Evidence regarding the cost-effectiveness of active implementation of CPGs for acute LBP is sparse. The IMPLEMENT study will consider the incremental benefits and costs of progressing beyond development and dissemination to implementation. METHODS/DESIGN: Cost-effectiveness and cost-utility analyses alongside the IMPLEMENT cluster randomised controlled trial (CRCT) from a societal perspective to quantify the additional costs (savings) and health gains associated with a targeted implementation strategy as compared with access to the CPG via dissemination only. DISCUSSION: The protocol provided here registers our intent to conduct an economic evaluation alongside the IMPLEMENT study, facilitates peer-review of proposed methods and provides a transparent statement of planned analyses.