Background In Australia, one-third of people ≥15 years perform regular resistance training and 90% of those do not meet current health guidelines. All age groups should engage in regular resistance exercise, to maintain strength and function. Objectives To identify trends in powerlifting competition participation in Australia by sex and age group from 1968 to 2022, and to compare the strength of powerlifting competitors to population age- and sex-based normative values. Method The number of unique participants and total competition entries for each year were analysed using Australian powerlifting competition data. Subdomains of age and sex were investigated, and mean ± SD, frequency, range, and trend analyses reported. United Nations age classifications were used to identify age trends. Comparisons to population strength norms were explored descriptively. Results We included 21,514 individual competitors from 1942 powerlifting competitions between 1968 and 2022. Exponential growth was seen in competition entries from 115 in 1981, to 759 in 1994, 1014 in 2011, and to 6803 in 2022, (R2 = 0.86). At first participation 18–25-year olds (51.1%) followed by ≥36 years (16%) were most represented. Strength comparison to available population norms demonstrates superior upper- (bench press [most competitors above 70th percentile) and lower-body (squat [majority rated ‘excellent’) strength. Conclusions Superior strength levels of powerlifters further the evidence base for this sport as an effective way to develop muscular strength, with low injury. We advocate for public health promotion and additional support for powerlifting as an underutilised community health tool.

Objective: Gastrointestinal (GI) discomfort is experienced by millions of people every day. This study aimed to evaluate the effect of PhenActivTM, a novel green kiwifruit extract, on gastrointestinal tract (GIT) function in otherwise healthy adults. Methods: 41 healthy adults with mild GI discomfort were enrolled in this double-blind, randomized, placebo-controlled study. Participants were randomized to either take 3.0 g/day of PhenActivTM or a placebo for 6 weeks. Interviews were conducted at baseline, week 3 and week 6, with participants completing questionnaires regarding GI symptoms. Frequency of bowel movements was self-recorded daily. Results: There were no differences in daily and weekly defecation frequency and stool characteristics in either group. The active and placebo groups significantly improve GSRS scores (p , only the active group had a significant improvement in the IBSSS and PAC-QOL scores (p Conclusion: Supplementation of 3.0 g/day of PhenActivTM for 6 weeks did not improve defecation frequency or stool composition in healthy adults, but did improve perceived symptoms of GIT function, including symptoms of functional GIT disorders, IBS and constipation. The product was well tolerated and future trials investigating higher doses with more participants and/or a different population would be beneficial.

BACKGROUND:Indigenous peoples often have higher rates of morbidity and mortality associated with cardiometabolic disease (CMD) than non-Indigenous people and this may be even more so in urban areas. The use of electronic health records and expansion of computing power has led to mainstream use of artificial intelligence (AI) to predict the onset of disease in primary health care (PHC) settings. However, it is unknown if AI and in particular machine learning is used for risk prediction of CMD in Indigenous peoples. METHODS:We searched peer-reviewed literature using terms associated with AI machine learning, PHC, CMD, and Indigenous peoples. RESULTS:We identified 13 suitable studies for inclusion in this review. Median total number of participants was 19,270 (range 911-2,994,837). The most common algorithms used in machine learning in this setting were support vector machine, random forest, and decision tree learning. Twelve studies used the area under the receiver operating characteristic curve (AUC) to measure performance. Two studies reported an AUC of >0.9. Six studies had an AUC score between 0.9 and 0.8, 4 studies had an AUC score between 0.8 and 0.7. 1 study reported an AUC score between 0.7 and 0.6. Risk of bias was observed in 10 (77 %) studies. CONCLUSION:AI machine learning and risk prediction models show moderate to excellent discriminatory ability over traditional statistical models in predicting CMD. This technology could help address the needs of urban Indigenous peoples by predicting CMD early and more rapidly than conventional methods.

ABSTRACT Purpose Understanding strength changes with resistance training is important in human performance. It also enables better understanding into the expected magnitude of strength increase and factors that influence this change over time. Methods Squat, bench press, and deadlift scores were collated from 407 powerlifting meets (n = 1896 unique competitors: ~625 females, ~1270 males) between 2003 and 2018. Absolute (in kilograms) and relative starting strength (in kilograms per body weight) for each lift type was expressed for both sexes. Maximum and overall strength gain per day and per year (in kilograms) was calculated by comparing first and final, or maximum scores for each lift, respectively, and considered based on strength quartile classification. Paired and independent t-tests compared strength changes from baseline and between sexes. One-way ANOVAs compared strength changes between quartiles. Pearson correlations assessed relationships between strength changes over time, and baseline strength, number of competitions, and total days competing. Results Maximum strength adaptations were greater for squat (20.2–25.4 kg·yr−1) and deadlift (18.1–21.1 kg·yr−1) compared with bench press (10.5–12.8 kg·yr−1, P ≤ 0.001). However, the change in absolute (all lifts: P = 0.247–0.379) and relative strength (all lifts: P = 0.641–0.821) did not differ between sexes. For females, maximum strength gain per day did not differ by quartile (all lifts: P = 0.091–0.746), nor did overall strength gain per day (P = 0.151–0.575). Conversely, males in the fourth quartile generally displayed lower maximum and overall strength gain per day. Conclusions These findings show differences in strength gain between upper- and lower-body lifts, but not sex differences in the change in strength. In line with previous research, the strongest males likely gain strength more slowly than weaker counterparts. Professionals should consider this information in the training, assessment, and long-term benchmarking of athletes whose sports require a focus on muscular strength.

A functioning vascular access (VA) is crucial to providing adequate hemodialysis (HD) and considered a critically important outcome by patients and healthcare professionals. A validated, patient-important outcome measure for VA function that can be easily measured in research and practice to harvest reliable and relevant evidence for informing patient-centered HD care is lacking. Vascular Access outcome measure for function: a vaLidation study In hemoDialysis (VALID) aims to assess the accuracy and feasibility of measuring a core outcome for VA function established by the international Standardized Outcomes in Nephrology (SONG) initiative. VALID is a prospective, multi-center, multinational validation study that will assess the accuracy and feasibility of measuring VA function, defined as the need for interventions to enable and maintain the use of a VA for HD. The primary objective is to determine whether VA function can be measured accurately by clinical staff as part of routine clinical practice (Assessor 1) compared to the reference standard of documented VA procedures collected by a VA expert (Assessor 2) during a 6-month follow-up period. Secondary outcomes include feasibility and acceptability of measuring VA function and the time to, rate of, and type of VA interventions. An estimated 612 participants will be recruited from approximately 10 dialysis units of different size, type (home-, in-center and satellite), governance (private versus public), and location (rural versus urban) across Australia, Canada, Europe, and Malaysia. Validity will be measured by the sensitivity and specificity of the data acquisition process. The sensitivity corresponds to the proportion of correctly identified interventions by Assessor 1, among the interventions identified by Assessor 2 (reference standard). The feasibility of measuring VA function will be assessed by the average data collection time, data completeness, feasibility questionnaires and semi-structured interviews on key feasibility aspects with the assessors. Accuracy, acceptability, and feasibility of measuring VA function as part of routine clinical practice are required to facilitate global implementation of this core outcome across all HD trials. Global use of a standardized, patient-centered outcome measure for VA function in HD research will enhance the consistency and relevance of trial evidence to guide patient-centered care. Clinicaltrials.gov: NCT03969225. Registered on 31st May 2019.

Children with chronic kidney disease (CKD) require multidisciplinary care to meet their complex healthcare needs. Patient navigators are trained non-medical personnel who assist patients and caregivers to overcome barriers to accessing health services through care coordination. This trial aims to determine the effectiveness of a patient navigator program in children with CKD. The NAVKIDS2 trial is a multi-center, waitlisted, randomized controlled trial of patient navigators in children with CKD conducted at five sites across Australia. Children (0–16 years) with CKD from low socioeconomic status rural or remote areas were randomized to an intervention group or a waitlisted control group (to receive intervention after 6 months). The study primary and secondary endpoints include the self-rated health (SRH) (primary), and utility-based quality of life, progression of kidney dysfunction of the child, SRH, and satisfaction with healthcare of the caregiver at 6 months post-randomization. The trial completed recruitment in October 2021 with expected completion of follow-up by October 2022. There were 162 patients enrolled with 80 and 82 patients randomized to the immediate intervention and waitlisted groups, respectively. Fifty-eight (36%) participants were from regional/remote areas, with a median (IQR) age of 9.5 (5.0, 13.0) years, 46% were of European Australian ethnicity, and 65% were male. A total of 109 children (67%) had CKD stages 1–5, 42 (26%) were transplant recipients, and 11 (7%) were receiving dialysis. The NAVKIDS2 trial is designed to evaluate the effectiveness of patient navigation in children with CKD from families experiencing socioeconomic disadvantage.

We thank Bajpai et al. for their interest in our Policy Forum describing implementation strategies for kidney trials. 1 Reidlinger D.M. Johnson D.W. Craig J.C. et al. Implementation strategies for high impact nephrology trials: the end of the trial is just the beginning. Kidney Int. 2022; 102: 1222-1227 Abstract Full Text Full Text PDF PubMed Scopus (2) Google Scholar Their letter 2 Bajpai D. Willows J.K. Topf J.M. Hiremath S. User-generated social media content in knowledge dissemination. Kidney Int. 2022; 102: 1428-1429 Abstract Full Text Full Text PDF PubMed Scopus (1) Google Scholar suggests our hierarchical framing of social media as a knowledge dissemination strategy for medical research (Figure 3: practical actions to enhance trial implementability) fails to recognize that widespread use of social media has created a rich medium of user-generated content that facilitates bilateral conversations across many platforms. The authors are particularly keen for free open access medical education, a rapidly expanding social media–based medical education platform, to be incorporated into future models of strategic knowledge dissemination. We acknowledge the growing body of literature on social media as an effective avenue for dissemination of health research information, 3 Roland D. Social media, health policy, and knowledge translation. J Am Coll Radiol. 2018; 15: 149-152 Abstract Full Text Full Text PDF PubMed Scopus (20) Google Scholar a topic that was beyond the scope of our article. We also agree the subject deserves more consideration and appreciate Bajpai et al. for raising this important issue, including their elegant graphical representation of user-generated knowledge translation strategies with social media. User-generated social media content in knowledge disseminationKidney InternationalVol. 102Issue 6PreviewThe policy forum on implementation strategies for trials emphasizes the need for knowledge translation strategies.1 The authors describe the roles of medical societies, industry, health regulators, and health research funders, and reference “social media release” as a strategy in Table 2. However, this hierarchical and unidirectional knowledge dissemination paradigm is incomplete in the current era of the widespread use of social media. Free open access medical education is a growing part of trainees’ and mature practitioners' educational diet. Full-Text PDF Implementation strategies for high impact nephrology trials: the end of the trial is just the beginningKidney InternationalVol. 102Issue 6PreviewThere remains wide variation in treatment patterns and outcomes for kidney patients, and nephrology continues to lag behind other medical specialties in the number and quality of randomized controlled trials (RCTs).1 As currently conducted, RCTs require substantial investment in time and resources with enormous effort poured into trial design, funding, partnerships, data acquisition, analysis, and publications. Less attention is paid to activities to maximize practice and policy impact, and evaluation of evidence uptake commonly occurs only through the narrow lens of output metrics in peer-reviewed literature. Full-Text PDF Open Access

There remains wide variation in treatment patterns and outcomes for kidney patients, and nephrology continues to lag behind other medical specialties in the number and quality of randomized controlled trials (RCTs).1Bello A.K. Levin A. Lunney M. et al.Status of care for end stage kidney disease in countries and regions worldwide: international cross sectional survey.BMJ. 2019; 367: l5873Crossref PubMed Scopus (121) Google Scholar As currently conducted, RCTs require substantial investment in time and resources with enormous effort poured into trial design, funding, partnerships, data acquisition, analysis, and publications. Less attention is paid to activities to maximize practice and policy impact, and evaluation of evidence uptake commonly occurs only through the narrow lens of output metrics in peer-reviewed literature. Implementation (or research utilization, knowledge transfer, knowledge exchange, and knowledge translation) is the process of integrating new practices within a setting, and de-implementation (or de-commission, disinvest, de-adopt, and discontinue) is the removal from practice of low-value, wasteful or harmful treatments. Substantial and avoidable research waste, whereby promising research results fail to transform health care and improve patient outcomes or healthcare system efficiency, occurs as a result of low uptake of trial evidence.2Grimshaw J.M. Eccles M.P. Lavis J.N. et al.Knowledge translation of research findings.Implement Sci. 2012; 7: 50Crossref PubMed Scopus (1452) Google Scholar Publication of trial results does not signal the "end" of a trial; publication signals the beginning of activities to ensure implementation of high-value care, or de-implementation of low-value care, into healthcare policy and practice (Figure 1). The current mechanism for reporting new research involves several knowledge exchange pathways including journal publications, presentations, commentaries, opinion pieces, regulatory reviews, and evidence synthesis into clinical practice guidelines. In addition, pharmaceutical companies invest considerably in marketing new products, including "me-too" drugs (drugs within the same therapeutic class) that increase clinical treatment options. Ongoing global harm reduction and healthcare quality campaigns (e.g., Choosing Wisely; Too Much Medicine) may also support clinicians' point of care decisions. However, ample evidence shows that wide variation in evidence-based practice remains a problem,3Van Der Veer S.N. Tomson C.R.V. Jager K.J. Van Biesen W. Bridging the gap between what is known and what we do in renal medicine: improving implementability of the European Renal Best Practice guidelines.Nephrol Dial Transplant. 2014; 29: 951-957Crossref PubMed Scopus (21) Google Scholar implying key drivers in clinical decision-making are not adequately addressed by current knowledge-transfer mechanisms. Moreover, although multiple theories and frameworks have been designed to identify key drivers and inform strategies to bridge the knowledge–healthcare practice divide, practical application of these frameworks by researchers is at best modest, and reliable empirical data on their efficacy are scant.4Waltz T.J. Powell B.J. Chinman M.J. et al.Expert recommendations for implementing change (ERIC): protocol for a mixed methods study.Implement Sci. 2014; 9: 39Crossref PubMed Scopus (84) Google Scholar Although evidence is limited, it seems few kidney trials, particularly end-user focused, investigator-initiated trials, preplan for implementation or de-implementation. Two examples of kidney-related trials are discussed because they demonstrate how uptake of new knowledge into practice can be highly variable. The chosen examples meet commonly applied indicators of high impact research: (i) publication in a journal with a high journal impact factor, (ii) highly cited in the literature by peers, and (iii) sustained long-term relevance to and impact on clinical practice.S1 The Initiation of Dialysis Early And Late (IDEAL) trial was a landmark study conducted in Australia and New Zealand and published in the New England Journal of Medicine in 2010: The primary aim was to determine whether initiation of dialysis at an estimated glomerular filtration rate of 10–14 ml/min per 1.73 m2 compared with 5–7 ml/min per 1.73 m2 reduced all-cause mortality.S2 The trial showed that earlier dialysis initiation was not associated with improved outcomes or survival. In Canada, an immediate change in dialysis initiation timing was observed after publication of the IDEAL trial, with associated lower dialysis costs and no change in quality of life.S3 Similarly, in Australia and New Zealand, a rapid reduction in the trend for dialysis commencement at higher estimated glomerular filtration rate values was reported post-IDEAL, with accompanying substantial healthcare system economic benefits.S4 In the United States, uptake has been less marked; the percentage of patients commencing dialysis at higher estimated glomerular filtration rates increased from 1996 until 2010 but remained stable or has been slightly decreasing since 2010.S5 The international Trial to Reduce Cardiovascular Events with Aranesp Therapy (TREAT) study was published in the New England Journal of Medicine in 2009.S6 TREAT investigated the use of an erythropoiesis-stimulating agent (ESA), darbepoietin alfa to treat anemia in patients with type 2 diabetes mellitus and chronic kidney disease (CKD), and examined the benefit of aiming for a high hemoglobin (Hb) target, >13 g/dl in this cohort compared with a placebo group, whose hemoglobin levels were allowed to fall to around 9 g/dl before a prespecified rescue therapy could be invoked. The trial found no benefit compared with placebo and a harm signal. Globally, prescription of ESA therapy had already been in decline after safety concerns raised by earlier trials (Correction of Anemia with Epoetin Alfa in Chronic Kidney Disease [CHOIR]S7 and Cardiovascular risk Reduction by Early Anemia Treatment with Epoetin Beta [CREATE]S8); however, this decline accelerated in the post-TREAT period. In the United States, despite changes to regulatory and clinical guidelines, post-TREAT ESA use only significantly declined in 2011, after the introduction of Medicare's new payment system for dialysis providers that replaced a lucrative fee-for-service ESA reimbursement model. Although patient characteristics remained unchanged, Medicare's new payment model triggered an immediate alignment of dialysis unit practices with ESA treatment guidelines,S9 signaling a potential role for healthcare payment reform in de-implementing low-value or harmful practices. Within this complex environment, implementation science theory, a potential tool for enhancing knowledge exchange, remains underused by clinical researchers. Inconsistent nomenclature, alongside an extensive and growing array of conceptual implementation frameworks, many of which are yet to be empirically tested, may deter researchers from applying a theoretical framework to their knowledge-transfer activities.4Waltz T.J. Powell B.J. Chinman M.J. et al.Expert recommendations for implementing change (ERIC): protocol for a mixed methods study.Implement Sci. 2014; 9: 39Crossref PubMed Scopus (84) Google Scholar Thus, the translation of evidence into clinical practice does not always occur or is often significantly delayed. Grimshaw et al.2Grimshaw J.M. Eccles M.P. Lavis J.N. et al.Knowledge translation of research findings.Implement Sci. 2012; 7: 50Crossref PubMed Scopus (1452) Google Scholar suggested that implementation activities targeting healthcare professionals and consumers are more likely to be effective if informed by 5 key knowledge-transfer questions:(i)What should be transferred?(ii)To whom should it be transferred?(iii)By whom should it be transferred?(iv)How should it be transferred?(v)With what effect should it be transferred? Additionally, for kidney research, methodical consideration of structural or situational barriers and enablers will explain "why" knowledge from landmark kidney trials might fail to be translated, and these should inform early knowledge-transfer planning activities. The Reach, Effectiveness, Adoption, Implementation, Maintenance (RE-AIM) framework is a frequently applied public health research framework that provides (i) practical information to enhance knowledge translation activities of evidence-based interventions into practice and (ii) enables evaluation of implementation reach and effectiveness for sustained practice change. However, RE-AIM does not explain the structural or situational conditions that may impact knowledge-transfer outcomes. The Consolidated Framework for Implementation Research (CFIR), a widely used conceptual framework, addresses the systemic contexts not currently considered by RE-AIM. Therefore, although RE-AIM promotes understanding of the what, to whom, by whom, how, and with what outcome questions of evidence-based knowledge transfer, the CFIR uses 5 domains (intervention characteristics, outer and inner setting, individual characteristics, and process) to address why an implementation strategy may (or may not) be likely to succeed.5King D.K. Shoup J.A. Raebel M.A. et al.Planning for implementation success using RE-AIM and CFIR frameworks: a qualitative study.Front Public Health. 2020; 8: 59Crossref PubMed Scopus (75) Google Scholar Successful implementation of evidence-based treatments depends on a 2-pronged top-down and bottom-up approach. Used in isolation, the top-down approach, which involves rigid compliance with scientifically robust protocols to produce an evidence base, may conflict with a bottom-up approach, which focuses on utility of the intervention to end-users. The integrated RE-AIM and CFIR framework approach has previously been successfully used in other health settings5King D.K. Shoup J.A. Raebel M.A. et al.Planning for implementation success using RE-AIM and CFIR frameworks: a qualitative study.Front Public Health. 2020; 8: 59Crossref PubMed Scopus (75) Google Scholar,6Holtrop J.S. Estabrooks P.A. Gaglio B. et al.Understanding and applying the RE-AIM framework: clarifications and resources.J Clin Translat Sci. 2021; 5: e126Crossref PubMed Scopus (66) Google Scholar and has recently been identified as the planned approach for a multistage implementation and evaluation protocol of an electronic health self-management tool for kidney patients.7Donald M. Beanlands H. Straus S. et al.A research protocol for implementation and evaluation of a patient-focused ehealth intervention for chronic kidney disease.Global Implement Res Appl. 2022; 2: 85-94Crossref PubMed Google Scholar For RCTs in kidney disease, the integrated use of the 2 frameworks may allow a complementary top-down (RE-AIM), bottom-up (CFIR) approach to implementation that would enable researchers to strategically plan for implementation and impact measurement (Figure 2). Perhaps the most important enabler of implementation is ensuring that a trial is implementable in the first place. Implementability refers to the generation of new evidence underpinned by prior consideration of practical components related to the validity, relevance, and usability of results that may influence evidence uptake.8Cumpston M.S. Webb S.A. Middleton P. et al.Understanding implementability in clinical trials: a pragmatic review and concept map.Trials. 2021; 22: 232Crossref PubMed Scopus (8) Google Scholar Trial implementability can therefore be enhanced by paying proper attention to appropriate design, conduct, and reporting to facilitate uptake of research results by diverse kidney care centers and for patient groups in many settings (metropolitan vs. regional and remote, academic vs. nonacademic, low vs. high resource, private vs. public, and so on). A recent literature review conducted for the Australian Clinical Trials Alliance drew on a broad group of disciplines to produce a concept map for use by trialists to enhance the implementability of their research.8Cumpston M.S. Webb S.A. Middleton P. et al.Understanding implementability in clinical trials: a pragmatic review and concept map.Trials. 2021; 22: 232Crossref PubMed Scopus (8) Google Scholar Concepts such as co-design and applying standardized statistical and analytical methods to assist end-user interpretation were among 38 items presented in the tool. Importantly, several activities require little or no additional resources that research teams can readily apply to their trials (Figure 3). In many developed countries, agencies such as the U.K.'s National Institute for Health and Care Excellence (NICE) and the U.S.'s Institute for Clinical and Economic Review (ICER) use an economic and ethical lens to review evidence, including from RCTs, to conduct independent health technology assessments on new healthcare therapies. Although independent agencies such as NICE and ICER may act as "watchdogs" to ensure equitable access to treatments at a fair price, health technology assessments are developed for population-level decisions and are not intended as a tool for individual patient healthcare choices. Furthermore, health technology assessments draw heavily on comparative clinical effectiveness evidence from RCTs, considered the most reliable for assessing treatment effectiveness. However, many RCTs lack external validity or generalizability, making extrapolation of treatment efficacy to treatment effectiveness in clinical practice difficult. Medical societies are powerful vehicles for supporting practice change and promoting evidence uptake. In the absence of a prespecified systematic implementation plan for the results of the IDEAL trial, the trial's rapid uptake and consequent practice change in Australia and New Zealand and Canada were likely supported through the extensive knowledge-translation activities facilitated by local nephrology societies. The interest generated from these events was followed soon after by subsequent synthesis of IDEAL's evidence into updated versions of the Canadian Society of Nephrology, Kidney Disease: Improving Global Outcomes (KDIGO), and European Renal Association–European Dialysis and Transplant Association (ERA-EDTA) guidelines. In contrast, in the United States where no immediate significant early dialysis decrease occurred, the 2015 Kidney Disease Outcomes Quality Initiative (KDOQI) clinical practice guidelines maintained a more conservative approach and stopped short of recommending deferral, thus potentially tempering IDEAL's global impact. Although there are complexities around the influence of industry partners on guideline development, a link between industry payments and favorable nephrology guideline recommendations was reported and discussed extensively after the 2006 update of the KDOQI anemia guidelines.S10 Recently, major departures by KDIGO from the national standards for managing financial conflicts of interests, alongside the (not necessarily related) conclusion that many KDIGO guidelines are predicated on the weak evidence of expert opinion, has renewed interest in the relationship between industry partners and guideline producers.9Chengappa M. Herrmann S. Poonacha T. Self-reported financial conflict of interest in nephrology clinical practice guidelines.Kidney Int Rep. 2021; 6: 768-774Abstract Full Text Full Text PDF PubMed Scopus (3) Google Scholar Clearly, this issue is not unique to nephrology clinical practice guidelines; however, compliance with a minimum set of standards for managing financial conflicts of interests, enforced by journal editors, may enhance synthesis of RCT evidence into guideline recommendations. For kidney research around dialysis and transplantation, measurement of evidence uptake, policy change, and impact on patient outcomes can be derived from registries, such as the Scientific Registry of Transplant Recipients, Australia and New Zealand Dialysis and Transplant Registry, and the ERA-EDTA Registry. Although more work is required in this area, a scoping search of the literature revealed that impact measurement using registry data was rarely systematically performed for kidney trials. Furthermore, there are few large-scale, clinical, quality CKD registries or existing longitudinal observational datasets with sufficient data granularity for research. These are valuable hypothesis-generating resources and, where an RCT may not be feasible, can aid discovery of clinical care practice patterns and relationships to inform future research. Additionally, conducting individual patient data meta-analyses using "raw" observational data rather than aggregated data from published RCTs enables researchers to examine person-level heterogeneity of treatment effects and assess generalizability of RCT evidence. However, considerable challenges exist, possibly related to disparate approaches to registry data collection and exacerbated by the extensive resource use (technical and human) required for data access, an obstacle in many typically under-resourced research settings. Therefore, the challenges of outcome measurement in the CKD population often rests on the independent capture of current CKD management practices by individual research groups using qualitative research methods and self-reported survey instruments. As can be seen, there are several leverage points along the translation pathway to enhance evidence uptake, but the difficulty lies in how individual components might be synergized to create an appropriate, unbiased structure to drive evidence translation. For the present, critical appraisal of implementation barriers and enablers using the CFIR methodology, in conjunction with alignment of the RE-AIM framework to the trial design during the development stages of kidney trials, may assist research teams to address some of the current issues. Resourcing for implementation and impact measurement remains a challenge. A 2008 study found most funders consider knowledge translation to be the shared responsibility of the funding agency and the researcher.S11 However, beyond the grant itself, which typically ends with the main results publication, funding agencies and institutions rarely explicitly provide financial support for knowledge-transfer activities. Furthermore, many trial research groups consider it a conflict of interest to perform knowledge-translation activities for their own research. Although funders and researchers have a role in translating research knowledge, other stakeholders may be better positioned to ensure trial outcomes inform treatment practices.2Grimshaw J.M. Eccles M.P. Lavis J.N. et al.Knowledge translation of research findings.Implement Sci. 2012; 7: 50Crossref PubMed Scopus (1452) Google Scholar The type of trial and characteristics of its reported outcomes, such as any identified safety or cost issues, could act to identify the group with the leading responsibility for implementation of results (or de-implementation of disproven therapies). This deserves wider debate, however, and Figure 4 provides a suggested approach for defining implementation responsibility. For example, implementation of results from kidney trials reporting a safety concern, such as those investigating ESAs to find the optimal degree of anemia correction in patients with CKD, might be expected to fall under the auspices of regulatory agencies, such as the U.S. Food and Drug Administration (FDA). A recent example in the context of the current coronavirus disease 2019 (COVID-19) pandemic highlights the critical role regulatory agencies can play in fast-tracking the implementation of promising therapies. Based on data from a single (ongoing) phase III trial (PROVENT), the FDA issued an emergency use authorization for the unapproved product Evusheld (AstraZeneca), a combination of 2 monoclonal antibodies tixagevimab and cilgavimab. Monoclonal antibodies provide an alternative method of protection for immunocompromised populations who are likely to continue to have greater vulnerability to COVID-19 illness, even after multiple doses of vaccine. Although the FDA's evidence standard for an emergency use authorization is lower than the standard for product approvals, given the severity of COVID-19 infection in solid organ transplant recipients and the urgency to find effective alternative strategies to COVID-19 vaccination to protect high-risk patients, Evusheld was authorized for emergency use as a pre-exposure prophylaxis for prevention of COVID-19 in certain immunocompromised adults and pediatric patients.S12 For studies reporting outcomes from repurposed established therapies or processes of care and for which implementation will provide no commercial advantage (or may even provide a possible disadvantage) for pharmaceutical companies, responsibility would likely fall to clinicians (via their professional collaborations and medical societies) to ensure appropriate uptake or de-implementation. Defining these actors has important implications for reducing research waste, maximizing efficient use of scarce health resources, minimizing patient harm, and improving patient quality of life. For many trials, evidence uptake after publication has been insufficient to confer a broader benefit to the global kidney care community. Publication of results is not the end of a trial; rather, publication signals commencement of activities to enhance evidence uptake by stakeholders. More research is required to inform and evaluate strategies for these activities. Nevertheless, the CFIR and RE-AIM frameworks are promising avenues of enquiry for kidney researchers. However, the greatest challenge for the kidney research community is how we might synergize our needs with the needs of influential, key knowledge translation stakeholders (pharmaceutical companies, health translation agencies, medical societies, and guideline producers) to create an unbiased translation pathway for evidence implementation.

Previous evidence suggests that resistance training in combination with specific collagen peptides (CP) improves adaptive responses of the muscular apparatus. Although beneficial effects have been repeatedly demonstrated, the underlying mechanisms are not well understood. Therefore, the primary objective of the present randomized trial was to elucidate differences in gene expression pathways related to skeletal muscle signal transduction following acute high-load resistance exercise with and without CP intake. Recreationally active male participants were equally randomized to high-load leg extension exercise in combination with 15 g CP or placebo (PLA) supplementation. Muscle biopsies from the vastus lateralis muscle were obtained at baseline as well as 1, 4 and 24 h post exercise to investigate gene expression using next generation sequencing analysis. Several important anabolic pathways including PI3K-Akt and MAPK pathways were significantly upregulated at 1 and 4 h post-exercise. Significant between-group differences for both pathways were identified at the 4 h time point demonstrating a more pronounced effect after CP intake. Gene expression related to the mTOR pathway demonstrated a higher visual increase in the CP group compared to PLA by trend, but failed to achieve statistically significant group differences. The current findings revealed a significantly higher upregulation of key anabolic pathways (PI3K-Akt, MAPK) in human skeletal muscle 4 h following an acute resistance training combined with intake of 15 g of specific collagen peptides compared to placebo. Further investigations should examine potential relationships between upregulated gene expression and changes in myofibrillar protein synthesis as well as potential long-term effects on anabolic pathways on the protein level.

Abstract Background Sleep is essential for wellbeing, yet sleep disturbance is a common problem linked to a wide range of health conditions. Palmitoylethanolamide (PEA) is an endogenous fatty acid amide proposed to promote better sleep via potential interaction with the endocannabinoid system. Methods This double-blind, randomised study on 103 adults compared the efficacy and tolerability of 8 weeks of daily supplemented PEA formulation (350 mg Levagen + ®) to a placebo. Sleep quality and quantity were measured using wrist actigraphy, a sleep diary and questionnaires. Results At week 8, PEA supplementation reduced sleep onset latency, time to feel completely awake and improved cognition on waking. After 8 weeks, both groups improved their sleep quality and quantity scores similarly. There was no difference between groups at baseline or week 8 for sleep quantity or quality as measured from actigraphy or sleep diaries. Conclusion These findings support PEA as a potential sleeping aid capable of reducing sleep onset time and improving cognition on waking. Trial registration Australian New Zealand Clinical Trials Registry ACTRN12618001339246 . Registered 9th August 2018.

To examine the effect of a Caralluma Fimbriata extract (CFE) on biomarkers of satiety and body composition in overweight adults. A double-blind, randomised, placebo controlled trial to examine the effect of a Caralluma Fimbriata extract (CFE) on biomarkers of satiety and body composition in overweight adults. Eighty-three men and women aged between 20 and 50 years of age completed 16 weeks of daily supplementation with either CFE or placebo. Plasma cardiometabolic (lipid profile, glucose, insulin) and satiety (ghrelin, leptin, neuropeptideY) biomarkers, body composition, diet history and gastrointenstinal function were assessed at baseline, weeks 4, 8, 12 and 16. Subjects in the CFE and placebo groups were well matched and predominatly female 93% and 87.5%, with a mean age of 40.9 ± 6.7 and 39.5 ± 7.5 years and body mass index (BMI) of 30.0 ± 3.1 and 30.2 ± 2.9 kg/m 2 respectively. There was a significant difference in plasma leptin concentration change between groups at week 16 ( p = 0.04), with the placebo group increasing concentration (2.27 ± 4.80 ng/mL) while the CFE group (0.05 ± 4.69 ng/mL) remained the same. At week 16, the CFE group had significantly reduced their calorie intake from baseline compared to the placebo group (245 cal vs 15.8 cal respectively p < 0.01). The CFE group also had a significant reduction in waist circumference of 2.7 cm compared to an increase of 0.3 cm in the placebo group ( p = 0.02). A weight increase from baseline was seen in the placebo group that was not observed in the CFE group (1.33 kg weight gain vs 0.37 kg weight loss respectively; p = 0.03). The placebo group also had a significant increase in fat mass, android fat mass, BMI and leptin compared to the CFE group ( p = 0.04, 0.02, < 0.01 respectively). CFE was effective at maintaining bodyweight during a non-calorie controlled diet compared to a placebo. The mechanism responsible for this action is requiring further research and could be due to an increase in satiety receptor sensitivity.

Introduction Bronchodilator response (BDR) is a measurement of acute bronchodilation in response to short-acting β2-agonists (SABA), with a heritability between 10–40%. Identifying genetic variants associated with BDR may lead to a better understanding of its complex pathophysiology. Methods We performed a genome-wide association study (GWAS) of BDR in six adult cohorts with participants of European ancestry (EA) and African ancestry (AA) including community cohorts and cohorts ascertained on the basis of obstructive pulmonary disease. Validation analysis was carried out in two pediatric asthma cohorts. Results A total of 10,623 EA and 3,597 AA participants were included in the analyses. No single nucleotide polymorphism (SNP) was associated with BDR at the conventional genome-wide significance threshold (p<5×10−8). Performing fine-mapping and using a threshold of p<5×10−6 to identify suggestive variants of interest, we identified three SNPs with possible biological relevance: rs35870000 (within FREM1), which may be involved in IgE- and IL5-induced changes in airway smooth muscle cell responsiveness; rs10426116 (within ZNF284), a zinc finger protein, which have been implicated in asthma and BDR previously; rs4782614 (near ATP2C2), involved in calcium transmembrane transport. Validation in pediatric cohorts yielded no significant SNPs, possibly due to age-genotype interaction effects. Conclusion Ancestry-stratified and ancestry-combined GWAS meta-analyses of over 14,000 participants did not identify genetic variants associated with BDR at the genome-wide significance threshold, although a less stringent threshold identified three variants showing suggestive evidence of association. A common definition and protocol for measuring BDR in research may improve future efforts to identify variants associated with BDR.

Chronic metabolic health diseases are increasing worldwide placing strain on healthcare systems and importantly, impacting individuals' quality of life. It is well established that many chronic diseases are associated with inflammation and oxidative stress. Exercise is a known strategy to manage and treat inflammation in animals and humans. Understanding the mechanisms which cause acute and chronic changes to systems via various exercise protocols may provide insights into how we can better clinically manage patients with inflammatory and oxidative stress associated diseases. Nrf2 is a basic leucine transcription factor which regulates the expression of antioxidant proteins to protect against damage caused by electrophilic or oxidative stress. The aim of this narrative review is to provide an overview of the literature which has investigated the relationship between acute and chronic exercise training and Nrf2 protein, mRNA and Nrf2-ARE binding activity. This narrative review presents analysis of twenty-nine articles presenting studies using animals and humans. Findings from animal models suggest that exercise increases all molecular aspects of the Nrf2-ARE pathway in all tissues studied. It was noted that there seems to be an age-related decline in Nrf2 protein upregulation with exercise training. In humans, however, there is a lack of evidence to support this claim.

The aim of this study was to evaluate the effect of palmitoylethanolamide (PEA), a cannabimimetic compound and lipid messenger, on recovery from muscle damaging exercise. Twenty-eight healthy young male participants attended the laboratory four times on subsequent days. In the first visit, baseline characteristics were recorded before participants were randomized to consume either liquid PEA (167.5 mg Levagen+ with 832.5 mg maltodextrin) or a matched placebo (1 g maltodextrin) drink. Leg press exercise consisted of four sets at 80% of one repetition maximum followed by a performance set. Muscle soreness, thigh circumference, blood lactate concentration, biomarkers of muscle damage and inflammation, and transcription factor pathways were measured pre- and immediately post-exercise and again at 1, 2, 3, 24, 48, and 72 h post-exercise. The leg press exercise increased (p < 0.05) blood lactate concentration and induced muscle damage as evidenced by increased muscle soreness, thigh circumference, biomarkers of muscle damage, and concentrations of tumor necrosis factor-α. PEA reduced (p < 0.05) myoglobin and blood lactate concentrations and increased protein kinase B phosphorylation following exercise. Taken together, these results indicate PEA supplementation may aid in muscle recovery from repeat bouts of exercise performed within a short duration by reducing myoglobin and lactate concentration.

This randomised, placebo controlled, double-blind study aimed to examine changes in muscular strength and endurance, body composition, functional threshold power, and sex hormones in response to an 8-week calisthenic programme with daily supplementation with Testofen((R)) (Fenugreek extract) or a placebo. A total of 138 male participants (25-47yrs) were enrolled and randomized to three equal groups: 600 mg Testofen((R))/day, 300 mg Testofen((R))/day or placebo. Muscle strength and endurance, functional threshold power, body composition, and sex hormones were measured at baseline, weeks 4 and 8. Participants completed a whole-body calisthenic programme three times a week. All groups improved their maximal leg press from baseline to 8 weeks, however, both Testofen((R)) treated groups improved more than placebo (P < .05). The 600 mg group showed decreases in body mass of 1.2 kg, -1.4% body fat and an increase in lean mass (1.8%) at 8 weeks. The 600 mg group also demonstrated an increase in testosterone concentration from baseline to 8 weeks. This study indicates that Testofen(<(R)>) may be an effective ergogenic aid for individuals wanting to rapidly improve their exercise performance capabilities and body composition above and beyond that of calisthenic exercise alone.

The efficacy of curcumin supplementation is traditionally limited due to its poor bioavailability. Despite this, curcumin has previously been shown to improve biomarkers of muscle damage. The addition of a novel drug delivery system that improves bioavailability could improve exercise recovery. The purpose of this randomized double-blind placebo-controlled study was to assess the effect of curcumin (combined with LipiSperse) when consumed as a drink on exercise recovery in recreationally trained healthy males aged 18-35 yrs. The study included 28 young healthy males with strength training experience. The participants undertook lower limb resistance exercise to exhaustion. Fourteen participants received curcumin dispersed in water pre and postexercise and 14 received a matched placebo drink. Pain (visual analogue scale), thigh circumference (TC), lactate, creatine kinase, lactate dehydrogenase, high sensitivity C-reactive protein, myoglobin, interleukin-6, interleukin-10, and tumor necrosis factor-alpha were assessed pre, postexercise and 1, 2, 3, 24, 48, and 72 h postexercise. There was less appearance of postexercise capillary lactate in the curcumin group compared to placebo (7.4 vs 8.8 mmol/L). The placebo group rated overall muscle pain as higher compared to the curcumin group at 48- and 72-h postexercise. TC was reduced in the curcumin group compared to the placebo group at 24- and 48-h postexercise. The results suggest curcumin may facilitate a quicker return to exercise training and/or allow a higher training intensity than a placebo by reducing postexercise pain, modulating inflammatory pathways and reducing lactate accumulation in an exercising population.