Tolerance, physical dependence, and conditioned place preference were not evident in that species. The finding that bivalent ligands in this series, with spacers 19 atoms or greater, were devoid of tolerance and dependence led to the proposal that MDAN-21 targets heteromeric mu-delta-opioid receptors. The present study focused on its effects in nonhuman primates (Macaca mulatta), a species with a physiology and behavioral repertoire not unlike humans. With regard to opioids, this species usually better predicts clinical outcomes. MDAN-21 substituted for morphine in morphine-dependent monkeys in the remarkably low dose range 0.006–0.032 mg/kg, subcutaneously. Although MDAN-21 failed to produce reliable thermal analgesia in the dose range 0.0032–0.032 mg/kg, intramuscularly, it was active in the same dose range and by the same route of administration, in the capsaicin-induced thermal allodynia assay. The results suggest that MDAN-21 may be useful in the treatment of opioid dependence and allodynia. The data provide additional evidence that opioid withdrawal is associated with sensitized pain.MDAN-21, 7′-{2-[(7-{2-[({(5 The alkaloid morphine has been used in the treatment of pain, cough, and diarrhea. Unfortunately, unpleasant and/or potentially dangerous side effects such as respiratory depression, nausea, vomiting, and constipation can accompany its use. Psychological and physiological processes such as abuse, tolerance, and physical dependence have been associated with chronic use and limit the utility of morphine and other mu-opioid agonists in the treatment of chronic pain.α, 6α)-4,5-Epoxy-3,14-dihydroxy-17-methylmorphin-6-yl}-aminocarbonyl)-metoxy]-acetylamino}-heptylaminocarbonyl)-methoxy]-acetylamino}-naltrindole or MDAN-21,  served as subjects. All monkeys had prior exposure to drugs and to the behavioral procedures in which they were tested. The subjects in the substitution of morphine assay were housed in groups, whereas those in the thermal nociception and capsaicin-induced thermal allodynia assays were individually housed. Food and water were freely available. Their diet consisted of Purina Lab Diet Fiber-Plus Monkey Biscuits no. 5049  supplemented with fresh fruit twice weekly. A 12 h light/12 h dark cycle was in effect (lights on from 7AM–7PM).Male and female rhesus monkeys  was utilized for these analyses. In all cases, significance (P) was set at 0.05.Twenty-four monkeys in the weight range 3.5–7.5 kg comprised the group tested. The assay was based on that originally described by Deneau . Modific Three adult rhesus monkeys were studied in this assay as described previously . They weMDAN-21 was completely ineffective up to the highest doses tested in two monkeys. Accordingly, a follow-up experiment was conducted in these two monkeys to determine whether MDAN-21 might function as an antagonist of the high-efficacy mu-agonist methadone. For these studies, monkeys were pretreated with vehicle or 0.32 mg/kg MDAN-21 15 min before treatment with 0.32 mg/kg methadone. Tail-withdrawal latencies were then determined 10, 20, and 30 min after methadone administration. Drug effects were expressed as Percent Maximum Possible Effect (%MPE) using the following equation: “%MPE = (Test Latency − Baseline Latency)/(20 − Baseline Latency)∗100”, where “Test Latency” was the tail-withdrawal latency from 50°C water obtained during each cycle after drug administration, “Baseline Latency” was the latency from 50°C water during the baseline determinations before drug injection, and “20” was the cutoff latency in s.Three different male rhesus monkeys 5–12 kg were studied. Monkeys were seated in acrylic restraint chairs as described above. To determine tail-withdrawal latencies, the lower 15 cm of each monkeys shaved tail was immersed into a thermal container of warm water heated to the designated temperature (see below for temperatures). The latency in seconds for the monkey to remove its tail from the water was measured using a hand-held stopwatch. If the subject did not withdraw its tail within 20 s, the tail was removed from the water by the experimenter, and a latency of 20 s was assigned to that measurement. Experimental sessions were conducted once per week. At the beginning of each session, tail withdrawal latencies were determined for each monkey from water heated to 38, 42, 46, and 50°C, and the order of temperature presentations was randomized across sessions. By this procedure, baseline temperature-effect curves were determined in each monkey at the beginning of each session, and the highest temperature to produce a tail withdrawal latency >15 s was identified. Water heated to this “threshold” temperature then served as the thermal stimulus for subsequent studies of allodynia during that session. The threshold stimulus intensity was 42°C for two monkeys and 46°C for the third monkey throughout the study.Allodynia was elicited by topical application of capsaicin as described previously , 16. FolRaw tail withdrawal latencies obtained 15, 30, 45, and 60 min after removal of the capsaicin patch were converted to Percent Maximum Possible Effect (%MPE) using the equation %MPE = [(Test Latency − Capsaicin Alone Latency)/(20 − Capsaicin Alone Latency)∗100)], where “test latency” was the tail withdrawal latency obtained at each time point after drug pretreatment + capsaicin patch treatment, and “Capsaicin Alone Latency” was the latency obtained at the corresponding time point after treatment with the capsaicin patch alone.MDAN-21 was synthesized by Dr. Eyup Akgun . Morphine sulfate was purchased from Mallinckrodt, Inc., Hazelwood, MO. Methadone HCl was provided by the NIDA Drug Supply Program. All drugs were dissolved in sterile water for injection . Capsaicin  was dissolved in vehicle composed of 70% alcohol and 30% sterile water and was delivered transdermally  as described previously , 16. TheP values are as follows: 30 min-0.01; 60 min-0.0002; 90 min-0.0002; 120 min-0.0001; 150 min-0.0001. Post hoc Mann-Whitney comparisons with probability values of 0.05 or less are indicated in figure legends and with appropriate superscript letters in Results of this assay are illustrated in The mean ± S.E.M baseline tail withdrawal latency from 50°C was 0.75 ± 0.18 s. The mean ± S.E.M baseline tail withdrawal latency at the threshold temperature was 19.59 ± 0.41 s, and treatment with capsaicin alone reduced tail withdrawal latencies at the threshold temperature to mean ± S.E.M. values of 1.71 ± 0.42, 1. 66 ± 0.23, 1.65 ± 0.41, and 1.49 ± 0.10 s at times 15, 30, 45, and 60 min after capsaicin patch removal, respectively. MDAN-21 was very effective in suppressing withdrawal signs in morphine-dependent monkeys. Its action was prompt. It had a remarkably long duration of action compared to that in the capsaicin-thermal assay in nondependent monkeys. Perhaps, MDAN-21 is much more effective in situations involving physical dependence. Increased pain sensitivity in chronic pain patients and opioid abusers has been reported –19. MDANThis profile of results is consistent with the possibility that MDAN-21 does not readily cross the blood-brain barrier in rhesus monkeys . On the Nevertheless, MDAN-21was potently active in the capsaicin-induced thermal allodynia assay in the dose range of 0.032–0.32 mg/kg. It also attenuated withdrawal signs in morphine-dependent monkeys in spontaneous withdrawal for a longer time period. The results are in accord with the findings of other investigators that pain sensitivity is increased in opioid-treated animals, chronic pain patients and opioid abusers (see references above). The results also suggest that MDAN-21 may be useful in the pharmacotherapy of chronic pain and chronic opioid use.


EnhanceFitness (EF) is a prime example of an evidence-based physical activity program that has been disseminated far beyond its original study site. This commentary will provide an overview of the evidence, history, successes, challenges, and vision for increasing the availability and accessibility of EF. This overview is intended to be an example for evidence-based programs that want to move beyond their study sites to wider dissemination.In 1994, researchers at the University of Washington Health Promotion Research Center (UW HPRC) and Group Health Cooperative  collaborated with Senior Services, a non-profit community-based organization, to conduct a trial of a multicomponent disability prevention program. One hundred older adults were recruited for a 6-month study at a State of Washington senior center. Even before the pilot study ended, participants requested to keep the exercise class component of the intervention as a permanent activity at the center. Not only were the center members excited about participating, but study measures showed that the intervention group significantly improved in fitness and health: 13% improvement in social function; 52% improvement in depression; and 35% improvement in physical functioning. The control group (center members who did not participate in the program but who attended other senior center activities) deteriorated in these measures over the same period  included EF as one of the approved programs for the Choices for Independence grants, placing it in the AoA’s highest tier of evidence-based programs  study beginning in 2014 is another step toward a long-time vision of EF becoming a Medicare reimbursable benefit. Continued work with the University of Washington on the adaptation of the EF program for participants with cognitive impairment will fill an ever-growing need. Expansion of locations through national partners, such as the Y of the USA and its 2,600 branches, will strengthen the EF network as a whole. Lastly, focus on increased referrals of patients from healthcare providers will fortify the links between the healthcare system and older adult wellness and self-efficacy. This is all possible based on the strong foundation built over the last two decades.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.This paper is included in the Research Topic, “Evidence-Based Programming for Older Adults.” This Research Topic received partial funding from multiple government and private organizations/agencies; however, the views, findings, and conclusions in these articles are those of the authors and do not necessarily represent the official position of these organizations/agencies. All papers published in the Research Topic received peer review from members of the Frontiers in Public Health  panel of Review Editors. Because this Research Topic represents work closely associated with a nationwide evidence-based movement in the US, many of the authors and/or Review Editors may have worked together previously in some fashion. Review Editors were purposively selected based on their expertise with evaluation and/or evidence-based programming for older adults. Review Editors were independent of named authors on any given article published in this volume.


Anticoagulation with unfractionated heparin in cardiac surgery patients has several limitations, and above all the risk of heparin-induced thrombocytopenia. Bivalirudin is a direct thrombin inhibitor, use of which in cardiac surgery patients has expanded in recent years. The aim of the study was to analyze two strategies for introducing bivalirudin in this setting (as secondary drug switching from heparin or as primary anticoagulant) and to evaluate clinical outcomes.n = 50) or bivalirudin , from January 2009 to January 2012, in a cardiac surgery ICU of a university hospital were analyzed. Bivalirudin was administered as either first-line or second-line drug after heparin discontinuation if heparin-induced thrombocytopenia was presumed.Data from 100 propensity matched patients who received heparin  compared with the control group. Interestingly, in an intention-to-treat analysis, patients receiving primary bivalirudin showed a significant reduction in minor bleeding (P = 0.04), and mortality (P = 0.01) compared with the secondary bivalirudin group, and similarly if compared with UFH and secondary bivalirudin patients (P = 0.01 and P = 0.05 respectively). Predictors of hospital mortality at multivariate analysis included urgent admission , septic shock  and primary therapy with UFH .Bivalirudin treatment was associated with a reduction of major bleeding (Novel anticoagulant strategies might play a crucial role in critically ill cardiac surgery patients. In a propensity-matched population, our study showed that primary bivalirudin anticoagulation may reduce bleeding complications and mortality. Further studies are therefore warranted.


The literature base regarding the development of sporting talent is extensive, and includes empirical articles, reviews, position papers, academic books, governing body documents, popular books, unpublished theses and anecdotal evidence, and contains numerous models of talent development. With such a varied body of work, the task for researchers, practitioners and policy makers of generating a clear understanding of what is known and what is thought to be true regarding the development of sporting talent is particularly challenging. Drawing on a wide array of expertise, we address this challenge by avoiding adherence to any specific model or area and by providing a reasoned review across three key overarching topics: (a) the performer; (b) the environment; and (c) practice and training. Within each topic sub-section, we review and calibrate evidence by performance level of the samples. We then conclude each sub-section with a brief summary, a rating of the quality of evidence, a recommendation for practice and suggestions for future research. These serve to highlight both our current level of understanding and our level of confidence in providing practice recommendations, but also point to a need for future studies that could offer evidence regarding the complex interactions that almost certainly exist across domains. With the competition for medals at Olympics and World Championships intensifying, there is greater investment than ever in sporting systems and structures to identify and develop exceptionally talented athletes. The Australian Institute of Sport has been credited with boosting Australia’s medal haul from five medals in the 1976 Montreal Olympics to 60 medals in the 2000 Sydney Olympics. Team Great Britain (GB)’s fourth position in the 2008 Beijing Olympics medals table was supported by a markedly increased investment (£235M), and this funding continued to support Team GB’s climb to third position in the 2012 London Olympics (£261M). When organizations such as UK Sport (the UK’s high performance sports agency) commit a further £355M of public funds to the Rio 2016 Olympic cycle, it becomes increasingly necessary to be able to draw on an evidence-based understanding of the identification and development of the world’s best sporting talent to maintain the success that is expected with this expenditure. This is the context for the present review, which seeks to identify what is known and what is thought likely to be true in relation to understanding the development of the world’s best sporting talent.In September 2009, UK Sport invited all UK academic institutions to submit tenders to (a) “research and understand elements of identification and development, to ultimately inform the prediction of future elite sporting talent”; and (b) “conclude unique recommendations from the research that highlight key accelerants and retardants in the pathway development of elite performers”. As part of the subsequent work, the research team (led by the two first authors) drew together a panel of international research experts, elite athletes, coaches from the GB World Class Programme and expertise from UK Sport’s Research and Innovation, and Athlete Development disciplines, and UK Sport’s Senior Management Team. An initial series of meetings, presentations and workshops was held between April 2010 and January 2011. The topics highlighted and conclusions drawn from these sessions guided the development of a review/position statement with regard to current understanding of the performance and development of ‘super-elite athletes’. This review/position statement was used both in strategic planning for Rio 2016 (in March 2013) and to inform a separate research study which further explored the development of super-elite athletes. This process provided the initial guide for the present article, which was subsequently further revised and up-dated through 2015. Of particular note was the first meeting of the collaborative team at UK Sport’s headquarters in Loughborough, UK in June 2010. At this meeting, contributors were asked to present on their key topic(s) of expertise and calibrate evidence in relation to non-elite, junior elite, elite and super-elite levels of performance.There is a voluminous literature devoted to understanding the development of sporting talent. In addition to numerous peer-reviewed journal articles, there are various academic books –4, revienon-elite , junior elite , elite  or super-elite ;1Categorization of the performance level of the study samples as ,Employing a modification to the GRADE  system  to rate 2Offering a recommendation  refers to a biased distribution of elite athletes’ birthdates, with an over-representation of those born at the beginning of any given competitive year (e.g. September in most Western societies) and an under-representation of those born at the end (e.g. August). A meta-analysis [Athletic success may be influenced by birthdate. The analysis  of studianalysis –61 has pAlthough the above results appear convincing, there is evidence that RAEs may be inconsistent. In some elite samples –65, RAEsResearch , 70 withmoderate study design, low consistency and moderate direct evidence (up to elite level), the quality of the evidence that being relatively older is an advantage with regard to the development of super-elite performance in sport is moderate to low. The evidence suggests that any advantage associated with being born in the first two quarters of the year may disappear by the time athletes reach elite level. We therefore recommend that practitioners do not make use of RAEs for talent selection [With election  or develelection , 73. MorVO2max. Specific gene variants appear to influence participation in physical activity [It would appear no longer a case of whether there is a genetic component to sporting performance, but rather which genetic profiles make the greatest contribution . There iactivity —the GENEactivity , 82. Indactivity .A significant heritable component has been identified with non-elite samples in agility, sprinting, jumping, throwing, kinematics and reaction time , 84–86, Genetics are also related to susceptibility to injury . The E4 high study designs, moderate consistency and moderate direct evidence (up to elite level), the quality of the evidence that genetics could make an important contribution to talent selection and development in sport is at least moderate. Indeed, although rare combinations of gene variants are likely to act in concert to yield propensity to super-elite athlete status [recommend that policy makers and practitioners consider the possibility of using genetic profiling to help athletes make more informed and appropriate decisions about sport type and discipline during their development years. We may only be able to evaluate the true benefits of genetic testing when geneticists and sports scientists collaborate in large prospective cohort studies that empirically determine the utility of genetic analyses in predicting future performance. The potential impact of genetics could be great, and thus further research in this area is warranted, in particular in relation to specific performance genes, training/learning genes and genes underpinning injury proneness.With e status , and elie status . GeneticVO2max. This research has examined a wide range of sports, including: Australian Rules football, basketball, canoe polo, field hockey, football, handball, netball, rowing, rugby league and tennis. Clearly, aerobic capacity, anaerobic endurance and anaerobic power [There is a long history of anthropometric studies of Olympic athletes, dating back to documenting the physique of track and field athletes at the 1960 Rome Olympics . As a reic power  are impoic power , 135.Although morphology-related factors may be involved in directing some athletes to specific sports —e.g. gymhigh study design, high consistency and high direct relevance (up to super-elite level), the quality of the evidence that anthropometric and physiological factors contribute to the development of super-elite performance in sport is high. However, changes during puberty make the prediction of adult performance from adolescent data unreliable. We therefore recommend that practitioners make use of physiological testing for purposes of informing the training process, and make use of anthropometric profiling and physiological tests for both talent selection and development purposes, but policy makers and practitioners should ensure that such action is accompanied by appropriate procedures  to ‘re-capture’ lost/missed late maturers. The most obvious issue for talent identification researchers in sport to solve is the problem of predicting adult performance from adolescent anthropometric and physiological data. Solving this conundrum could have an enormous impact on talent identification procedures.With As long ago as 1977, Mahoney and Avener  attempteEvidence at elite , 153 andThere is evidence at non-elite and elite level –181 thatmoderate study design, high consistency and high direct relevance (up to super-elite level), the quality of the evidence that psychological factors are an important contributor to the development of super-elite performance in sport is high to moderate, although the evidence is more widespread across some psychological characteristics than others. We therefore recommend that practitioners make use of psychological profiling for talent development purposes. Key questions for future research include examining the causes of exceptional levels of motivation, resilience and mental toughness, including assessing whether and how psychological skills at junior level influence long-term adult elite/super-elite performance. How do exceptional performers use their anxiety in a positive way? How do the world’s best performers maintain focus and concentration, while avoiding lapses into conscious control? How can these skills be trained?With adaptive perfectionism—a tendency to maintain perspective on performances while striving to achieve exceptional standards. This contrasts with the many negative outcomes  associated with  perfectionism [narcissism on performance. Narcissists have an inherent  belief in their ability [There is evidence at non-elite –188, elictionism . There ictionism –198 for  ability , but thimoderate study design, moderate to low consistency  and high direct relevance (including super-elite level), the quality of the evidence that personality is an important contributor to the development of super-elite performance in sport is moderate. Furthermore, the risks associated with practitioners acting on the available evidence for talent development purposes seem to be only modest, although the same cannot be said with regard to using it for talent selection purposes. We therefore recommend that practitioners might make use of personality profiling for talent development but not talent selection purposes. Future research could focus on whether there are other important (combinations of) personality characteristics that are necessary for the development of a strong competitive personality and how these characteristics might be best developed.With There is evidence across junior elite , 201 andmoderate study design, high consistency and high direct relevance (up to super-elite level), the quality of the evidence that birthplace offers an advantage with regard to the development of super-elite performance in sport is high to moderate. We therefore recommend that policy makers and practitioners at least take consideration of birthplace when designing talent search initiatives as well as profiling athletes during talent selection and development. Understanding more about the physical and social environment, organisation of resources and the number of participants competing for available places in sports are key areas for research—i.e. understanding more about the environments and neighbourhoods that potential sporting talents are exposed to, and less about birthplace population size.With The importance of family and siblings during athletes’ developmental years has been highlighted . Evidencmoderate study design, moderate consistency and high direct relevance (up to super-elite level), the quality of the evidence that support plays a role in the development of super-elite performance in sport is at least moderate. We therefore recommend that policy makers and practitioners heed the important influence of the support process during talent development. However, it is worthy of note that the nuances of providing appropriate support appear to be much more complex than most lay people realize. There is still a relative lack of knowledge with regard to the influence of early family experiences, and we need to know more about the role of the family  more generally with respect to who reaches super-elite level in sport.With Evidence from 19 European countries  suggestsmoderate study design, moderate to low consistency (i.e. consistent but infrequent), and high direct relevance (up to super-elite level), the quality of the evidence regarding early athlete support programmes’ contribution to the development of super-elite performance in sport is moderate. The trajectory to super-elite status appears distinctly non-linear [recommend that policy makers and practitioners appreciate that junior success does not contribute significantly to predicting long-term senior success, that early athlete support programmes are not the sole route to the development of talent, that support programmes be open for access at all age ranges, and thus that de-selected athletes be monitored for potential return. Empirical evaluations of the efficacy of athlete support programmes would appear a priority for future research, with the potential to encourage a major re-think of some of the components of the current support programme strategy. At a more theoretical level, why do some apparently ‘talented’, highly motivated athletes fail to progress at key transition points ? Do sport systems typically require the talented athlete to ‘fit in’ more than they adapt to allow the athlete to thrive toward excellence?With n-linear , involvin-linear . We therDespite wide variation across sports, most junior elite, elite and super-elite athletes have accumulated enormous volumes of organized practice and training , 241–260A widely held view, based on seminal work in chess  and musiDP theory also asserts  that theSuch differences have not been observed between super-elite and elite athletes in field hockey, soccer, tennis, swimming , 266 andAlthough the DP framework has gained popularity in sport science and in popular literature, its applicability to high-performance sport may be limited. The suggestion of 10 years/10,000 h was originally based on: (a) musicians, not outstanding athletes; and (b) a strict interpretation of DP, excluding intrinsically enjoyable activities, team practice, play, competition, non-organized sporting activities, and also ruling out implicit (improved task performance in the absence of conscious awareness) and incidental learning (learning in the absence of an intention to learn). DP also implies full attention and concentration, while research indicates that full concentration does not always generate optimal learning/performance. Increasing conscious awareness may even result in poorer performance , the quality of evidence that extensive DP is an important contributor to the development of super-elite performance in sport is high to moderate, while high/moderate quality of evidence suggests that the applicability of the 10 years/10,000 h rule is limited and that DP alone does not guarantee sporting success. Additionally, the contribution of practice/training to the development of sporting expertise may only apply to domain-specific practice accrued during late adolescence or adulthood, with practice volume not discriminating elite from super-elite athletes. Finally, there is some low quality evidence to suggest that automaticity and implicit learning may contribute to the development of sporting expertise. We therefore recommend that policy makers and practitioners continue to promote deliberate practice, but consider the present evidence before routinely increasing practice volumes with junior athletes, and acknowledge the potential benefits of automaticity, implicit learning and also enjoyment in practice and play. The links between early sport-specific practice/training and short- and long-term outcomes are a research priority. How is intensified specific training related to long-term enjoyment, motivation, stress-recovery and prolonged involvement? Future research should also further explore the roles of explicit and implicit/incidental learning in the development of expert performance. This implies scrutiny of the intentions and specific activities performed during practice/training and play, their combinations, variability, potential interactions and relative influence through different developmental age ranges.With within their respective sports. A super-elite sample of rhythmic gymnasts also experienced reduced involvement in other sports compared to their elite counterparts [Where peak performance in sport is achieved before biological maturity, early specialization may be necessary to reach elite level. For example, super-elite athletes in artistic composition sports  performterparts . Howeverterparts , 270–274terparts , 275–278terparts , 266 havcombination of above-average volume of organized soccer training/practice with either above-average involvement in other sports or above-average non-organized soccer play.There is also evidence at non-elite, junior elite, elite and super-elite level that many athletes have spent considerable time in non-organized play during childhood , 270. A moderate study design, moderate /low (play) consistency, and high direct relevance (up to super-elite level), the quality of the evidence that early specialization or sampling represent the best route to the development of super-elite performance in sport is moderate. Both early specialization and sampling (and play) may be routes to expertise under optimal conditions. However, the probability of attaining elite or super-elite level may be enhanced by the coupling of a large volume of intensive, organized specific training/practice in the main sport with appreciable amounts of organized training/practice and competitions in other sports and/or non-organized play in the main or other sports. We thus recommend policy makers and practitioners to draw on this evidence, bearing in mind the need to minimize the potential hazards of early specialization when such specialization is necessary, and with regard to promoting opportunities for young athletes to experience non-organized play and sampling in a variety of sports. Future research is needed to understand how participation in various sports benefits super-elite performance in one main sport. Further, how does the process of late specialization following prior diversification or ‘talent transfer’ proceed? Are there certain sports or clusters that lay the best foundation for super-elite success in a final sport?With There are a number of additional topics that have been raised in the literature, which do not meet the level of evidence of the other topics in this review . Under-studied in sport, the quality of evidence for these topics is thus low, and we cannot make recommendations to act. Nonetheless, they may still be intriguing ‘candidates’ for future examination. They include: the role of the family’s socioeconomic status in different sports and countries , 280–282We reviewed key topics (see Table


To reverse the global epidemic of physical inactivity that is responsible for more than 5 million deaths per year, many groups recommend creating “activity-friendly environments.” Such environments may have other benefits, beyond facilitating physical activity, but these potential co-benefits have not been well described. The purpose of the present paper is to explore a wide range of literature and conduct an initial summary of evidence on co-benefits of activity-friendly environments. An extensive but non-systematic review of scientific and “gray” literature was conducted. Five physical activity settings were defined: parks/open space/trails, urban design, transportation, schools, and workplaces/buildings. Several evidence-based activity-friendly features were identified for each setting. Six potential outcomes/co-benefits were searched: physical health, mental health, social benefits, safety/injury prevention, environmental sustainability, and economics. A total of 418 higher-quality findings were summarized. The overall summary indicated 22 of 30 setting by outcome combinations showed “strong” evidence of co-benefits. Each setting had strong evidence of at least three co-benefits, with only one occurrence of a net negative effect. All settings showed the potential to contribute to environmental sustainability and economic benefits. Specific environmental features with the strongest evidence of multiple co-benefits were park proximity, mixed land use, trees/greenery, accessibility and street connectivity, building design, and workplace physical activity policies/programs. The exploration revealed substantial evidence that designing community environments that make physical activity attractive and convenient is likely to produce additional important benefits. The extent of the evidence justifies systematic reviews and additional research to fill gaps.The online version of this article (doi:10.1186/s12966-015-0188-2) contains supplementary material, which is available to authorized users. Physical inactivity accounts for 5 million deaths annually worldwide . Most pePhysical activity has been engineered out of people’s lives through urban planning and transportation investments that favor travel by automobile, labor-saving devices at home and in the work place, and a proliferation of electronic entertainment options ,6. BuiltMany decisions affecting physical activity environments occur at the local government level. Though mayors, city council members, and other officials work every day to balance competing interests, they likely do not consider that environments supporting physical activity could produce additional benefits for their communities. For example, changing zoning codes to favor mixed use developments can enhance property values and reduce carbon emissions ,15. HaviThere is no resource that examines the wide range of potential co-benefits of communities designed to support active living, which can be called “activity-friendly environments”. Therefore, the aim of the current study was to compile evidence about the relation of activity-friendly environmental attributes to multiple potential outcomes. The expectation was that several co-benefits would be documented, but negative effects were also included. The intent of the present exploration of the literature was to provide an initial summary of the evidence on co-benefits that may be useful for determining whether and which systematic reviews are justified, identifying areas for further research, and educating policy makers about likely co-benefits.The present literature review covered diverse topics across multiple academic and practice fields, so dozens of systematic reviews were not feasible. Therefore an exploratory approach was taken to provide an initial overview of the potential co-benefits of communities designed for active living. We searched both scientific and gray literature. Gray literature was included because we expected many of the topic areas to be rarely addressed in the scientific literature but studied by government agencies and policy groups. The objective of the literature exploration was not to systematically review or quantify all evidence, but to create a profile of the potential multiple benefits, and negative effects, of each environmental feature as a tool for policy-making and a guide for future research.Specific built and social environment attributes in five settings  that research had shown to be related to physical activity were identified and used to structure the search Table . The envBased on the input of authors and informants, the following co-benefit outcomes were included in the searches: physical health, mental health, safety/injury prevention, social benefits, economic benefits, and environmental sustainability focusing on carbon emissions and air pollution Table . These owww.activelivingresearch.org) network, 20 experts in various disciplines were contacted to nominate 1) groups/organizations working on the built environment and non-physical activity co-benefits, 2) key reports and papers, both peer-reviewed and gray literature, 3) websites, 4) case studies of cities that have implemented activity-friendly built environment changes, 5) recommendations for other experts. Of the 20 experts contacted, 13 provided input.Through the Active Living Research  and the direction of association. The weighted scores for associations in each direction were summed for each direction of effect category , and recorded in the online tables. Thus, there was a weighted score for each direction, such as 24 “ + ”, 7 “-”, and 4 “0”. “Net” scores were calculated by subtracting the weighted negative and zero scores from the weighted positive scores. In the preceding example, 24 minus (7 + 4) equals 13 (summary score). To be conservative, negative and zero findings were subtracted from positive findings, so the summary scores roughly indicated both the quantity and quality of the evidence. To make the summarization process even more conservative, only resources with quality scores of 3 or above were included, as resources with a lower score, such as unreferenced advocacy documents and consensus reports, lacked credibility.Cells in each summary table were labeled based on summary scores. Table Abstractors identified a total of 521 results from 221 sources, coming from at least 17 countries. Four hundred eighteen of these results were from a source with a quality score of at least “3” and were used in the results reported here. The five setting-specific tables with notes about each study and codes for findings are available online , homeowners, real estate developers, health insurance companies, employers, retailers, commercial property owners, and taxpayers. This is an extremely broad range of beneficiaries, and some of them may not be aware of the economic benefits of activity-friendly environments.Policy-makers worldwide are faced with many problems and challenges . Rates oIf decisions about built environments were informed by evidence, then the features with the best evidence of co-benefits listed in Table The strength of the literature exploration was the breadth of topics explored. For each setting several features were identified that were related to physical activity, and each of these features was evaluated for six types of co-benefits. A quasi-quantitative approach was used to code the level of evidence of 521 findings and weight each finding by the quality of the source. To avoid basing findings on lower quality evidence, such as poorly-substantiated claims in advocacy documents, lower-quality evidence was not included in the numerical summaries.The main limitations were a consequence of the breadth. Because of the large number of topics searched, it was not possible to conduct a systematic review. A requirement of systematic reviews is assessment of the quality of each study, but this was not feasible given the number and diverse types of studies. It would have been helpful to code studies as being cross-sectional, longitudinal, or experimental in design. Existing reviews were used whenever possible to reflect the best evidence in the literature. Literature searches and coding were conducted by several investigators with a semi-structured process. Therefore there were undoubtedly differences across topics in thoroughness of search and classification of levels of evidence.The searches were limited to English language documents, but one-quarter of the findings were from countries other than the US, and another quarter of findings were from reviews that included international literature. Another limitation was publication bias that favors positive findings, though this may have been countered somewhat by inclusion of gray literature, including technical reports. The intent of the literature exploration was to identify as many relevant sources as possible to determine whether it is worthwhile to pursue the topic of co-benefits, but a weakness was that the quality of each source was merely categorized and not based on an analysis of methodological quality.The summary scores are not intended to be interpreted literally as the actual strength of evidence, but they provide a rough indication of the extent of evidence: pro, con, and neutral. If the net scores for the level of evidence are strong, there is reason to have confidence in the finding for a connection between a feature and an outcome because a strong rating required findings from multiple sources.Substantial evidence indicated that designing and creating parks, communities, transportation systems, schools, and buildings that make physical activity attractive and convenient is also likely to produce a wide range of additional benefits. Present findings provide new information to decision-makers in numerous sectors that could change the perceived benefits of activity-friendly designs. Benefits were found for environmental sustainability, economics, and multiple dimensions of health. Though the present review is not definitive, the large number of sources identified for such policy-relevant issues provides a compelling justification for more original research and systematic reviews of the very broad range of topics. If “a good solution solves multiple problems,” then building places that support physical activity may be considered a superlative solution.


Continuous escalation in methodological and procedural rigor for evidence-based processes in guideline development is associated with increasing costs and production delays that threaten sustainability. While health research methodologists are appropriately responsible for promoting increasing rigor in guideline development, guideline sponsors are responsible for funding such processes.This paper acknowledges that other stakeholders in addition to methodologists should be more involved in negotiating trade-offs between methodological procedures and efficiency in guideline production to produce guidelines that are ‘good enough’ to be trustworthy and affordable under specific circumstances. The argument for reasonable methodological compromise to meet practical circumstances is consistent with current implicit methodological practice. This paper proposes a conceptual tool as a framework to be used by different stakeholders in negotiating, and explicitly reporting, reasonable compromises for trustworthy as well as cost-worthy guidelines. The framework helps fill a transparency gap in how methodological choices in guideline development are made. The principle, ‘when good is good enough’ can serve as a basis for this approach.The conceptual tool ‘Efficiency-Validity Methodological Continuum’ acknowledges trade-offs between validity and efficiency in evidence-based guideline development and allows for negotiation, guided by methodologists, of reasonable methodological compromises among stakeholders. Collaboration among guideline stakeholders in the development process is necessary if evidence-based guideline development is to be sustainable. In the The evidence-based health care movement has harnessed and honed the methods of the evaluation and decision sciences to enhance the rigor with which we generate, critically evaluate, interpret, and apply clinical scientific knowledge for health care practice and policy decisions. This has been extended in the guideline context to consider the population perspective, guideline applicability, editorial independence, and the like. There are many tools and methods to support optimal guideline development, for example, the Appraisal of Guidelines for Research & Evaluation (AGREE) II , the GuiIncreased methodological expectations translate into increased guideline development time, costs, and delays in their release. For example, the AGREE II, a commonly used quality rating instrument that also informs reporting and development, has 23 quality criteria . Direct These are critical and pragmatic questions for guideline developers who create the documents, for those who use guidelines and must wait for recommendations, for those who fund guideline development and need to ration limited resources, and for those ultimately responsible for the implementation of recommendations. The short answer to these questions is that we simply do not know at what point increasing methodological rigor leads to appreciably more valid and implementable recommendations that, in turn, lead to better outcomes or more affordable care.The evidence underpinning the value of available methodological tools or quality features as a means to reduce bias varies considerably . For exaMethodologists have been the main drivers of continuously increasing procedural rigor in guideline development. However, the burden of escalating demands for rigor has been borne by others whose perspectives need to be taken into account to ensure timely completion of recommendations, continued guideline funding, and ongoing participation by guideline panel members (often voluntary). We contend that it is time for the guideline community, as a whole, to ask whether more efficient and affordable processes for guideline development can be used with credible results, towards achieving a better balance between rigor and pragmatism that addresses the needs of all stakeholders who are affected by guidelines. To this end, and consistent with the spirit of transparency and accountability that are at the core of an evidence-based guideline strategy, we argue for greater collaboration among methodologists and other guideline developers, researchers, consumers, funders, and other stakeholders in the application of guideline development methods. Arguably, there should be less emphasis on blind adherence to common, putative standards whose generalizability and impact are uncertain.Efficiency-Validity Methodological Continuum  the inherent level of uncertainty about the evidence base and impacts associated with methodological expectations in guideline development or (b) where evidence is certain, the risk threshold for tolerating compromise in validity to gain efficiency. The principle of ‘good enough’ reflects the notions that continuous improvement will happen, that we must cope with a messy world that defies perfection, that one starts and chooses processes or materials whose ‘bugs’ are already known, and that judgment is required when defining what is good enough ,11.For those concerned with the erosion of quality associated with this approach, it has been observed that ‘Good enough has nothing to do with mediocrity; it has to do with rational choices, as opposed to compulsive behavior’ . MoreoveThe circumstances that pose difficulties for highly rigorous guideline development are variable enough that it should be up to the relevant stakeholders to determine what constitutes an acceptable trade-off between rigor and efficiency in either developing or using a particular guideline. Figure Zones of ‘preference’ and ‘acceptability’ along the continuum Figure  both refThe proposed ‘efficiency-validity trade-off continuum’ is intended to raise awareness within organizations and among guideline sponsors and developers about the prospect that, as stakeholders, they have choices to negotiate among themselves towards credible compromises without delegating all methodological choices to the methodologist. Where there is little research-derived information that meets minimal standards for health care evidence, but where there is a demand or a need for guidance, consensus approaches may be most appropriate. The framework here may be modified for that purpose, negotiating an optimal balance between informal and formal consensus methods .We envision the ‘efficiency-validity trade-off continuum’ as an opportunity for promoting collaborative negotiation within multi-representative guideline development panels at the stage of protocol development for an evidence-based guideline to determine what is acceptable for a given project. Questions from the good enough quality paradigm  may servWe postulate that using such a negotiating tool will over time limit unnecessary costs and, therefore, encourage increased investment in guidelines; opportunities towards further methodological refinement; and improved consensus about quality, trustworthiness, implementability, and ‘cost-worthiness’ of evidence-based guidelines. We predict furthermore that failure to address all stakeholder concerns around appropriate levels of investment in guidelines that are circumstance-sensitive will gradually erode the evidence-based guideline movement. This erosion is already demonstrated through the rising popularity and credibility of alternative, more affordable, and largely consensus-based models and by reasonable concerns that the efforts and costs associated with rigorous evidence-based methods may often produce recommendations that are not substantially different from those resulting from less rigorous and less costly approaches -19.We propose a re-examination of the trend towards ever-increasing methodological standards for guideline development with respect to the costs, efforts, and delays involved for the benefits gained. We suggest that decisions about guideline development procedures be circumstance-sensitive and therefore negotiated among all stakeholders who may be affected, rather than left solely to the research methodologist. We offer a conceptual tool, the ‘Efficiency-Validity Methodological Continuum,’ to help guideline stakeholders  to respectfully negotiate credible compromises in methodological rigor imposed by practical constraints in developing a guideline. Compromises are already being made implicitly through the use of quality rating scales for individual studies and existing systematic reviews and guidelines, few of which are without flaws. Based on negotiated explicit and transparent decisions, guideline consumers can judge whether a guideline has achieved a level of quality, trustworthiness, and implementability that is ‘good enough.’


Respiratory tract infectious diseases are a group of the most common, widespread diseases, from common cold and influenza to tuberculosis and pneumonia; some of them may cause serious and even life-threatening health problems. Most cases of upper respiratory tract infectious diseases include common cold and influenza, which are mainly caused by various virus infections, and tuberculosis, pneumonia, and other low respiratory tract infectious diseases caused by different bacterial infections.Releasing the symptoms and preventing complicated bacterial infection are a rule of treating virus infected upper respiratory tract infectious diseases. Traditionally, herbal medicines are used to treat and prevent the respiratory tract infectious diseases such as common cold and influenza worldwide. For example, more than two hundred patent products of traditional Chinese medicines have been approved into market for treatment and prevention of the common cold as well as influenza. In the past decades, some herbal medicines are developed as injections for clinical use for treating respiratory tract infections, such as Caihu injection, Shuanghuanglian injection, Yuxincao injection, and Qinkailing injection. Some of these medicines are believed to effectively release the symptoms; some are believed to strengthen the immune function of patient and therefore result in the virus and bacteria being eliminated; some are believed to kill the microorganisms directly.A fact is that although a lot of herbal medicines are widely used clinically, most evidence supporting their use came from poorly reported published clinical studies or studies with questionable methodology, as Drs. Q. Yang, H. Zhang, C. Zou, and L. Wu, concluded in their systematic reviews. Call for high quality evidence is a mission of this special issue.Fortunately, Dr. J. Chang and her colleagues contributed high quality evidence about a patent Chinese medicine Shi-Cha capsule for common cold by a well-designed, well-conducted, and well-reported randomized controlled trial. In this multicenter study, they have done very well on the ethicas issues including protocol aproval by ethical committee, properly informed consent and registered their protocol in a public clinical trial registry—Chinese Clinical Trial Registry; and high quality methodological issues, including the randomization method and allocation procedure, the recruitment of patients, the data management, the analysis method of results, all of these were described in detail and very clearly according to CONSORT statement. This transparency makes readers confident to trust the result of the study and we believe such evidence should be graded as high quality. if the reporting referes to CONSORT for TCM to provide more information of the principle of using Shi-Cha capsule for with “wind-cold type common cold” will makes readers better understanding on the rational of this medicine. Another advantage of this trial is that placebo control was used for comparison with Shi-Cha capsule. Usually, use of a medicine in which “the effect is accepted by public recognition” as the control is one of rules of the new medicine development clinical trial in China. The shortcoming of this rule is that it caused difficulty to assess the effects for a lot of traditional Chinese medicines because of the lack of evidence of effect of the controls. For the self-limited disease, a placebo control should be encouraged to be used in the treatment study. We believe that this study and its report could be a good example of high quality study and good reporting.Another valuable thing we have seen is that Dr. C. Zou and his colleagues, physicians of traditional Chinese medicine, are using evidence-based medicine (EBM) method to critically appraise the evidence and using the results to guide their clinical practice successfully. This absolutely is a revolutionary event in the field while most traditional medical clinicians may not know EBM exactly. We hope more and more clinicians in the field can use EBM method to guide their practices and make the health care service better and better.Studies came from France, Japan, South Africa, and Taiwan provide from in vitro and animal study suggesting that some herbal medicines may have antimicrobial activity or can strengthen the immune function. It is expected that these lines of evidence will result in more confidence to support the clinical use of complementary and alternative medicines.Taixiang WuTaixiang WuZhao-Xiang BianZhao-Xiang BianMinawaer AbuduMinawaer AbuduDenise AdamsDenise AdamsSeong-Gyu KoSeong-Gyu Ko


Clinical Practice guidelines (CPGs) have emerged as a potentially effective intervention in delivering a high quality, consistent, safe and evidence-based health care. CPGs can either be developed by de novo synthesis or by adaptation of existing guidelines formed in another organization. Guideline recommendations are formulated based on strength of the evidence, validity, clinical relevance and patient values. Support of the organization leadership, role modeling of senior staff and involvement of stakeholders is a key to the success of implementation of guidelines. This article aims to enhance a practicing pediatrician's understanding of how guidelines are developed, disseminated, and potentially utilized. The elements of CPGs development and implementation include assessment of the need of the organization, review of current practice experience in the institute and prioritize topics that require guidelines in place. Drafting of guidelines by an experienced multi-disciplinary panel after a systematic review of literature to appraise and select recommenddations, is the cornerstone of the guidelines development. Dissemination and implementation of the drafted guidelines needs a program surveillance to track variances and provide feedback to participants, periodic review with assessment of value added, and program modification whenever necessary. This review article aims at providing the practicing pediatrician with an insight into these processes. In the last two decades, there has been an enormous interest among heath care providers, policy makers as well as patients in clinical practice guidelines (CPGs) as a tool for knowledge translation into bedside practiceDefinition of Clinical Practice Guidelines [4]. While broadly similar to CPGs, Clinical Pathways (CPs) differ by being more conscious about the sequence, timing, and provision of interventions. In fact the vast majority of CPs are extracts from CPGs. On the other hand, clinical protocols are used to outline the management steps for a single clinical condition. Clinical protocols are more precise, specific and have little scope of variation compared with CPGs. Reflecting on the existing literature and the growing recognition of the importance of guidelines, professional CPG-constructing organizations focus on standardizing terminology. In 2011, The Institute of Medicine of United States defined CPGs as: “statements that include recommendations intended to optimize patient care that are informed by a systematic review of evidence and an assessment of the benefits and harms of different care options”Benefits of CPG[7-11]. This is accomplished by adopting evidence-based recommendations and facilitating the delivery of efficient medical care that closes the gap between research and practice[12-17]. As care becomes more standardized, CPGs often lead to a reduction in health care expenditure, particularly if the CPGs support improved efficiency of care and better organization of hospital contracting. CPGs also provide a mechanism by which healthcare professionals can be made accountable for their clinical activities[6]. It may be argued that CPGs discourage independent clinical judgment and limit the autonomy of physicians. In fact, the evidence-based culture promoted by CPGs encourages physicians to consider the degree to which their current practice choices align with the best available evidence, instead of depending on expert opinion or anecdotal training biases. Ultimately the decisions, which are made by physicians who utilize CPGs, remain autonomous. There is always an option to remove patients from clinical pathways or make independent decisions within the guideline. Such variations in care should, however, be documented as variances and reviewed when the CPG is updated.The ultimate goal of CPGs is to enhance the quality of care and improve patient outcome indicatorsHow CPGs are developed?[13]. It is critical for organizations intending to develop guidelines to choose between these two methods depending on the availability of resources and expertise.CPGs are developed by either de novo guideline synthesis or by adaptation of existing guidelinesDe novo development of CPGs[4]. Careful consideration should be given to the problem being addressed and the likelihood that the proper development and implementation of CPGs will translate into tangible results in mitigating or alleviating the problem for a large number of patients. Once that is considered, attention can turn toward assembling the GDG. The GDG should be multidisciplinary and balanced, comprising a variety of methodological experts and clinicians, and populations expected to be affected by the CPG. This group consists of all stakeholders involved in the clinical care or administrative support of patients with a specific condition, such as physicians, nurses, ancillary staff, policy makers, and support groups. The GDG prepares the scene by providing access to resources and expertise and defines the clinical question(s) that will be addressed by the proposed guidelines. Well-built clinical questions are the key to evidence-based decisions. PICO  or PIPOH  formats are usually used to assemble these questions. De novo guideline development is time and labor intensive. A guideline development group (GDG) essentially starts from scratch and performs all of the necessary steps to initiate and implement a unique guideline for a specific setting. The first step in CPG development is the identification of a clinical process or condition for which a CPG has the potential to improve care in an important and lasting way. This going on line with the Institute of Medicine (IOM) recommendation, which prioritizes quality improvement initiatives according to their impact, improvability, and inclusiveness. CPGs databases such as Guideline International Network (GIN), National Guideline Clearinghouse (NGC), Scottish Intercollegiate Network (SIGN), National Institute for Health and Care Excellence (NICE) and Trip Database constitute the main sources of existing guidelines. Searching multiple databases increases the likelihood of a comprehensive review using a combination of both MeSH terms and TEXT words will identify a pool of articles on the guideline topic. Selected articles then undergo meticulous critical appraisal to formulate evidence-based recommendations that form the backbone of the proposed CPG[25]. Different score systems and models for assessment of level and grading of evidence are used to assess the quality and validate the recommendations[26-28]. Varying levels of evidence will be identified in the literature review. There is a pyramid of prioritization of these levels of evidence ranging from expert opinion at the bottom level and increasing progressively through case reports, case series, case control studies, cohort studies, randomized control trials, and eventually leading to the top of the evidence pyramid which is occupied by meta-analysis of a series of well designed randomized controlled trials through systematic review.Sources that are commonly used to conduct literature searches include the National Library of Medicine’s Medline database, PubMed, and the Cochrane Library[29-32]. GRADE has widely been perceived as having a more rigorous development process for the grading of evidence and recommendations, with adequate description of the quality, quantity and consistency of the evidence[33]. Currently, more than 65 national and international organizations have adopted the GRADE approach [34]. Recently, an expansion of GRADE system was proposed to make it more usable and reproducible[31]. Guidelines recommendations are then formulated based on consistency, clinical relevance, validity and the strength of the evidence. These recommendations are put together in a CPG draft that is reviewed by peer reviewers as well as other stakeholders including patient support groups. This draft should be pilot-tested prior to its dissemination and publication. The Grading of Recommendations Assessment, Development, and Evaluation (GRADE) instrument is developed by the GRADE Working Group that assesses both the quality of the evidence and the strength of the recommendationGuideline adaptation. It is simply a mechanism by which a guideline is produced by an institute and implemented with or without modifications in another institute. This process is referred to as “adoption” when no changes were added to the mother CPGs. To adopt a CPG, it has to be evidence based, clear, usable, and accessible. Adaptation of CPGs may entail customizing existing guidelines to suit the local context. Adaptation reduces duplication of effort and takes advantage of existing guidelines especially for organizations where resources are limited. Guideline adaptation is a systematic approach to the endorsement and/or modification of a guideline produced in one cultural and organizational setting for application in a different context[13]. The ADAPTE collaboration has developed a manual and a framework for adaptation of guidelines. This framework is divided into three phases: set up, adaptation and finalization , National Institute for Health and Care Excellence (NICE), Scottish Intercollegiate Network (SIGN), National Guideline Clearinghouse (NGC), and PubMed. ADAPTE collaboration is an international collaboration of researchers, guideline developers, and guideline implementers who aim to promote the development and use of clinical practice guidelines through the adaptation of existing guidelineslization . In the Assessment of guidelines.After selection of existing guidelines through searching of databases, the guidelines undergo extensive review and assessment regarding their quality, currency, content, consistency, acceptability and applicabilityAppraisal of guidelines[11]. This tool has been developed initially in English and currently translated to many languages. The AGREE format was refined and updated in 2009 forming AGREE 11 instrument, which is widely accepted and endorsed by international health care organizations. The AGREE 11 instrument contains 23 key items categorized in six domains  instrument was developed in 2003 by a group of guideline developers and researchers aiming at forming a tool for assessing the quality and methodology of CPGs domains  . Rate of 1 indicates that the item is poorly reported while score of 7 shows that the item is exceptionally reported and all criteria are covered. At least two appraisers independently assess and score guidelines. The average score of the guidelines is calculated according to a known formula. Following the overall assessment of the appraisers, the guideline is accepted for implementation with or without modifications or otherwise rejected. Recently, an electronic calculator of AGREE 11 rater has been developed by McMaster University[38]. When more than one CPG is identified to be relevant for implementation, the need for an objective tool to choose the best guideline arises. AGREE 11 invented a rating scale for each of its 23 items. The scale is from 1 to 7 If a decision is taken to accept a CPG with modifications, a thorough literature search and assessment of strength and level of evidence of amended recommendations is undertaken.[39]. Accepted CPG will then be reviewed by external reviewers including: policy makers, experts in the field and patient groups. A final report of CPG is drafted after pilot testing for target users. Published guidelines required review and updating every few years. Update explores the controversial issues and difficulties seen during the implementation of the guidelines and suggests changes to deal with these points. When reviewing guidelines, a fresh, detailed literature review is undertaken aiming to add new emerging evidence into the updated guidelines. A recent systematic review evaluated the quality, methodlogy, and consistency of recommendations of CPGs illustrated that more effort is needed to improve the quality of guidelines in order to improve health outcomesGuideline Implementation[40-44]. Despite this, an even greater amount of effort will be required during the dissemination and implementation of the CPGs. Once a guideline is finalized an implementation committee needs to be formed by the organization. The role of the committee is to increase the awareness of the staff and try to get everybody on board. Regular seminars, lectures and small group discussions with intended users of guidelines cannot be over emphasized[45]. These sessions explain the importance of guidelines; the road map for implementation and the possible challenges may be faced during this long journey. Support of the organization leadership and role modeling of senior staff is a key to the success of implementation of guideline. Good communications with stakeholders, meticulous follow up of implementation details improves adherence to and compliance with guidelines . Demonstration of the positive changes and closing the loop by auditing and re-auditing improves the outcome of guidelines[49]. Adherence to the guidelines can be improved by anticipating and overcoming organizational and system level barriers. Providing active feedback to the stakeholders on a recurring basis will allow the demonstration of a positive change, which has occurred following implementation. This also allows the team to close the loop by reporting the results of program audits regarding the level of compliance with the guidelines. Development of CPG is a lengthy and time-consuming process. It requires a lot of resource allocation in addition to commitment of involved personnel in order to yield a simple, concise and easy to follow guideline[52]. Utilization of computerized clinical guidelines (CCG) might improve the compliance of physicians and advance implementation and outcome of guidelines. Implementation of CCG may be integrated with more training and investment in user-friendly hardware and software. This process places the evidence in the hands of providers at the site of care by embedding electronic order sets for treatment and medications using available guidelines. This also enhances implementation strategies by increasing the awareness of staff, facilitating easy access to evidence and encouraging feedback from stakeholders[3]. Similarly, involving patients and the public in development and implementation of guidelines has a tremendous effect on the yield of guidelines[54-56]. Utilization of an electronic medical record (EMR) and computerized physician order entry (CPOE) with specific order sets can improve physician compliance in settings where this technology exists. In certain circumstances, decision support tools may be embedded in the electronic medical record as a reminder to physicians when they should consider placing specific orders, which are triggered by specific criteriaCPGs are highly important tools for delivering consistent, reliable, and safe care that decrease variation in practice among heath care professionals and promote standardization of care. It is important that physicians have a clear understanding of the entire process of guideline development and implementation in order to achieve tangible and sustained improvement in clinical practice.


There is a substantial need among clinicians for health-related, evidence-based recommendations. Evidence-based recommendations help distill research findings and aid health care providers in making clinical decisions. However, it is infeasible for providers to sort through thousands of available guidelines, and heterogeneity among recommendation developers  can make it difficult for clinicians to identify which recommendations are trustworthy, feasible, and applicable to their patient population. Even when there is broad consensus about the quality and utility of recommendations, a range of contextual factors  can impede implementation. This study examined the diffusion of evidence-based recommendations through professional societies to clinically-trained members, and explored knowledge, attitudes, beliefs, and behaviors regarding evidence-based recommendations and practice. The study had three aims: 1.) Describe the role primary care professional societies play in developing and/or disseminating evidence-based reports and recommendations; 2.) Determine if the needs of primary care providers and their professional societies for evidence-based reports and recommendations are being met; 3.) Describe the value that the federal government contributes to evidence-based practice.To achieve these aims, content analysis was used to examine transcripts from 34 semi-structured telephone interviews of leaders and members from eight health-related professional societies. Nonprobability, purposive sampling of knowledgeable experts enabled in-depth exploration of phenomena. An interview guide was developed using theory-driven concepts and theoretical frameworks, and was pilot tested using cognitive interviewing techniques. The codebook included theory-and data-driven codes and was revised through an iterative process that included intercoder reliability assessments.There were differing views on the meaning of "evidence-based", but there was broad agreement on its scientific underpinning and the importance of conducting "evidence-based practice." Professional societies can play several roles  in the promotion of evidence-based recommendations and practice. Views varied on whether the needs of primary care providers and their professional societies for evidence-based reports and recommendations were being met. Federally-sponsored recommendation developers were viewed as valuable contributors to evidence-based practice because of their objectivity, transparency, balance, methodological rigor, and prioritization. Study participants offered many suggestions for improving the development, feasibility, readability, acceptability, and dissemination of evidence-based recommendations. Participants also offered input on how federally-sponsored recommendation developers could strengthen their partnerships with stakeholders, including professional societies and their members.The issue of trust was central to participants' attitudes and beliefs; therefore, recommendation developers should integrate transparency and three factors that bolster trust  into their processes. Federally-sponsored recommendation developers should consider collaborating with professional societies in a variety of ways to develop and disseminate recommendations to facilitate evidence-based practice. The federal government can also promote the use of evidence-based recommendations by improving its guideline clearinghouse, expanding health insurance coverage to more Americans, requiring that recommendations be covered by insurance, and supporting research on point-of-care decision support tools, electronic health records, and workflow training for health providers.


Human resources for health (HRH) represents an essential component for well-functioning health systems. In recent years, there has been increased attention on the determinants of health workers (HWs) motivation, and in particular the role of financial incentives. Some countries have embarked on reforms to increase salaries and revise incentive packages, for example introducing rural allowance and/or performance-based financing. Sierra Leone provides an interesting case as, since 2009, a series of HRH reforms have been introduced, linked with the Free Healthcare Initiative.Twenty-three key informant interviews at central level and 18 interviews at district level in Bo, Kenema and Moyamba were carried out, with staff from the Ministry of Health and Sanitation, development partners and local and international NGOs. Additionally, a survey of 266 HWs and in-depth interviews with 32 HWs were carried out in the same three districts. Making use of these data and policy analyses tools, the study looks in turn at (i) decision-making at central level, (ii) implementation of HRH policies in the districts, and (iii) impact on individual HWs incentives.The case study illustrates the challenges in the process of transformation of evidence into national policies, and policies into effective practices at local level. In the case of Sierra Leone, the initial evidence-base upon which HRH reforms were introduced was relatively thin. However, these changes are generally recognized, especially by actors at central level, as ‘successful’ in addressing some of the HRH challenges as well as contributing to the Free Healthcare Initiative. At district level, other factors re-shaped the HRH strategies. In particular, the number, type and focus of external organizations present in the districts created different ‘political economy’ dynamics and contexts for the implementation of the reforms, which influenced their functioning and effects. Finally, the HRH measures eventually interacted with the existing district-specific incentive environment for HWs, affecting their performance in different ways.The analysis allows reflecting on the role and the ‘political space’ available for evidence-based policy-making in post-conflict, data-poor environments, and in particular in situations where there is tension between the role of evidence and the essentially political concerns of a brief, fast-moving ‘window of opportunity’ for reform. Moreover, moving to the local level, the study highlights how the local context and the presence of different actors and pre-existing incentives affect the actual functioning of the measures and influence their impact on HWs behaviour.