Describe the current food and nutrition policy environment in the USExamine how science is used in federal food and nutrition policymaking efforts, using the Dietary Guidelines for Americans (DGA) as an exampleDescribe strong versus weak science as well as what types of studies are most appropriate for use in policymakingDiscuss the potential effects and consequences of making policy recommendations in the absence of scientific consensus or agreementMake recommendations to support the present and ongoing development of science-based policy likely to positively impact public healthIn my over three decades of work in the field of food and nutrition, I have participated in many efforts that seek new policy initiatives in the hopes that these programs can curb rates of obesity and chronic disease and help consumers make healthier dietary choices. Because of the profound effect that many of these policies have on consumers, the food environment, federal nutrition assistance programs and subsequent policy and regulatory recommendations, it is imperative that only the strongest, best available evidence is used to set policy. This review evaluates methods by which current nutrition policies use scientific research as well as provides recommendations for how best to ensure future nutrition policies are truly science-based and likely to have a meaningful impact on public health. Specifically, this review will: The US food and nutrition policy and regulatory environment is highly active. The current administration, federal agencies and regulators are increasingly looking to policy and systems-change interventions to improve public health in America. For example, within the last five years, federal and state/local governments have instituted significant changes to the school food environment , proposeThe process by which federal agencies and policymakers consult scientific research in developing proposed regulations and policies varies, and greatly impacts the nature of the ultimate recommendations. An investigation into this process would yield important understanding about how science is used to set policy and what impact this process is likely to have on consumers.Science is used by all agencies to set nutrition policy. Yet, guidelines for how to identify, evaluate, and translate scientific research into policy recommendations vary among agencies. Policymakers generally rely on published research and consensus reports by scientific authorities and government bodies; however the manner in which research findings and report conclusions are interpreted and applied can differ from one initiative to the next. Government agencies have outlined their approach for evaluation of scientific studies to be used in decision-making. For example, NIH uses the AHRQ system  and FDA One example of a US scientific authority with significant influence is the Institute of Medicine (IOM). The IOM is one of the premier authoritative bodies that conducts health-related research and promulgates health and nutrition recommendations for policymaking purposes. IOM reports are frequently commissioned by government agencies for topics where policy and/or regulatory interest exists but research gaps remain. Some recent examples include sodium  and fronFor example, the IOM completes the Dietary Reference Intake (DRI) reports, which are considered the most reliable sources of nutrient recommendations – they inform the very basis of our current nutrition understanding. The DRIs are summarized in the 2006 volume  and are Researchers and policymakers also rely heavily on the National Health and Nutrition Examination Survey (NHANES), an ongoing group of studies designed to assess the health and nutritional status of adults and children in the United States. These studies are based on self-reporting; they consist of 24-hour dietary recalls completed through individual surveys. NHANES also collects biological data and anthropometrical data with mobile units. NHANES information is a valuable resource on changes in nutrient intake and health status of a cross-sectional group of US consumers.Critics suggest the data are flawed because of biases that accompany self-reporting measures . As one These examples raise important questions about the data that US nutrition policymakers have available to them. How confident can we be that federal dietary guidance is evidence-based when our foundational measures are outdated and significantly limited? What controls can be put in place to ensure that policies and regulations are likely to have demonstrated, positive public health impact?Healthy People objectives, and USDA Food and Nutrition Service nutrition assistance programs including the Supplemental Nutrition Assistance Program (SNAP) and the National School Lunch Program (NSLP). As a result, DGA reach and impact are extensive.Another highly influential scientific authority is the Dietary Guidelines Advisory Committee (DGAC), the appointed review committee responsible for formulating and publishing (in the form of a comprehensive report) an evidence-based review that provides scientific support for the Dietary Guidelines for Americans (DGA) policy document. The DGA are statutorily mandated ) and are a collaborative effort between the Department of Health and Human Services (HHS) and Department of Agriculture (USDA); the DGA have been published every five years since 1980. The DGA aim to provide “sound advice for making food and physical activity choices that promote good health, a healthy weight, and help prevent disease for Americans ages 2 years and over, including Americans at increased risk of chronic disease” . DGA recDietary Guidelines for Americans, take into consideration new scientific evidence and current resource documents, and then develop a report to be submitted to the Secretaries that outlines its science-based recommendations and rationale which will serve as a basis for developing the eighth edition of Dietary Guidelines for Americans” [The 2015 DGA process is underway, with the current DGAC holding meetings to share their evidence review process and findings with the general public. According to the 2015 DGAC charter, the Committee’s official responsibilities are to “examine the current ericans” .The DGAC is governed by Federal Advisory Committee Act (FACA) guidelines and an official charter and charge . While tThe DGAC process to identify, review, and evaluate available nutrition research for a variety of topics is complex and time-intensive. Typically, DGAC members are divided into subcommittees to address specific research areas based on topic importance and DGAC member expertise. In 2010, the DGAC consisted of thirteen scientists with expertise in nutrition, physical activity, food behavior and nutrition through the lifecycle. There were eight subcommittees focusing on the following dietary issues: 1) alcohol; 2) carbohydrate; 3) energy balance and weight maintenance; 4) fatty acids and cholesterol; 5) food safety and technology; 6) nutrient adequacy; 7) protein; and, 8) sodium, potassium and water. As a member of the 2010 DGAC, the author of this paper served as chair of the carbohydrate and protein subcommittees and also as a member of the energy balance and the nutrient adequacy subcommittees.The 2015 DGAC is organized somewhat differently, with fourteen scientists serving on five subcommittees: 1) Food and Nutrient Intakes, and Health: 2) Current Status and Trends; Dietary Patterns, Foods and Nutrients, and Health Outcomes; 3) Diet and Physical Activity Behavior Change; 4) Food and Physical Activity Environments; and 5) Food Sustainability and Safety. There are separate working groups for sodium, added sugar, saturated fat and physical activity. The 2015 Committee is also using expert consultants to inform its evidence reviews.One of the first steps in the DGAC evidence review process is to develop research questions regarding the relationship between diet and health outcomes, including disease risk or health benefits . These questions should reflect the research gaps identified by the previous DGAC, as well as areas of nutrition where there is new, influential evidence since the previous edition of the DGA. Once the research questions have been agreed upon, the DGAC, in concert with USDA Nutrition Evidence Library (NEL) staff, gathers the relevant available studies.The research studies are then closely examined and evaluated based on strength of study design as well as relevance of outcomes. In past years, the DGAC used the NEL evidence-based review process , a stricOnce the DGAC has determined which studies to examine for each research question, evidence conclusion statements are written. Within the NEL system, the conclusions drawn can be deemed as strong, moderate, limited, or lacking data to support them. There may also be strong evidence of no relationship. For example, strong evidence was found of no relationship between glycemic index and disease outcomes in the 2010 DGAC review . AgreeinThe DGAC process is transparent and open to input from scientists and consumers. The 2015 DGAC will hold 7 public meetings with public comments accepted throughout the process. Although the final DGAC report is not released, the committee regularly updates their progress on reviewing scientific questions at the public meetings.in vitro studies have been considered due to their relative weakness and because their findings cannot prove cause and effect in humans. Typically cross-sectional studies are only included in DGAC reviews if no stronger prospective studies are available.The evidence-based medicine (EBM) hierarchy ranks research design in the following order of strength (from highest to lowest): systematic reviews of randomized-controlled trials (RCT), RCT, prospective cohort studies, case control studies, cross-sectional studies, case series/case reports and editorials/expert opinions. RCT are the strongest study designs for determining cause and effect between a dietary exposure and a health outcome . FollowiFollowing this reasoning, food and nutrition policies would be best served if only the strongest types of evidence – perhaps RCT alone – informed their development. However, this is an unrealistic ideal as not all diet and health outcome relationships can be practically or ethically evaluated using RCT. For example, it is difficult to carry out blind food treatments in dietary studies (subjects know they are consuming an apple versus apple juice). However, such trials can work with nutrients, as nutrients can be added to food or drinks without the knowledge of the participants or investigators (the double-blind mechanism).Further, all RCT data are not created equal. RCT generally use biomarkers as outcome measures rather than disease incidence due to the length of time it takes healthy people to manifest disease symptoms. Biomarker data can be extrapolated to infer relationships regarding population health without adequately accounting for weaknesses in the relationship between the biomarker and the disease state. Ultimately, this can result in a strong study methodology being misapplied and used to make assumptions that are not actually supported by the research. For example, RCT are clear that sodium intake or excretion is directly related to blood pressure, yet prospective cohort studies show that too low sodium intakes actually increase risk of cardiovascular disease (CVD). Thus, at low levels of sodium consumption, blood pressure does not account for all of the CVD risks. Biomarker data fail to tell the complete story.In reality, many dietary recommendations are supported by evidence primarily from observational data, particularly those from prospective, cohort studies. Nutrition scientists and policymakers often underappreciate limitations of such data. Some of the limitations of observational evidence for diet-disease relationships include imprecise exposure measures, collinearity among dietary exposures, displacement/substitution effects, healthy/unhealthy consumer bias, and residual confounding. Maki et al.  recommenFor these reasons and because nutrition science is complex and changeable, it is critical that study methodology is carefully considered and applied to our interpretation of nutrition science. Ideally, observational data would be validated by stronger research methods before being used to inform policy. While observational research may be valuable to our understanding of nutrition and health, its limitations must be acknowledged. Consider the 2015 DGAC investigation into sustainable dietary patterns. This field of research is arguably in its infancy – in fact, there is no scientific consensus for even a definition of sustainability . Any susWe don’t have to travel very far back in time to witness examples of dietary guidance recommendations that were made prematurely and are now challenged as more research is introduced. Our understanding of fats has evolved considerably, with dietary recommendations now emphasizing healthy consumption of monounsaturated and polyunsaturated fats, proving that healthier dietary patterns include, rather than exclude, foods higher in fat content.More recently, it could be argued that the 2010 DGA sodium intake recommendation was made in the absence of scientific consensus. The policy document recommends that individuals over 51 years old, African Americans or those with hypertension, diabetes, or chronic kidney disease reduce their daily sodium intake to 1,500 milligrams. This applies to about half the US population, including children and the majority of adults.Sodium Intake in Populations: Assessment of Evidence report. Findings stated that recent studies “support current efforts to reduce excessive sodium intake in order to lower risk of heart disease and stroke. However, the evidence on health outcomes is not consistent with efforts that encourage lowering of dietary sodium in the general population to 1,500 mg/day. Further research may shed more light on the association between lower—1,500 to 2,300 mg—levels of sodium and health outcomes [Since then, the IOM published its outcomes .The 2010 DGA recommendations are now inconsistent with our most recent scientific understanding of sodium and health. As noted, this conflict could have been avoided if the DGA policy document had withheld such extreme guidance until more rigorous studies were fielded, reviewed, and published. Recent papers in the New England Journal of Medicine cast further doubt on our low sodium recommendations for the general public .The sodium example is important because of the aforementioned impact of DGA recommendations on other food and nutrition policies. The Final Rule for the Nutrition Standards in the National School Lunch and School Breakfast Programs  states tInaccurate and conflicting dietary guidance messages are also detrimental to consumers’ understanding of nutrition and their ability to build healthy diets. At a time when consumers are already subjected to an overabundance of nutrition and health information, government agencies should be held accountable for developing policies and regulations that are rooted in strong science, and are realistic and achievable for the majority of the population. In the case of sodium, not only is there insufficient evidence to link highly restrictive sodium intakes to improved health outcomes, but encouraging the general public to reduce intakes from the estimated current average of 3,400 mg/day to 1,500 mg/day is self-defeating and unachievable .“U.S. consensus reports have determined that inadequate evidence exists to support the direct contribution of added sugars to obesity or heart disease. Specifically, although it is recognized that sugar-sweetened beverages increase adiposity (body fat) in children Ref. 30), neither the 2010 DGA nor the IOM macronutrient report concluded that added sugars consumption from all dietary sources, in itself, increases obesity. In fact, the 2010 DGA states that added sugars do not contribute to weight gain more than any other source of calories…” [0, neitheAnother example can be seen in the use of the 2010 DGAC review to support the FDA proposal to mandate added sugars labeling on the Nutrition Facts panel . Added sFDA states that the basis for this proposed labeling requirement is the 2010 DGA recommendation to reduce intakes of added sugars to assist consumers in maintaining healthy dietary practices. The DGA rationale is that lower intakes of added sugars will result in decreased calorie intakes and increased nutrient density of individual diets, not reduced risk of adverse health outcomes. Specifically, the 2010 DGAC energy balance subcommittee investigated sugar-sweetened beverage intakes and found that “strong evidence shows that children who consume more sugar-sweetened beverages have greater adiposity (body fat) compared to those with a lower intake” . HoweverFurthermore, it is unclear why FDA proposed mandatory added sugars labeling in the absence of consumer research to demonstrate whether the change will in fact influence consumer understanding and purchasing behavior. The proposed rules even preceded the agency’s own study. Existing consumer research suggests that consumers already find aspects of the current nutrition label confusing . In addiIt is extremely difficult to reverse or change public policy, once enacted, without causing consumer confusion. There are few mechanisms available to regulators and policymakers to make adjustments that reflect new science and understanding. Furthermore, nutrition policy recommendations, once adopted, appear frequently in the media and online. Reversing consumer misunderstanding about nutrition is an incredibly difficult task; providing the public with accurate, realistic and achievable information first would go a long way in improving our understanding of nutrition and health, and ultimately contributing to improved public health outcomes.It is imperative that food and nutrition policies reflect, and do not get ahead of the strongest available scientific evidence. It is unlikely we will ever have RCT data available to answer most nutrition questions, but we should rely on our strongest designs, including prospective cohort studies. We should not accept cross-sectional studies as influential drivers of policy development. We must demand stronger scientific standards from our appointed committee members who serve on advisory IOM and DGAC panels.A transparent system that grades evidence quality would help achieve consistency in science interpretation and use across nutrition policies and regulations. Grading schemes should be vetted and discussed by experts across the wide expertise needed in dietary guidance, including nutritionists, dietitians, food scientists, physicians, applied economists, and food processors so that findings and recommendations could be supported across a wide array of credible groups. This would also help ensure that the dietary guidance messages consumers are receiving are factual and consistent.When policy recommendations are developed by committees, such as the DGAC, those committees should be comprised of a balanced and well-rounded set of perspectives and expertise. Ideally a scientific nutrition committee would not only include experts in nutrition, biochemistry, physiology, epidemiology and statistics, but also food science, food production and processing, food policy and behavior. This combination of skills would ensure that the ultimate recommendations adequately reflect our entire food system and food environment.Scientists who understand how we “learn” about nutrition must be included, even if they have worked on research supported by commodity groups or food companies. The IOM process considers bias of individual committee members and whether they have taken such strong public stands on issues that it is not possible for them to move to another position based on the deliberations of the committee. Any linkages to the food industry are criticized, yet there seems to be little concern about committee members who are closely linked to professional groups, such as American Heart Association or other advocacy groups. Improvements to our food system and public health can only be realized if we work together, respecting the strengths of all parties. Nutrition advice that is produced in such a collaborative system will more likely be translatable and realistic for the general public.Policies should reflect what is practical and likely to have the most impact on the general population. Simple, flexible and straightforward messages that are rooted in the best available evidence are likely to be most effective. For example, the majority of Americans are unlikely to be interested in or able to prioritize building sustainable diets, shop at farmers markets, or avoid processed foods, which provide nutrition and convenience for individuals with less access to full-service grocery stores and fresh produce.I would finally suggest that the US government consider elongating the DGA publication schedule. The DRI reports and nutrition labeling regulations are not updated every 5 years; instead they are reexamined when there is a sufficient level of new research to warrant a change. Without new science to review, the DGAC may choose to focus on fads and trends instead of updating the scientific data for the core areas of dietary guidance. As every DGAC wants to be bold and set new direction, nutrition science would support that first we must do no harm with our dietary guidance. Moderation and variety must be kept front and center, as well as an appreciation that a teenage active boy may need 2 or 3 times more calories than an elderly man or young child. A suggestion that all Americans should reduce sodium intakes is not sound and is potentially dangerous. Targeting certain foods and beverages, including chocolate milk, processed meats, added sugars, and even the noble potato as villains in the nutrition wars is not a science-based strategy and may need to be countered on the political front if appointed scientific review committees continue to take this approach.As described by Schneeman , science


For this to be possible we need the ideal cooling equipment/technique and a reliable temperature monitoring technique. Many techniques are available [To be fully effective, control is needed for all three phases of TTM.Induction – the how and when are to an extent disease dependent. The evidence is mainly animal based  and the Maintenance – how deep and how long? Some guidance does exist for depth on a disease process basis . Most evidence is available for post-cardiac arrest, cooling to <34°C. However, recent evidence suggests that preventing fever by cooling to 36°C is just as effective as cooling to 33°C . DuratioRewarming – often the Cinderella, but it has been long known that it can affect the neurological outcome. The question that has as yet to be answered is how fast? The consensus based on evidence available is that slow is best for the brain for both mortality and neurological outcome , whilst So how can you choose which device to use, as each seems to be effective in all three phases? Long-term use of endovascular devices for fever control is associated with a higher incidence of VTE and PE . Thus, fIn conclusion, effective temperature control is essential for TTM, this is best achieved with temperature feedback control devices, and management of complications is an essential part of the care. Is fever control the new goal for post-cardiac arrest and ischaemic stroke?IT has received an honorarium and travel costs from C. R. BARD.


Objectives To evaluate the implementation of four high evidence practices for the care of very preterm infants to assess their use and impact in routine clinical practice and whether they constitute a driver for reducing mortality and neonatal morbidity.Design Prospective multinational population based observational study.Setting 19 regions from 11 European countries covering 850 000 annual births participating in the EPICE  project.Participants 7336 infants born between 24+0 and 31+6 weeks’ gestation in 2011/12 without serious congenital anomalies and surviving to neonatal admission.Main outcome measures Combined use of four evidence based practices for infants born before 28 weeks’ gestation using an “all or none” approach: delivery in a maternity unit with appropriate level of neonatal care; administration of antenatal corticosteroids; prevention of hypothermia ; surfactant used within two hours of birth or early nasal continuous positive airway pressure. Infant outcomes were in-hospital mortality, severe neonatal morbidity at discharge, and a composite measure of death or severe morbidity, or both. We modelled associations using risk ratios, with propensity score weighting to account for potential confounding bias. Analyses were adjusted for clustering within delivery hospital.Results Only 58.3% (n=4275) of infants received all evidence based practices for which they were eligible. Infants with low gestational age, growth restriction, low Apgar scores, and who were born on the day of maternal admission to hospital were less likely to receive evidence based care. After adjustment, evidence based care was associated with lower in-hospital mortality  and in-hospital mortality or severe morbidity, or both , corresponding to an estimated 18% decrease in all deaths without an increase in severe morbidity if these interventions had been provided to all infants.Conclusions More comprehensive use of evidence based practices in perinatal medicine could result in considerable gains for very preterm infants, in terms of increased survival without severe morbidity. Very preterm infants—those born before 32 weeks’ gestation—represent fewer than 2% of all births but up to half of infant deaths.Wide disparities in the risk adjusted mortality and morbidity of very preterm infants across countries and neonatal units suggests that substantial gains are possible using current medical knowledge.13The promotion of applied evidence based care may thus be an important driver for achieving better outcomes in this high risk population, as shown in other areas of medicine.The EPICE  project established a population based cohort of very preterm infants in 19 regions in 11 European countries to investigate the use of evidence based practices and their association with outcomes in real life clinical settings. We investigated the use of four practices that have a high level of evidence for the care of very preterm infants and measured their association with mortality or neonatal morbidity, or both.The EPICE cohort is a geographically defined prospective study of all very preterm stillborn and liveborn infants from 22+0 weeks to 31+6 weeks of gestation, delivered in all public and private maternity hospitals in 19 regions in 11 European countries covering over 850 000 births annually: Belgium (Flanders), Denmark (eastern region), Estonia (entire country), France , Germany (Hesse and Saarland), Italy , the Netherlands , Poland (Wielkopolska), Portugal (Lisbon and northern region), Sweden (greater Stockholm), and the United Kingdom . Regions were selected for geographical and organisational diversity, feasibility (on-site infrastructure and expertise for implementing the protocol), and sample size considerations. Data were collected on births occurring between April 2011 and September 2012; in each region inclusions occurred over 12 months, except in France (six months).Investigators abstracted data from medical records in obstetrical and neonatal units using a pretested standardised questionnaire with common definitions. Gestational age was defined as the best obstetric assessment based on information on last menstrual period and antenatal ultrasound examinations, which are part of routine obstetrical care in all regions. When there were several estimates, we used the following hierarchy to determine gestational age for the study: in vitro fertilisation treatment, ultrasound result based on earliest estimate, last menstrual period, fundal height measurement, and neonatal assessment at birth. We cross checked inclusions against delivery ward registers or another external data source. Infants were followed up until discharge home from hospital or into long term care or death.The EPICE study included a European parent organisation in stakeholder meetings about the project’s preliminary results and analyses, including this study. EPICE maintains contact with parents in the cohort through regional newsletters, letters, and its website. A European parent organisation is part of our consortium for follow-up studies of the cohort.The study population comprised all infants without severe congenital anomalies born at 24+0 to 31+6 weeks’ gestation and admitted to a neonatal unit . We excluded infants born before 24 weeks’ gestation because there is no consensus across the regions about active treatment for these birthsWe used an all or none approach to study the use of evidence based practices. In contrast with an item by item assessment of performance or the creation of a composite measure, this approach considers whether all measures have been provided to each eligible patient.Selected indicators were: delivery in a maternity unit with appropriate neonatal care servicesOur outcomes were in-hospital mortality, defined as death before discharge home or into long term paediatric care; severe neonatal morbidity among infants discharged alive; and a composite of in-hospital mortality or severe neonatal morbidity, or both. Severe neonatal morbidity comprised intraventricular haemorrhage grade III or IV, cystic periventricular leukomalacia, retinopathy of prematurity stages III to V, and severe necrotising enterocolitis. Intraventricular haemorrhage grades were determined using Papile’s classification,32We identified clinical and healthcare factors likely to influence both the probability of receiving evidence based care and our outcomes based on the scientific literature and biological plausibility. These factors included gestational age, sex, multiple pregnancy, pregnancy complications  syndrome), small for gestational age , type of delivery , and Apgar score at five minutes. We categorised small for gestational age as less than the third and less than the 10th centile for gestational age and sex with Hadlock’s references adapted to national population values using Gardosi’s model.Most variables had low proportions of missing data: less than 1% , 1-3% , and 4-5% (Apgar score and admission to delivery time). In contrast, admission temperature was missing in 12.1% of cases (n=886). We used multiple imputations chained equations to impute missing data, based on all variables in the study.We described the use of each evidence based practice and investigated the factors associated with our all or none composite (full evidence based care). We then investigated the association of full evidence based care with our three primary outcome variables. For both analyses, we used generalised linear models to take into consideration the clustering of births within hospitals, assuming a Poisson distribution with robust standard errors to estimate risk ratios.To assess the impact of use of evidence based care on outcomes, we developed propensity scores to control for observed confounding factors. Probabilities of receiving full evidence based care were generated using logistic regression models, including investigator selected covariables and other possible confounders . Missing values for these additional variables were included as a separate category. After consideration of the propensity score using standardised differences, we assessed the balance in our covariables between infants receiving and not receiving evidence based care. The propensity score was included in our primary analyses by weighting each infant by the inverse propensity of his or her group.To check that our findings did not reflect the influence of only one of the evidence based practices, we reran our models four times, removing each indicator in turn. We also assessed the impact of non-receipt of one versus two or three, or four practices, compared with receiving all interventions, using the multivariable model with investigator selected covariables. To estimate the impact of receipt of evidence based care, we predicted cases of death and severe morbidity if all infants and almost all infants received the evidence based practices for which they were eligible by keeping coefficients and variables values constant and setting the evidence based care variable to “yes” for all infants, or “yes” for 90% of the infants. The 10% of infants assigned to continued non-evidence based care in the latter model were those with the lowest propensity scores, reflecting their likelihood of receiving evidence based care based on their characteristics.Analyses were carried out using STATA 13.0 SE .The mean gestational age in our sample was 28.7 weeks, with a mean birth weight of 1224 g , two fewer of 1.55 (1.23 to 1.95), and three or four fewer of 1.81 (1.26 to 2.61). These estimates for death or severe neonatal morbidity, or both were 1.20 (1.10 to 1.34), 1.32 , respectively. Most infants not receiving evidence based care, however, received only one fewer practice (77.0%).Table 4Only 58.3% of very preterm infants received all of four high evidence practices for which they were eligible, including delivery in a maternity unit with appropriate level of neonatal care, administration of antenatal corticosteroids, prevention of hypothermia, and surfactant used within two hours of birth or early nasal continuous positive airway pressure. In-hospital mortality as well as a combined outcome of mortality or severe neonatal morbidity, or both were lower for infants who received all components of evidence based care in our all or none measure. These results suggest that more comprehensive use of these high evidence and widely accessible practices could yield substantial gains in survival without severe morbidity for these infants at high risk.The strengths of our study are its large and heterogeneous multiregional population based sample, including public and private healthcare facilities, which ensure the generalisability of our results to a wide range of settings. The EPICE study also developed common study instruments and protocols to obtain comparable high quality data across regions. Our study also has limitations. It was challenging to define evidence based practices that were adapted to diverse cultural and organisational settings and could be identified from data systematically available in medical records; we thus selected the most liberal criteria to ensure high acceptability of our thresholds in all contexts. Others may prefer more stringent thresholds—for example, higher temperatures on admission, or administration of full courses of antenatal steroids. Although choosing conservative cut-off points overestimates the use of evidence based care, it does not invalidate our main finding of low use of these practices and the gains associated with the improvement in evidence based perinatal management. We excluded deaths on the labour ward because these were more likely to result from emergency situations where there was no opportunity to arrange a maternal transfer or to administer antenatal steroids and also because of concerns with reverse causality. However, suboptimal use of evidence based care probably contributes to the risks of death on the labour ward, leading us to underestimate total effects; future studies with data on exact timing of maternal arrival at the hospital, resuscitation practices in the delivery room, and parental opinions are needed to explore this issue further. We had some missing data on interventions and, in particular, on admission temperature. These cases may reflect less focus on hypothermia prevention and have led to an overestimation of evidence based care and an underestimation of the impact on outcomes. Finally, our study only included short term neonatal outcomes; the longer term impacts on child neurodevelopment and other measures of child and family wellbeing are an important area for further investigation.An all or none approach makes it possible to evaluate the process of care and the potential for improvement for high evidence based interventions that are already widely used. We identified four interventions for the care of very preterm infants, which are supported by evidence, linked to better health outcomes, and could be measured in our study in a standardised way. Two of these refer to the management of pregnant women with threatened preterm delivery and two to the early management of infants. This selection reflects our conviction that optimal outcomes for very preterm infants require both prenatal and postnatal interventions.Our all or none composite comprises practices that have been shown in meta-analyses of randomised controlled trials or observational studies to improve outcome and have been accepted as standard care for over a decade. For the first practice—delivery in an appropriate maternity unit—meta-analyses of observational studies have shown that birth in a maternity unit with on-site neonatal intensive care (often termed a level 3 unit) is associated with better outcomes for very preterm infants.42We found high rates for use of each practice—between 75% and 90%, corroborating network and single country studies.46While it seems surprising that such a low proportion of infants received these key elements of care, our results corroborate research from many disciplines showing the difficulty of translating effective interventions into routine clinical practice. Barriers include the doctors’ education, knowledge, and attitudes,50Our results also showed that the organisational challenges of managing unexpected deliveries contributed to low use of evidence based care for very preterm infants, although this did not explain the shortfall in use of evidence based care that existed even for inborn babies whose mothers were admitted to hospital for at least one day before their birth. Further investigation is needed to assess whether actions targeting the organisation and provision of care in situations involving unexpected or precipitous deliveries could achieve rates of the all or none composite close to 100%.Only 58.3% of very preterm infants admitted for perinatal care in 19 European regions received all of the four evidence based practices for which they were eligible; receipt of evidence based care was associated with improved survival after taking into consideration clinical and delivery factors that may affect access to care and outcomes. Maximising the number of very preterm infants who receive the complete set of these well proved practices could yield substantial gains in survival without increasing severe neonatal morbidity in survivors.Very preterm infants face high risks of mortality and severe neonatal morbidity compared with infants born at termEffective perinatal interventions exist to improve survival and reduce neonatal morbidityCountry and unit variations in very preterm outcome are large and may reflect suboptimal use of evidence based careOnly 58.3% of very preterm infants admitted for neonatal care in 19 European regions received all of the four evidence based practices for which they were eligibleThese very preterm infants had higher risk adjusted survival without severe morbidity, suggesting more comprehensive provision of evidence based practices could yield substantial gainsThe study’s findings support the growing focus on bundling effective practices to improve processes of care and to achieve best outcomes


The Canadian Society of Nephrology (CSN) was established to promote the highest quality of care for patients with renal diseases and to encourage research related to the kidney and its disorders. The CSN Clinical Practice Guideline (CPG) Committee develops guidelines with clear recommendations to influence physicians’ practice and improve the health of patients with kidney disease in Canada.In this review we describe the CSN process in prioritizing CPGs topics. We document the CSN experience using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. We then detail the CSN process in developing de novo CPGs and in adapting existing CPGs and developing accompanying commentaries. We also discuss challenges faced during this process and suggest solutions. Furthermore, we summarize the CSN effort in disseminating and implementing their guidelines. Additionally, we describe recent development and partnerships that allow evaluation of the effect of the CSN guidelines and commentaries.The CSN follows a comprehensive process in identifying priority areas to be addressed in CPGs. In 2010, the CSN adopted GRADE, which enhanced the rigor and transparency of guideline development. This process focuses on systematically identifying best available evidence and carefully assessing its quality, balancing benefits and harms, considering patients’ and societies’ values and preferences, and when possible considering resource implications. Recent partnership allows wider dissemination and implementation among end users and evaluation of the effects of CPG and commentaries on the health of Canadians. The Canadian Society of Nephrology (CSN) mission includes promoting the highest quality of care for patients with renal diseases and encouraging research related to the kidney and its disorders. The Clinical Practice Guidelines (CPG) Committee is one of five subcommittees of the CSN, with a mandate to develop CPG with clear recommendations for CSN members . BroadlyThe primary objective of the CSN CPG Committee is to develop de novo guidelines for CSN members to improve the health of patients with kidney disease in Canada. High quality CPG development requires considerable resources. While the CSN continues to develop de novo guidelines, collaboration with, and adaptation of, guidelines produced by other relevant organizations including Kidney Disease Improving Global Outcomes (KDIGO), has also been identified as a priority by the CSN membership. To this end the CPG committee has developed principles and a process for the two main activities of the Committee: 1) the development of de novo guidelines, and 2) the adaptation of existing guidelines through a review and written commentary.The CPG Committee is guided by Terms of Reference that outline roles and responsibilities of the Chair and Members. The Chair is appointed by the CSN President for a 4-year term, and also serves as a member of the CSN Council. Consideration for the CPG committee composition includes representation from other relevant CSN subcommittees, representatives from pediatrics, transplantation and those with expertise in guideline development. As the provision of renal health care services occurs at the provincial level, and in some instances the regional level, consideration of geographic representation on the CPG Committee as well as workgroups in charge of developing de novo CPG and commentaries is also important. All members are required to disclose potential conflicts of interest, including members involved in the working groups for developing de novo CPGs as well as commentaries on existing guidelines. The conflict of interest disclosures are published along with the manuscripts.In this review we describe the CSN process of adapting existing CPG and developing accompanying commentaries, and document the CSN process and experience of creating de novo CPG using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach .Surveys of the CSN membership  were undertaken in 2009 and 2013 to get members’ input on the need for guidelines to be produced by the CSN, and the focus of future guidelines. The survey was sent via email to members using Fuildsurveys, and included a combination of multiple choice and open ended questions. In the 2009 survey, 84% of respondents felt that the CSN should continue to produce guidelines, with the majority (72%) indicating that the CSN should not duplicate guidelines produced by other organizations such as KDIGO. A CPG for the management of intensive hemodialysis was identified as a priority topic area with the 2009 survey, and has since been completed [In general the CSN CPGs and Commentaries focus on the effect of an intervention  on clinical outcomes that are important to patients  and not on surrogate outcomes . The CSN CPG developers and Commentary writers are cautious not to draw strong conclusions if an intervention has not been shown to influence important patient outcomes. Since the CSN has adopted the GRADE process its CPGs and Commentaries have been guided by a systematic and transparent “Evidence-to-Recommendations” framework; that includes the following factors: 1) emphasis on available evidence and its quality; 2) balance of benefits and harms; 3) patients’ and societies’ values and preferences and 4) resource implications and feasibility considerations. The quality of the body of evidence is an important consideration as it refers to the confidence guideline developers can place in the available evidence. In other words, the guideline panel confidence that an additional body of evidence addressing the same question is unlikely to change what we already know. Patients’ and societies’ values and preferences are another critical factor that is considered in CSN CPGs and commentaries, with a focus on the specific values in the Canadian context. Where possible resource, feasibility, and cost considerations (from a Canadian perspective), are included, such as the use of Canadian micro-costing data to show resource implications of a recommendation in the Canadian healthcare setting .The CSN has developed multiple CPGs since it was established. The CSN process to develop CPGs since adopting GRADE include the following steps:Priority setting to determine CPG topics.Choose CPG chair/s and establish the working group with representatives from different specialties , allied health , different practice settings  and different geographical and provincial areas. Methodological and guideline development expertise are also considerations when composing CPG working groups.Establish CPG development processes and means of communications with clear deadlines for each step.Identify target audience and specific topics selection including a focus on treatment vs. diagnosis or a specific populationInvolve end users and stakeholders. This has become a focus for the CSN to ensure CPGs meet the needs of users by developing productive and effective partnerships.Generate and select specific answerable questions using PICO format  when appropriate.Select outcomes and intervention that are important to patients.Conduct a systematic search for relevant evidence including registries of trials and contacting authors of unpublished results that may inform the guidelines.http://www.guidelinedevelopment.org) .Summarize the body of evidence and generate additional information. For example, in the intensive hemodialysis CPG, we surveyed programs to systematically collect information about their experience with the use of “closed connector” devices in patients using a central venous catheter as their access due to paucity of published data. Summarizing the evidence is done using GRADE summary tables (GRADE Evidence Profiles) that can be produced using the Guideline Development Tool   with clinical and content expertise, relevant physician specialty groups  and members of the allied health community , with consideration for geographical representation across Canada.The working group identifies recommendations that require further exposition. Examples of the recommendation that are relevant for interpretation and application may include “challenging” the evidence on which recommendations are based, consideration of resource constraints (frequently excluded from guideline development), and consideration of factors specific to funding and delivery of health care in Canada. A discussion of the “Implications for Canadian Health Care” is created for each identified recommendation. Additionally, recommendations that can be the basis for targeted knowledge translation activities relevant to the local, regional and national context are highlighted.Existing guidelines are assessed using the Appraisal of Guidelines Research and Evaluation (AGREE II)  instrumeThe CSN CPG arranges peer review of the commentary with up to three experts in the field, following which the working group undertakes revisions based on reviewer comments.Dissemination and implementation of the Commentaries are as outlined in a later section, including publication in a nephrology journal.Some may argue that in certain situations CPGs should not be developed either due to the lack of high quality evidence, or even when high quality evidence exists, when there is close balance between benefits and harms and lack of clear evidence about patients’ values in relations to these benefits or harms. Although guidance is typically more needed when evidence is of low quality, some are concerned that developing recommendations may be misconceived as indorsing this low quality evidence. Hence, outlining the quality of evidence when it is poor is crucial to prevent the promotion of false confidence regarding the best management strategies.It is generally well recognized that nephrology lags behind other medical sub-specialties in the availability of clinical trials to inform decision making, and hence guidelines. The use of the GRADE process is particularly beneficial in this regard, given the transparency of the process and summary of available evidence. It was clear that reviewers of the CSN CPGs appreciated this transparency and found particular value in the “Evidence-to-Recommendation” tables. In addition to summarizing the evidence, these evidence summaries highlight the shortcomings of the evidence, emphasize the knowledge gaps and identify priorities for future research. There is an emphasis not only on identifying knowledge gaps of the effects of specific interventions but also regarding unknown patients’ values and preferences, physicians’ perceptions, and feasibility and resources consideration. Additionally, comprehensive evidence review and consensus regarding the recommendations promoted valuable new research collaborations to conceive new studies, and strengthened the position of different groups in applying for funding opportunities to support these new studies. An example of an evidence-to-recommendations table is published as a supplementary material of the CSN intensive hemodialysis and timing the initiation of dialysis guidelines , 5.There remain challenges in applying a transparent and rigorous process such as GRADE. These challenges include need for: 1) resources, and in particular those needed to conduct well done systematic reviews, 2) methodological expertise to synthesize the body of evidence and summarize it including experience with appraising and summarizing evidence across different study design, 3) experience in the process used to develop the CPGs such as GRADE, 4) training of the guideline panels to explain the process, 5) communication of the process between clinical and methodological experts to identify and critically appraise the body of the evidence.The CSN has realized the importance of addressing these challenges by: 1) providing funds to facilitate conducting comprehensive high quality systematic reviews. A process that proved beneficial for the development of CPG despite the limited amount of this funding. The by-product of this process is the opportunity for the guideline panels to coauthor high impact publications and publish in international journals, which offers an additional professional and intellectual incentive and facilitates academic advancement, 2) encouraging the guideline groups to focus the scope of the CPG and maintain the rigor rather than attempting to address a wide range of clinical questions without the availability of the needed resources including panel members time, 3) providing GRADE training to the CSN CPG committee members, panels of different CPG, and members of the CSN utilizing a variety of options including online webinars and in person workshops, 4) ensuring that each guideline working group has clinical and methodological experts, 5) including less experienced panel members in each working group to guide them into the process, 6) facilitating good communication among panel members along the process of developing CPGs including supporting conference calls and in person meetings at national and international nephrology conferences including the CSN annual meeting, 7) reviewing the process after the guideline has been published to identify areas that can be modified in future guideline development. The CSN remains open to incorporate new methodological advances in the area of CPGs development and to help its members keep up to date.An active implementation process is required to ensure uptake of guidelines and commentaries. Dissemination of the CSN CPG and Commentaries is done through a variety of approaches including publication in peer-reviewed nephrology journals, posting of the full documents on the CSN website with relevant links, posting of summaries and links to other nephrology guideline sites and presentation of the CPG and commentaries in appropriate local, national and international forums. The CSN CPG also partners with the Canadian Kidney Knowledge Translation and Generation Network (CANN-NET) , a natioThe CSN CPGs are viewed favorably internationally due to the rigor, transparency and focused scope. Recently the Saudi Ministry of Health adapted the CSN CPG on timing the initiation of chronic dialysis. The evidence tables summarizing available evidence and discussing its strength simplified the adaptation process. Additionally, the “evidence-to-recommendations” framework facilitated incorporation of local values, preferences and resources that are unique to the Saudi context. We anticipate that use of GRADE will allow other international groups to easily adopt or adapt the CSN recommendations and further facilitates their dissemination.In addition to dissemination and implementation, evaluation of the impact of the guidelines and commentaries on physician practice and patient outcomes is also a CSN priority. In the past, a formal evaluation of the effect of the guidelines and commentaries on practice change has not been undertaken. However through CANN-NET, and with the availability of data from the Canadian Organ Replacement Registry (CORR), the effectiveness of these knowledge translation activities on process of care and clinical outcomes can be tracked. Canada is fortunate to having universal healthcare with fairly robust health services data at provincial and national level.The CSN follows a comprehensive process in developing de novo CPGs and writing Commentaries. In 2010, the CSN adopted GRADE, which enhanced the rigor and transparency of guideline development. This process focuses on systematically identifying all available evidence and carefully assessing its quality, balancing all important patient outcomes including benefits and harms, considering patients’ and societies’ values and preferences, and when possible considering feasibility and resource implications. The CSN also follows a comprehensive and transparent process in identifying priority areas to be addressed in CPGs. This process includes surveying its members and its collaborators’ members to address questions that are of relevance to the national nephrology community. Some of these questions have been identified as priority questions in other countries and led to adaptation of the CSN CPG internationally. One very interesting development is the creation of new partnerships allowing wider dissemination and implementation among end users. Moreover, these partnerships permit evaluating the effects of different knowledge translation products like CPG and commentaries on the health of Canadians. Following this process clearly addresses the CSN mission of promoting the highest quality of care for patients with kidney disease and encouraging research related to the kidney and its disorders.


This paper addresses the use of systematic review and meta-analysis to evaluate the strength of evidence for health benefits of probiotic foods, especially relating to health claim substantiation in the European Union. A systematic review is a protocol-driven, transparent and replicable approach, widely accepted in a number of scientific fields, and used by many policy-setting organizations to evaluate the strength of evidence to answer a focused research question. Many systematic reviews have been published on the broad category of probiotics for many different outcomes. Some of these reviews have been criticized for including poor quality studies, pooling heterogeneous study results, and not considering publication bias. Well-designed and -conducted systematic reviews should address such issues. Systematic reviews of probiotics have an additional challenge – rarely addressed in published reviews - in that there must be a scientifically sound basis for combining evidence on different strains, species or genera. The European Food Safety Authority (EFSA) is increasingly adopting the systematic review methodology. It remains to be seen how health claims supported by systematic reviews are evaluated within the EFSA approval process. The EFSA Panel on Dietetic Products, Nutrition and Allergies deems randomized trials to be the best approach to generating evidence about the effects of foods on health outcomes. They also acknowledge that systematic reviews  are the best approach to assess the totality of the evidence. It is reasonable to use these well-established methods to assess objectively the strength of evidence for a probiotic health claim. Use of the methods to combine results on more than a single strain or defined blend of strains will require a rationale that the different probiotics are substantively similar, either in identity or in their mode of action. Probiotics are live microorganisms that, when administered in adequate amounts, confer a health benefit on the host . AlthougOne tool that can provide the most objective assessment of evidence on a given endpoint is a systematic review (SR), with or without a meta-analysis (MA) . By systematically and rigorously identifying and critiquing as much of the available evidence for a pre-specified intervention, comparator and endpoint as possible, an assessment of the relevant body of evidence can be made. Based on this assessment, it may be possible to draw conclusions about the strength of the evidence for a specific intervention versus a specific comparator. This is a well-established approach that has been used in many fields including health and social care  and has Our focus is not to build a case for any specific probiotic health claim, but to discuss the scientific basis for appropriate application of the systematic review and meta-analysis approach to assessing the totality within the field of probiotics. Although the literature is replete with meta-analyses where data on different strains and probiotic preparations have been pooled, critics hold that such techniques should be reserved for data on the same probiotic strain or strain blend. We propose that in certain well-considered situations, it is possible to pool results on different probiotics. Developing a scientific rationale based on substantial identity or common modes of action may justify such an approach. Although some probiotic functions are certainly strain-specific, we suggest conversely that not all probiotics function differently. When it is possible to link different probiotic strains by a common mechanism of action, pooling data on these strains may be appropriate.Step 1: Framing the questionStep 2: Identifying potentially relevant studiesStep 3: Study selectionStep 4: Data extractionStep 5: Quality assessmentStep 6: Synthesizing the evidenceStep 7: Interpreting the findingsA SR is a review that follows a pre-specified protocol to identify, select, critique, synthesize and summarize evidence to answer a focused research question -24. GenePopulation of interest, Intervention(s) received by the population, Comparator interventions, Outcome(s) (or endpoints), and Study types of interest. This type of conceptual breakdown of the research question is known as ‘PICOS’. It is generally recommended that the protocol be peer-reviewed by external reviewers and then registered  it may be possible to quantitatively synthesize the outcomes using statistical techniques such as meta-analysis (MA). MA pools results from different studies to obtain an average estimate of effect across studies. In simple terms, studies may be weighted so that larger studies have a greater impact on the pooled result than smaller studies. This method increases the statistical power to detect a difference in effect that may not be detected in individual studies, and increases the precision of the estimate of the effect of the intervention ,24. Inevce alone . Sensitice alone . Meta-reThe last step of the SR process includes interpretation of the findings in the context of the quality of the body of evidence ,27. If tWhen reporting a SR, transparent reporting of the review methods and assumptions should be the main objective. SRs should conform to reporting guidance such as the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) framework . IdeallyWas the intervention defined appropriately?Was the search extensive and was publication bias assessed? SRs which have not searched widely for studies and which have not assessed publication bias may produce biased results.Were results combined appropriately?Were analyses conducted to assess study quality? SRs and MAs that do not explore the effect of including lower quality studies run the risk of providing unreliable results.The SR process is used in several arenas to assess the evidence base in support of regulatory and policy recommendations. Despite the robustness of SR methodology for assessing a body of evidence, we identify four issues relating to the use of meta-analysis in the field of probiotics:Lactobacillus, Bifidobacterium, Propionibacterium, Streptococcus and Bacillus. Strains of the yeast, Saccharomyces cerevisiae (biovariant boulardii), are also used.Defining the intervention can be a particular challenge for SRs of probiotics, which comprise a broad range of different genera, species and strains of live microbes. An intervention, or the class of substance (such as a probiotic) that is the subject of the review, does not have to be a single substance. But in the case of grouping multiple substances into one class, there must be a sound rationale that the members of the class as defined are expected to function in a similar manner Table . A probiin vitro or animal studies, clearly indicate that different strains of the same species may behave differently. Van Hemert et al. [Lactobacillus plantarum strains and found a 14-fold difference in the strains’ ability to induce peripheral blood mononuclear cells to secrete interleukin-10. Similar strain-specific responses are seen in many other in vitro and animal studies that assess biological properties of different probiotics. The body of literature in human studies reveals few head-to-head comparisons of probiotics. A few examples are available in the literature where different probiotic products or different genera or species are compared. Canani et al. [Lactobacillus salivarius strain and a Bifidobacterium infantis strain in subjects with irritable bowel syndrome and found that only the B. infantis strain significantly alleviated symptoms. Such studies show that in some cases, different clinical outcomes result from using different strains. However, in other conditions, different strains of probiotics have a similar impact on a particular clinical endpoint. This is the case with necrotizing enterocolitis [L. rhamnosus GG [S. boulardii [L. reuteri [Observations by early researchers on probiotic functionality, especially with regard to outcomes from t et al.  illustrai et al.  comparedi et al.  comparedocolitis , antibioocolitis , where Socolitis . Some SRocolitis . A few Snosus GG ,46, S. boulardii  or L. re reuteri .Bifidobacterium animalis subsp. lactis where evidence shows little diversity in the members of this subspecies. Lee and O’Sullivan state that four strains of B. animalis subsp. lactis exhibited >99% sequence identity over their entire genomes, indicating a very closely related group [B. lactis strains are indistinguishable. Barrangou et al. [B. lactis strains had essentially the same strain-specific pattern as indicated by a random amplified polymorphic DNA technique. Such taxonomic grouping may, however, be criticized in the absence of information on the mechanism of action for the benefit, since it is possible that the part of the genome that is not shared encodes the functional activity.A scientific justification may exist for grouping multiple strains, species or even genera of probiotics into one class of intervention for the purpose of conducting a SR and MA. It may be appropriate to group multiple strains of a narrow taxonomic cluster, such as ed group . Masco eed group  have alsu et al.  also fouu et al.  showed tLactobacillus bulgaricus and Streptococcus thermophilus) could improve lactose digestion [Lactobacillus genus, as mixed results have been reported among other tested Lactobacillus species. In another example, it is conceivable that a class could be defined as members of a specific taxonomic cluster that also produce certain levels of a certain metabolite in vivo, such as specific short chain fatty acids.It may also be appropriate to propose that several probiotics might be legitimately grouped based on the production of common “structures”, such as peptidoglycan, flagellae or exopolysaccharides, known to evoke specific physiological responses in the host or could be grouped based on a common mechanism of action. This latter example is the case with the yogurt cultures, where aiding lactose digestion is linked to the microbial production of beta-galactosidase. EFSA approved the health claim that “yogurt cultures”  that enable a specific health benefit, they should not be grouped in a MA since results from one strain cannot inform (or predict) effects of another strain of the same genus or species. However, if there is a scientifically sound basis for defining a class that encompasses different strains, information on all members of that class can be used to provide a more comprehensive set of supporting data. If a study does not show an effect for one of the strains in the class, this may simply represent a study with null results, some of which will be expected in any body of research. If a strain is not represented in the collection of reviewed studies, it also does not mean that it should be excluded from the general conclusions on the benefit or otherwise of that class. Alternatively, subgroup analysis that shows efficacy for specific members of the defined class may enable researchers to refine the class more narrowly. Of note to this discussion is that in theory, EFSA accepts pooling data from studies of a well-defined food constituent that is responsible for a claimed effect when given at the appropriate dose [When clustering different probiotics into one intervention group, the conclusions of the SR could only apply to the intervention class as defined. Therefore, if the intervention was defined as the subspecies, ate dose . HoweverChallenges emerge if one intends to use pooled data from studies on different strains clustered into one intervention group as part of a dossier to substantiate an EU health claim. One pillar of such a dossier is characterization of the substance under consideration. This section clearly defines what food or food ingredient is the subject of the health claim. EFSA requires that characterization is very specific. A strategy for definition of the substance under review must be developed if data from different strains, potentially delivered in different matrices, are to be combined in a MA. It is possible that a SR for a defined set of probiotics can be used as evidence for a dossier for one specific member of that class. Then the characterization information should be specific for that one member.Although the SR might be useful to bring the studies together, the MA should not be undertaken when there is likely to be serious publication bias, since this is likely to provide an unreliable estimate of the true effect size . Publicaa priori).When deciding whether to conduct a MA, input from a topic expert is often helpful to ascertain whether it is appropriate to combine the results of the identified studies . Currentonly poor quality studies in MA  should be avoided, as they may cast doubt on any subsequent conclusions, or even hinder any correct interpretation.MAs of poor quality studies may result in an erroneous interpretation . DiffereIn 2010, EFSA published its guidance on the conduct of SRs of relevance to food and feed safety . EFSA noa priori in clear eligibility criteria for studies to be included in the review.The EFSA guidance  clearly In cases where there is a large quantity of evidence, the SR method can formally and systematically summarize that evidence (with MA where data permit) and provide more precise estimates of effects than an individual study can provide. The value of the SR approach also lies in its presentation of all of the available evidence with an assessment of the quality of that evidence: the strengths and limitations of the evidence base can thus be seen in a clearer way. The more controversial the topic, the more important it is for the SR process to be described in detail, so that the methods can be understood and alternative approaches discussed. The EFSA guidance provides a clear outline of a suitable process for conducting a SR and some recommendations on the reporting of a SR, without providing a formal reporting structure such as the PRISMA guidance described earlier. In the recent framework tender documents , suppliea priori objectives for the SR and the results identified. Again, adhering to this approach and documenting the rationale in full will contribute to the rigour and objectivity of a particular SR.The use of MA within SRs is guided by the suitability of the data for pooling; the considerations informing a decision to use MA are described in Appendix E of the EFSA guidance . AlthougIn Europe, Article 6 of EC Regulation 1924/2006 states that health claims for food labeling must be based on and substantiated by ‘generally accepted scientific evidence’ . In ordeThe EFSA ‘General guidance for Article 13.1, 13.5 and 14 health claims evaluation’  indicateWhile the NDA panel did not propose a formula for how many or what type of studies are needed to substantiate a claim, the reproducibility of the effect of the food as indicated by consistency between studies is an important consideration for their final assessment. Thus, a comprehensive review of the data from human studies addressing the specific relationship between the food and the claimed effect is required from the applicant.The NDA panel guidelines make it clear that in evaluating and weighing the evidence to substantiate health claims on foods, SR and MA can play an important role . EFSA asStudies are underpowered due to a smaller effect size than predicted, so none of the studies reaches statistical significance. But, when data are analyzed together as part of a MA, a statistically significant average result is obtained.One pivotal study has been conducted which is in favor of the intervention, and other studies with null results have been published. This reflects a genuine evidence base and the review of all contributing studies should allow exploration of heterogeneity and provide information on the true direction and size of the health benefit. All studies, with all results, contribute to an overall picture of the effect.a priori and perform randomized trials with the appropriate population subset, or to unpick the studies into the relevant subgroups. On the other hand, acceptance of the health claim has the potential to benefit a subset of the population consuming the product, which is of benefit to those consumers. Subgroup analyses defined a priori may enable identification of the responding subgroup and convincing evidence in support of a claim for the subgroup may be revealed.Studies are underpowered due a heterogeneous population within each study, comprising responders and non-responders, which cancel each other out in the analysis of the individual study. The best approach to this situation is to better identify the target population The incidence of the health endpoint is low (such as incidence of flu during the winter season) and very large sample sizes among the study population are required. Such sample sizes are better achieved by pooling the results of several randomized trials, providing that these studies collectively provide sufficient power.Many statistically significantly positive randomized trials exist, but no two trials investigate the same strain. If there is a scientifically valid basis to expect that a group of different strains would function similarly on an endpoint, then they can be reasonably grouped into one intervention for a meta-analysis, and the resulting meta-analysis would be sufficient evidence to support a health claim.The NDA panel does require that the SR provides convincing evidence on the consistency and reproducibility of the effect when analyzing the totality of the data. EFSA considers randomized trials as the best tools to generate evidence on the effects of interventions and considers SR and MA to be the best tools to evaluate the totality of the evidence and inform a final opinion. MA and SR may be useful to address the following scenarios that we envision could emerge in submitted dossiers:We recognize that SRs are only one input to a decision-making process regarding formulation of policy derived from evidence. The health technology assessment process, for example, also considers information on the economic and legal aspects of competing interventions.In population P, does intervention I affect outcome O when assessed using comparator C?SR and MA are transparent and rigorous approaches to synthesizing evidence. It is widely accepted in many scientific disciplines and by many policy-setting organizations as the best way to evaluate the strength of evidence available to answer a focused question. EFSA guidance acknowledges the validity of well-conducted SRs for closed-framed questions, which seems appropriate for assessing evidence for probiotics: EFSA endorses the SR process to inform their judgment when deciding health claims, as observed with the decision on maternal folate intake and reduced risk of neural tube defects. This suggests the method is also suitable for probiotic health claims.Applying the SR approach to probiotics to obtain evidence on a single strain  or on a single, defined multi-strain probiotic  is scientifically justifiable. Applying the SR approach to studies conducted on a broader range of probiotics  requires a scientifically valid justification for definition of the class. However, EFSA precedent has allowed such ‘clustering’ of all yogurt cultures into a category of food that can improve lactose digestion, even though the possibility exists that a particular strain may not deliver adequate lactase to improve lactose digestion. EFSA seems to recognize that available evidence provides a reasonable certainty that yogurt cultures will provide this benefit. However, 100% certainty is not possible and should not be required.Lactobacillus, Bifidobacterium, E. coli, Saccharomyces and others. If the overall effect is positive, the conclusion from such reviews has generally been that ‘probiotics’ are effective for the particular indication. However, they have not concluded that every possible probiotic strain will necessarily be effective, and they have generally acknowledged that effects may be due to only specific, tested strains. A strict application of the SR approach should enable application of the conclusions of the review to every member of the class as defined.The majority of SRs published on probiotics to date has been conducted on a broad group of live microorganisms without stated justification for clustering into one class. In many cases, this includes studies using Procedures within EFSA, including their approach to definition and characterization of the substance under review, presents a challenge for use of the SR and MA approaches on a defined class of different strains of probiotics for primary health claim substantiation.In conclusion, SR and MA represent a well-developed and widely applied means to evaluate the strength of research evidence and should be acceptable by EFSA for substantiating probiotic claims. Use of SR to combine studies on multiple probiotic strains, however, requires a valid scientific rationale that combining evidence from different strains is biologically and physiologically justified.


Background: Public health is committed to evidence-based practice, yet there has been minimal discussion of how to apply an evidence-based practice framework to climate change adaptation.Objectives: Our goal was to review the literature on evidence-based public health (EBPH), to determine whether it can be applied to climate change adaptation, and to consider how emphasizing evidence-based practice may influence research and practice decisions related to public health adaptation to climate change.Methods: We conducted a substantive review of EBPH, identified a consensus EBPH framework, and modified it to support an EBPH approach to climate change adaptation. We applied the framework to an example and considered implications for stakeholders.Discussion: A modified EBPH framework can accommodate the wide range of exposures, outcomes, and modes of inquiry associated with climate change adaptation and the variety of settings in which adaptation activities will be pursued. Several factors currently limit application of the framework, including a lack of higher-level evidence of intervention efficacy and a lack of guidelines for reporting climate change health impact projections. To enhance the evidence base, there must be increased attention to designing, evaluating, and reporting adaptation interventions; standardized health impact projection reporting; and increased attention to knowledge translation. This approach has implications for funders, researchers, journal editors, practitioners, and policy makers.Conclusions: The current approach to EBPH can, with modifications, support climate change adaptation activities, but there is little evidence regarding interventions and knowledge translation, and guidelines for projecting health impacts are lacking. Realizing the goal of an evidence-based approach will require systematic, coordinated efforts among various stakeholders.http://dx.doi.org/10.1289/ehp.1307396Citation: Hess JJ, Eidson M, Tlumak JE, Raab KK, Luber G. 2014. An evidence-based public health approach to climate change adaptation. Environ Health Perspect 122:1177–1186;  For public health, climate change has gone from a possible concern to what appears to be an actual threat in just over two decades. When the health impacts of climate change were first broached in the health literature, they were referred to as a possible eventuality . ClimateAs climatic shifts have become increasingly dramatic in recent years , public Whereas evidence has always been brought to bear in public health practice, the formal discipline of EBPH has evolved relatively recently and is now generally considered standard public health practice . Here weHistory and scope. EBPH has been defined as “the development, implementation, and evaluation of effective programs and policies in public health through application of principles of scientific reasoning” . EBPH theorists and practitioners have considered how evidence generation and application differ in the domain of public health compared with EBM. In response, EBPH has evolved to incorporate a framework with less emphasis on evidence hierarchy and more emphasis on knowledge translation—the process of synthesizing, disseminating, and applying knowledge to improve public health practice . As partTypes of evidence used in EBPH and relevant reporting guidelines. Review and evaluation of available evidence is a key requirement of EBPH  lists almost 200 health study reporting guidelines  Network website  issues arising from the need to reconcile established approaches to EBPH and to CCA in public health, and b) issues arising from prioritizing an evidence-based approach. In the remainder of this section, we consider the first subset, specifically the questions of whether the established EBPH framework needs to be modified to accommodate established conventions of CCA in public health, how a modified framework might be applied, and whether such a framework would resonate with existing approaches. Following that discussion, we explore the second subset and examine how prioritizing an EBPH approach to CCA might affect programming, research, and policy making going forward.Several issues arise in particular when considering how to apply EBPH to public health adaptation efforts. These issues can be grouped into two subsets: Modification of the established EBPH framework. There is considerable literature on the process of CCA in public health, which entails a process of vulnerability assessment; identification of how relevant exposures and population vulnerabilities are likely to shift; and preparation, implementation, and evaluation of adaptation plans , Google Scholar (http://scholar.google.com/), and Google (http://google.com/) for the following terms: “heat wave,” “heat event,” “extreme heat,” “extreme temperature,” “temperature event,” “intervention,” “adaptation,” “mitigation,” “warning,” “advisory,” “cooling center,” and “cool center.” Studies were used for Services . KeywordThe example highlights several important dimensions of risks related to extreme heat in the region and also significant knowledge gaps. The surveyed literature revealed that there are several dimensions to the hazard in question, including extreme heat event magnitude, duration, and the role of temperature variability in population vulnerability. It also highlighted the diversity of health risks associated with this one relatively narrowly defined exposure. Evident also was the potential for cascading or compound risks, such as blackouts during extreme heat events, and that these events have their own distinct risk profiles.http://summaries.cochrane.org/) or the Guide to Community Preventive Services , but there is considerably less regionally specific information regarding intervention implementation and efficacy [both generally and specific to the identified decision space (step 2)], which affects successive steps in the framework (steps 4–6).Third, although Fourth, and perhaps most important, there is a dearth of relevant evidence overall, particularly in the areas of intervention efficacy and implementation. We chose the example of extreme heat in New York given the resources and studies available for such a review in that area. Nevertheless, despite a high level of climate and health expertise in New York’s academic and public sectors and a substantial commitment on the part of the regional governments to characterize and prepare for risks associated with climate change, evidence that can be used to select specific interventions for extreme heat and to guide their implementation is relatively rare. A recent systematic review of evidence related to other climate-sensitive diseases found little evidence related to interventions to reduce impacts for other climate-sensitive conditions, as well . Thus, aThe extreme heat example is meant to be illustrative, but it is important to note that applying the framework to a different climate-sensitive health concern, for example, air pollution, would likely yield a very different set of findings. There would be more (or less) evidence in each category, different levels of agreement in the identified evidence for both problem assessment and adaptation interventions, and different intervention priorities. In some cases, for example, vector-borne and zoonotic diseases, potential harms from interventions will need to be considered alongside potential benefits and appropriate risk–benefit decisions made. Space considerations preclude exploration of other examples here.Integrating the revised framework into other existing approaches. Although the above-mentioned review by Guide to Community Preventive Services  that will be increasingly important as adaptation activities come online and the need for evidence of effective adaptation policies becomes more important .Regardless of the underlying framework used, committing to an evidence-based approach to CCA in public health has several potential implications and is likely to pose several significant challenges, as other authors have noted e.g., . Some ofGuideline adherence. Consensus reporting guidelines, particularly if incorporated into editorial standards, should translate into better reporting of study design elements and findings, thereby enhancing the quality of studies adhering to reporting guidelines as well as study intercomparability and allowing for systematic review using Grading of Recommendations Assessment, Development and Evaluation (GRADE) scoring methods  functions. Researchers projecting climate change health impacts have taken a wide variety of approaches, some dynamic, some equilibrium, and some mechanistic, and as a result, approaches to model construction, sensitivity testing of results, and reporting vary. Most work to date has focused on various scenarios of heat exposure (http://www.consort-statement.org/)] or sponsored by a leading public health professional association or funder.exposure , althougexposure , infectiexposure , and malexposure . The worexposure ] to faciKnowledge translation guidance. The literature on knowledge translation is growing alongside the literature on climate and health. As the need for CCA becomes more apparent and a greater number of adaptation decisions affecting public health are made, it will be important to capture the rationale for, context of, and results of these decisions in the literature. As Coordinated attention to adopting an evidence-based approach. Climate change is a significant and looming public health threat. Whereas evidence related to projected health impacts is mounting, evidence related to adaptation interventions is lacking. A recent systematic review of evidence of intervention efficacy related to several climate-sensitive conditions found significant gaps in primary evidence, particularly for areas such as extreme weather events, droughts, floods, air pollution, and food security, as well as variability in prior assessments of the evidence that is available  PDFClick here for additional data file.


This eve status  could he Many traditional and contemporary theories of motor learning emphasize the apparently “spontaneous” nature of skilled performance. For example, reflective awareness of their bodily selves when they consider their intentions or actions and assess whether they are appropriate to a certain situation. By contrast, pre-reflective awareness occurs when we are immersed in an activity but our attention is not on our bodily selves. However, in the latter case, Interestingly, evidence suggests that many skilled performers remain “somaesthetically” aware . Indeed, few studies have sought to capture athletes’ attentional processes over time  or across different situations . Given the dearth of studies in psychology on the temporal and/or contextual dynamics of attentional processes, we question the degree to which available evidence supports the received wisdom that conscious attention will Against this background, we argue that there is ample empirical evidence that “continuous improvement” at the elite level is heavily dependent upon the performer’s ability to effectively utilize reflective modes of bodily awareness. Skill-focused attention (including conscious bodily awareness) appears to be a key feature of skilled performance because athletes operating at this level are driven by the desire to learn “new and better techniques” , p. 127.Somaesthetic awareness appears to play an important role in “continuous improvement” by allowing performers to identify movements that are causing them discomfort or outcomes which are unusual or undesirable. Indeed, evidence suggests that these forms of self- awareness are important mediators of “flow” or optimal competitive performance in sport. On the basis of their pioneering research on flow in sport, Although some performers may choose to reinvest conscious attention by adjusting movement in the performance context, others may choose to use cue words as “instructional nudges”  that emphasize the proceduralized nature of skilled performance, we may require theoretical accounts which focus on the learning , 2009 thlearning , p. 676.Additionally, we propose that the AIR model may help researchers to interpret the accumulating body of empirical evidence which suggests that skilled performers seek to avoid automaticity by ensuring that performance remains open to strategic control in both the practice and performance context. In another study, In summary, a significant volume of evidence shows that skilled performers’ foci of attention may change dramatically over the course of a competitive season  or during a competitive event . Unfortunately, as most studies of attentional processes in psychology are limited to static snapshots of the phenomena of interest, they shed little light on the dynamical nature of attention. Against this background, the current paper has argued how 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.