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Elevated blood pressure, or hypertension, is the leading cause of preventable deaths globally. Diets high in sodium (predominantly sodium chloride) and low in potassium contribute to elevated blood pressure. The WHO recommends decreasing mean population sodium intake through effective and safe strategies to reduce hypertension and its associated disease burden. Incorporating low-sodium salt substitutes (LSSS) into population strategies has increasingly been recognised as a possible sodium reduction strategy, particularly in populations where a substantial proportion of overall sodium intake comes from discretionary salt. The LSSS contain lower concentrations of sodium through its displacement with potassium predominantly, or other minerals. Potassium-containing LSSS can potentially simultaneously decrease sodium intake and increase potassium intake. Benefits of LSSS include their potential blood pressure-lowering effect and relatively low cost. However, there are concerns about potential adverse effects of LSSS, such as hyperkalaemia, particularly in people at risk, for example, those with chronic kidney disease (CKD) or taking medications that impair potassium excretion.To assess the effects and safety of replacing salt with LSSS to reduce sodium intake on cardiovascular health in adults, pregnant women and children.We searched MEDLINE (PubMed), Embase (Ovid), Cochrane Central Register of Controlled Trials (CENTRAL), Web of Science Core Collection (Clarivate Analytics), Cumulative Index to Nursing and Allied Health Literature (CINAHL, EBSCOhost), ClinicalTrials.gov and WHO International Clinical Trials Registry Platform (ICTRP) up to 18 August 2021, and screened reference lists of included trials and relevant systematic reviews. No language or publication restrictions were applied.We included randomised controlled trials (RCTs) and prospective analytical cohort studies in participants of any age in the general population, from any setting in any country. This included participants with non-communicable diseases and those taking medications that impair potassium excretion. Studies had to compare any type and method of implementation of LSSS with the use of regular salt, or no active intervention, at an individual, household or community level, for any duration.Two review authors independently screened titles, abstracts and full-text articles to determine eligibility; and extracted data, assessed risk of bias (RoB) using the Cochrane RoB tool, and assessed the certainty of the evidence using GRADE. We stratified analyses by adults, children (≤ 18 years) and pregnant women. Primary effectiveness outcomes were change in diastolic and systolic blood pressure (DBP and SBP), hypertension and blood pressure control; cardiovascular events and cardiovascular mortality were additionally assessed as primary effectiveness outcomes in adults. Primary safety outcomes were change in blood potassium, hyperkalaemia and hypokalaemia.We included 26 RCTs, 16 randomising individual participants and 10 randomising clusters (families, households or villages). A total of 34,961 adult participants and 92 children were randomised to either LSSS or regular salt, with the smallest trial including 10 and the largest including 20,995 participants. No studies in pregnant women were identified. Studies included only participants with hypertension (11/26), normal blood pressure (1/26), pre-hypertension (1/26), or participants with and without hypertension (11/26). This was unknown in the remaining studies. The largest study included only participants with an elevated risk of stroke at baseline. Seven studies included adult participants possibly at risk of hyperkalaemia. All 26 trials specifically excluded participants in whom an increased potassium intake is known to be potentially harmful. The majority of trials were conducted in rural or suburban settings, with more than half (14/26) conducted in low- and middle-income countries. The proportion of sodium chloride replacement in the LSSS interventions varied from approximately 3% to 77%. The majority of trials (23/26) investigated LSSS where potassium-containing salts were used to substitute sodium. In most trials, LSSS implementation was discretionary (22/26). Trial duration ranged from two months to nearly five years. We assessed the overall risk of bias as high in six trials and unclear in 12 trials. LSSS compared to regular salt in adults: LSSS compared to regular salt probably reduce DBP on average (mean difference (MD) -2.43 mmHg, 95% confidence interval (CI) -3.50 to -1.36; 20,830 participants, 19 RCTs, moderate-certainty evidence) and SBP (MD -4.76 mmHg, 95% CI -6.01 to -3.50; 21,414 participants, 20 RCTs, moderate-certainty evidence) slightly. On average, LSSS probably reduce non-fatal stroke (absolute effect (AE) 20 fewer/100,000 person-years, 95% CI -40 to 2; 21,250 participants, 3 RCTs, moderate-certainty evidence), non-fatal acute coronary syndrome (AE 150 fewer/100,000 person-years, 95% CI -250 to -30; 20,995 participants, 1 RCT, moderate-certainty evidence) and cardiovascular mortality (AE 180 fewer/100,000 person-years, 95% CI -310 to 0; 23,200 participants, 3 RCTs, moderate-certainty evidence) slightly, and probably increase blood potassium slightly (MD 0.12 mmol/L, 95% CI 0.07 to 0.18; 784 participants, 6 RCTs, moderate-certainty evidence), compared to regular salt. LSSS may result in little to no difference, on average, in hypertension (AE 17 fewer/1000, 95% CI -58 to 17; 2566 participants, 1 RCT, low-certainty evidence) and hyperkalaemia (AE 4 more/100,000, 95% CI -47 to 121; 22,849 participants, 5 RCTs, moderate-certainty evidence) compared to regular salt. The evidence is very uncertain about the effects of LSSS on blood pressure control, various cardiovascular events, stroke mortality, hypokalaemia, and other adverse events (very-low certainty evidence). LSSS compared to regular salt in children: The evidence is very uncertain about the effects of LSSS on DBP and SBP in children. We found no evidence about the effects of LSSS on hypertension, blood pressure control, blood potassium, hyperkalaemia and hypokalaemia in children.When compared to regular salt, LSSS probably reduce blood pressure, non-fatal cardiovascular events and cardiovascular mortality slightly in adults. However, LSSS also probably increase blood potassium slightly in adults. These small effects may be important when LSSS interventions are implemented at the population level. Evidence is limited for adults without elevated blood pressure, and there is a lack of evidence in pregnant women and people in whom an increased potassium intake is known to be potentially harmful, limiting conclusions on the safety of LSSS in the general population. We also cannot draw firm conclusions about effects of non-discretionary LSSS implementations. The evidence is very uncertain about the effects of LSSS on blood pressure in children.

Vitamin D deficiency (25-hydroxyvitamin D[25(OH)D] p < 0.001). However, no association between participants with hyperparathyroidism (PTH >6.9 pmol/L) and vitamin D deficiency was seen (p = 0.42). In conclusion, we report that season is the major determinant of vitamin D status among Cape Town primary schoolchildren, with prevalence of vitamin D deficiency ranging from 1.4% in January–March to 22.8% in July–September.

Background Debates on effective and safe diets for managing obesity in adults are ongoing. Low‐carbohydrate weight‐reducing diets (also known as 'low‐carb diets') continue to be widely promoted, marketed and commercialised as being more effective for weight loss, and healthier, than 'balanced'‐carbohydrate weight‐reducing diets. Objectives To compare the effects of low‐carbohydrate weight‐reducing diets to weight‐reducing diets with balanced ranges of carbohydrates, in relation to changes in weight and cardiovascular risk, in overweight and obese adults without and with type 2 diabetes mellitus (T2DM). Search methods We searched MEDLINE (PubMed), Embase (Ovid), the Cochrane Central Register of Controlled Trials (CENTRAL), Web of Science Core Collection (Clarivate Analytics), ClinicalTrials.gov and WHO International Clinical Trials Registry Platform (ICTRP) up to 25 June 2021, and screened reference lists of included trials and relevant systematic reviews. Language or publication restrictions were not applied. Selection criteria We included randomised controlled trials (RCTs) in adults (18 years+) who were overweight or living with obesity, without or with T2DM, and without or with cardiovascular conditions or risk factors. Trials had to compare low‐carbohydrate weight‐reducing diets to balanced‐carbohydrate (45% to 65% of total energy (TE)) weight‐reducing diets, have a weight‐reducing phase of 2 weeks or longer and be explicitly implemented for the primary purpose of reducing weight, with or without advice to restrict energy intake. Data collection and analysis Two review authors independently screened titles and abstracts and full‐text articles to determine eligibility; and independently extracted data, assessed risk of bias using RoB 2 and assessed the certainty of the evidence using GRADE. We stratified analyses by participants without and with T2DM, and by diets with weight‐reducing phases only and those with weight‐reducing phases followed by weight‐maintenance phases. Primary outcomes were change in body weight (kg) and the number of participants per group with weight loss of at least 5%, assessed at short‐ (three months to < 12 months) and long‐term (≥ 12 months) follow‐up. Main results We included 61 parallel‐arm RCTs that randomised 6925 participants to either low‐carbohydrate or balanced‐carbohydrate weight‐reducing diets. All trials were conducted in high‐income countries except for one in China. Most participants (n = 5118 randomised) did not have T2DM. Mean baseline weight across trials was 95 kg (range 66 to 132 kg). Participants with T2DM were older (mean 57 years, range 50 to 65) than those without T2DM (mean 45 years, range 22 to 62). Most trials included men and women (42/61; 3/19 men only; 16/19 women only), and people without baseline cardiovascular conditions, risk factors or events (36/61). Mean baseline diastolic blood pressure (DBP) and low‐density lipoprotein (LDL) cholesterol across trials were within normal ranges. The longest weight‐reducing phase of diets was two years in participants without and with T2DM. Evidence from studies with weight‐reducing phases followed by weight‐maintenance phases was limited. Most trials investigated low‐carbohydrate diets (> 50 g to 150 g per day or < 45% of TE; n = 42), followed by very low (≤ 50 g per day or < 10% of TE; n = 14), and then incremental increases from very low to low (n = 5). The most common diets compared were low‐carbohydrate, balanced‐fat (20 to 35% of TE) and high‐protein (> 20% of TE) treatment diets versus control diets balanced for the three macronutrients (24/61). In most trials (45/61) the energy prescription or approach used to restrict energy intake was similar in both groups. We assessed the overall risk of bias of outcomes across trials as predominantly high, mostly from bias due to missing outcome data. Using GRADE, we assessed the certainty of evidence as moderate to very low across outcomes. Participants without and with T2DM lost weight when following weight‐reducing phases of both diets at the short (range: 12.2 to 0.33 kg) and long term (range: 13.1 to 1.7 kg). In overweight and obese participants without T2DM: low‐carbohydrate weight‐reducing diets compared to balanced‐carbohydrate weight‐reducing diets (weight‐reducing phases only) probably result in little to no difference in change in body weight over three to 8.5 months (mean difference (MD) −1.07 kg, (95% confidence interval (CI) −1.55 to −0.59, I2 = 51%, 3286 participants, 37 RCTs, moderate‐certainty evidence) and over one to two years (MD −0.93 kg, 95% CI −1.81 to −0.04, I2 = 40%, 1805 participants, 14 RCTs, moderate‐certainty evidence); as well as change in DBP and LDL cholesterol over one to two years. The evidence is very uncertain about whether there is a difference in the number of participants per group with weight loss of at least 5% at one year (risk ratio (RR) 1.11, 95% CI 0.94 to 1.31, I2 = 17%, 137 participants, 2 RCTs, very low‐certainty evidence). In overweight and obese participants with T2DM: low‐carbohydrate weight‐reducing diets compared to balanced‐carbohydrate weight‐reducing diets (weight‐reducing phases only) probably result in little to no difference in change in body weight over three to six months (MD −1.26 kg, 95% CI −2.44 to −0.09, I2 = 47%, 1114 participants, 14 RCTs, moderate‐certainty evidence) and over one to two years (MD −0.33 kg, 95% CI −2.13 to 1.46, I2 = 10%, 813 participants, 7 RCTs, moderate‐certainty evidence); as well in change in DBP, HbA1c and LDL cholesterol over 1 to 2 years. The evidence is very uncertain about whether there is a difference in the number of participants per group with weight loss of at least 5% at one to two years (RR 0.90, 95% CI 0.68 to 1.20, I2 = 0%, 106 participants, 2 RCTs, very low‐certainty evidence). Evidence on participant‐reported adverse effects was limited, and we could not draw any conclusions about these. Authors' conclusions There is probably little to no difference in weight reduction and changes in cardiovascular risk factors up to two years' follow‐up, when overweight and obese participants without and with T2DM are randomised to either low‐carbohydrate or balanced‐carbohydrate weight‐reducing diets., Plain language summary Low‐carbohydrate diets or balanced‐carbohydrate diets: which works better for weight loss and heart disease risks? Key messages • There is probably little to no difference in the weight lost by people following low‐carbohydrate weight‐reducing diets (also known as 'low‐carb diets') compared to the weight lost by people following balanced‐carbohydrate weight‐reducing diets, for up to two years. • Similarly, there is probably little to no difference between the diets for changes in heart disease risks, like diastolic blood pressure, glycosylated haemoglobin (HbA1c, a measure of blood sugar levels over 2‐3 months) and LDL cholesterol (‘unhealthy’ cholesterol) up to two years. • This was the case in people with and without type 2 diabetes. What are low‐carbohydrate and balanced‐carbohydrate weight‐reducing diets? People spend lots of money on trying to lose weight using diets, products, foods and books, and continue to debate about which diets are effective and safe. So, examining the scientific evidence behind claims made is important. Low‐carbohydrate diets are a broad category of weight‐reducing diets that manipulate and restrict carbohydrates, protein and fat in diets. There are no consistent, widely‐accepted definitions of these diets and different descriptions are used (such as, 'low‐carbohydrate, high‐protein’, 'low‐carbohydrate, high‐fat', or ‘very low‐carbohydrate’). Low‐carbohydrate diets are implemented in different ways, but they restrict grains, cereals and legumes, and other carbohydrate‐containing foods; such as dairy, most fruit and certain vegetables. These foods are then typically replaced with foods higher in fat and protein; such as meats, eggs, cheese, butter, cream, oils. Some low‐carbohydrate diets recommend eating as desired, while others recommend restricting the amount of energy eaten. Balanced‐carbohydrate diets contain more moderate amounts of carbohydrates, protein and fats, in line with current healthy eating advice from health authorities. When used for weight reduction, balanced diets recommend restricting the amount of energy eaten by guiding people to reduce their portion sizes and choose healthier foods (e.g. lean instead of fatty meat). Low‐carbohydrate weight‐reducing diets are widely promoted, marketed and commercialised as being more effective for weight loss, and healthier, than 'balanced'‐carbohydrate weight‐reducing diets. What did we want to find out? We wanted to find out if low‐carbohydrate weight‐reducing diets were better for weight loss and heart disease risk factors than balanced‐carbohydrate weight‐reducing diets in adults who were overweight or living with obesity. We wanted to find this out for people with and without type 2 diabetes. What did we do? We searched six electronic databases and trial registries for all trials* that compared low‐carbohydrate weight‐reducing diets with balanced‐carbohydrate weight‐reducing diets in adults who were overweight or living with obesity. The trials had to last for at least three months. We compared and summarised the results of the trials and rated our confidence in the combined evidence, based on factors such as study methods and sizes. *A trial is a type of study in which participants are assigned randomly to two or more treatment groups. This is the best way to ensure similar groups of participants. What did we find? We found 61 trials involving 6925 people who were overweight or living with obesity. The biggest trial was in 419 people and the smallest was in 20 people. All except one of the trials were conducted in high‐income countries worldwide, and nearly half were undertaken in the USA (26). Most trials (36) were undertaken in people who did not have heart disease or risk factors. Most people (5118 people) did not have type 2 diabetes. The average starting weight of people across the trials was 95 kg. Most studies (37) lasted for six months or less; and the longest studies (6) lasted for two years. Main results Low‐carbohydrate weight‐reducing diets probably result in little to no difference in weight loss over the short term (trials lasting 3 to 8.5 months) and long term (trials lasting one to two years) compared to balanced‐carbohydrate weight‐reducing diets, in people with and without type 2 diabetes. In the short term, the average difference in weight loss was about 1 kg and in the long term, the average difference was less than 1 kg. People lost weight on both diets in some trials. The amount of weight lost on average varied greatly with both diets across the trials from less than 1 kg in some trials and up to about 12 kg in others in the short term and long term. Similarly, low‐carbohydrate weight‐reducing diets probably result in little to no difference in diastolic blood pressure, glycosylated haemoglobin (HbA1c) and LDL cholesterol (‘unhealthy’ cholesterol) for up to two years. We could not draw any conclusions about unwanted effects reported by participants because very few trials reported these. What are the limitations of the evidence? We are moderately confident in the evidence. Our confidence was lowered mainly because of concerns about how some the trials were conducted, which included that many trials did not report all their results. Further research may change these results. How up to date is this evidence? The evidence is up‐to‐date to June 2021.

BACKGROUND: Aflatoxins are carcinogenic mycotoxins that contaminate many food crops. Maize and groundnuts are prone to aflatoxin contamination, and are the major sources of human exposure to aflatoxins, due to their high intake as staple foods, particularly in low‐ and middle‐income countries (LMICs). Observational studies suggest an association between dietary exposure to aflatoxins during pregnancy and early childhood and linear growth in infants and young children. OBJECTIVES: To assess the effects on pre‐ and postnatal growth outcomes when agricultural and nutritional education interventions during the post‐harvest period that aim to reduce aflatoxin exposure are compared to usual support or no intervention. We assessed this in infants, children, and pregnant and lactating women at the household or community level in LMICs. SEARCH METHODS: In July and August 2019, we searched: CENTRAL, MEDLINE, Embase, CINAHL, Web of Science Core Collection, Africa‐Wide, LILACS, CAB Abstracts, Agricola, and two trials registers. We also checked the bibliographies of the included studies and contacted relevant mycotoxin organisations and researchers for additional studies. SELECTION CRITERIA: We included randomised controlled trials (RCTs) and cluster‐RCTs of agricultural education and nutritional education interventions of any duration, at the household or community level, aimed at reducing aflatoxin intake by infants, children, and pregnant and lactating women, in LMICs during the post‐harvest period, compared to no intervention or usual support. We excluded studies that followed participants for less than four weeks. We assessed prespecified prenatal (at birth) and postnatal growth outcomes (during infancy, childhood, and adolescence), with linear growth (as the primary outcome), infectious disease morbidity, and unintended consequences. DATA COLLECTION AND ANALYSIS: Two authors independently assessed study eligibility using prespecified criteria, extracted data, and assessed risk of bias of included RCTs. We evaluated the certainty of the evidence using GRADE, and presented the main results in a 'Summary of findings' table. MAIN RESULTS: We included three recent cluster‐RCTs reporting the effects of agricultural education plus post‐harvest technologies, compared to usual agricultural support or no intervention. The participants were pregnant women and their children, lactating women and their infants (< 6 months), women of childbearing age, and young children (< 59 months), from rural, subsistence maize‐farming communities in Kenya, Zimbabwe, and Tanzania. Two trials randomised villages to the intervention and control groups, including a total of at least 979 mother‐child pairs from 60 villages. The third trial randomised 420 households, including 189 mother‐child pairs and 231 women of childbearing age. Duration of the intervention and follow‐up ranged between five and nine months. Due to risk of attrition bias, the overall risk of bias was unclear in one trial, and high in the other two trials. None of the included studies addressed the effects of nutritional education on pre‐ and postnatal growth. One trial reported outcomes not prespecified in our review, and we were unable to obtain unpublished growth data from the second trial, even after contacting the authors. The third trial, in lactating women and their infants in Tanzania, reported on the infants' weight‐for‐age z‐score (WAZ) after six months. This trial found that providing agricultural education aimed at changing farmers' post‐harvest practices to reduce aflatoxin exposure, by using demonstrations (e.g. handsorting, de‐hulling of maize, drying sheets, and insecticides), may improve WAZ in infants from these farmers' households, on average, by 0.57 (95% confidence interval (CI) 0.16 to 0.98; 1 study; 249 participants; very low‐certainty evidence), compared to infants from households where the farmers received routine agricultural extension services. Another way of reporting the effect on WAZ is to compare the proportion of underweight infants (WAZ > 2 SD below the reference median value) per group. This trial found that the intervention may reduce the proportion of underweight infants in the intervention households by 6.7% (95% CI ‐12.6 to ‐1.4; 249 participants; very low‐certainty evidence) compared to control households. No studies reported on unintended effects of agricultural and nutritional education. AUTHORS' CONCLUSIONS: Evidence on the effects on child growth in LMICs of agricultural or nutritional education interventions that reduce aflatoxin exposure was very limited; no included study reported on linear growth. Very low‐certainty evidence suggested that agricultural education aimed at changing farmers' post‐harvest practices to reduce aflatoxin exposure by using demonstrations, may result in an increase in WAZ, when compared to usual or no education.

Hypothyroidism due to iodine deficiency can impair physical development, most visibly in the marked stunting of myxedematous cretinism caused by severe in utero iodine deficiency. Whether iodine repletion improves growth in noncretinous children is uncertain. Therefore, the aim of our systematic review was to assess the effects of iodine fortification or supplementation on prenatal and postnatal growth outcomes in noncretinous children. Following Cochrane methods and PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) reporting guidelines, we searched 10 databases including 2 Chinese databases (latest search February 2017). We included randomized and nonrandomized controlled trials (RCTs; non-RCTs), controlled before-after (CBA) studies, and interrupted time-series studies in pregnant women and children (≤18 y), which compared the effects of iodine (any form, dose, regimen) to placebo, noniodized salt, or no intervention on prenatal and postnatal growth outcomes. We calculated mean differences with 95% CIs, performed random-effects meta-analyses, and assessed the quality of evidence with the use of GRADE (Grading of Recommendations Assessment, Development and Evaluation). We included 18 studies (13 RCTs, 4 non-RCTs, 1 CBA) (n = 5729). Iodine supplementation of severely iodine-deficient pregnant women increased mean birthweight [mean difference (MD): 200 g; 95% CI: 183, 217 g; n = 635; 2 non-RCTs] compared to controls, but the quality of this evidence was assessed as very low. Iodine repletion across the other groups showed no effects on primary growth outcomes (quality of evidence mostly low and very low). Meta-analyses showed a positive effect in moderate-to-mildly iodine-deficient schoolchildren on insulin-like growth factor-1 (MD: 38.48 ng/mL; 95% CI: 6.19, 70.76 ng/mL; n = 498; 2 RCTs, low-quality evidence) and insulin-like growth factor binding protein-3 (MD: 0.46 μg/mL; 95% CI: 0.25, 0.66 μg/mL; n = 498; 2 RCTs, low-quality evidence). In conclusion, we identified few well-designed trials examining the effects of iodine repletion on growth. We are uncertain whether prenatal iodine repletion increases infant growth. Postnatal iodine repletion may improve growth factors but has no clear effects on somatic growth. Our systematic review was registered with PROSPERO as CRD42014012940.

Evidence-informed guideline development methods underpinned by systematic reviews ensure that guidelines are transparently developed, free from overt bias, and based on the best available evidence. Only recently has the nutrition field begun using these methods to develop public health nutrition guidelines. Given the importance of following an evidence-informed approach and recent advances in related methods, this study sought to describe the methods used to synthesize evidence, rate evidence quality, grade recommendations, and manage conflicts of interest (COIs) in national food-based dietary guidelines (FBDGs). The Food and Agriculture Organization’s FBDGs database was searched to identify the latest versions of FBDGs published from 2010 onward. Relevant data from 32 FBDGs were extracted, and the findings are presented narratively. This study shows that despite advances in evidence-informed methods for developing dietary guidelines, there are variations and deficiencies in methods used to review evidence, rate evidence quality, and grade recommendations. Dietary guidelines should follow systematic and transparent methods and be informed by the best available evidence, while considering important contextual factors and managing conflicts of interest.

Background All countries face significant challenges from complex manifestations of malnutrition, which affects one in three people globally. Systematic reviews provide ready-to-use syntheses of quality-appraised evidence to inform decision-making for actions. To enhance the utility and quality of future Cochrane nutrition evidence, we described the scope and quality of all nutrition systematic reviews in the Cochrane Database of Systematic Reviews (CDSR). Methods We screened all active CDSR records (31 July 2015) to identify reviews and protocols using pre-specified eligibility criteria and definitions. Duplicate, independent data extraction included criteria for inclusion of studies in completed reviews (PICOS). We assessed methodological quality (AMSTAR), use of GRADE, mapped reviews against 2013 Global Burden of Disease data, and categorised the paradigm (medical, lifestyle and socio-ecological) of the review question. We analysed our results using descriptive statistics. Results We screened 8484 records, and included 470 (8%) completed reviews (in 45 Cochrane Review Groups (CRGs)) and 169 (7%) protocols (in 41 CRGs) published by 47 of 53 CRGs with reviews. Most completed reviews were produced by the Pregnancy and Childbirth (n = 73), Neonatal (n = 64), Metabolic and Endocrine Disorders (n = 33), Developmental, Psychosocial and Learning Problems (n = 26), Kidney and Transplant (n = 18) and Heart (n = 18) CRGs. Only 27% (n = 129) of reviews had searches for new studies in 2013 or thereafter. Supplementation/supplement interventions were most common (50%; n = 235; majority with micronutrients; 73%, n = 173), followed by food interventions (20%; n = 95). All reviews included randomised controlled trials; about 5% included other designs; 25% used GRADE; the median AMSTAR score was 9 (interquartile range: 7 t o 10), 51% were high (AMSTAR 9-11) and 49% moderate (AMSTAR 5-8) quality. More than 80% framed questions using a medical paradigm. For top causes of years-of-life-lost, most reviews addressed preterm birth, diabetes and ischaemic heart disease; for leading risk factors for disability-adjusted-life-years, most targeted childhood undernutrition and high body mass index. Conclusions Nutrition reviews comprised 8% of active CDSR records, were widely distributed across nearly all CRGs and reflected the double nutrition burden. This analysis presents a comprehensive description of the scope and quality of Cochrane nutrition reviews, and identifies gaps for future activities to support actions to address the nutrition burden, in line with the current nutrition agenda and impetus.

Tallis, Heather; Kreis, Katharine; Olander, Lydia; Ringler, Claudia; Ameyaw, David; Borsuk, Mark E.; Fletschner, Diana; Game, Edward; Gilligan, Daniel O.; Jeuland, Marc; Kennedy, Gina; Masuda, Yuta J.; Mehta, Sumi; Miller, Nicholas; Parker, Megan; Pollino, Carmel; Rajaratnam, Julie; Wilkie, David; Zhang, Wei; Ahmed, Selena; Ajayi, Oluyede C.; Alderman, Harold; Arhonditsis, George; Azevedo, Ines; Badola, Ruchi; Bailis, Rob; Balvanera, Patricia; Barbour, Emily; Bardini, Mark; Barton, David Nicholas; Baumgartner, Jill; Benton, Tim G.; Bobrow, Emily; Bossio, Deborah; Bostrom, Ann; Braimoh, Ademola; Brondizio, Eduardo; Brown, Joe; Bryant, Benjamin P.; Calder, Ryan S.D.; Chaplin-Kramer, Becky; Cullen, Alison; DeMello, Nicole; Dickinson, Katherine L.; Ebi, Kristie L.; Eves, Heather E.; Fanzo, Jessica; Ferraro, Paul J.; Fisher, Brendan; Frongillo, Edward A.; Galford, Gillian; Garrity, Dennis; Gatere, Lydiah; Grieshop, Andrew P.; Grigg, Nicola J.; Groves, Craig; Gugerty, Mary Kay; Hamm, Michael; Hou, Xiaoyue; Huang, Cindy; Imhoff, Marc; Jack, Darby; Jones, Andrew D.; Kelsey, Rodd; Kothari, Monica; Kumar, Ritesh; Lachat, Carl; Larsen, Ashley; Lawrence, Mark; DeClerck, Fabrice; Levin, Phillip S.; Mabaya, Edward; Gibson, Jacqueline MacDonald; McDonald, Robert I.; Mace, Georgina; Maertens, Ricardo; Mangale, Dorothy I.; Martino, Robin; Mason, Sara; Mehta, Lyla; Meinzen-Dick, Ruth; Merz, Barbara; Msangi, Siwa; Murray, Grant; Murray, Kris A.; Naude, Celeste E.; Newlands, Nathaniel K.; Nkonya, Ephraim; Peterman, Amber; Petruney, Tricia; Possingham, Hugh; Puri, Jyotsna; Remans, Roseline; Remlinger, Lisa; Ricketts, Taylor H.; Reta, Bedilu; Robinson, Brian E.; Roe, Dilys; Rosenthal, Joshua; Shen, Guofeng; Shindell, Drew; Stewart-Koster, Ben; Sunderland, Terry; Sutherland, William J.; Tewksbury, Josh; Wasser, Heather; Wear, Stephanie; Webb, Chris; Whittington, Dale; Wilkerson, Marit; Wittmer, Heidi; Wood, Benjamin D.K.; Wood, Stephen; Wu, Joyce; Yadama, Gautam; Zobrist, Stephanie. Aligning evidence generation and use across health, development, and environment. Current Opinion in Environmental Sustainability 2019 ;Volum 39. s. 81-93

This is a protocol for a Cochrane Review (Intervention). The objectives are as follows: To assess the effects of agricultural and nutritional educational interventions that aim to reduce the intake of aflatoxins in infants, children, and pregnant and lactating women at the household or community level in low‐ and middle‐income countries (LMIC), on prenatal and postnatal growth.

Background Program decision-making to prevent and treat acute malnutrition in an emergency can be hampered by a lack of accessible and relevant overviews of directly available robust research evidence. There is often evidence from related settings such as from low-income countries, but this is dispersed across many databases, may be inaccessible and requires assessment of its relevance to the humanitarian setting. We describe a process whereby a multi-disciplinary, international group of specialists worked together to build relevant and effective collections of available systematic reviews on acute malnutrition, published and disseminated as online collections, to improve access to the evidence and concise, synthesised, relevant up to date evidence for programming. By describing this process, we hope to inspire other professional groups to take part in similar multi-stakeholder, multi-disciplinary projects. Objectives This project was designed to make the evidence from relevant systematic reviews about malnutrition as accessible as possible to support evidence-based decision-making and to guide future research on the prevention and treatment of acute malnutrition in humanitarian emergencies. Methods Between March 2017 and March 2018, a large group (21 volunteers and stakeholders) with different backgrounds collaborated to review and curate collections of systematic reviews of interventions for the prevention and treatment of moderate and severe acute malnutrition relevant to humanitarian emergencies. The methodology loosely followed general guidance for overviews of systematic reviews with a pre-defined question (formulated using the PICOS format) and search strategies applied to multiple databases. Pairs of collaborators first screened the search yields to identify potentially eligible reviews, where after other pairs screened the list of potentially eligible reviews for relevance and thus included in the final collections. Results Search strategies were run in 12 databases, in the week of 15 September 2017, yielding a total of 4646 records after de-duplication. At this point, Cochrane reviews (n = 463) and non-Cochrane reviews (n = 4183) were separated and handled by different teams to compile three linked collections, namely the Evidence Aid Collection, consisting of relevant non-Cochrane reviews, and two Cochrane Special Collections, consisting of relevant Cochrane reviews, one for prevention and the other for treatment of acute malnutrition. The collections were published on the Evidence Aid website on 12 March 2018 and Cochrane website in August 2018. Discussion Through this collaboration, we have successfully generated three collections of systematic reviews to guide prevention and management of acute malnutrition in humanitarian emergencies: an Evidence Aid collection of non-Cochrane reviews, and two Cochrane Special Collections of Cochrane reviews. These collections provide accessible synthesised evidence that can be used to inform decision-making on strategies and policies in the humanitarian emergency and disaster risk reduction sectors and to guide future research by identifying gaps in robust evidence and areas that are under-researched. These collections did not set out to assess methodological quality, appraise in detail what the reviews found or summarise the evidence, but rather to curate the identified relevant systematic reviews into online resources for others to use. This unique collaboration of different individuals, organisations and stakeholders, and the collation of robust evidence can be repeated for other subjects, and Evidence Aid is eager to support new collections around other topics relevant to humanitarian emergencies.

This is a protocol for a Cochrane Review (Intervention). The objectives are as follows: To compare the effects of low carbohydrate weight‐reducing diets to weight‐reducing diets with balanced ranges of carbohydrates, in relation to changes in weight and cardiovascular risk, in overweight and obese adults without type 2 diabetes (comparison 1) and with type 2 diabetes (comparison 2).

Dialogue and exchange between researchers and policy personnel may increase the use of research evidence in policy. We piloted and evaluated a programme of formalised dialogue between researchers and provincial health policymakers in South Africa, called the buddying programme. An external evaluation examined implementation and short-term impact, drawing on documents, in-depth interviews with policymakers, a researcher buddies focus group and our own reflection on what we learnt. We set up buddying with seven policymakers and five researchers on six policy questions. Researchers knew little about policymaking or needs of policymakers. Policymakers respected the contact with researchers, respected researchers’ objectivity and appreciated the formalised approach. Having policymaker champions facilitated the dialogue. Scenarios for policy questions and use were different. One topic was at problem identification stage (contraceptives and HIV risk), four at policy formulation stage (healthy lifestyles, chronic illness medication adherence, integrated care of chronic illness and maternal transmission of HIV to infants) and one at implementation stage (task shifting). Research evidence were used to identify or solve a policy problem (two scenarios), to legitimise a predetermined policy position (three scenarios) or the evidence indirectly influenced the policy (one scenario). The formalised dialogue required in this structured buddying programme took time and commitment from both sides. The programme illustrated the importance of researchers listening, and policymakers understanding what research can offer. Both parties recognised that the structured buddying made the dialogue happen. Often the evidence was helpful in supporting provincial policy decisions that were in the roll-out phase from the national government.

BACKGROUND: As part of efforts to prevent childhood overweight and obesity, we need to understand the relationship between total fat intake and body fatness in generally healthy children. OBJECTIVES: To assess the effects and associations of total fat intake on measures of weight and body fatness in children and young people not aiming to lose weight. SEARCH METHODS: For this update we revised the previous search strategy and ran it over all years in the Cochrane Library, MEDLINE (Ovid), MEDLINE (PubMed), and Embase (Ovid) (current to 23 May 2017). No language and publication status limits were applied. We searched the World Health Organization International Clinical Trials Registry Platform and ClinicalTrials.gov for ongoing and unpublished studies (5 June 2017). SELECTION CRITERIA: We included randomised controlled trials (RCTs) in children aged 24 months to 18 years, with or without risk factors for cardiovascular disease, randomised to a lower fat (30% or less of total energy (TE)) versus usual or moderate‐fat diet (greater than 30%TE), without the intention to reduce weight, and assessed a measure of weight or body fatness after at least six months. We included prospective cohort studies if they related baseline total fat intake to weight or body fatness at least 12 months later. DATA COLLECTION AND ANALYSIS: We extracted data on participants, interventions or exposures, controls and outcomes, and trial or cohort quality characteristics, as well as data on potential effect modifiers, and assessed risk of bias for all included studies. We extracted body weight and blood lipid levels outcomes at six months, six to 12 months, one to two years, two to five years and more than five years for RCTs; and for cohort studies, at baseline to one year, one to two years, two to five years, five to 10 years and more than 10 years. We planned to perform random‐effects meta‐analyses with relevant subgrouping, and sensitivity and funnel plot analyses where data allowed. MAIN RESULTS: We included 24 studies comprising three parallel‐group RCTs (n = 1054 randomised) and 21 prospective analytical cohort studies (about 25,059 children completed). Twenty‐three studies were conducted in high‐income countries. No meta‐analyses were possible, since only one RCT reported the same outcome at each time point range for all outcomes, and cohort studies were too heterogeneous to combine. Effects of dietary counselling to reduce total fat intake from RCTs Two studies recruited children aged between 4 and 11 years and a third recruited children aged 12 to 13 years. Interventions were combinations of individual and group counselling, and education sessions in clinics, schools and homes, delivered by dieticians, nutritionists, behaviourists or trained, supervised teachers. Concerns about imprecision and poor reporting limited our confidence in our findings. In addition, the inclusion of hypercholesteraemic children in two trials raised concerns about applicability. One study of dietary counselling to lower total fat intake found that the intervention may make little or no difference to weight compared with usual diet at 12 months (mean difference (MD) ‐0.50 kg, 95% confidence interval (CI) ‐1.78 to 0.78; n = 620; low‐quality evidence) and at three years (MD ‐0.60 kg, 95% CI ‐2.39 to 1.19; n = 612; low‐quality evidence). Education delivered as a classroom curriculum probably decreased BMI in children at 17 months (MD ‐1.5 kg/m(2), 95% CI ‐2.45 to ‐0.55; 1 RCT; n = 191; moderate‐quality evidence). The effects were smaller at longer term follow‐up (five years: MD 0 kg/m(2), 95% CI ‐0.63 to 0.63; n = 541; seven years; MD ‐0.10 kg/m(2), 95% CI ‐0.75 to 0.55; n = 576; low‐quality evidence). Dietary counselling probably slightly reduced total cholesterol at 12 months compared to controls (MD ‐0.15 mmol/L, 95% CI ‐0.24 to ‐0.06; 1 RCT; n = 618; moderate‐quality evidence), but may make little or no difference over longer time periods. Dietary counselling probably slightly decreased low‐density lipoprotein (LDL) cholesterol at 12 months (MD ‐0.12 mmol/L, 95% CI ‐0.20 to ‐0.04; 1 RCT; n = 618, moderate‐quality evidence) and at five years (MD ‐0.09, 95% CI ‐0.17 to ‐0.01; 1 RCT; n = 623; moderate‐quality evidence), compared to controls. Dietary counselling probably made little or no difference to HDL‐C at 12 months (MD ‐0.03 mmol/L, 95% CI ‐0.08 to 0.02; 1 RCT; n = 618; moderate‐quality evidence), and at five years (MD ‐0.01 mmol/L, 95% CI ‐0.06 to 0.04; 1 RCT; n = 522; moderate‐quality evidence). Likewise, counselling probably made little or no difference to triglycerides in children at 12 months (MD ‐0.01 mmol/L, 95% CI ‐0.08 to 0.06; 1 RCT; n = 618; moderate‐quality evidence). Lower versus usual or modified fat intake may make little or no difference to height at seven years (MD ‐0.60 cm, 95% CI ‐2.06 to 0.86; 1 RCT; n = 577; low‐quality evidence). Associations between total fat intake, weight and body fatness from cohort studies Over half the cohort analyses that reported on primary outcomes suggested that as total fat intake increases, body fatness measures may move in the same direction. However, heterogeneous methods and reporting across cohort studies, and predominantly very low‐quality evidence, made it difficult to draw firm conclusions and true relationships may be substantially different. AUTHORS' CONCLUSIONS: We were unable to reach firm conclusions. Limited evidence from three trials that randomised children to dietary counselling or education to lower total fat intake (30% or less TE) versus usual or modified fat intake, but with no intention to reduce weight, showed small reductions in body mass index, total‐ and LDL‐cholesterol at some time points with lower fat intake compared to controls. There were no consistent effects on weight, high‐density lipoprotein (HDL) cholesterol or height. Associations in cohort studies that related total fat intake to later measures of body fatness in children were inconsistent and the quality of this evidence was mostly very low. Most studies were conducted in high‐income countries, and may not be applicable in low‐ and middle‐income settings. High‐quality, longer‐term studies are needed, that include low‐ and middle‐income settings to look at both possible benefits and harms.

Tuberculosis and nutrition are intrinsically linked in a complex relationship. Altered metabolism and loss of appetite associated with tuberculosis may result in undernutrition, which in turn may worsen the disease or delay recovery. We highlight an updated Cochrane review assessing the effects of oral nutritional supplements in people with active tuberculosis who are receiving antituberculosis drug therapy. The review authors conducted a comprehensive search (February 2016) for all randomised controlled trials comparing any oral nutritional supplement, given for at least 4 weeks, with no nutritional intervention, placebo or dietary advice only in people receiving antituberculosis treatment. Of the 35 trials (N=8 283 participants) included, seven assessed the provision of free food or high-energy supplements, six assessed multi-micronutrient supplementation, and 21 assessed single- or dual-micronutrient supplementation. There is currently insufficient evidence to indicate whether routinely providing free food or high-energy supplements improves antituberculosis treatment outcomes (i.e. reduced death and increased cure rates at 6 and 12 months), but it probably improves weight gain in some settings. Plasma levels of zinc, vitamin D, vitamin E and selenium probably improve with supplementation, but currently no reliable evidence demonstrates that routine supplementation with multi-, single or dual micronutrients above the recommended daily intake has clinical benefits (i.e. reduced death, increased cure rate at 6 and 12 months, improved nutritional status) in patients receiving antituberculosis treatment. In South Africa, most provinces implement a supplementation protocol based on nutritional assessment and classification of individuals rather than on disease diagnosis or treatment status.Â

We read the perspective article “NutriGrade: A Scoring system to Assess and Judge the Meta-Evidence of Randomized Controlled Trials and Cohort Studies in Nutrition Research” published in November 2016 in Advances in Nutrition [1]. We agree it is important to assess the trustworthiness of evidence.

Background The translation of research into policy and practice is enhanced by policymakers who can recognise and articulate their information needs and researchers that understand the policymakers’ environment. As researchers, we sought to understand the policymaking process and how research evidence may contribute in South Africa and Cameroon. Methods We conducted qualitative in-depth interviews in South Africa and focus group discussions in Cameroon with purposively sampled subnational (provincial and regional) government health programme managers. Audio recorded interviews were transcribed, thematically coded and analysed. Results Participants in both countries described the complex, often lengthy nature of policymaking processes, which often include back-and-forth consultations with many diverse stakeholder groups. These processes may be influenced by political structures, relationships between national and subnational levels, funding and international stakeholder agendas. Research is not a main driver of policy, but rather current contextual realities, costs, logistics and people (clinicians, NGOs, funders) influence the policy, and research plays a part. Research evidence is frequently perceived as unavailable, inaccessible, ill-timed or not applicable. The reliability of research on the internet was questioned. Evidence-informed health decision-making (EIDM) is regarded as necessary in South Africa but is less well understood in Cameroon. Insufficient time and capacity were hindrances to EIDM in both countries. Good relationships between researchers and policymakers may facilitate EIDM. Researchers should have a good understanding of the policymaking environment if they want to influence it. Greater interaction between policymakers and researchers is perceived as beneficial when formulating research and policy questions as it raises researchers’ awareness of implementation challenges and enables the design of tailored and focused strategies to respond to policymakers’ needs. Conclusions Policymaking is complicated, lengthy and mostly done at national level. Provinces/regions are tasked with implementation, with more room for adaptation in South Africa than in Cameroon. Research evidence plays a role in policy but does not drive it and is seen as mostly unavailable. Researchers need a thorough understanding of the policy process and environment, how the health system operates, as well as the priorities of policymakers. This can inform effective dialogue between researchers and policymakers, and contribute to enhancing use of research evidence in decision-making. Electronic supplementary material The online version of this article (doi:10.1186/s13012-015-0315-0) contains supplementary material, which is available to authorized users.

Cape Town, South Africa, has a seasonal pattern of UVB radiation and a predominantly dark-skinned urban population who suffer high HIV-1 prevalence. This coexistent environmental and phenotypic scenario puts residents at risk for vitamin D deficiency, which may potentiate HIV-1 disease progression. We conducted a longitudinal study in two ethnically distinct groups of healthy young adults in Cape Town, supplemented with vitamin D3 in winter, to determine whether vitamin D status modifies the response to HIV-1 infection and to identify the major determinants of vitamin D status (UVB exposure, diet, pigmentation, and genetics). Vitamin D deficiency was observed in the majority of subjects in winter and in a proportion of individuals in summer, was highly correlated with UVB exposure, and was associated with greater HIV-1 replication in peripheral blood cells. High-dosage oral vitamin D3 supplementation attenuated HIV-1 replication, increased circulating leukocytes, and reversed winter-associated anemia. Vitamin D3 therefore presents as a low-cost supplementation to improve HIV-associated immunity.

To assess the evidence from systematic reviews on the effect on morbidity and mortality of blanket screening for hypertension or diabetes mellitus compared with targeted, opportunistic or no screening, we searched for relevant systematic reviews and conducted duplicate study selection, data extraction and quality appraisal. Results were summarised narratively. We included two completed reviews of moderate quality and one ongoing Cochrane review. In one completed review, general health checks had no effect on total morbidity or mortality or on healthcare services compared with no health checks. In the other, intensive hypertension screening methods were ineffective in increasing screening uptake or detecting new cases compared with less intensive methods. Both reviews included studies in high-income settings. There is insufficient evidence from currently available systematic reviews to confirm a beneficial effect of blanket screening for hypertension and/or diabetes compared with other types of screening methods in low- and middle-income settings. Scarce resources are being mobilised to implement mass screening intervention for diabetes and hypertension without adequate evidence of its effects. A systematic review is needed to assess clinical effectiveness, cost-effectiveness and overall impact on the health system of screening strategies, especially in low- and middle-income settings such as exist in South Africa. Robust evaluation of these outcomes would then be necessary to inform secondary prevention strategies.

Background Iodine deficiency can adversely affect child development including stunted growth. However, the effect of iodine supplementation or fortification on prenatal and postnatal growth in children (

Introduction Iodine is an essential micronutrient and component of the thyroid hormones. Sufficient ingestion of iodine is necessary for normal growth and development. If iodine requirements are not met, growth can be impaired. Salt iodisation and supplementation with iodine can prevent iodine deficiency disorders and stunted growth. No systematic review has yet collated the evidence linking iodine to growth. With an increased emphasis on stunting within the WHO Global Nutrition Targets for 2025, we propose a systematic review to address this question. Methods and analysis We will undertake a systematic review, and if appropriate, meta-analyses, evaluating the effects of iodised salt or iodine supplements on prenatal and postnatal somatic growth, until age 18. We will search a number of databases, including MEDLINE, EMBASE, Web of Science, CINAHL, PsychINFO, the Cochrane Library, including the CENTRAL register of Controlled Trials and also the WHO library and ICTRP (International Clinical Trials Registry Platform), which includes the Clinicaltrials.gov repository. We will also search Wanfang Data and the China Knowledge Resource Integrated Database. Included studies must have compared exposure to iodised salt, iodine supplements or iodised oil, to placebo, non-iodised salt or no intervention. Primary outcomes will be continuous and categorical markers of prenatal and postnatal somatic growth. Secondary outcomes will cover further measures of growth, including growth rates and indirect markers of growth such as insulin-like growth factor-1 (IGF-1). Ethics and dissemination The systematic review will be published in a peer-reviewed journal, and will be sent directly to the WHO, United Nations Children's Fund, International Council for the Control of Iodine Deficiency Disorders and other stakeholders. The results generated from this systematic review will provide evidence to support future programme recommendations regarding iodine fortification or supplementation and child growth., BMJ Open, 5, ISSN:2044-6055

Background Susceptibility to reactivate tuberculosis infection is influenced by immunosuppression. Amongst the greatest risk factors for active TB are HIV-1 infection and vitamin D deficiency. These risks factors are not mutually exclusive and may exacerbate each other. However, the phenotype of immunodeficiency induced by each is different. Vitamin D deficiency not only associates with TB risks, but it is greater in HIV-co-infected patients. The effects of vitamin D on the immune system are pleiotropic, being both anti-inflammatory and antimicrobial. Evidence suggests that vitamin D may not only reduce risk of TB by increasing anti-mycobacterial immunity and reducing inflammation, but it may also reduce HIV replication and the associated effects on innate and adaptive immunity; thus concomitantly reducing the associated risk of HIV on TB. Methods We investigated in vitro and ex vivo the effect of vitamin D supplementation on the response of monocyte-derived macrophages (MDM) and peripheral blood mononuclear cells (PBMC), respectively, to HIV- M. tuberculosis ( Mtb) co-infection. The effects of pathogen growth and susceptibility to infection were correlated to cytokine, chemokine and antimicrobial peptide production, by expression, secretion and flow cytometry analysis. Results MDM differentiated in the presence of vitamin D metabolites, significantly restricted HIV-1 replication, alone and during co-infection with Mtb . Type 2 MDM were considerably more susceptible to HIV-1 infection than type 1. This correlated with the level of CCL2 production, which was significantly inhibited by vitamin D metabolites. PBMC isolated from healthy individuals in summer and in winter after receiving vitamin D, significantly restricted HIV-1 infection, compared to PBMC collected in winter before supplementation. There was a significant difference in circulating cell populations and serum cytokines/chemokines in summer, compared to winter, and these were investigated for correlations with HIV replication. Conclusions Vitamin D may prove a cheap, effective, tool for preventing TB-HIV disease progression and clinical trials are warranted in at-risk populations.

Over two billion people suffer from micronutrient deficiencies. Food fortification is a prominent nutrition intervention to combat such deficiencies; however, its effectiveness, risks, and ethical implications vary depending on the contexts associated with the deficiency it is addressing and the circumstances with its implementation. The aim of this research was to analyse the profile of nutrition interventions for combating micronutrient deficiency with particular focus on food fortification reported in existing systematic reviews (SRs), guidelines and policy statements, and implementation actions for nutrition. A review of secondary data available from online databases of SRs, guidelines and policy statements, and implementation actions, categorised as either "nutrition-specific interventions" (NSpI) or "nutrition-sensitive interventions" (NSeI), was conducted. Currently, there is evidence available for a diversity of food fortification topics, and there has been much translation into action. Indeed, food fortification and micronutrient supplementation interventions and NSpI more broadly dominate the profile of interventions for which there were SRs, guidelines, and policy statements available. The findings demonstrate that, although there is a rational linear relationship between evidence synthesis and translation in formulating policy and actions to combat micronutrient deficiencies, the various nutrition interventions available to help combat micronutrient deficiencies are not equally represented in the evidence synthesis and translation processes. Effective and safe policies and actions to combat micronutrient deficiencies require decisions to be informed from a body of evidence that consists of evidence from a variety of interventions. Into the future, investment in making available a higher number of SRs, guidelines and policy statements, and actions of NSeI is indicated.