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World Journal of Gastroenterology Oct 2020Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, mostly causing respiratory symptoms, is also known to affect the gastrointestinal tract. Several...
BACKGROUND
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, mostly causing respiratory symptoms, is also known to affect the gastrointestinal tract. Several case reports hypothesize that SARS-CoV-2 could be an etiological factor in acute pancreatitis (AP).
AIM
To assess all the available evidence in the literature relating to coronavirus disease 2019 (COVID-19) and AP.
METHODS
We performed a systematic review of the available literature on the topic. The systematic search was conducted on 15 May 2020 on MEDLINE, EMBASE, CENTRAL, Web of Science and Scopus with a search key using the terms "amylase," "lipase," "pancr*," "COVID-19" and synonyms. Due to the low quality and poor comparability of the studies, a meta-analysis was not performed.
RESULTS
Six case reports and two retrospective cohorts were included, containing data on eleven COVID-19 patients with AP. Five patients had AP according to the Atlanta classification. Other publications did not provide sufficient information on the diagnostic criteria. Most cases were considered SARS-CoV-2-induced, while several established etiological factors were not investigated. We were able to identify other possible causes in most of them.
CONCLUSION
We strongly highlight the need for adherence to the guidelines during a diagnostic and etiological workup, which could alter therapy.
Topics: Acute Disease; Betacoronavirus; COVID-19; COVID-19 Testing; Clinical Laboratory Techniques; Coronavirus Infections; Guideline Adherence; Humans; Pancreatitis; Pandemics; Pneumonia, Viral; Practice Guidelines as Topic; SARS-CoV-2
PubMed: 33177799
DOI: 10.3748/wjg.v26.i40.6270 -
European Review For Medical and... Mar 2023Chinese herbal medicine (CHM) has been widely used in the treatment of hyperlipidemic acute pancreatitis (HLAP), but the credibility of the evidence for this practice is... (Meta-Analysis)
Meta-Analysis
OBJECTIVE
Chinese herbal medicine (CHM) has been widely used in the treatment of hyperlipidemic acute pancreatitis (HLAP), but the credibility of the evidence for this practice is unclear. We systematically reviewed the efficacy and safety of CHM therapy for HLAP.
MATERIALS AND METHODS
In this systematic review and meta-analysis, we searched the Cochrane Central Register of Controlled Trials, Ovid MEDLINE, PubMed, EMBASE, CBM, CNKI, VIP, and Wanfang databases from inception to October 16, 2022, for randomized controlled trials comparing the combination of CHM and Western medicine therapy vs. Western medicine therapy alone in HLAP adults. This study is registered with PROSPERO (No. CRD 42022371052).
RESULTS
A total of 50 eligible studies involving 3,635 patients were assessed in this meta-analysis. Compared with Western medicine therapy, the combination of CHM increased the total effective rate by 19% in HLAP patients [relative risk (RR): 1.19, 95% CI: (1.16, 1.23)]. There were significant differences between the two groups in improving clinical symptoms, promoting serum amylase and triglyceride recovery, reducing mortality [RR: 0.28, 95% CI: (0.14, 0.56)] and complication rates [RR:0.40, 95% CI: (0.31, 0.52)], and shortening the length of hospital stay [MD: -3.96, 95% CI: (-4.76, -3.16)]. Adverse reactions were similar between groups. Findings were robust in the sensitivity analysis.
CONCLUSIONS
The combined CHM treatment was more effective than Western medicine alone in HLAP patients. However, due to the methodological shortcoming of the eligible studies, caution is needed when interpreting these findings.
Topics: Adult; Humans; Drugs, Chinese Herbal; Acute Disease; Pancreatitis; Randomized Controlled Trials as Topic; Phytotherapy
PubMed: 37013744
DOI: 10.26355/eurrev_202303_31760 -
Scandinavian Journal of Gastroenterology Jul 2021To review clinical and laboratory findings in patients with SARS-Cov-2 (COVID-19) related acute pancreatitis.
OBJECTIVES
To review clinical and laboratory findings in patients with SARS-Cov-2 (COVID-19) related acute pancreatitis.
METHODS
This systematic review was based on a database search for articles of COVID-19 related acute pancreatitis in adult patients with confirmed COVID-19 infection that included age, gender, presenting symptoms, the onset of symptoms, laboratory values, imaging findings and exclusion of common causes of pancreatitis.
RESULTS
Altogether 35 articles comprising 37 patients were included. Acute pancreatitis was the first presentation of COVID-19 in 43% of patients, concurrent with general or respiratory symptoms in 14% of patients or delayed after general or pulmonary symptoms by an average of 10 ± 5 d (range, 1 - 19 d) in 43% of patients. Serum amylase and lipase levels were elevated in 87% and 100% of patients. In 50% and 84%, amylase and lipase levels exceeded three-fold the upper normal limit. Pancreatic necrosis was reported in 6% of patients and in 12% of patients, the pancreas appeared normal. Three patients died.
CONCLUSIONS
We conclude that the bi-modal pattern of the onset of symptoms supports both the cytotoxic and the immune-related pathogenesis of the pancreatic injury. Acute pancreatitis may be the first symptom of COVID-19 infection. Necrosis of the pancreas is rare.
Topics: Acute Disease; Adult; Amylases; COVID-19; Humans; Lipase; Pancreas; Pancreatitis; SARS-CoV-2; Tomography, X-Ray Computed
PubMed: 33989101
DOI: 10.1080/00365521.2021.1922751 -
The Cochrane Database of Systematic... Dec 2016The advent of highly active antiretroviral therapy (ART) has reduced the morbidity and mortality due to HIV infection. The World Health Organization (WHO) ART guidelines... (Meta-Analysis)
Meta-Analysis Review
Efavirenz or nevirapine in three-drug combination therapy with two nucleoside or nucleotide-reverse transcriptase inhibitors for initial treatment of HIV infection in antiretroviral-naïve individuals.
BACKGROUND
The advent of highly active antiretroviral therapy (ART) has reduced the morbidity and mortality due to HIV infection. The World Health Organization (WHO) ART guidelines focus on three classes of antiretroviral drugs, namely nucleoside or nucleotide reverse transcriptase inhibitors (NRTI), non-nucleoside reverse transcriptase inhibitors (NNRTI) and protease inhibitors. Two of the most common medications given as first-line treatment are the NNRTIs, efavirenz (EFV) and nevirapine (NVP). It is unclear which NNRTI is more efficacious for initial therapy. This systematic review was first published in 2010.
OBJECTIVES
To determine which non-nucleoside reverse transcriptase inhibitor, either EFV or NVP, is more effective in suppressing viral load when given in combination with two nucleoside reverse transcriptase inhibitors as part of initial antiretroviral therapy for HIV infection in adults and children.
SEARCH METHODS
We attempted to identify all relevant studies, regardless of language or publication status, in electronic databases and conference proceedings up to 12 August 2016. We searched MEDLINE, Embase, the Cochrane Central Register of Controlled Trials (CENTRAL), the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP) and ClinicalTrials.gov to 12 August 2016. We searched LILACS (Latin American and Caribbean Health Sciences Literature) and the Web of Science from 1996 to 12 August 2016. We checked the National Library of Medicine (NLM) Gateway from 1996 to 2009, as it was no longer available after 2009.
SELECTION CRITERIA
We included all randomized controlled trials (RCTs) that compared EFV to NVP in people with HIV without prior exposure to ART, irrespective of the dosage or NRTI's given in combination.The primary outcome of interest was virological success. Other primary outcomes included mortality, clinical progression to AIDS, severe adverse events, and discontinuation of therapy for any reason. Secondary outcomes were change in CD4 count, treatment failure, development of ART drug resistance, and prevention of sexual transmission of HIV.
DATA COLLECTION AND ANALYSIS
Two review authors assessed each reference for inclusion using exclusion criteria that we had established a priori. Two review authors independently extracted data from each included trial using a standardized data extraction form. We analysed data on an intention-to-treat basis. We performed subgroup analyses for concurrent treatment for tuberculosis and dosage of NVP. We followed standard Cochrane methodological procedures.
MAIN RESULTS
Twelve RCTs, which included 3278 participants, met our inclusion criteria. None of these trials included children. The length of follow-up time, study settings, and NRTI combination drugs varied greatly. In five included trials, participants were receiving concurrent treatment for tuberculosis.There was little or no difference between EFV and NVP in virological success (RR 1.04, 95% CI 0.99 to 1.09; 10 trials, 2438 participants; high quality evidence), probably little or no difference in mortality (RR 0.84, 95% CI 0.59 to 1.19; 8 trials, 2317 participants; moderate quality evidence) and progression to AIDS (RR 1.23, 95% CI 0.72 to 2.11; 5 trials, 2005 participants; moderate quality evidence). We are uncertain whether there is a difference in all severe adverse events (RR 0.91, 95% CI 0.71 to 1.18; 8 trials, 2329 participants; very low quality evidence). There is probably little or no difference in discontinuation rate (RR 0.93, 95% CI 0.69 to 1.25; 9 trials, 2384 participants; moderate quality evidence) and change in CD4 count (MD -3.03; 95% CI -17.41 to 11.35; 9 trials, 1829 participants; moderate quality evidence). There may be little or no difference in treatment failure (RR 0.97, 95% CI 0.76 to 1.24; 5 trials, 737 participants; low quality evidence). Development of drug resistance is probably slightly less in the EFV arms (RR 0.76, 95% CI 0.60 to 0.95; 4 trials, 988 participants; moderate quality evidence). No studies were found that looked at sexual transmission of HIV.When we examined the adverse events individually, EFV probably is associated with more people with impaired mental function (7 per 1000) compared to NVP (2 per 1000; RR 4.46, 95% CI 1.65 to 12.03; 6 trials, 2049 participants; moderate quality evidence) but fewer people with elevated transaminases (RR 0.52, 95% CI 0.35 to 0.78; 3 trials, 1299 participants; high quality evidence), fewer people with neutropenia (RR 0.48, 95% CI 0.28 to 0.82; 3 trials, 1799 participants; high quality evidence), and probably fewer people withrash (229 per 100 with NVP versus 133 per 1000 with EFV; RR 0.58, 95% CI 0.34 to 1.00; 7 trials, 2277 participants; moderate quality evidence). We found that there may be little or no difference in gastrointestinal adverse events (RR 0.76, 95% CI 0.48 to 1.21; 6 trials, 2049 participants; low quality evidence), pyrexia (RR 0.65, 95% CI 0.15 to 2.73; 3 trials, 1799 participants; low quality evidence), raised alkaline phosphatase (RR 0.65, 95% CI 0.17 to 2.50; 1 trial, 1007 participants; low quality evidence), raised amylase (RR 1.40, 95% CI 0.72 to 2.73; 2 trials, 1071 participants; low quality evidence) and raised triglycerides (RR 1.10, 95% CI 0.39 to 3.13; 2 trials, 1071 participants; low quality evidence). There was probably little or no difference in serum glutamic oxaloacetic transaminase (SGOT; MD 3.3, 95% CI -2.06 to 8.66; 1 trial, 135 participants; moderate quality evidence), serum glutamic- pyruvic transaminase (SGPT; MD 5.7, 95% CI -4.23 to 15.63; 1 trial, 135 participants; moderate quality evidence) and raised cholesterol (RR 6.03, 95% CI 0.75 to 48.78; 1 trial, 64 participants; moderate quality evidence).Our subgroup analyses revealed that NVP slightly increases mortality when given once daily (RR 0.34, 95% CI 0.13 to 0.90; 3 trials, 678 participants; high quality evidence). There were little or no differences in the primary outcomes for patients who were concurrently receiving treatment for tuberculosis.
AUTHORS' CONCLUSIONS
Both drugs have similar benefits in initial treatment of HIV infection when combined with two NRTIs. The adverse events encountered affect different systems, with EFV more likely to cause central nervous system adverse events and NVP more likely to raise transaminases, cause neutropenia and rash.
Topics: Adult; Alkynes; Anti-HIV Agents; Benzoxazines; Cyclopropanes; Drug Therapy, Combination; HIV Infections; Humans; Nevirapine; Randomized Controlled Trials as Topic; Reverse Transcriptase Inhibitors; Viral Load
PubMed: 27943261
DOI: 10.1002/14651858.CD004246.pub4 -
International Journal of Surgery... Jun 2019We conducted a systematic review on the diagnostic accuracy of classical and newly reported hematological parameters which are easily available in a resource limited...
BACKGROUND
We conducted a systematic review on the diagnostic accuracy of classical and newly reported hematological parameters which are easily available in a resource limited setting in making a diagnosis of Acute Mesenteric Ischemia (AMI).
METHODS
We searched the PubMed, Scopus, and Cochrane library from January 1940 to April 2018. The search was limited to studies published in English and those involving human subjects only. The diagnostic accuracy of conveniently available parameters: Mean Platelet Volume (MPV), Neutrophil to Lymphocyte Ratio (NLR), Red Cell Distribution Width (RDW), lactate, D-dimer, alkaline aminotransferase, aspartate amino transferase, white blood cell count, lactate dehydrogenase, and amylase were assessed in this review. Studies were only included if they provided sufficient information allowing us to make a diagnostic accuracy contingency table and define a gold standard test. We excluded letters, editorials, and case reports. There were no restrictions to any particular study design. The QUADAS 2 protocol was used for quality appraisal. This study protocol was registered on Prospero with ID CRD42018088953.
RESULTS
Of 560 articles which were initially retrieved, 20 studies, comprising of 2043 participants, were eligible for this review. AMI was diagnosed in 518 patients. D-dimer had the highest median sensitivity of 93% while the median specificity of lactate and NLR were 85.9 and 85.8, respectively.
CONCLUSION
Observing the high heterogeneity among the studies, currently it is difficult to suggest any single marker for diagnosing AMI. Compared to the classical markers, RDW, NLR and MPV showed higher specificities. Using these new markers alongside with the classical markers in the context of a scoring system might help in making a diagnosis of AMI in emergency settings.
Topics: Acute Disease; Aspartate Aminotransferases; Biomarkers; Erythrocyte Indices; Fibrin Fibrinogen Degradation Products; Humans; Leukocyte Count; Lymphocytes; Mean Platelet Volume; Mesenteric Ischemia; Neutrophils; Sensitivity and Specificity
PubMed: 30999055
DOI: 10.1016/j.ijsu.2019.04.005 -
HPB : the Official Journal of the... Jan 2020Early recognition of postoperative pancreatic fistula might decrease the risk of subsequent life threatening complications. The aim of this review was to systematically...
BACKGROUND
Early recognition of postoperative pancreatic fistula might decrease the risk of subsequent life threatening complications. The aim of this review was to systematically evaluate the accuracy of postoperative clinical, biochemical and radiologic variables for early recognition of clinically relevant postoperative pancreatic fistula.
METHODS
A systematic literature search was performed up to August 2018. Clinical studies reporting on the association between postoperative variables and clinically relevant postoperative pancreatic fistula were included. Variables were stratified: early prediction (postoperative day 1-2) versus early diagnosis (day 3) and had to be reported in 2 cohorts.
RESULTS
Overall, 37 included studies reported on 17 different diagnostic variables after 8701 pancreatic resections. Clinically relevant postoperative pancreatic fistula occurred in 1532/8701 patients (18%). Early prediction variables included elevated serum and drain amylase (day 1). Identified variables for early diagnosis were: non-serous drain efflux (day 3); positive drain culture (day 3); elevated temperature (any day); elevated C-Reactive Protein (CRP; day 4); elevated white blood cell count (day 4) and peripancreatic collections on computed tomography (CT; day 5-10).
CONCLUSION
This review provides a comprehensive overview of postoperative variables associated with clinically relevant pancreatic fistula. Incorporation of variables in future algorithms could potentially mitigate the clinical impact of postoperative pancreatic fistula.
Topics: Early Diagnosis; Humans; Pancreatectomy; Pancreatic Fistula; Postoperative Complications; Predictive Value of Tests; Risk Factors
PubMed: 31445782
DOI: 10.1016/j.hpb.2019.07.005 -
International Journal of Molecular... Oct 2020Saliva as a biological fluid has a remarkable potential in the non-invasive diagnostics of several systemic disorders. Inflammatory bowel diseases are chronic...
Saliva as a biological fluid has a remarkable potential in the non-invasive diagnostics of several systemic disorders. Inflammatory bowel diseases are chronic inflammatory disorders of the gastrointestinal tract. This systematic review was designed to answer the question "Are salivary biomarkers reliable for the diagnosis of inflammatory bowel diseases?". Following the inclusion and exclusion criteria, eleven studies were included (according to PRISMA statement guidelines). Due to their heterogeneity, the potential salivary markers for IBD were divided into four groups: oxidative status markers, inflammatory cytokines, microRNAs and other biomarkers. Active CD patients manifest decreased activity of antioxidants (e.g., glutathione, catalase) and increased lipid peroxidation. Therefore, malondialdehyde seems to be a good diagnostic marker of CD. Moreover, elevated concentrations of proinflammatory cytokines (such as interleukin 1β, interleukin 6 or tumour necrosis factor α) are associated with the activity of IBD. Additionaly, selected miRNAs are altered in saliva (overexpressed miR-101 in CD; overexpressed miR-21, miR-31, miR-142-3p and underexpressed miR-142-5p in UC). Among other salivary biomarkers, exosomal PSMA7, α-amylase and calprotectin are detected. In conclusion, saliva contains several biomarkers which can be used credibly for the early diagnosis and regular monitoring of IBD. However, further investigations are necessary to validate these findings, as well as to identify new reliable salivary biomarkers.
Topics: Biomarkers; Cytokines; Humans; Inflammation Mediators; Inflammatory Bowel Diseases; MicroRNAs; Oxidative Stress; Prognosis; Reproducibility of Results; Saliva; Sensitivity and Specificity
PubMed: 33050496
DOI: 10.3390/ijms21207477 -
Nutrients Aug 2020Evidence synthesizing the effects of acute body water losses on various markers of glycemic regulation, appetite, metabolism, and stress is lacking. Thus, the purpose of... (Meta-Analysis)
Meta-Analysis
Evidence synthesizing the effects of acute body water losses on various markers of glycemic regulation, appetite, metabolism, and stress is lacking. Thus, the purpose of this review was to summarize the response of various hormonal changes involved in these physiologic functions to dehydration. A comprehensive literature search for peer-reviewed research in the databases PubMed, Scopus, CINAHL, and SportDiscus was conducted. Studies were included if they contained samples of adults (>18 years) and experimentally induced dehydration as measured by acute body mass loss. Twenty-one articles were eligible for inclusion. Findings suggested cortisol is significantly elevated with hypohydration (standard mean difference [SMD] = 1.12, 95% CI [0.583, 1.67], < 0.0001). Testosterone was significantly lower in studies where hypohydration was accompanied by caloric restriction (SMD= -1.04, 95% CI [-1.93, -0.14], = 0.02), however, there were no changes in testosterone in studies examining hypohydration alone (SMD = -0.17, 95% CI [-0.51 0.16], = 0.30). Insulin and ghrelin were unaffected by acute total body water losses. Acute hypohydration increases markers of catabolism but has a negligible effect on markers of glycemic regulation, appetite, anabolism and stress. Given the brevity of existing research, further research is needed to determine the impact of hydration on glucagon, leptin, peptide YY and the subsequent outcomes relevant to both health and performance.
Topics: Adolescent; Adult; Appetite; Blood Glucose; Caloric Restriction; Dehydration; Female; Ghrelin; Humans; Hydrocortisone; Leptin; Male; Peptide YY; Stress, Physiological; Testosterone; Young Adult; alpha-Amylases
PubMed: 32825404
DOI: 10.3390/nu12092526 -
Maternal & Child Nutrition Apr 2008[Table: see text] (Review)
Review
UNLABELLED
[Table: see text]
SUMMARY
INTRODUCTION
Complementary feeding interventions are usually targeted at the age range of 6–24 months, which is the time of peak incidence of growth faltering, micronutrient deficiencies and infectious illnesses in developing countries. After 2 years of age, it is much more difficult to reverse the effects of malnutrition on stunting, and some of the functional deficits may be permanent. Therefore, interventions that are effective at reducing malnutrition during this vulnerable period should be a high priority. Although several types of interventions can be targeted to this age range (e.g. micronutrient supplementation), a food‐based, comprehensive approach may be more effective and sustainable than programmes targeting individual nutrient deficiencies. For this review, a broad definition of ‘complementary feeding interventions’ is used so as to capture the full range of strategies that can be used.
SCOPE AND METHODS OF THE REVIEW
The interventions described in this review generally include one or more components related to the (PAHO/WHO 2003). The 10 guiding principles cover: (1) duration of exclusive breastfeeding and age of introduction of complementary foods; (2) maintenance of breastfeeding; (3) responsive feeding; (4) safe preparation and storage of complementary foods; (5) amount of complementary food needed; (6) food consistency; (7) meal frequency and energy density; (8) nutrient content of complementary foods; (9) use of vitamin‐mineral supplements or fortified products for infant and mother; and (10) feeding during and after illness. This review includes any relevant intervention that targeted children within the age range of 6–24 months. In some cases, the intervention may have included children older than 24 months, but in all studies at least some of the children were between 6 and 24 months. The assumption is that many of the children in these studies were breastfed, although a certain proportion will have terminated breastfeeding before 24 months. Although strategies for optimizing the duration of exclusive breastfeeding or increasing the total duration of breastfeeding may have a direct influence on several of the outcomes of interest, this review will not cover those strategies because another report will review those results. The primary outcomes of interest for this review include growth, morbidity and child development. Micronutrient intake and micronutrient status were also included as outcomes because of their link to these key functional outcomes. Studies that assessed the impact of complementary feeding interventions on feeding practices only were not included because of time constraints and because it has been demonstrated previously that appropriately designed interventions can have a positive impact on feeding practices (Caulfield 1999). For most intervention strategies and outcomes, the literature search was focused on the period from 1996 to 2006, as the previous review by Caulfield (1999) covered the period from 1970 to 1997. For certain interventions not covered in the previous review (i.e. using amylase to increase energy density and interventions focused on iron status outcomes), studies dating back to 1990 were included. Only studies conducted in developing countries were included. The search was conducted using electronic methods, inspection of websites of key private voluntary organizations and the bibliographies of published papers, and personal contacts. The two authors of this review independently assessed the quality of each of the reviewed studies, and those scored as 2– (non‐randomized studies with a high risk of bias) were not included in the tabulation of results. In total, 42 papers were included in the review. These papers report results from 29 efficacy trials and 13 effectiveness studies or programme reports from 25 developing countries. Interventions were considered efficacy trials if there was a high degree of assurance of delivery of the ‘treatment’, generally under carefully controlled research conditions (e.g. provision of a fortified complementary food with frequent follow‐up to assess adherence). Evaluations of interventions carried out in a programme setting, generally with less ability to control delivery of and adherence to ‘treatment’, were considered effectiveness studies. To compare growth (weight and length) results across studies (when these results were reported as means ± SD), we calculated the treatment effect size for each outcome of interest using the formula: When possible, the effect sizes for each outcome were averaged across interventions to obtain a rough estimate of overall impact. Effect size can be categorized as small (∼0.2), medium (∼0.5) or large (∼0.8). Interventions were grouped into five categories depending on the main strategy used: 1.. education about complementary feeding as the main treatment, 2.. complementary food or a food product offering extra energy (with or without added micronutrients) provided as the only treatment, 3.. provision of food combined with some other strategy, usually education for mothers, 4.. fortification of complementary foods (centrally processed fortified foods or home‐fortification products) with micronutrients (with no difference in energy provided to intervention vs. control groups), and 5.. increased energy density and/or nutrient bioavailability of complementary foods through the use of simple technologies. Some studies had more than one intervention group and may thus be included in more than one of the categories. In these situations, only the results for the intervention groups that are relevant to the comparison in question are included in that section. Some of the interventions targeted only malnourished children, but most were aimed at all children in the target age range.
RESULTS
GROWTH
Nearly all of the studies assessed growth as an outcome. There were six efficacy trials and five effectiveness studies in which the main intervention strategy was education about complementary feeding. Taking these 11 studies together, educational interventions had a modest effect on weight (mean effect size = 0.28; range −0.06, 0.96) and linear growth (mean effect size 0.20, range 0.04, 0.64). The two educational interventions with the greatest impact on both weight and length gain (effect sizes of 0.34–0.96) were the projects in Peru (Penny 2005) and China (Guldan 2000). In both of these, a key message was to regularly provide an animal‐source food to the infant (chicken liver, egg or fish in Peru; egg in China). The other educational intervention with a relatively large impact on weight (though not on length) was a study in Bangladesh that targeted children with low weight‐for‐age at baseline (Roy 2005). That intervention also promoted the home preparation of a complementary food mixture that included egg, meat or fish. There were seven efficacy trials and one effectiveness study in which the only intervention strategy was provision of complementary food (often fortified). The results were somewhat inconsistent: there was a positive impact in Ghana and Malawi but no impact in South Africa, Indonesia or Brazil. The overall mean effect size was 0.60 (range −0.02, 2.99) for weight and 0.47 (range −0.04, 1.81) for linear growth, but these effects are inflated by the results from Nigeria (Obatolu 2003) (effect sizes: weight = 2.99, length = 1.81). Excluding that study, the mean effect size was 0.26 (range −0.02, 0.57) for weight and 0.28 (range −0.04, 0.69) for length. For the combination of provision of complementary food with some other strategy (usually education), there were two efficacy trials and six effectiveness studies. With these eight studies combined, the average effect size for weight was 0.35 (range 0.18, 0.66) and that for linear growth was 0.17 (range 0, 0.32). Two studies specifically evaluated whether provision of food plus education was more effective than education alone (Bhandari 2001; Roy 2005). In India (Bhandari 2001), the food plus education group gained 250 g more weight and 0.4 cm more than the control group during the 8‐month intervention, whereas the education‐only group gained only 90 g more than the control group and did not have any advantage in length gain. In Bangladesh (Roy 2005), results for the education‐only group were intermediate between those of the food plus education and control groups. Thus, in these two settings the inclusion of a food supplement was more effective than education alone. The effect of fortification of complementary foods (with no difference in the amount of energy provided to intervention and control groups) on growth was evaluated in six efficacy trials, three of which involved home fortification using micronutrient supplements (powders or crushable tablets). The other three studies used cereal/legumes mixes or a milk formulation to which the micronutrients were added during processing. Only in the fortified‐milk study (conducted in India) was there a significant impact on growth. The average effect size for all six studies was 0.11 (range −0.22, 0.37) for weight and 0.12 (range −0.02, 0.45) for length. There were no effectiveness studies identified within this category. There were five efficacy trials in which the main strategy was aimed at increasing the energy density of the usual complementary food. Only two of these trials had a significant impact on growth (John & Gopaldas 1993; Moursi 2003). In the other three (Mamiro 2004; Hossain 2005a; Owino 2007), there was no increase in energy intake, so the lack of impact on growth is not surprising. The average effect size across all trials was 0.35 (range −0.13, 1.37) for weight and 0.23 (range −0.25, 0.71) for linear growth. 1, 2 compare the effect sizes for growth across each category of intervention. The average effect sizes are in the small to medium range, which is in agreement with estimates from the previous review of interventions completed between 1970 and 1997 [effect size generally 0.10–0.50 (Caulfield 1999)].
MORBIDITY
Only 10 of the intervention studies included data on morbidity outcomes. In most of these, there were no significant effects on morbidity. Most studies included morbidity as a secondary outcome and were not designed or powered to detect differences in morbidity. Two of the educational interventions showed a beneficial effect: a reduction in diarrhoea in Brazil (Vitolo 2005) and a reduction in upper respiratory infection in Vietnam (Schroeder 2002). The fortified‐milk study in India demonstrated a significant reduction in both diarrhoea and acute lower respiratory illness (Sazawal 2007), and a study evaluating home fortification with a micronutrient powder (‘Sprinkles™’) in Pakistan showed beneficial effects on diarrhoea and fever (Sharieff 2006). However, in three studies the interventions were associated with symptoms of morbidity. This was evident in food supplementation interventions in Bangladesh [during the first 2 months of the intervention (Roy 2005)] and in India (Bhandari 2001) and in an energy‐density intervention in Congo (Moursi 2003). In India, the adverse effects on fever and dysentery could have been due to the reduction in breastfeeding that occurred in the intervention group. Unhygienic preparation and storage of complementary foods is another possible explanation for adverse effects of these interventions on morbidity.
BEHAVIOURAL DEVELOPMENT
Only four studies, all efficacy trials, included data on behavioural development. The provision of a fat‐based fortified food product or micronutrients alone improved gross motor development in Ghana (Adu‐Afarwuah 2007) but these types of interventions did not have any significant effect on developmental outcomes in South Africa (Oelofse 2003) or India (Dhingra 2004). Positive results of supplementation with extra energy in Indonesia were seen only in a subgroup (Pollitt 2002).
MICRONUTRIENT INTAKE
Only a few studies reported data on iron, zinc and vitamin A intakes. Education for mothers significantly increased child iron intake in Malawi, India and Peru, but did not have any significant effect on intakes in Brazil. Taking those four studies together, the intervention increased iron intake from complementary foods by 24% (range −7%, 60%) and zinc intake by 26% (range 9%, 53%). Despite those increases, mean iron and zinc intake from complementary foods was still well below recommended intakes in some sites. In Brazil (Santos 2005) a large‐scale food supplementation programme failed to have an impact on intakes of these three micronutrients. There was also no impact of traditional processing of complementary foods in Tanzania (Mamiro 2004). The largest impact on micronutrient intakes resulted from fortification strategies, which increased iron intake by 145–207% in Mexico and Ghana, zinc intake by 201–271% in Ecuador and Ghana, and vitamin A intake by 107% to more than 2300% in Ecuador and Ghana.
ANAEMIA AND IRON STATUS
Four studies of educational interventions included data on anaemia and/or iron status. In India and China there was an increase in mean haemoglobin but in Nicaragua and Brazil there was no significant effect. The difference in impact across studies could be due to the specificity of the messages regarding enhancement of iron intake in the two former studies, compared with the latter two projects. Overall, for these four studies the average impact was an increase of 4 g L in mean haemoglobin and a reduction in the prevalence of anaemia of 5 percentage points. In 12 studies, the target group was provided with a complementary food that was fortified with iron (and sometimes other micronutrients as well). The comparison group received either no additional food (five studies: two efficacy trials and three programme evaluations), or an unfortified complementary food (seven efficacy trials). For the former group of five studies, the average impact was an increase of 4 g L in mean haemoglobin and a reduction in the prevalence of anaemia of 13 percentage points. For the latter group of seven studies, the average effect was an increase of 6 g L in mean haemoglobin and a reduction in the prevalence of anaemia of 17 percentage points. Another seven studies (five efficacy trials, two programme evaluations) evaluated the effect of home fortification of complementary foods using powders, crushable tablets or fat‐based products. Taking these seven studies together, the average impact was an increase of 8 g L in mean haemoglobin and a reduction in the prevalence of anaemia of 21 percentage points. Some of the above studies included direct assessments of iron status, such as ferritin values. In most cases, the impact on the prevalence of iron deficiency was greater than the impact on anaemia, indicating that other factors such as malaria contribute to the persistently high rates of anaemia in certain populations.
ZINC STATUS
Only five studies reported plasma zinc concentrations, all of which involved evaluation of a fortified complementary food (three efficacy trials, one programme evaluation), or a home‐fortification product (efficacy trial). The fortified foods provided 3–6.5 mg day zinc, and the daily home‐fortification ‘foodlet’ (crushable tablet) provided 10 mg day. In the four studies using fortified foods, none demonstrated a significant difference between intervention and control groups in mean plasma zinc concentration or the percentage of children with low plasma Zn. In the foodlet intervention trial in South Africa, the group receiving daily micronutrients had significantly higher plasma zinc than the placebo group (Smuts 2005). Overall, these results indicate that complementary foods fortified with multiple micronutrients, including zinc, have little impact on plasma zinc concentration, perhaps because of the relatively low bioavailability of zinc when consumed with cereal‐based or cereal/legume blend foods.
VITAMIN A STATUS
Seven intervention studies to evaluate the impact of a fortified complementary food (three efficacy trials, two programme evaluations) or home‐fortification products (two efficacy trials) included data on vitamin A status. There was a significant impact on mean serum vitamin A concentration in four of the five interventions using fortified complementary foods, and a reduction in the incidence of vitamin A deficiency in the two studies (of these five) that evaluated this outcome. There was no significant impact on serum vitamin A concentration in the two studies using home‐fortification products, which the investigators attributed to widespread participation in vitamin A supplementation programmes that occurred during the study time period. Taken together, these seven studies indicate that complementary foods fortified with vitamin A can reduce the incidence of vitamin A deficiency (by an average of ∼−13 percentage points in the two studies that reported this), although this impact may be obscured by concurrent vitamin A supplementation programmes.
CONCLUSIONS
The results of this review indicate that there is no single universal ‘best’ package of components in complementary feeding interventions because the needs of the target population vary greatly. The impact of such interventions is thus context specific, and depends on factors such as the initial prevalence of malnutrition, the degree of household food insecurity, the energy density of traditional complementary foods and the availability of micronutrient‐rich local foods. Child growth was the most common outcome measured, but it may not be the most sensitive indicator of benefit because of other constraints that limit the extent to which a child's growth (particularly height) can respond to post‐natal interventions. The impact of these interventions on child growth was mixed. When the primary approach was education about child feeding, interventions that included a strong emphasis on feeding nutrient‐rich animal‐source foods were more likely to show an effect. When a complementary food was provided, with or without concurrent strategies such as nutrition education, the studies in Africa and South Asia generally showed positive effects, while those in other regions were more variable. This may be related to the relatively high prevalence of food insecurity in Africa and South Asia. In such contexts, providing additional food – not just education – may facilitate the ability of families to follow complementary feeding guidelines. In several studies, the impact of providing a complementary food, in combination with nutrition education, was evident only in the younger children. This underscores the importance of beginning complementary feeding programmes during infancy, when nutrient needs relative to energy intake are the highest and the ability of the child to respond to a nutritional intervention is the greatest. Because most interventions in which a complementary food was provided used fortified foods, it is not possible to determine whether the positive effects on growth are due to greater energy/protein/fat intake, greater micronutrient intake, or the combination. It is noteworthy that the interventions in which micronutrient fortification was the sole component (i.e. comparisons of fortified vs. unfortified complementary foods, or evaluations of home fortification) generally had little or no effect on growth. Further research on the biological mechanisms underlying growth effects, including the potential roles of milk protein and essential fatty acids, is needed. Increasing the energy density of complementary foods may have a positive effect on growth when the traditional complementary food has a low energy density and infants are unable to adequately compensate by consuming a higher volume or being fed more frequently. However, before including this strategy in a complementary feeding programme, it is advisable to first demonstrate that increasing energy density of the traditional food will actually result in increased total daily energy intake (including energy intake from breastmilk). It should be noted that increasing energy density will not necessarily result in adequate micronutrient intake, so this strategy should be accompanied by other efforts to improve dietary adequacy. The potential for an impact on growth appears to be greater with interventions using key educational messages, provision of complementary food with or without fortification, or increased energy density of complementary foods than with interventions based on fortification alone. Although the effect sizes for growth were generally modest (0.1–0.5), the potential impact is larger (0.5–0.6) if programmes are optimally designed and implemented. Furthermore, the impact on the lower tail of the distribution – that is, on stunting rates – could be considerably larger than the effect on the mean height ‐score. In general, effect sizes for growth of interventions providing complementary foods were greater for efficacy trials than for programmes. This is not surprising, given the logistical challenges of ensuring consistent delivery of food (and education) in large‐scale programmes. Some of the complementary feeding interventions reviewed had a beneficial impact on morbidity rates, but there is the potential for adverse effects of strategies such as food supplementation and increased energy density. This may be due to excessive displacement of breastmilk and/or unhygienic preparation and storage of complementary foods. This highlights the need to couple complementary feeding interventions with counselling regarding continued breastfeeding, responsive feeding and hygienic practices. There is very little information on the impact of complementary feeding interventions on behavioural development, but recent studies in infants have yielded promising results. It is important to include assessments of behavioural development in such evaluations, as these outcomes may be more sensitive to improvements in child nutrition than outcomes such as growth and morbidity. With regard to micronutrient intake, the results of educational interventions indicate that it is difficult to achieve adequate iron intake from unfortified local foods at 6–12 months of age. Fortification (either processed complementary foods or home fortification) is the most feasible option in most circumstances given the cost of iron‐rich foods (such as liver or meat). Adequate zinc and vitamin A intakes can be achieved from local foods, but this requires very careful attention to dietary choices. Fortification can help ensure zinc and vitamin A intakes when nutrient‐rich local foods are costly or unavailable (e.g. seasonally). The results also indicate that fortification can be highly effective at improving iron and vitamin A status. Although this could be accomplished by other strategies, such as iron or vitamin A supplementation, using complementary foods as the vehicle may be less risky [given recent concerns about adverse effects of iron supplements in certain situations (WHO & UNICEF 2007)] and more acceptable to caregivers. Further research is needed to understand why zinc‐fortified foods have generally little effect on plasma zinc concentrations. Complementary feeding interventions, by themselves, cannot change the underlying conditions of poverty and poor sanitation that contribute to child malnutrition. They need to be implemented in conjunction with a larger strategy that includes improved water and sanitation, better health care and adequate housing. Nonetheless, the results of this review indicate that carefully designed programmes that include pre‐tested educational messages provided through multiple channels, with fortified foods or home‐fortification products made available depending on the needs of the target population, can substantially improve growth and micronutrient status and may also reduce morbidity and enhance behavioural development. The key challenge is how to implement high‐quality programmes that are sustainable when delivered on a large scale.
Topics: Developing Countries; Dietary Supplements; Female; Food, Fortified; Humans; Infant; Infant Food; Infant Nutrition Disorders; Male; Outcome and Process Assessment, Health Care; Weaning
PubMed: 18289157
DOI: 10.1111/j.1740-8709.2007.00124.x -
Frontiers in Neurology 2021Ketogenic diet therapies (KDT) are high-fat, low carbohydrate diets used as an effective treatment option for drug-resistant epilepsy. There is limited research on the...
Ketogenic diet therapies (KDT) are high-fat, low carbohydrate diets used as an effective treatment option for drug-resistant epilepsy. There is limited research on the efficacy of KDT for super-refractory status epilepticus (SRSE). We systematically review evidence for use of KDT in children with SRSE and present a single UK tertiary centre's experience. Thirty one articles were included, of which 24 were "medium" or "low" quality. One hundred and forty seven children with SRSE started KDT, of which 141 (96%) achieved ketosis. KDT was started mean 5.3 days (range 1-420) after status epilepticus (SE) started. SRSE resolved in 85/141 (60%) children after mean 6.3 days (range 0-19) post SE onset, but it is unclear whether further treatments were initiated post-KDT. 13/141 (9%) children died. Response to KDT was more likely when initiated earlier ( = 0.03) and in females ( = 0.01). Adverse side effects were reported in 48/141 (34%), mostly gastrointestinal; potentially serious adverse effects occurred in ≤4%. Eight children with SRSE, all diagnosed with febrile infection-related epilepsy syndrome, were treated with KDT at Great Ormond Street Hospital for Children. KDT was initiated enterally at mean day 13.6+/- 5.1 of admission. Seven of 8 (88%) children reported adverse side effects, which were potentially serious in 4/8 (50%), including metabolic acidosis, hypoglycaemia and raised amylase. SE ceased in 6/8 (75%) children after mean 25+/- 9.4 days post onset, but other treatments were often started concomitantly and all children started other treatments post-KDT. Two of 8 (25%) children died during admission and another died post-admission. Four of the remaining 5 children continue to have drug-resistant seizures, one of whom remains on KDT; seizure burden was unknown for one child. Our findings indicate that KDT is possible and safe in children with SRSE. Cessation of SRSE may occur in almost two-thirds of children initiated with KDT, but a causal effect is difficult to determine due to concomitant treatments, treatments started post-KDT and the variable length of time post-KDT onset when SRSE cessation occurs. Given that serious adverse side effects seem rare and response rates are (cautiously) favorable, KDT should be considered as an early treatment option in this group.
PubMed: 33776895
DOI: 10.3389/fneur.2021.643105