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The Cochrane Database of Systematic... Aug 2018Phosphate binders are used to reduce positive phosphate balance and to lower serum phosphate levels for people with chronic kidney disease (CKD) with the aim to prevent... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Phosphate binders are used to reduce positive phosphate balance and to lower serum phosphate levels for people with chronic kidney disease (CKD) with the aim to prevent progression of chronic kidney disease-mineral and bone disorder (CKD-MBD). This is an update of a review first published in 2011.
OBJECTIVES
The aim of this review was to assess the benefits and harms of phosphate binders for people with CKD with particular reference to relevant biochemical end-points, musculoskeletal and cardiovascular morbidity, hospitalisation, and death.
SEARCH METHODS
We searched the Cochrane Kidney and Transplant Register of Studies up to 12 July 2018 through contact with the Information Specialist using search terms relevant to this review. Studies in the Register are identified through searches of CENTRAL, MEDLINE, and EMBASE, conference proceedings, the International Clinical Trials Register (ICTRP) Search Portal and ClinicalTrials.gov.
SELECTION CRITERIA
We included randomised controlled trials (RCTs) or quasi-RCTs of adults with CKD of any GFR category comparing a phosphate binder to another phosphate binder, placebo or usual care to lower serum phosphate. Outcomes included all-cause and cardiovascular death, myocardial infarction, stroke, adverse events, vascular calcification and bone fracture, and surrogates for such outcomes including serum phosphate, parathyroid hormone (PTH), and FGF23.
DATA COLLECTION AND ANALYSIS
Two authors independently selected studies for inclusion and extracted study data. We applied the Cochrane 'Risk of Bias' tool and used the GRADE process to assess evidence certainty. We estimated treatment effects using random-effects meta-analysis. Results were expressed as risk ratios (RR) for dichotomous outcomes together with 95% confidence intervals (CI) or mean differences (MD) or standardised MD (SMD) for continuous outcomes.
MAIN RESULTS
We included 104 studies involving 13,744 adults. Sixty-nine new studies were added to this 2018 update.Most placebo or usual care controlled studies were among participants with CKD G2 to G5 not requiring dialysis (15/25 studies involving 1467 participants) while most head to head studies involved participants with CKD G5D treated with dialysis (74/81 studies involving 10,364 participants). Overall, seven studies compared sevelamer with placebo or usual care (667 participants), seven compared lanthanum to placebo or usual care (515 participants), three compared iron to placebo or usual care (422 participants), and four compared calcium to placebo or usual care (278 participants). Thirty studies compared sevelamer to calcium (5424 participants), and fourteen studies compared lanthanum to calcium (1690 participants). No study compared iron-based binders to calcium. The remaining studies evaluated comparisons between sevelamer (hydrochloride or carbonate), sevelamer plus calcium, lanthanum, iron (ferric citrate, sucroferric oxyhydroxide, stabilised polynuclear iron(III)-oxyhydroxide), calcium (acetate, ketoglutarate, carbonate), bixalomer, colestilan, magnesium (carbonate), magnesium plus calcium, aluminium hydroxide, sucralfate, the inhibitor of phosphate absorption nicotinamide, placebo, or usual care without binder. In 82 studies, treatment was evaluated among adults with CKD G5D treated with haemodialysis or peritoneal dialysis, while in 22 studies, treatment was evaluated among participants with CKD G2 to G5. The duration of study follow-up ranged from 8 weeks to 36 months (median 3.7 months). The sample size ranged from 8 to 2103 participants (median 69). The mean age ranged between 42.6 and 68.9 years.Random sequence generation and allocation concealment were low risk in 25 and 15 studies, respectively. Twenty-seven studies reported low risk methods for blinding of participants, investigators, and outcome assessors. Thirty-one studies were at low risk of attrition bias and 69 studies were at low risk of selective reporting bias.In CKD G2 to G5, compared with placebo or usual care, sevelamer, lanthanum, iron and calcium-based phosphate binders had uncertain or inestimable effects on death (all causes), cardiovascular death, myocardial infarction, stroke, fracture, or coronary artery calcification. Sevelamer may lead to constipation (RR 6.92, CI 2.24 to 21.4; low certainty) and lanthanum (RR 2.98, CI 1.21 to 7.30, moderate certainty) and iron-based binders (RR 2.66, CI 1.15 to 6.12, moderate certainty) probably increased constipation compared with placebo or usual care. Lanthanum may result in vomiting (RR 3.72, CI 1.36 to 10.18, low certainty). Iron-based binders probably result in diarrhoea (RR 2.81, CI 1.18 to 6.68, high certainty), while the risks of other adverse events for all binders were uncertain.In CKD G5D sevelamer may lead to lower death (all causes) (RR 0.53, CI 0.30 to 0.91, low certainty) and induce less hypercalcaemia (RR 0.30, CI 0.20 to 0.43, low certainty) when compared with calcium-based binders, and has uncertain or inestimable effects on cardiovascular death, myocardial infarction, stroke, fracture, or coronary artery calcification. The finding of lower death with sevelamer compared with calcium was present when the analysis was restricted to studies at low risk of bias (RR 0.50, CI 0.32 to 0.77). In absolute terms, sevelamer may lower risk of death (all causes) from 210 per 1000 to 105 per 1000 over a follow-up of up to 36 months, compared to calcium-based binders. Compared with calcium-based binders, lanthanum had uncertain effects with respect to all-cause or cardiovascular death, myocardial infarction, stroke, fracture, or coronary artery calcification and probably had reduced risks of treatment-related hypercalcaemia (RR 0.16, CI 0.06 to 0.43, low certainty). There were no head-to-head studies of iron-based binders compared with calcium. The paucity of placebo-controlled studies in CKD G5D has led to uncertainty about the effects of phosphate binders on patient-important outcomes compared with placebo.It is uncertain whether the effects of binders on clinically-relevant outcomes were different for patients who were and were not treated with dialysis in subgroup analyses.
AUTHORS' CONCLUSIONS
In studies of adults with CKD G5D treated with dialysis, sevelamer may lower death (all causes) compared to calcium-based binders and incur less treatment-related hypercalcaemia, while we found no clinically important benefits of any phosphate binder on cardiovascular death, myocardial infarction, stroke, fracture or coronary artery calcification. The effects of binders on patient-important outcomes compared to placebo are uncertain. In patients with CKD G2 to G5, the effects of sevelamer, lanthanum, and iron-based phosphate binders on cardiovascular, vascular calcification, and bone outcomes compared to placebo or usual care, are also uncertain and they may incur constipation, while iron-based binders may lead to diarrhoea.
Topics: Adult; Aged; Calcium; Calcium Compounds; Cause of Death; Chelating Agents; Chronic Disease; Chronic Kidney Disease-Mineral and Bone Disorder; Disease Progression; Fibroblast Growth Factor-23; Humans; Hypercalcemia; Iron Compounds; Lanthanum; Middle Aged; Parathyroid Hormone; Phosphorus; Polyamines; Randomized Controlled Trials as Topic; Renal Dialysis; Sevelamer
PubMed: 30132304
DOI: 10.1002/14651858.CD006023.pub3 -
Frontiers in Endocrinology 2023Reprogramming of cellular metabolism is now a hallmark of tumorigenesis. In recent years, research on pancreatic neuroendocrine tumors (pNETs) has focused on genetic and... (Review)
Review
INTRODUCTION
Reprogramming of cellular metabolism is now a hallmark of tumorigenesis. In recent years, research on pancreatic neuroendocrine tumors (pNETs) has focused on genetic and epigenetic modifications and related signaling pathways, but few studies have been devoted to characterizing the metabolic profile of these tumors. In this review, we thoroughly investigate the metabolic pathways in pNETs by analyzing the transcriptomic and metabolomic data available in the literature.
METHODOLOGY
We retrieved and downloaded gene expression profiles from all publicly available gene set enrichments (GSE43797, GSE73338, and GSE117851) to compare the differences in expressed genes based on both the stage and MEN1 mutational status. In addition, we conducted a systematic review of metabolomic data in NETs.
RESULTS
By combining transcriptomic and metabolomic approaches, we have identified a distinctive metabolism in pNETs compared with controls without pNETs. Our analysis showed dysregulations in the one-carbon, glutathione, and polyamine metabolisms, fatty acid biosynthesis, and branched-chain amino acid catabolism, which supply the tricarboxylic acid cycle. These targets are implicated in pNET cell proliferation and metastasis and could also have a prognostic impact. When analyzing the profiles of patients with or without metastasis, or with or without MEN1 mutation, we observed only a few differences due to the scarcity of published clinical data in the existing research. Consequently, further studies are now necessary to validate our data and investigate these potential targets as biomarkers or therapeutic solutions, with a specific focus on pNETs.
Topics: Humans; Pancreatic Neoplasms; Neuroendocrine Tumors; Prognosis; Epigenesis, Genetic; Neuroectodermal Tumors, Primitive
PubMed: 37908747
DOI: 10.3389/fendo.2023.1248575 -
Journal of the American Society of... Jan 2022Benefits of phosphate-lowering interventions on clinical outcomes in patients with CKD are unclear; systematic reviews have predominantly involved patients on dialysis.... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Benefits of phosphate-lowering interventions on clinical outcomes in patients with CKD are unclear; systematic reviews have predominantly involved patients on dialysis. This study aimed to summarize evidence from randomized controlled trials (RCTs) concerning benefits and risks of noncalcium-based phosphate-lowering treatment in nondialysis CKD.
METHODS
We conducted a systematic review and meta-analyses of RCTs involving noncalcium-based phosphate-lowering therapy compared with placebo, calcium-based binders, or no study medication, in adults with CKD not on dialysis or post-transplant. RCTs had ≥3 months follow-up and outcomes included biomarkers of mineral metabolism, cardiovascular parameters, and adverse events. Outcomes were meta-analyzed using the Sidik-Jonkman method for random effects. Unstandardized mean differences were used as effect sizes for continuous outcomes with common measurement units and Hedge's g standardized mean differences (SMD) otherwise. Odds ratios were used for binary outcomes. Cochrane risk of bias and GRADE assessment determined the certainty of evidence.
RESULTS
In total, 20 trials involving 2498 participants (median sample size 120, median follow-up 9 months) were eligible for inclusion. Overall, risk of bias was low. Compared with placebo, noncalcium-based phosphate binders reduced serum phosphate (12 trials, weighted mean difference -0.37; 95% CI, -0.58 to -0.15 mg/dl, low certainty evidence) and urinary phosphate excretion (eight trials, SMD -0.61; 95% CI, -0.90 to -0.31, low certainty evidence), but resulted in increased constipation (nine trials, log odds ratio [OR] 0.93; 95% CI, 0.02 to 1.83, low certainty evidence) and greater vascular calcification score (three trials, SMD, 0.47; 95% CI, 0.17 to 0.77, very low certainty evidence). Data for effects of phosphate-lowering therapy on cardiovascular events (log OR, 0.51; 95% CI, -0.51 to 1.17) and death were scant.
CONCLUSIONS
Noncalcium-based phosphate-lowering therapy reduced serum phosphate and urinary phosphate excretion, but there was an unclear effect on clinical outcomes and intermediate cardiovascular end points. Adequately powered RCTs are required to evaluate benefits and risks of phosphate-lowering therapy on patient-centered outcomes.
Topics: Chelating Agents; Ferric Compounds; Humans; Hyperphosphatemia; Lanthanum; Phosphates; Renal Insufficiency, Chronic; Sevelamer
PubMed: 34645696
DOI: 10.1681/ASN.2021040554 -
Clinical Infectious Diseases : An... May 2023Optimal doses of first-line drugs for treatment of drug-susceptible tuberculosis in children and young adolescents remain uncertain. We aimed to determine whether... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Optimal doses of first-line drugs for treatment of drug-susceptible tuberculosis in children and young adolescents remain uncertain. We aimed to determine whether children treated using World Health Organization-recommended or higher doses of first-line drugs achieve successful outcomes and sufficient pharmacokinetic (PK) exposures.
METHODS
Titles, abstracts, and full-text articles were screened. We searched PubMed, EMBASE, CENTRAL, and trial registries from 2010 to 2021. We included studies in children aged <18 years being treated for drug-susceptible tuberculosis with rifampicin (RIF), pyrazinamide, isoniazid, and ethambutol. Outcomes were treatment success rates and drug exposures. The protocol for the systematic review was preregistered in PROSPERO (no. CRD42021274222).
RESULTS
Of 304 studies identified, 46 were eligible for full-text review, and 12 and 18 articles were included for the efficacy and PK analyses, respectively. Of 1830 children included in the efficacy analysis, 82% had favorable outcomes (range, 25%-95%). At World Health Organization-recommended doses, exposures to RIF, pyrazinamide, and ethambutol were lower in children than in adults. Children ≤6 years old have 35% lower areas under the concentration-time curve (AUCs) than older children (mean of 14.4 [95% CI 9.9-18.8] vs 22.0 [13.8-30.1] μg·h/mL) and children with human immunodeficiency virus (HIV) had 35% lower RIF AUCs than HIV-negative children (17.3 [11.4-23.2] vs 26.5 [21.3-31.7] μg·h/mL). Heterogeneity and small sample sizes were major limitations.
CONCLUSIONS
There is large variability in outcomes, with an average of 82% favorable outcomes. Drug exposures are lower in children than in adults. Younger children and/or those with HIV are underexposed to RIF. Standardization of PK pediatric studies and individual patient data analysis with safety assessment are needed to inform optimal dosing.
Topics: Adult; Adolescent; Child; Humans; Antitubercular Agents; Pyrazinamide; Ethambutol; Tuberculosis; Rifampin; Isoniazid; HIV; HIV Infections
PubMed: 36609692
DOI: 10.1093/cid/ciac973 -
Metabolites Mar 2022Oral squamous cell carcinoma (OSCC) is the most common type of oral cancer in which the consumption of tobacco and alcohol is considered to be the main aetiological... (Review)
Review
Oral squamous cell carcinoma (OSCC) is the most common type of oral cancer in which the consumption of tobacco and alcohol is considered to be the main aetiological factor. Salivary metabolome profiling could identify novel biochemical pathways involved in the pathogenesis of various diseases. This systematic review was designed to answer the question "Are salivary metabolites reliable for the diagnosis of oral squamous cell carcinoma?". Following the inclusion and exclusion criteria, nineteen studies were included (according to PRISMA statement guidelines). In all included studies, the diagnostic material was unstimulated whole saliva, whose metabolome changes were determined by different spectroscopic methods. At the metabolic level, OSCC patients differed significantly not only from healthy subjects but also from patients with oral leukoplakia, lichen planus or other oral potentially malignant disorders. Among the detected salivary metabolites, there were the indicators of the impaired metabolic pathways, such as choline metabolism, amino acid pathways, polyamine metabolism, urea cycle, creatine metabolism, glycolysis or glycerolipid metabolism. In conclusion, saliva contains many potential metabolites, which can be used reliably to early diagnose and monitor staging in patients with OSCC. However, further investigations are necessary to confirm these findings and to identify new salivary metabolic biomarkers.
PubMed: 35448481
DOI: 10.3390/metabo12040294 -
PloS One 2014HIV viral load (VL) testing is the gold standard for antiretroviral treatment monitoring, but many barriers exist to VL testing in resource-limited settings, including... (Review)
Review
BACKGROUND
HIV viral load (VL) testing is the gold standard for antiretroviral treatment monitoring, but many barriers exist to VL testing in resource-limited settings, including storage and transport limitations for whole blood and plasma. Data from various studies indicate that HIV RNA is stable beyond current recommendations. We conducted a systematic review to assess stability data of HIV RNA in whole blood and plasma across times and temperatures.
METHODS AND FINDINGS
Using a pre-defined protocol, five databases were searched for studies where blood samples from HIV patients were stored at time and temperature points that exceeded manufacturer recommendations. RNA stability, the primary outcome, was measured by the difference in means compared to samples stored within established thresholds. RNA stability was defined as ≤0.5 log degradation. The search identified 10,716 titles, of which nine full-text articles were included for review. HIV RNA maintained stability in EDTA whole blood and plasma at all measured time points up to 168 hours when stored at 4°C, while stability was detected at 72 hours (95% confidence) in whole blood at 25°C, with data points before and beyond 72 hours suggesting stability but not reaching statistical significance. For EDTA plasma stored at 30°C, stability was maintained up to 48 hours (95% confidence), with OLS linear regression estimates up to 127 hours, suggesting stability. Overall, quality of studies was moderate. Limitations included small sample sizes, few studies meeting inclusion criteria, and no studies examining RNA stability in low viremia (<3,000 copies/mL) environments.
CONCLUSIONS
Whole blood and plasma samples in EDTA may remain stable under conditions exceeding current manufacturer recommendations for HIV VL testing. However, given the limited number of studies addressing this question, especially at low levels of viremia, additional evaluations on HIV RNA stability in EDTA tubes and PPT in field conditions are needed.
Topics: Edetic Acid; HIV Infections; HIV-1; Humans; RNA Stability; RNA, Viral; Specimen Handling; Temperature; Viral Load
PubMed: 25437009
DOI: 10.1371/journal.pone.0113813 -
Minerva Urologica E Nefrologica = the... Oct 2018Recurrence after primary treatment of prostate cancer is one of the major challenges facing urologists. Biochemical recurrence is not rare and occurs in up to one third... (Review)
Review
INTRODUCTION
Recurrence after primary treatment of prostate cancer is one of the major challenges facing urologists. Biochemical recurrence is not rare and occurs in up to one third of the patients undergoing radical prostatectomy. Management of biochemical recurrence is tailored according to the site and the burden of recurrence. Therefore, developing an imaging technique to early detect recurrent lesions represents an urgent need. Positron emission tomography (PET) of 68Ga-labelled prostate-specific membrane antigen (68Ga-PSMA) is an emerging imaging modality that seems to be a promising tool with capability to localize recurrent prostate cancer. A systematic review of literature was done to evaluate the role of 68Ga-PSMA PET/CT scan in patients with recurrent prostate cancer after primary radical treatment.
EVIDENCE ACQUISITION
A systematic and comprehensive review of literature was performed in September 2017 analyzing the MEDLINE and Cochrane Library following the Preferred Reporting Items for Systematic Review and Meta-analysis (PRISMA) statement. The following key terms were used for the search "PSMA," "prostate-specific membrane antigen," "positron emission tomography," "PET," "recurrent," "prostate cancer," "prostate neoplasm," "prostate malignancy," and "68Ga." Risk of bias was assessed using the Quality Assessment of Diagnostic Accuracy Studies-2 tool.
EVIDENCE SYNTHESIS
Thirty-seven articles met our inclusion criteria and were included in the analysis of this systematic review. Of the 37 articles selected for analysis only four studies were prospective. The overall detection rate of 68Ga-PSMA PET scan ranged from 47% up to 96.6%. The main advantage of this imaging technique is its relatively high detection rates at low serum PSA levels below 0.5 ng/mL (ranging from 11.1% to 75%). Higher serum PSA level was strongly associated with increased positivity on 68Ga-PSMA PET scan. 68Ga-PSMA PET scan was found superior to conventional imaging techniques (CT and MRI) in this setting of patients and even it seems to outperform choline-based PET scan. This technique provided significant changes in the therapeutic management of 28.6-87.1% of patients.
CONCLUSIONS
After biochemical recurrence, the primary goal is to locate the recurrent lesions' site. 68Ga-PSMA PET/CT seems to be effective in identifying recurrence localization also for very low levels of PSA (<0.5 ng/mL) thus permitting to choose the best therapeutic strategy as early as possible. However, data available cannot be considered exhaustive and prospective randomized trials are needed.
Topics: Antigens, Surface; Edetic Acid; Gallium Isotopes; Gallium Radioisotopes; Glutamate Carboxypeptidase II; Humans; Male; Neoplasm Recurrence, Local; Oligopeptides; Positron Emission Tomography Computed Tomography; Prostatic Neoplasms; Radiopharmaceuticals
PubMed: 29664244
DOI: 10.23736/S0393-2249.18.03081-3 -
The Cochrane Database of Systematic... Nov 2015Bone disease is common in children with chronic kidney disease (CKD) and when untreated may result in bone deformities, bone pain, fractures and reduced growth rates.... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Bone disease is common in children with chronic kidney disease (CKD) and when untreated may result in bone deformities, bone pain, fractures and reduced growth rates. This is an update of a review first published in 2010.
OBJECTIVES
This review aimed to examine the benefits (improved growth rates, reduced risk of bone fractures and deformities, reduction in PTH levels) and harms (hypercalcaemia, blood vessel calcification, deterioration in kidney function) of interventions (including vitamin D preparations and phosphate binders) for the prevention and treatment of metabolic bone disease in children with CKD.
SEARCH METHODS
We searched the Cochrane Kidney and Transplant Specialised Register to 8 September 2015 through contact with the Trial's Search Co-ordinator using search terms relevant for this review.
SELECTION CRITERIA
We included randomised controlled trials (RCTs) comparing different interventions used to prevent or treat bone disease in children with CKD stages 2 to 5D.
DATA COLLECTION AND ANALYSIS
Data were assessed for study eligibility, risk of bias and extracted independently by two authors. Results were reported as risk ratios (RR) or risk differences (RD) with 95% confidence intervals (CI) for dichotomous outcomes. For continuous outcomes the mean difference (MD) or standardised mean difference (SMD) with 95% confidence intervals (CI) was used. Statistical analyses were performed using the random-effects model.
MAIN RESULTS
This review included 18 studies (576 children); three new studies were added for this update. Adequate sequence generation and allocation concealment were reported in 12 and 11 studies respectively. Only four studies reported blinding of children, investigators or outcome assessors. Nine studies were at low risk of attrition bias and 12 studies were at low risk of selective reporting bias.Eight different interventions were compared. Two studies compared intraperitoneal (IP) with oral calcitriol. PTH levels were significantly lower with IP compared with oral calcitriol (1 study: MD -501.00 pg/mL, 95% CI -721.54 to -280.46) but the number of children with abnormal bone histology did not differ between treatments. Three studies compared intermittent with daily oral calcitriol. The change in mean height SDS (1 study: MD 0.13, 95% CI -0.22 to 0.48) and the percentage fall in parathyroid hormone (PTH) levels at eight weeks (1 study: MD -5.50%, 95% CI -32.37 to 21.37) and 12 months (1 study: MD -6.00% 95% CI -25.27 to 13.27) did not differ between treatments.Four studies compared active vitamin D preparations (calcitriol, paricalcitol, 1α-hydroxyvitamin D) with placebo or no specific treatment. One study reported vitamin D preparations significantly reduced PTH levels (-55.00 pmol/L, 95% CI -83.03 to -26.97). There was no significant difference in hypercalcaemia risk with vitamin D preparations compared with placebo or no specific treatment (4 studies, 103 children: RD 0.08 mg/dL, 95% CI -0.08 to 0.24). However, there was heterogeneity (I(2) = 55%) with one study showing a significantly greater risk of hypercalcaemia with intravenous (IV) calcitriol administration. Two studies (97 children) compared calcitriol with other vitamin D preparations and both found no significant differences in growth between preparations.Two studies compared ergocalciferol in patients with CKD and vitamin D deficiency. Elevated PTH levels developed significantly later in ergocalciferol treated children (1 study: hazard ratio 0.30, 95% CI 0.09 to 0.93) though the number with elevated PTH levels did not differ between groups (1 study, 40 children: RR 0.33, 95% CI 0.11 to 1.05).Two studies compared calcium carbonate with aluminium hydroxide as phosphate binders. One study (17 children: MD -0.86 SDS, 95% CI -2.24 to 0.52) reported no significant difference in mean final height SDS between treatments. Three studies compared sevelamer with calcium-containing phosphate binders. There were no significant differences in the final calcium, phosphorus or PTH levels between binders. More episodes of hypercalcaemia occurred with calcium-containing binders. One study reported no significant differences between calcitriol and doxercalciferol in bone histology or biochemical parameters.
AUTHORS' CONCLUSIONS
Bone disease, assessed by changes in PTH levels, is improved by all vitamin D preparations. However, no consistent differences between routes of administration, frequencies of dosing or vitamin D preparations were demonstrated. Although fewer episodes of high calcium levels occurred with the non-calcium-containing phosphate binder, sevelamer, compared with calcium-containing binders, there were no differences in serum phosphorus and calcium overall and phosphorus values were reduced to similar extents. All studies were small with few data available on patient-centred outcomes (growth, bone deformities) and limited data on biochemical parameters or bone histology resulting in considerable imprecision of results thus limiting the applicability to the care of children with CKD.
Topics: Aluminum Hydroxide; Bone Density Conservation Agents; Bone Diseases, Metabolic; Calcitriol; Calcium; Calcium Carbonate; Child; Chronic Disease; Ergocalciferols; Humans; Kidney Diseases; Parathyroid Hormone; Phosphorus; Polyamines; Randomized Controlled Trials as Topic; Sevelamer; Vitamin D
PubMed: 26561037
DOI: 10.1002/14651858.CD008327.pub2 -
The Cochrane Database of Systematic... Nov 2017Approximately 600 million children of preschool and school age are anaemic worldwide. It is estimated that at least half of the cases are due to iron deficiency.... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Approximately 600 million children of preschool and school age are anaemic worldwide. It is estimated that at least half of the cases are due to iron deficiency. Point-of-use fortification of foods with micronutrient powders (MNP) has been proposed as a feasible intervention to prevent and treat anaemia. It refers to the addition of iron alone or in combination with other vitamins and minerals in powder form, to energy-containing foods (excluding beverages) at home or in any other place where meals are to be consumed. MNPs can be added to foods either during or after cooking or immediately before consumption without the explicit purpose of improving the flavour or colour.
OBJECTIVES
To assess the effects of point-of-use fortification of foods with iron-containing MNP alone, or in combination with other vitamins and minerals on nutrition, health and development among children at preschool (24 to 59 months) and school (five to 12 years) age, compared with no intervention, a placebo or iron-containing supplements.
SEARCH METHODS
In December 2016, we searched the following databases: CENTRAL, MEDLINE, Embase, BIOSIS, Science Citation Index, Social Science Citation Index, CINAHL, LILACS, IBECS, Popline and SciELO. We also searched two trials registers in April 2017, and contacted relevant organisations to identify ongoing and unpublished trials.
SELECTION CRITERIA
Randomised controlled trials (RCTs) and quasi-RCTs trials with either individual or cluster randomisation. Participants were children aged between 24 months and 12 years at the time of intervention. For trials with children outside this age range, we included studies where we were able to disaggregate the data for children aged 24 months to 12 years, or when more than half of the participants were within the requisite age range. We included trials with apparently healthy children; however, we included studies carried out in settings where anaemia and iron deficiency are prevalent, and thus participants may have had these conditions at baseline.
DATA COLLECTION AND ANALYSIS
Two review authors independently assessed the eligibility of trials against the inclusion criteria, extracted data from included trials, assessed the risk of bias of the included trials and graded the quality of the evidence.
MAIN RESULTS
We included 13 studies involving 5810 participants from Latin America, Africa and Asia. We excluded 38 studies and identified six ongoing/unpublished trials. All trials compared the provision of MNP for point-of-use fortification with no intervention or placebo. No trials compared the effects of MNP versus iron-containing supplements (as drops, tablets or syrup).The sample sizes in the included trials ranged from 90 to 2193 participants. Six trials included participants younger than 59 months of age only, four included only children aged 60 months or older, and three trials included children both younger and older than 59 months of age.MNPs contained from two to 18 vitamins and minerals. The iron doses varied from 2.5 mg to 30 mg of elemental iron. Four trials reported giving 10 mg of elemental iron as sodium iron ethylenediaminetetraacetic acid (NaFeEDTA), chelated ferrous sulphate or microencapsulated ferrous fumarate. Three trials gave 12.5 mg of elemental iron as microencapsulated ferrous fumarate. Three trials gave 2.5 mg or 2.86 mg of elemental iron as NaFeEDTA. One trial gave 30 mg and one trial provided 14 mg of elemental iron as microencapsulated ferrous fumarate, while one trial gave 28 mg of iron as ferrous glycine phosphate.In comparison with receiving no intervention or a placebo, children receiving iron-containing MNP for point-of-use fortification of foods had lower risk of anaemia prevalence ratio (PR) 0.66, 95% confidence interval (CI) 0.49 to 0.88, 10 trials, 2448 children; moderate-quality evidence) and iron deficiency (PR 0.35, 95% CI 0.27 to 0.47, 5 trials, 1364 children; moderate-quality evidence) and had higher haemoglobin (mean difference (MD) 3.37 g/L, 95% CI 0.94 to 5.80, 11 trials, 2746 children; low-quality evidence).Only one trial with 115 children reported on all-cause mortality (zero cases; low-quality evidence). There was no effect on diarrhoea (risk ratio (RR) 0.97, 95% CI 0.53 to 1.78, 2 trials, 366 children; low-quality evidence).
AUTHORS' CONCLUSIONS
Point-of-use fortification of foods with MNPs containing iron reduces anaemia and iron deficiency in preschool- and school-age children. However, information on mortality, morbidity, developmental outcomes and adverse effects is still scarce.
Topics: Anemia, Iron-Deficiency; Child; Child, Preschool; Dietary Supplements; Edetic Acid; Ferric Compounds; Ferrous Compounds; Food, Fortified; Humans; Iron; Micronutrients; Point-of-Care Systems; Powders; Trace Elements; Vitamins
PubMed: 29168569
DOI: 10.1002/14651858.CD009666.pub2 -
Frontiers in Endocrinology 2023Some studies have reported that the topical forms with aminophylline as the active ingredient appear to be relatively effective on local fat burning while having...
BACKGROUND AND AIMS
Some studies have reported that the topical forms with aminophylline as the active ingredient appear to be relatively effective on local fat burning while having no/minimal side effects. This systematic review accumulates all of the data on the local fat-burning potency of aminophylline topical formulation.
METHODS
Documents were retrieved from PubMed, Web of Science, and Scopus databases until Aug 2022. Data were extracted from clinical trials reporting the reduction in thigh or waist circumference as a result of using topical forms containing aminophylline. Screening of included studies was performed independently by two authors and the quality assessment of included studies was performed based on the Cochrane Collaboration's approach.
RESULTS
Of the 802 initial studies, 5 studies were included in the systematic review. Several concentrations of aminophylline were used in different studies. Most studies administred the topical formulation on participants' one thigh, and the other thigh was considered to be the control for comparing the fat reduction amount. Except for one study, all other studies reported that all participants lost more fat on the treated area than the control groups. The amount of fat reduction differed in studies regarding their different aminophylline concentrations and administration routines. In the case of side effects, except for some studies reporting skin rashes, other studies reported no significant side effects at all.
CONCLUSIONS
Aminophylline topical formulation offers a safe, effective, and much less invasive alternative to cosmetic surgery for localized fat reduction. It seems that the 0.5% concentration, administered five times a week for five weeks is the most potent concentration. However, more high-quality clinical trials are needed to verify this conclusion.
SYSTEMATIC REVIEW REGISTRATION
https://www.crd.york.ac.uk/prospero/, identifier CRD42022353578.
Topics: Humans; Aminophylline; Plastic Surgery Procedures; Drug-Related Side Effects and Adverse Reactions; Control Groups; Databases, Factual
PubMed: 36875487
DOI: 10.3389/fendo.2023.1087614