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Medicine Oct 2018Recent evidence has shown that nicotinamide treatment may have an impact on phosphorus metabolism in hemodialysis patients. Nevertheless, the treatment remains... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Recent evidence has shown that nicotinamide treatment may have an impact on phosphorus metabolism in hemodialysis patients. Nevertheless, the treatment remains controversial. This study aimed to precisely estimate the efficacy and safety of nicotinamide on phosphorus, calcium and iPTH in hemodialysis patients.
METHODS
We searched numerous information sources regarding randomized controlled trials (RCTs) of nicotinamide treatment in hemodialysis patients, including PubMed, EMBASE, and the Cochrane Library.
RESULTS
Nine relevant studies (n = 428) were included in the meta-analysis. Meta-analysis showed that levels of serum phosphorus (SMD -1.06; 95% CI, -1.27 to -0.85, P < .001), parathyroid hormone (SMD -1.09; 95% CI, -1.49 to -0.70, P < .001), and calcium-phosphorus (SMD -0.65; 95% CI, -0.97 to -0.34, P < .001) in the nicotinamide group were significantly lower than those of the control group. There was no significant difference in the levels of serum calcium (SMD 0.08; 95% CI, -0.15 to 0.30, P = .51) between the groups. The meta-analysis showed that the nicotinamide group had a significantly higher risk of adverse events (OR 3.99; 95% CI, 1.94-8.23, P < .001) than did the control group, especially for thrombocytopenia (OR 49.00; 95% CI, 2.68-897.36, P = .009). However, no serious adverse reactions were observed. There was no significant difference in the incidence of withdrawal (OR 3.51; 95% CI, 0.49-25.00, P = .21) between the groups.
CONCLUSION
Evidence to date clearly indicates that nicotinamide is safe and effective for improving phosphorus metabolism in hemodialysis patients. However, nicotinamide probably causes thrombocytopenia. Further large-sample size, high-quality RCTs are needed.
Topics: Calcium; Humans; Hyperphosphatemia; Lipids; Niacinamide; Parathyroid Hormone; Phosphorus; Randomized Controlled Trials as Topic; Renal Dialysis
PubMed: 30313075
DOI: 10.1097/MD.0000000000012731 -
Kidney & Blood Pressure Research 2018Hemodialysis (HD) patients often have inadequate nutrition, especially with respect to ascorbic acid (AA). It is reported that every HD session may cause a 50%- 75%... (Meta-Analysis)
Meta-Analysis
BACKGROUND/AIMS
Hemodialysis (HD) patients often have inadequate nutrition, especially with respect to ascorbic acid (AA). It is reported that every HD session may cause a 50%- 75% decrease in plasma AA levels. Some studies have shown that supplementation of AA can change the outcome of chronic kidney disease-mineral bone disorders (CKD-MBD), but the effect of AA on HD patients with CKD-MBD remains controversial. Consequently, we decided to perform a meta-analysis to evaluate the efficacy of AA supplementation in CKD-MBD patients requiring dialysis.
METHODS
A search was conducted using Pubmed, EMBASE, Cochrane Central Register of Controlled Trials, Chinese National Knowledge Infrastructure (CNKI), Wanfang database and VIP information database up to April 2018 for all English and Chinese language publications. The main indicators of our study were changes in serum phosphate (P), calcium (Ca) and parathyroid hormone (PTH) levels after AA treatment. The efficacy of AA was evaluated by weighted mean difference (WMD) and confidence intervals (CI). Cardiovascular events, mortality and adverse events reported during the experiment were also noted.
RESULTS
In total, 371 patients in six studies were involved in this meta-analysis. Compared to placebo, AA treatment had no positive effect on serum P (353 patients; WMD = -0.05; 95% CI, -0.3 to 0.2; I2 = 28%) or PTH levels (275 patients; WMD = -17.04; 95%CI, -63.79 to 29.72; I2 = 75%). The pooled mean difference of the change of Ca levels from baseline was higher in the AA therapy group versus placebo (353 patients; WMD = 0.15; 95% CI, 0.01 to 0.3; I2 = 0%). No side effects were observed.
CONCLUSION
Our systematic review and meta-analysis does not support prescription of AA to HD patients with CKD-MBD. AA had no positive effect on CKD-MBD patients as it couldn't influence the serum P or PTH levels but did raise serum Ca levels in the short-term.
Topics: Ascorbic Acid; Bone Diseases; Calcium; Humans; Kidney Failure, Chronic; Minerals; Parathyroid Hormone; Phosphorus; Randomized Controlled Trials as Topic; Renal Dialysis
PubMed: 30248670
DOI: 10.1159/000493661 -
PloS One 2018This systematic review aims to determine the potential effects of oral nutritional supplements (ONS) in patients receiving maintenance dialysis therapy (MDT). (Meta-Analysis)
Meta-Analysis
BACKGROUND/OBJECTIVE
This systematic review aims to determine the potential effects of oral nutritional supplements (ONS) in patients receiving maintenance dialysis therapy (MDT).
METHODS
Electronic databases were searched without language limits through to July 2018. Randomized controlled trials (RCTs) that involved comparisons of ONS versus placebo or routine care are included in this meta-analysis. RevMan 5.3 statistical software was used for meta-analysis.
RESULTS
15 articles with 589 subjects were included in our study. There are insufficient comparable data of randomized trials to allow meta-analysis of mortality. Albumin levels may be improved by the macronutrient blends or protein/amino acid supplements in MDT patients. Compared with the control group, serum albumin levels and BMI in the ONS group were increased by 1.58 g/L (95% CI, 0.52-2.63, P = 0.003; I2 = 85%) and 0.40 kg/m2 (95% CI, 0.10-0.71, P = 0.01; I2 = 49%), respectively. In the subgroup analysis of patients receiving hemodialysis, albumin levels in ONS group were increased by 2.17 g/L (95% CI, 0.89-3.45, P<0.001; I2 = 90%). ONS may not influence serum phosphorus and potassium levels.
CONCLUSIONS
Very low-quality evidence suggests that Short-term oral energy or protein/amino acid supplements may improve nutritional status by increasing serum albumin levels and BMI in MDT patients, without influence on serum potassium levels. High-quality and large RCTs, particularly regarding the effects of ONS on mortality and quality of life, are needed to further validate our findings.
Topics: Body Mass Index; Databases, Factual; Dietary Supplements; Humans; Kidney Failure, Chronic; Nutritional Status; Quality of Life; Randomized Controlled Trials as Topic; Renal Dialysis; Serum Albumin
PubMed: 30212514
DOI: 10.1371/journal.pone.0203706 -
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 -
The British Journal of Nutrition Jun 2018Ca digestibility and utilisation in growing pigs are not well understood, and are usually neglected in diet formulation. This has implications not only for the accurate... (Meta-Analysis)
Meta-Analysis
Ca digestibility and utilisation in growing pigs are not well understood, and are usually neglected in diet formulation. This has implications not only for the accurate determination of its requirements but also for its interactions with other nutrients. A systematic review and meta-analysis (meta-regression) of published trials was carried out to quantify factors affecting Ca absorption and utilisation, and to derive an estimate of Ca endogenous excretion. The analysis was carried out on the data from forty studies, corresponding to 201 treatments performed on 1204 pigs. The results indicated that although Ca absorption and retention (g/kg of body weight per d) increased with increasing Ca intake (P<0·001), non-phytate-P intake (P<0·001) and exogenous phytase supplementation (P<0·001), these values decreased with increasing phytate-P intake (P<0·05). Interactions between exogenous phytase and Ca intake, indicating reduced efficacy of this enzyme (P<0·001), and between phytate-P intake and exogenous phytase, counteracting the direct negative effect of phytate-P (P<0·05) on Ca absorption and retention, were also detected. There were no effects of animal-related characteristics, such as pig genotype in Ca absorption and retention. The large amount of variance explained in Ca absorption (90 %) and retention (91 %) supported our choice of independent variables. Endogenous Ca losses obtained via linear regression were 239 mg/kg of DM intake (95 % CI 114, 364). These outcomes advance the current understanding of Ca digestibility and utilisation, and should contribute towards establishing requirements for digestible Ca. Consequently, pig diets will be more correctly formulated if digestible Ca values are used in estimating requirements for Ca.
Topics: Animal Feed; Animals; Calcium; Calcium, Dietary; Diet; Digestion; Swine
PubMed: 29609665
DOI: 10.1017/S0007114518000612 -
Journal of Cachexia, Sarcopenia and... Apr 2018Recent data pose the question whether conservative management of chronic kidney disease (CKD) by means of a low-protein diet can be a safe and effective means to avoid... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Recent data pose the question whether conservative management of chronic kidney disease (CKD) by means of a low-protein diet can be a safe and effective means to avoid or defer transition to dialysis therapy without causing protein-energy wasting or cachexia. We aimed to systematically review and meta-analyse the controlled clinical trials with adequate participants in each trial, providing rigorous contemporary evidence of the impact of a low-protein diet in the management of uraemia and its complications in patients with CKD.
METHODS
We searched MEDLINE (PubMed) and other sources for controlled trials on CKD to compare clinical management of CKD patients under various levels of dietary protein intake or to compare restricted protein intake with other interventions. Studies with similar patients, interventions, and outcomes were included in the meta-analyses.
RESULTS
We identified 16 controlled trials of low-protein diet in CKD that met the stringent qualification criteria including having 30 or more participants. Compared with diets with protein intake of >0.8 g/kg/day, diets with restricted protein intake (<0.8 g/kg/day) were associated with higher serum bicarbonate levels, lower phosphorus levels, lower azotemia, lower rates of progression to end-stage renal disease, and a trend towards lower rates of all-cause death. In addition, very-low-protein diets (protein intake <0.4 g/kg/day) were associated with greater preservation of kidney function and reduction in the rate of progression to end-stage renal disease. Safety and adherence to a low-protein diet was not inferior to a normal protein diet, and there was no difference in the rate of malnutrition or protein-energy wasting.
CONCLUSIONS
In this pooled analysis of moderate-size controlled trials, a low-protein diet appears to enhance the conservative management of non-dialysis-dependent CKD and may be considered as a potential option for CKD patients who wish to avoid or defer dialysis initiation and to slow down the progression of CKD, while the risk of protein-energy wasting and cachexia remains minimal.
Topics: Diet, Protein-Restricted; Disease Progression; Humans; Randomized Controlled Trials as Topic; Renal Insufficiency, Chronic
PubMed: 29094800
DOI: 10.1002/jcsm.12264 -
The Cochrane Database of Systematic... Mar 2017This is an update of the review published in Issue 4, 2003. Bone metastasis cause severe pain as well as pathological fractures, hypercalcaemia and spinal cord... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
This is an update of the review published in Issue 4, 2003. Bone metastasis cause severe pain as well as pathological fractures, hypercalcaemia and spinal cord compression. Treatment strategies currently available to relieve pain from bone metastases include analgesia, radiotherapy, surgery, chemotherapy, hormone therapy, radioisotopes and bisphosphonates.
OBJECTIVES
To determine efficacy and safety of radioisotopes in patients with bone metastases to improve metastatic pain, decrease number of complications due to bone metastases and improve patient survival.
SEARCH METHODS
We sought randomised controlled trials (RCTs) in MEDLINE, EMBASE, CENTRAL, and the PaPaS Trials Register up to October 2010.
SELECTION CRITERIA
Studies selected had metastatic bone pain as a major outcome after treatment with a radioisotope, compared with placebo or another radioisotope.
DATA COLLECTION AND ANALYSIS
We assessed the risk of bias of included studies by their sequence generation, allocation concealment, blinding of study participants, researchers and outcome assessors, and incomplete outcome data. Two review authors extracted data. We performed statistical analysis as an "available case" analysis, and calculated global estimates of effect using a random-effects model. We also performed an intention-to-treat (ITT) sensitivity analysis.
MAIN RESULTS
This update includes 15 studies (1146 analyzed participants): four (325 participants) already included and 11 new (821 participants). Only three studies had a low risk of bias. We observed a small benefit of radioisotopes for complete relief (risk ratio (RR) 2.10, 95% CI 1.32 to 3.35; Number needed to treat to benefit (NNT) = 5) and complete/partial relief (RR 1.72, 95% CI 1.13 to 2.63; NNT = 4) in the short and medium term (eight studies, 499 participants). There is no conclusive evidence to demonstrate that radioisotopes modify the use of analgesia with respect to placebo. Leucocytopenia and thrombocytopenia are secondary effects significantly associated with the administration of radioisotopes (RR 5.03; 95% CI 1.35 to 18.70; Number needed to treat to harm (NNH) = 13). Pain flares were not higher in the radioisotopes group (RR 0.74; 95% CI 0.27 to 2.06). There are scarce data of moderate quality when comparing Strontium-89 (Sr) with Samarium-153 (Sm), Rhenium-186 (Re) and Phosphorus-32 (P). We observed no significant differences between treatments. Similarly, we observed no differences when we compared different doses of Sm (0.5 versus 1.0 mCi).
AUTHORS' CONCLUSIONS
This update adds new evidence on efficacy of radioisotopes versus placebo, Sr compared with other radioisotopes, and dose-comparisons of Sm and Re. There is some evidence indicating that radioisotopes may provide complete reduction in pain over one to six months with no increase in analgesic use, but severe adverse effects (leucocytopenia and thrombocytopenia) are frequent.
Topics: Bone Neoplasms; Fractures, Bone; Humans; Hypercalcemia; Pain; Pain Measurement; Phosphorus Radioisotopes; Radioisotopes; Randomized Controlled Trials as Topic; Ruthenium Radioisotopes; Samarium; Spinal Cord Compression; Strontium Radioisotopes
PubMed: 28334435
DOI: 10.1002/14651858.CD003347.pub3 -
PloS One 2017Chronic kidney disease-mineral and bone disorder (CKD-MBD), a complication of chronic kidney disease, has been linked to reduced quality and length of life. High serum... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Chronic kidney disease-mineral and bone disorder (CKD-MBD), a complication of chronic kidney disease, has been linked to reduced quality and length of life. High serum phosphate levels that result from CKD-MBD require phosphate-lowering agents, also known as phosphate binders. The objective of this systematic review is to compare the effects of available phosphate binders on laboratory outcomes in patients with CKD-MBD.
METHODS
Data sources included MEDLINE and EMBASE from January 1996 to April 2016, and the Cochrane Register of Controlled Trials up to April 2016. Teams of two reviewers, independently and in duplicate, screened titles and abstracts and potentially eligible full text reports to determine eligibility, and subsequently abstracted data and assessed risk of bias in eligible randomized controlled trials (RCTs). Eligible trials enrolled patients with CKD-MBD and randomized them to receive calcium-based phosphate binders (delivered as calcium acetate, calcium citrate or calcium carbonate), non-calcium-based phosphate binders (NCBPB) (sevelamer hydrochloride, sevelamer carbonate, lanthanum carbonate, sucroferric oxyhydroxide and ferric citrate), phosphorus restricted diet (diet), placebo or no treatment and reported effects on serum levels of phosphate, calcium and parathyroid hormone. We performed Bayesian network meta-analyses (NMA) to calculate the effect estimates (mean differences) and 95% credible intervals for serum levels of phosphate, calcium and parathyroid hormone. We calculated direct, indirect and network meta-analysis estimates using random-effects models. We applied the GRADE (Grading of Recommendations, Assessment, Development and Evaluation) approach to rate the quality of evidence for each pairwise comparison.
RESULTS
Our search yielded 1108 citations; 71 RCTs were retrieved for full review and 16 proved eligible. Including an additional 13 studies from a previous review, 29 studies that enrolled 8335 participants proved eligible; 26 trials provided data for quantitative synthesis. Sevelamer, lanthanum, calcium, iron, diet and combinations of active treatments (calcium or sevelamer or lanthanum and combination of calcium and sevelamer) resulted in significantly lower serum phosphate as compared to placebo (moderate to very low quality of evidence). We found no statistically significant differences between active treatment categories in lowering serum phosphate. Sevelamer, lanthanum and diet resulted in lower serum calcium compared to calcium (moderate quality evidence for lanthanum and diet; low quality evidence for Sevelamer). Iron, sevelamer and calcium yielded lower parathyroid hormone levels as compared to lanthanum. Meta-regression analyses did not yield a statistically significant association between treatment effect and trial duration.
DISCUSSION/CONCLUSIONS
We found few differences between treatments in impact on phosphate and differences in parathyroid hormone. Relative to calcium, sevelamer, lanthanum and diet showed significant reduction in serum calcium from baseline. Treatment recommendations should be based on impact on patient-important outcomes rather than on surrogate outcomes. Systematic review registration: PROSPERO CRD-42016032945.
Topics: Calcium; Chronic Kidney Disease-Mineral and Bone Disorder; Female; Humans; Male; Parathyroid Hormone; Phosphates
PubMed: 28248961
DOI: 10.1371/journal.pone.0171028 -
The Cochrane Database of Systematic... Feb 2017Preterm infants are born with low skeletal stores of calcium and phosphorus. Preterm human milk provides insufficient calcium and phosphorus to meet the estimated needs... (Review)
Review
BACKGROUND
Preterm infants are born with low skeletal stores of calcium and phosphorus. Preterm human milk provides insufficient calcium and phosphorus to meet the estimated needs of preterm infants for adequate growth. Supplementation of human milk with calcium and phosphorus may improve growth and development of preterm infants.
OBJECTIVES
To determine whether addition of calcium and phosphorus supplements to human milk leads to improved growth and bone metabolism of preterm infants without significant adverse effects.
SEARCH METHODS
We used the standard search strategy of the Cochrane Neonatal Review Group to search the Cochrane Central Register of Controlled Trials (CENTRAL; 2016, Issue 3), MEDLINE via PubMed (1966 to 14 April 2016), Embase (1980 to 14 April 2016) and the Cumulative Index to Nursing and Allied Health Literature (CINAHL; 1982 to 14 April 2016). We also searched clinical trials databases (11 May 2016) and the reference lists of retrieved articles for randomised controlled trials and quasi-randomised trials.
SELECTION CRITERIA
Randomised and quasi-randomised trials comparing supplementation of human milk with calcium and/or phosphorus versus no supplementation in hospitalised preterm infants were eligible for inclusion in this review.
DATA COLLECTION AND ANALYSIS
Two review authors (JB, JW) independently extracted data and assessed trial quality using standard methods of the Cochrane Neonatal Review Group. We reported dichotomous data as risk ratios (RRs) and continuous data as mean differences (MDs) with 95% confidence intervals (CIs). We used the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach to assess the quality of evidence.
MAIN RESULTS
This is an update of a 2001 review that identified no eligible trials. One trial including 40 infants met the inclusion criteria for this review. Using GRADE criteria, we judged the quality of the evidence as low owing to risk of bias (inadequate reporting of methods of randomisation, allocation concealment and/or blinding) and imprecision (wide confidence intervals and data from a single small trial). We found no evidence of a difference between calcium and phosphorus supplementation versus no supplementation for neonatal growth outcomes (weight, length, head circumference) at any time point reported (two, four or six weeks postnatal age). At six weeks postnatal age, supplementation with calcium/phosphorus was associated with a decrease in serum alkaline phosphatase concentration (MD -56.85 IU/L, 95% CI -101.27 to -12.43; one randomised controlled trial (RCT); n = 40 infants). Investigators provided no data on growth at 12 to 18 months, neonatal fractures, feed intolerance, breastfeeding or any of the prespecified childhood outcomes for this review (fractures, growth, neurodevelopmental outcomes).
AUTHORS' CONCLUSIONS
We identified one small trial including only 40 infants that compared supplementation of human milk with calcium and phosphorus versus no supplementation in hospitalised preterm infants. We judged the evidence to be of low quality and found no evidence of differences between groups for clinically important outcomes including growth and fractures. Although serum alkaline phosphatase concentration was reduced in the group receiving supplementation at six weeks postnatal age, this difference is unlikely to be of clinical significance. We conclude that evidence is insufficient to determine whether benefit or harm ensues when human milk is supplemented with calcium and/or phosphorus for the hospitalised preterm infant. We see no advantage of conducting further trials of this intervention because with the advent of multi-component human milk fortifier, supplementation of human milk with calcium and/or phosphorus alone is no longer common practice. Future trials should consider assessing effects of multi-component fortifiers with different mineral compositions on clinically important outcomes during the neonatal period and in later childhood.
Topics: Alkaline Phosphatase; Calcium; Dietary Supplements; Humans; Infant, Newborn; Infant, Premature; Milk, Human; Phosphorus; Randomized Controlled Trials as Topic
PubMed: 28238222
DOI: 10.1002/14651858.CD003310.pub2 -
Clinical Interventions in Aging 2017The aim is to systematically assess the effectiveness and safety of Chinese herbal formula Erxian decoction (EXD) for treating osteoporosis. (Review)
Review
PURPOSE
The aim is to systematically assess the effectiveness and safety of Chinese herbal formula Erxian decoction (EXD) for treating osteoporosis.
MATERIALS AND METHODS
Six databases were searched from inception through September 17, 2016, without language restriction. All randomized controlled trials of EXD for osteoporosis were included. One or more outcome measures including fracture, change in bone mineral density (BMD), pain symptom improvement, bone biochemical markers, quality of life, adverse event or adverse drug reaction were evaluated. Study selection, data extraction, quality assessment, and data analyses were conducted according to Cochrane standards.
RESULTS
Eight trials including 644 patients investigated the effects of EXD in the treatment of osteoporosis. The methodological quality of the included trials was generally low. The meta-analysis from two trials showed favorable effects of EXD in improving BMD of lumbar spine (mean difference [MD]: 0.05 [0.03, 0.06]; =0%; <0.00001) and BMD of femoral great trochanter (MD: 0.06 [0.02, 0.10]; =59%; =0.005) compared with caltrate tablets. The other meta-analysis from two trials showed beneficial effects of EXD plus caltrate tablets and calcitriol in improving BMD of femoral neck (MD: 0.04 [0.00, 0.09]; =56%; =0.04), the level of calcium (MD: 0.20 [0.15, 0.24]; =0%; <0.00001), and phosphorus (MD: -0.28 [-0.39, -0.17]; =68%; <0.00001) compared with caltrate tablets and calcitriol alone. The adverse drug reactions of EXD were mainly slight gastrointestinal symptoms.
CONCLUSION
The study provides suggestive evidence of the superiority of EXD monotherapy or combination therapy over basic supplements for treating osteoporosis. However, the evidence remains weak. More rigorously designed and measured, randomized double-blind, placebo-controlled trials with larger sample size are needed to verify the current conclusions.
Topics: Biomarkers; Bone Density; Calcitriol; Drugs, Chinese Herbal; Humans; Lumbar Vertebrae; Meta-Analysis as Topic; Osteoporosis; Quality of Life; Randomized Controlled Trials as Topic
PubMed: 28115834
DOI: 10.2147/CIA.S117597