Concentration of dietary calcium supplied by calcium carbonate does not affect the apparent total tract digestibility of calcium, but decreases digestibility of phosphorus by growing pigs. Particle size of calcium carbonate does not affect apparent and standardized total tract digestibility of calcium, retention of calcium, or growth performance of growing pigs. Effects of microbial phytase on apparent and standardized total tract digestibility of calcium in calcium supplements fed to growing pigs. Estimation of true phosphorus digestibility and endogenous phosphorus loss in growing pigs fed conventional and low-phytate soybean meals. Requirement for digestible calcium by 25 to 50 kg pigs at different dietary concentrations of phosphorus as indicated by growth performance, bone ash concentration, and calcium and phosphorus balances. Calcium intake in health maintenance – a systematic review Effect of Dairy and Nondairy Calcium on Fecal Fat Excretion in Lactose Digester and Maldigester Obese Adults A diet high in meat protein and potential renal acid load increases fractional calcium absorption and urinary calcium excretion without affecting markers of bone resorption or formation in postmenopausal women. Calcium supplements and milk: effects on acid-base balance and on retention of calcium, magnesium, and phosphorus. Sources of evidence for systematic reviews of interventions in diabetes. Low-sodium diet in pregnancy: effects on blood pressure and maternal nutritional status. Single photon emission computed tomography for the diagnosis of coronary artery disease: an evidence-based analysis. Potassium bicarbonate, but not sodium bicarbonate, reduces urinary calcium excretion and improves calcium balance in healthy men. Bias due to selective inclusion and reporting of outcomes and analyses in systematic reviews of randomised trials of healthcare interventions. Growth and Development of Premature Infants Fed Predominantly Human Milk, Predominantly Premature Infant Formula, or a Combination of Human Milk and Premature Formula Standardized total tract digestibility of phosphorus in copra meal, palm kernel expellers, palm kernel meal, and soybean meal fed to growing pigs. Higher calcium urinary loss induced by a calcium sulphate-rich mineral water intake than by milk in young women. How Quickly Do Systematic Reviews Go Out of Date? A Survival Analysis Can systematic reviews with sparse data be trusted? Calcium and cholecalciferol: effects of small supplements in normal men. Effect of dairy calcium on fecal fat excretion: a randomized crossover trial Systematic reviews in endodontics--examples of GIGO? Bioavailability of enteric-coated microencapsulated calcium during pregnancy: a randomized crossover trial in Bangladesh.
A regional experiment was conducted to test the hypothesis that the concentration of dietary Ca does not affect the digestibility of Ca or P in diets fed to growing pigs .  Six diets based on corn , potato protein isolate , cornstarch , and soybean oil were formulated . All diets also contained monosodium phosphate , crystalline AA , salt , and a vitamin-micromineral premix . The only difference among the diets was that varying concentrations of calcium carbonate were used to create diets containing 0.33 , 0.46 , 0.51 , 0.67 , 0.92 , and 1.04 % Ca . All diets contained between 0.40 and 0.43 % P. Six universities participated in the experiment and each university contributed 2 replicates to the experiment for a total of 12 replicates ( initial BW : 23.1 ± 4.4 kg ) . Pigs were placed in metabolism cages that allowed total , but separate , collection of feces and urine from the pigs . Pigs within each replicate were r and omly allotted to the 6 diets and fed experimental diets for 14 d with urine and feces being collected over a 5-d period . Diets , feces , and urine sample s were analyzed for Ca and P , and the daily balance , the apparent total tract digestibility ( ATTD ) , and the retention of Ca and P were calculated . Results indicated that intake , fecal excretion , and urinary excretion of Ca increased ( linear , P<0.05 ) as dietary Ca concentration increased . The daily intake of P was not affected by the dietary concentration of Ca , but fecal excretion of P increased ( linear , P<0.05 ) as dietary Ca concentrations increased . In contrast , urinary P output was decreased ( linear , P<0.05 ) as dietary Ca increased . The retention of Ca increased ( linear , P<0.05 ) from 1.73 to 4.60 g/d , whereas the retention of P decreased ( linear , P<0.05 ) from 1.98 to 1.77 g/d as dietary Ca concentrations increased . However , if calculated as a percentage of intake , both Ca and P retention were decreased ( linear , P<0.05 ) as dietary Ca concentration increased ( from 55.4 to 46.1 % and from 48.4 to 43.5 % , respectively ) . The ATTD of Ca was not affected by the dietary concentration of Ca , but the ATTD of P was decreased ( linear , P<0.05 ) from 56.9 to 46.2 % as dietary Ca concentration increased . It is concluded that the dietary concentration of Ca does not affect the ATTD of Ca in calcium carbonate , but increased concentrations of dietary Ca may decrease the ATTD of P in diets based on corn , potato protein isolate , and monosodium phosphate Two experiments were conducted to evaluate particle size of calcium carbonate used in diets fed to growing pigs . Experiment 1 was conducted to determine apparent total tract digestibility ( ATTD ) , st and ardized total tract digestibility ( STTD ) , and retention of Ca among diets containing calcium carbonate produced to different particle sizes , and Exp . 2 was conducted to determine if growth performance of weanling pigs is affected by particle size of calcium carbonate . In Exp . 1 , 4 diets based on corn and potato protein isolate were formulated to contain 0.70 % Ca and 0.33 % st and ardized total tract digestible P , but the calcium carbonate used in the diets was ground to 4 different particle sizes ( 200 , 500 , 700 , or 1,125 μm ) . A Ca-free diet was formulated to determine basal endogenous losses of Ca . In Exp . 2 , 4 diets were based on corn and soybean meal and the only difference among diets was that each diet contained calcium carbonate ground to the 4 particle sizes used in Exp . 1 . In Exp . 1 , 40 barrows ( 15.42 ± 0.70 kg initial BW ) were allotted to the 5 diets with 8 replicate pigs per diet using a r and omized complete block design , and in Exp . 2 , 128 pigs with an initial BW of 9.61 ± 0.09 kg were r and omly allotted to 4 experimental diets . Results of Exp . 1 indicated that basal endogenous losses of Ca were 0.329 g/kg DMI . The ATTD of Ca was 70.0 ± 3.2 , 74.3 ± 2.7 , 70.0 ± 2.9 , and 72.1 ± 2.7 and the STTD of Ca was 74.2 ± 3.2 , 78.5 ± 2.7 , 74.1 ± 2.9 , and 76.2 ± 2.7 for calcium carbonate ground to 200 , 500 , 700 , or 1,125 μm , respectively . Retention of Ca was 67.4 ± 3.1 , 70.4 ± 2.6 , 63.9 ± 2.8 , and 67.2 ± 2.2 for diets containing calcium carbonate ground to 200 , 500 , 700 , or 1,125 μm , respectively . There were no differences among diets for ATTD of Ca , STTD of Ca , or retention of Ca . The ATTD of P was 64.5 ± 1.7 , 66.8 ± 2.6 , 64.2 ± 3.0 , and 63.2 ± 1.7 % and retention of P was 61.4 ± 1.4 , 63.8 ± 2.8 , 61.9 ± 2.8 , and 60.9 ± 1.5 for diets containing calcium carbonate ground to 200 , 500 , 700 , or 1,125 μm , respectively . Neither ATTD of P nor retention of P was influenced by the particle size of calcium carbonate . Results of Exp . 2 indicated that ADG , ADFI , and G : F were not impacted by the particle size of calcium carbonate . In conclusion , particle size of calcium carbonate did not affect ATTD of Ca , STTD of Ca , or retention of Ca ; ATTD of P or retention of P ; or growth performance of pigs . Any particle size of calcium carbonate in the range from 200 to 1,125 μm can therefore be used in diets fed to pigs An experiment was conducted to test the hypothesis that differences in the apparent total tract digestibility ( ATTD ) and st and ardized total tract digestibility ( STTD ) of Ca exist among Ca supplements and that inclusion of microbial phytase increases the ATTD and STTD of Ca . One hundred and four growing barrows ( average initial BW of 17.73 ± 2.53 kg ) were allotted to a r and omized complete block design with 13 dietary treatments and 8 pigs per treatment . A basal diet containing corn , cornstarch , potato protein isolate , soybean oil , calcium carbonate , monosodium phosphate , vitamins , and minerals was formulated . Five additional diets were formulated by adding monocalcium phosphate ( MCP ) , dicalcium phosphate ( DCP ) , calcium carbonate , Lithothamnium calcareum Ca , or a high-Ca sugar beet co-product to the basal diet at the expense of cornstarch . Six additional diets that were similar to the previous 6 diets with the exception that they also contained 500 units per kilogram of microbial phytase were also formulated . A Ca-free diet was used to determine basal endogenous losses of Ca . Feces were collected using the marker-to-marker approach . Results indicated that regardless of inclusion of microbial phytase , MCP had the greatest ( P < 0.05 ) ATTD and STTD of Ca . The ATTD and STTD of Ca in DCP were greater ( P < 0.05 ) than in calcium carbonate , L. calcareumC a , or in the sugar beet co-product , but no differences were observed among the ATTD and STTD of Ca in calcium carbonate , L. calcareum Ca , or sugar beet co-product . Inclusion of microbial phytase increased ( P < 0.05 ) the ATTD and STTD of Ca in the diets , but this was not the case in the Ca supplements . Regardless of inclusion of microbial phytase , the ATTD of P was greater ( P < 0.05 ) in pigs fed basal , MCP , or DCP diets than in pigs fed calcium carbonate , L. calcareum Ca , or the sugar beet co-product , but pigs fed calcium carbonate diets had greater ( P < 0.05 ) ATTD of P than pigs fed L. calcareumCa or the sugar beet co-product . Regardless of Ca source , inclusion of microbial phytase increased ( P < 0.001 ) the ATTD of P. In conclusion , MCP has the greatest ATTD and STTD of Ca  among the calcium supplements used in this experiment , followed by DCP . Basal , MCP , and DCP diets had greater ATTD of P than the other diets , and inclusion of microbial phytase increased the ATTD and STTD of Ca and the ATTD of P in the diets This study reevaluated the method of regressing of total P output against dietary P intake to simultaneously estimate true P digestibility and endogenous P loss in growing pigs fed either conventional or low-phytate soybean meal ( SBM ) . Four isocaloric diets were formulated to contain increasing concentrations of each type of SBM ( 8 diets total ) , and therefore contained increasing concentrations of dietary P. Dietary P and Ca concentrations were deficient because they were supplied solely by SBM , and Ca : total P ratios were less than 1:1 . Sixteen barrows ( initial BW 17.7 + /- 1.8 kg ) were surgically fitted with a simple T-cannula at the distal ileum , r and omly assigned to metabolism crates , and fed the experimental diets in a replicated 8 x 8 Latin square design . Feed was provided at 90 g/kg of BW(0.75 ) and fed in 2 equally sized meals at 0800 and 2000 , with diets containing Cr sesquioxide ( 3 g/kg ) as an indigestible marker . As the P concentration increased from 0.9 to 3.9 g/kg of DM , the apparent prececal P digestibility increased for conventional SBM ( P < 0.05 ) , but no relationship was observed for low-phytate SBM . The output of total P [ mg/(kg of BW(0.75).d ) ] , either prececal or total tract , exhibited a linear relationship ( P < 0.01 ) with increasing P intake . However , a quadratic response ( P = 0.02 ) was also detected for total tract P output from pigs fed low-phytate SBM . True P digestibility was not different between prececal and total tract collection sites ( P > 0.10 ) , but was greater ( P < 0.01 ) for low-phytate SBM ( 62.6 % ) compared with conventional SBM ( 44.5 % ) . Endogenous P estimates were not different between the SBM varieties and averaged 4.83 mg/(kg of BW(0.75).d ) . However , endogenous P estimates were highly variable between individual animals and , therefore , were not significantly different from zero . In this study , estimates of endogenous P loss from pigs were relatively low compared with previously reported values , and evidence of nonlinearity in P output was observed . These results suggest that the difference in true P digestibility between conventional SBM and low-phytate SBM is influenced by dietary phytate content when growing pigs are fed P-deficient diets Two experiments were conducted to determine the requirement for st and ardized total tract digestible ( STTD ) Ca by 25 to 50 kg pigs at different concentrations of STTD P. Twenty corn-soybean meal based diets were formulated with diets containing 4 concentrations of STTD P ( 0.15 , 0.31 , 0.39 , or 0.47 % ) and 5 concentrations of STTD Ca ( 0.13 , 0.27 , 0.42 , 0.57 , or 0.72 % ) . Diets were mixed in 1 batch and were used in both experiments . In Exp . 1 , 240 pigs ( initial average BW : 24.70 ± 1.27 kg ) were r and omly allotted to the 20 diets in 6 blocks with 1 pen per diet in each block using a 4 × 5 factorial design . There was 1 gilt and 1 barrow in each pen . At the conclusion of the 28 d experiment , all barrows were euthanized and the right femur was collected . Results indicated that there were interactions ( < 0.001 ) between concentration of STTD Ca and concentration of STTD P in diets for ADG , G : F , and bone ash . The predicted maximum ADG at STTD P concentrations of 0.15 , 0.31 , 0.39 , and 0.47 % were 0.76 , 0.87 , 0.90 , and 0.92 kg at STTD Ca concentrations of 0.12 , 0.36 , 0.47 , and 0.59 % , respectively , which correspond to STTD Ca : STTD P ratios of 0.80:1 , 1.16:1 , 1.21:1 , and 1.26:1 . The predicted maximum G : F ratio at the 4 STTD P concentrations were 0.43 , 0.46 , 0.48 , and 0.50 kg/kg at STTD Ca concentrations of 0.09 , 0.38 , 0.52 , and 0.67 % , respectively , and these values correspond to STTD Ca : STTD P ratios of 0.60:1 , 1.23:1 , 1.33:1 , and 1.43:1 . The predicted maximum bone ash at the 4 STTD P concentrations were 14.5 , 21.0 , 23.1 , and 24.5 g at STTD Ca concentrations of 0.41 , 0.56 , 0.64 , and 0.72 % , respectively , which correspond to STTD Ca : STTD P ratios of 2.73:1 , 1.81:1 , 1.64:1 , and 1.53:1 . In Exp . 2 , 120 pigs ( initial average BW : 29.45 ± 2.15 kg ) were placed in metabolism crates and r and omly allotted to the 20 diets in 6 blocks with 1 pig per diet in each block . Fecal and urine sample s were collected . Results indicated that the predicted maximum retention of Ca in the body at STTD P concentrations of 0.15 , 0.31 , 0.39 , and 0.47 % were 4.7 , 7.1 , 8.6 , and 10.2 g/d at STTD Ca concentrations of 0.77 , 0.96 , 1.06 , and 1.15 % , respectively , which correspond to STTD Ca : STTD P ratios of 5.13:1 , 3.10:1 , 2.72:1 , and 2.45:1 . These observations indicate that if STTD P meets or exceeds the requirement , the STTD Ca : STTD P ratio needed to maximize ADG and G : F by 25 to 50 kg pigs is between 1.16:1 and 1.43:1 . However , a greater ratio may be needed to maximize bone ash or Ca retention Background Calcium ( Ca ) is an essential nutrient for the human body . Despite lively research , there is uncertainty about Ca requirements in terms of desirable health outcomes including an upper intake level above which the potential for harm increases . Objectives The aim was to conduct a review to up date requirements and desirable or harmful health effects of Ca on the current scientific evidence . Methods We search ed Medline and Swemed from January 2000 to December 2011 and included all systematic review s that reported Ca supplementation or usual Ca intake on health outcomes . Meta-analyses , r and omized clinical trials and cohort studies were included in the second search between May 2009 and March 2011 and an additional search covering studies till the end of 2011 . This review concentrated on studies reporting independent effects of Ca , although a few recent trials report sole effects of Ca on health outcomes , most trials use Ca in combination with vitamin D vs. placebo . Results In total , we review ed 38 studies addressing the effects of Ca on bone , pregnancy-related outcomes , cancers , cardiovascular outcomes , obesity , and mortality .  There was a lot of heterogeneity in the study protocol s , which made it difficult to draw any strong conclusions . According to the literature , high Ca intake seems to have a small positive effect on bone mineral content ( BMC ) or bone mineral density ( BMD ) in children and postmenopausal women . We did not find any consistent evidence on the effects of Ca on bone health in premenopausal women or men . Also , the evidence that Ca supplementation reduces fracture incidence is scarce and inconsistent . Maternal diet may influence the peak bone mass of offspring but more studies are required . There was no overall effect of Ca intake on cancers . Ca was associated with a decreased risk of breast cancer and a slightly increased risk of prostate cancer in two of the three studies . No associations were found with other cancers . We found no consistent association between cardiovascular outcomes and  Ca  intake except for blood pressure . A small decrease of 2–4 mmHg in systolic blood pressure was found in pregnant and in hypertensive subjects with Ca supplementation . Review ed studies did not show consistent evidence relating Ca intake to either mortality or obesity . Conclusion Based on this evidence , there is no need to change the Nordic recommendations for Ca intake . However , due to heterogeneity in the studies it is difficult to interpret the results and provide single summary statement Background : The effect of dietary calcium ( Ca ) on fecal fat excretion in lactose maldigestion is not known . Objective : To investigate the effect of dairy and non-dairy dietary Ca on fecal fat excretion in lactose digesters and maldigesters during moderate energy restriction . Design : A r and omized cross-over trial comparing the effect of 500 mg versus 1500 mg dairy and non-dairy Ca on fecal fat excretion in 34 healthy adults during moderate ( −30 % ) energy restriction induced weight loss for 12 weeks . The participants were classified as lactose digester or maldigester on the basis of breath hydrogen test . Measurements : Anthropometric parameters and body composition , resting energy expenditure , energy and nutrient intake , fecal fat , physical activity , blood pressure , blood and urine sampling for pertinent measurements . Results : Fecal fat loss expressed as percent of fat intake was significantly higher with 1500 mg ( high Ca ) as compared with 500 mg ( low Ca ) Ca intake per day ( mean : 3.0 % ; 95 % CI : 2.3 to 3.7 % ; P<0.001 ) independent of Ca source and lactose digestion status . Conclusions : During a moderate energy restriction induced weight loss , a high-Ca diet causes an increase in fecal fat excretion independent of Ca source . Ca intake related fecal fat loss is also independent of the ability to digest lactose and it is not diminished over time ( US Clinical Trial Registration : Clinical trials.gov NCT00808275 Our objective in this study was to determine the effects of a high-protein and high-potential renal acid load ( PRAL ) diet on calcium ( Ca ) absorption and retention and markers of bone metabolism . In a r and omized crossover design , 16 postmenopausal women consumed 2 diets : 1 with low protein and low PRAL ( LPLP ; total protein : 61 g/d ; PRAL : -48 mEq/d ) and 1 with high protein and high PRAL ( HPHP ; total protein : 118 g/d ; PRAL : 33 mEq/d ) for 7 wk each separated by a 1-wk break . Ca absorption was measured by whole body scintillation counting of radio-labeled (47)Ca . Compared with the LPLP diet , the HPHP diet increased participants ' serum IGF-I concentrations ( P < 0.0001 ) , decreased serum intact PTH concentrations ( P < 0.001 ) , and increased fractional (47)Ca absorption ( mean ± pooled SD : 22.3 vs. 26.5 ± 5.4 % ; P < 0.05 ) and urinary Ca excretion ( 156 vs. 203 ± 63 mg/d ; P = 0.005 ) . The net difference between the amount of Ca absorbed and excreted in urine did not differ between 2 diet periods ( 55 vs. 28 ± 51 mg/d ) . The dietary treatments did not affect other markers of bone metabolism . In summary , a diet high in protein and PRAL  increases the fractional absorption of dietary Ca , which partially compensates for increased urinary Ca , in postmenopausal women . The increased IGF-I and decreased PTH concentrations in serum , with no change in biomarkers of bone resorption or formation , indicate a high-protein diet has no adverse effects on bone health The effect of supplementing a basal diet containing 697 mg calcium daily ( 17.4 mmol/d ) with an additional 900 mg Ca daily from milk , Ca chloride , or a Ca carbonate preparation was examined in eight adult males during a 56-d metabolic balance study . The ingestion of the milk or Ca supplements had no overall effect on Ca retention by these subjects because the milk and supplements depressed apparent absorption of Ca in the gut and fractional tubular reabsorption of Ca in the kidneys . Supplementation of the diet with CaCl and to a lesser extent with milk significantly increased renal acid excretion whereas supplementation with CaCO3 depressed renal acid excretion . The three Ca supplements significantly altered magnesium and phosphorus absorption and urinary excretion in different manners but had no overall effect on retention of P or Mg . The responses of our subjects to these treatments may be different than those of subjects who are chronically in negative balance in regard to Ca AIMS To analyse the effect on systematic review s in diabetes interventions of including only trials that are indexed in medline , and to assess the impact of adding trials from other data bases and the grey literature . METHODS All systematic review s of diabetes interventions which included a meta- analysis of r and omized controlled trials , and were published since 1996 , were selected . The impact on the meta- analysis of including only those trials indexed in medline , and the effect of then adding trials from other sources , was assessed . Where possible this was measured quantitatively , by redoing the meta- analysis , otherwise a qualitative estimate was made . RESULTS Forty-four systematic review s met our inclusion criteria . There were 120 articles reporting trial data which were not indexed in medline . These came from 52 % of the review s. In 34 % of the review s , basing a meta- analysis on a search of only medline would miss trials that could affect the result . Sources of non- medline data which had the biggest effect on the meta-analyses were journal articles from central and embase ( mainly in Diabetes , Nutrition and Metabolism ) and unpublished data ( mainly from industry ) . The exceptions were journal articles on herbal medicine , mostly indexed in Chinese language data bases . CONCLUSIONS A search of only the medline data base is insufficient for systematic review s of diabetes , because in about 34 % of review s the missed trials could affect the results of the meta- analysis . It is recommended that central ( on the Cochrane Library ) also be search ed . Scanning meeting abstract s , and seeking unpublished data are also recommended if the intervention has only recently been introduced In ninety-four Dutch nulliparous women the effects of a  low-Na diet  in pregnancy on blood pressure , energy and nutrient intake , Ca metabolism , Zn and Mg status and body composition were studied longitudinally . The women were r and omly divided into an intervention group ( n 41 ) , which used a low-Na diet ( mean urinary Na excretion 61 mmol/24 h ) from week 14 of pregnancy until delivery and a control group ( n 53 ; mean urinary Na excretion 142 mmol/24 h ) . No effect of the diet on blood pressure was observed . The use of a low-Na diet result ed in significantly reduced intakes of energy , protein , carbohydrates , fat , Ca , Zn , Mg , Fe and cholesterol . However , the women on the low-Na diet appeared to be able to adapt quite well to the reduced intake since Ca , Zn and Mg homeostasis was maintained . In the case of Ca and Mg this was probably due to the observed reduced urinary excretions of these nutrients . Non-significant reductions in weight gain ( 1.5 kg ) and fat-mass gain ( 0.9 kg ) over pregnancy were found in the women on the low-Na diet . No significant effects of the diet on birth weight or placental weight were observed UNLABELLED In July 2009 , the Medical Advisory Secretariat ( MAS ) began work on Non-Invasive Cardiac Imaging Technologies for the Diagnosis of Coronary Artery Disease ( CAD ) , an evidence -based review of the literature surrounding different cardiac imaging modalities to ensure that appropriate technologies are accessed by patients suspected of having CAD . This project came about when the Health Services Branch at the Ministry of Health and Long-Term Care asked MAS to provide an evidentiary platform on effectiveness and cost-effectiveness of non-invasive cardiac imaging modalities . After an initial review of the strategy and consultation with experts , MAS identified five key non-invasive cardiac imaging technologies for the diagnosis of CAD . Evidence -based analyses have been prepared for each of these five imaging modalities : cardiac magnetic resonance imaging , single photon emission computed tomography , 64-slice computed tomographic angiography , stress echocardiography , and stress echocardiography with contrast . For each technology , an economic analysis was also completed ( where appropriate ) . A summary decision analytic model was then developed to encapsulate the data from each of these reports ( available on the OHTAC and MAS website).The Non-Invasive Cardiac Imaging Technologies for the Diagnosis of Coronary Artery Disease series is made up of the following reports , which can be publicly accessed at the MAS website at : www.health.gov.on.ca/mas or at www.health.gov.on.ca/english/providers/program/mas/mas_about.htmlSINGLE PHOTON EMISSION COMPUTED TOMOGRAPHY FOR THE DIAGNOSIS OF CORONARY ARTERY DISEASE : An Evidence -Based Analysis STRESS ECHOCARDIOGRAPHY FOR THE DIAGNOSIS OF CORONARY ARTERY DISEASE : An Evidence -Based Analysis STRESS ECHOCARDIOGRAPHY WITH CONTRAST FOR THE DIAGNOSIS OF CORONARY ARTERY DISEASE : An Evidence -Based Analysis 64-Slice Computed Tomographic Angiography for the Diagnosis of Coronary Artery Disease : An Evidence -Based Analysis CARDIAC MAGNETIC RESONANCE IMAGING FOR THE DIAGNOSIS OF CORONARY ARTERY DISEASE : An Evidence -Based Analysis Pease note that two related evidence -based analyses of non-invasive cardiac imaging technologies for the assessment of myocardial viability are also available on the MAS website : POSITRON EMISSION TOMOGRAPHY FOR THE ASSESSMENT OF MYOCARDIAL VIABILITY : An Evidence -Based Analysis MAGNETIC RESONANCE IMAGING FOR THE ASSESSMENT OF MYOCARDIAL VIABILITY : an Evidence -Based Analysis The Toronto Health Economics and Technology Assessment Collaborative has also produced an associated economic report entitled : The Relative Cost-effectiveness of Five Non-invasive Cardiac Imaging Technologies for Diagnosing Coronary Artery Disease in Ontario [ Internet ] . Available from : http://theta.utoronto.ca/reports/?id=7 OBJECTIVE The objective of the analysis is to determine the diagnostic accuracy of single photon emission tomography ( SPECT ) in the diagnosis of coronary artery disease ( CAD ) compared to the reference st and ard of coronary angiography ( CA ) . The analysis is primarily meant to allow for indirect comparisons between non-invasive strategies for the diagnosis of CAD , using CA as a reference st and ard . SPECT : Cardiac SPECT , or myocardial perfusion scintigraphy ( MPS ) , is a widely used nuclear , non-invasive image acquisition technique for investigating ischemic heart disease . SPECT is currently appropriate for all aspects of detecting and managing ischemic heart disease including diagnosis , risk assessment /stratification , assessment of myocardial viability , and the evaluation of left ventricular function . Myocardial perfusion scintigraphy was originally developed as a two-dimensional planar imaging technique , but SPECT acquisition has since become the clinical st and ard in current practice . Cardiac SPECT for the diagnosis of CAD uses an intravenously administered radiopharmaceutical tracer to evaluate regional coronary blood flow usually at rest and after stress . The radioactive tracers thallium ( 201Tl ) or technetium-99 m ( 99mTc ) , or both , may be used to visualize the SPECT acquisition . Exercise or a pharmacologic agent is used to achieve stress . After the administration of the tracer , its distribution within the myocardium ( which is dependent on myocardial blood flow ) is imaged using a gamma camera . In SPECT imaging , the gamma camera rotates around the patients for 10 to 20 minutes so that multiple two-dimensional projections are acquired from various angles . The raw data are then processed using computational algorithms to obtain three-dimensional tomographic images . Since its inception , SPECT has evolved and its techniques/applications have become increasingly more complex and numerous . Accordingly , new techniques such as attenuation correction and ECG gating have been developed to correct for attenuation due to motion or soft-tissue artifact and to improve overall image clarity . RESEARCH QUESTIONS What is the diagnostic accuracy of SPECT for the diagnosis of CAD compared to the reference st and ard of CA?Is  SPECT cost-effective compared to other non-invasive cardiac imaging modalities for the diagnosis of CAD?What are the major safety concerns with SPECT when used for the diagnosis of CAD ? METHODS A preliminary literature search was performed across OVID MEDLINE , MEDLINE In-Process and Other Non-Indexed Citations , EMBASE , the Cochrane Library , and the International Agency for Health Technology Assessment ( INAHTA ) for all systematic review s/meta- analysis published between January 1 , 2004 and August 22 , 2009 . A comprehensive systematic review was identified from this search and used as a basis for an up date d search . A second comprehensive literature search was then performed on October 30 , 2009 across the same data bases for studies published between January 1 , 2002 and October 30 , 2009 . Abstract s were review ed by a single review er and , for those studies meeting the eligibility criteria , full-text articles were obtained . Reference lists were also h and - search ed for any additional studies . Inclusion Criteria Exclusion Criteria Systematic review s , meta-analyses , controlled clinical trials , and observational studies Minimum sample size of 20 patients who completed coronary angiographyUse of CA as a reference st and ard for the diagnosis of CAD Data available to calculate true positives ( TP ) , false positives ( FP ) , false negatives ( FN ) and true negatives (TN)Accuracy data reported by patient not by segmentEnglish language Non- systematic review s , case reportsGrey literature and abstract sTrials using planar imaging onlyTrials conducted in patients with non-ischemic heart disease Studies done exclusively in special population s ( e.g. , patients with left branch bundle block , diabetics , minority population s ) unless insufficient data available SUMMARY OF FINDINGS Eighty-four observational studies , one non-r and omized , single arm controlled clinical trial , and one poorly reported trial that appeared to be a r and omized controlled trial ( RCT ) met the inclusion criteria for this review . All studies assessed the diagnostic accuracy of myocardial perfusion SPECT  for the diagnosis of CAD using CA as a reference st and ard . Based on the results of these studies the following conclusions were made : According to very low quality evidence , the addition of attenuation correction to traditional or ECG-gated SPECT greatly improves the specificity of SPECT  for the diagnosis of CAD although this improvement is not statistically significant . A trend towards improvement of specificity was also observed with the addition of ECG gating to traditional SPECT.According to very low quality evidence , neither the choice of stress agent ( exercise or pharmacologic ) nor the choice of radioactive tracer ( technetium vs. thallium ) significantly affect the diagnostic accuracy of SPECT  for the diagnosis of CAD although a trend towards accuracy improvement was observed with the use of pharmacologic stress over exercise stress and technetium over thallium . Considerably heterogeneity was observed both within and between trials . This heterogeneity may explain why some of the differences observed between accuracy estimates for various subgroups were not statistically significant . More complex analytic techniques such as meta-regression may help to better underst and which study characteristics significantly influence the diagnostic accuracy of SPECT Previous studies demonstrated that the administration of NaHCO3 or sodium citrate had either only a small effect to reduce urinary Ca excretion or no effect , but that potassium citrate significantly reduced urinary Ca excretion . In order to further evaluate and compare the effects of NaHCO3 and of KHCO3 , we performed ten metabolic balances in healthy men during 18 control days , 12 days of NaHCO3 , 60 mmol/day and 12 days of KHCO3 , 60 mmol/day . Six subjects were fed a low Ca diet ( 5.2 + /- 0.7 SD mmol/day ) and three of these were also given calcitriol ( 0.5 microgram 6-hourly ) . Four subjects ate a normal Ca diet ( 19.5 + /- 1.3 mmol/day ) . For all 10 subjects , KHCO3 administration reduced urinary Ca excretion from control by -0.9 + /- 0.7 mmol/day , P less than 0.001 . Net intestinal Ca absorption did not change detectably so that Ca balances became less negative by a + 0.9 + /- 0.9 mmol/day ; P = 0.01 . KHCO3 administration was also accompanied by more positive PO4 and Mg balances .  NaHCO3 administration had no significant effect on urinary Ca excretion or Ca balance .  NaHCO3 and KHCO3 administration were accompanied by equivalently more positive Na or K balances , respectively and equivalently more negative acid balances ( HCO3 retention ) . Neither NaHCO3 or KHCO3 altered fasting serum HCO3 concentrations , blood pH , serum 1,25-(OH)2-D or PTH concentrations . We conclude that KHCO3 promotes more positive Ca balances by either enhancing renal Ca retention or skeletal Ca retention or both BACKGROUND Systematic review s may be compromised by selective inclusion and reporting of outcomes and analyses . Selective inclusion occurs when there are multiple effect estimates in a trial report that could be included in a particular meta- analysis ( e.g. from multiple measurement scales and time points ) and the choice of effect estimate to include in the meta- analysis is based on the results ( e.g. statistical significance , magnitude or direction of effect ) . Selective reporting occurs when the reporting of a subset of outcomes and analyses in the systematic review is based on the results ( e.g. a protocol -defined outcome is omitted from the published systematic review ) . OBJECTIVES To summarise the characteristics and synthesis e the results of empirical studies that have investigated the prevalence of selective inclusion or reporting in systematic review s of r and omised controlled trials ( RCTs ) , investigated the factors ( e.g. statistical significance or direction of effect ) associated with the prevalence and quantified the bias . SEARCH METHODS We search ed the Cochrane Methodology Register ( to July 2012 ) , Ovid MEDLINE , Ovid EMBASE , Ovid PsycINFO and ISI Web of Science ( each up to May 2013 ) , and the US Agency for Healthcare Research and Quality ( AHRQ ) Effective Healthcare Program 's Scientific Re source Center ( SRC ) Methods Library ( to June 2013 ) . We also search ed the abstract books of the 2011 and 2012 Cochrane Colloquia and the article alerts for method ological work in research synthesis published from 2009 to 2011 and compiled in Research Synthesis Methods . SELECTION CRITERIA We included both published and unpublished empirical studies that investigated the prevalence and factors associated with selective inclusion or reporting , or both , in systematic review s of RCTs of healthcare interventions . We included empirical studies assessing any type of selective inclusion or reporting , such as investigations of how frequently RCT outcome data is selectively included in systematic review s based on the results , outcomes and analyses are discrepant between protocol and published review or non-significant outcomes are partially reported in the full text or summary within systematic review s. DATA COLLECTION AND ANALYSIS Two review authors independently selected empirical studies for inclusion , extracted the data and performed a risk of bias assessment . A third review author resolved any disagreements about inclusion or exclusion of empirical studies , data extraction and risk of bias . We contacted authors of included studies for additional unpublished data . Primary outcomes included overall prevalence of selective inclusion or reporting , association between selective inclusion or reporting and the statistical significance of the effect estimate , and association between selective inclusion or reporting and the direction of the effect estimate . We combined prevalence estimates and risk ratios ( RRs ) using a r and om-effects meta- analysis model . MAIN RESULTS Seven studies met the inclusion criteria . No studies had investigated selective inclusion of results in systematic review s , or discrepancies in outcomes and analyses between systematic review registry entries and published systematic review s. Based on a meta- analysis of four studies ( including 485 Cochrane Review s ) , 38 % ( 95 % confidence interval ( CI ) 23 % to 54 % ) of systematic review s added , omitted , up grade d or down grade d at least one outcome between the protocol and published systematic review . The association between statistical significance and discrepant outcome reporting between protocol and published systematic review was uncertain . The meta-analytic estimate suggested an increased risk of adding or upgrading ( i.e. changing a secondary outcome to primary ) when the outcome was statistically significant , although the 95 % CI included no association and a decreased risk as plausible estimates ( RR 1.43 , 95 % CI 0.71 to 2.85 ; two studies , n = 552 meta-analyses ) . Also , the meta-analytic estimate suggested an increased risk of downgrading ( i.e. changing a primary outcome to secondary ) when the outcome was statistically significant , although the 95 % CI included no association and a decreased risk as plausible estimates ( RR 1.26 , 95 % CI 0.60 to 2.62 ; two studies , n = 484 meta-analyses ) . None of the included studies had investigated whether the association between statistical significance and adding , upgrading or downgrading of outcomes was modified by the type of comparison , direction of effect or type of outcome ; or whether there is an association between direction of the effect estimate and discrepant outcome reporting . Several secondary outcomes were reported in the included studies . Two studies found that reasons for discrepant outcome reporting were infrequently reported in published systematic review s ( 6 % in one study and 22 % in the other ) . One study ( including 62 Cochrane Review s ) found that 32 % ( 95 % CI 21 % to 45 % ) of systematic review s did not report all primary outcomes in the abstract . Another study ( including 64 Cochrane and 118 non-Cochrane review s ) found that statistically significant primary outcomes were more likely to be completely reported in the systematic review abstract than non-significant primary outcomes ( RR 2.66 , 95 % CI 1.81 to 3.90 ) . None of the studies included systematic review s published after 2009 when reporting st and ards for systematic review s ( Preferred Reporting Items for Systematic review s and Meta-Analyses ( PRISMA ) Statement , and Method ological Expectations of Cochrane Intervention Review s ( MECIR ) ) were disseminated , so the results might not be generalisable to more recent systematic review s. AUTHORS ' CONCLUSIONS Discrepant outcome reporting between the protocol and published systematic review is fairly common , although the association between statistical significance and discrepant outcome reporting is uncertain . Complete reporting of outcomes in systematic review abstract s is associated with statistical significance of the results for those outcomes . Systematic review outcomes and analysis plans should be specified prior to seeing the results of included studies to minimise post-hoc decisions that may be based on the observed results . Modifications that occur once the review has commenced , along with their justification , should be clearly reported . Effect estimates and CIs should be reported for all systematic review outcomes regardless of the results . The lack of research on selective inclusion of results in systematic review s needs to be addressed and studies that avoid the method ological weaknesses of existing research are also needed Background In a recent meta- analysis , human milk feeding of low birth-weight ( LBW ) infants was associated with a 5.2 point improvement in IQ tests . However , in the studies in this meta- analysis , feeding regimens were used ( unfortified human milk , term formula ) that no longer represent recommended practice . Objective To compare the growth , in-hospital feeding tolerance , morbidity , and development ( cognitive , motor , visual , and language ) of LBW infants fed different amounts of human milk until term chronologic age ( CA ) with those of LBW infants fed nutrient-enriched formulas from first enteral feeding . Methods The data in this study were collected in a previous r and omized controlled trial assessing the benefit of supplementing nutrient-enriched formulas for LBW infants with arachidonic acid and docosahexaenoic acid .  Infants ( n = 463 , birth weight , 750–1,800 g ) were enrolled from nurseries located in Chile , the United Kingdom , and the United States . If human milk was fed before hospital discharge , it was fortified ( 3,050–3,300 kJ/L , 22–24 kcal/oz ) . As infants were weaned from human milk , they were fed nutrient-enriched formula with or without arachidonic and docosahexaenoic acids ( 3,300 kJ/L before term , 3,050 kJ/L thereafter ) until 12 months CA . Formula fed infants were given nutrient-enriched formula with or without added arachidonic and docosahexaenoic acids ( 3,300 kJ/L to term , 3,050 kJ/L thereafter ) until 12 months CA . For the purpose s of this evaluation , infants were categorized into four mutually exclusive feeding groups : 1 ) predominantly human milk fed until term CA ( PHM-T , n = 43 ) ; 2 ) ≥ 50 % energy from human milk before hospital discharge ( ≥ 50 % HM , n = 98 ) ; 3 ) < 50 % of energy from human milk before hospital discharge ( < 50 % HM , n = 203 ) ; or 4 ) predominantly formula fed until term CA ( PFF-T , n = 119 ) . Results PFF-T infants weighed approximately 500 g more at term CA than did PHM-T infants . This absolute difference persisted until 6 months CA . PFF-T infants were also longer ( 1.0–1.5 cm ) and had larger head circumferences ( 0.3–1.1 cm ) than both PHM-T and ≥ 50 % HM infants at term CA . There was a positive association between duration of human milk feeding and the Bayley Mental Index at 12 months CA ( P = 0.032 full and P = 0.073 reduced , statistical models ) after controlling for the confounding variables of home environment and maternal intelligence . Infants with chronic lung disease fed ≥ 50 % HM until term CA ( n = 22 ) had a mean Bayley Motor Index about 11 points higher at 12 months CA compared with infants PFF-T ( n = 24 , P = 0.033 full model ) . Conclusion Our data suggest that , despite a slower early growth rate , human milk fed LBW infants have development at least comparable to that of infants fed nutrient-enriched formula . Exploratory analysis suggests that some subgroups of  human milk fed LBW infants may have enhanced development , although this needs to be confirmed in future studies Sixty-six barrows ( initial BW : 27.4 ± 2.8 kg ) were used to determine the st and ardized total tract digestibility ( STTD ) of P in copra meal ( CM ) , palm kernel expellers from Indonesia ( PKE-IN ) , palm kernel expellers from Costa Rica ( PKE-CR ) , palm kernel meal from Costa Rica ( PKM ) , and soybean meal ( SBM ) without or with exogenous phytase . Pigs were housed individually in metabolism cages and allotted to 11 diets with 6 replicate pigs per diet in a generalized r and omized block design . Five diets were formulated by mixing cornstarch and sugar with CM , PKE-IN , PKE-CR , PKM , or SBM . Five additional diets , which were identical to the initial 5 diets but supplemented with 800 units of phytase , were also formulated . A P-free diet was used to measure basal endogenous losses of P by the pigs . Feces were collected for 5 d using the marker to marker approach after a 5-d adaptation period . Analyzed total P in CM , PKE-IN , PKE-CR , PKM , and SBM was 0.52 , 0.51 , 0.53 , 0.54 , and 0.67 % , respectively . Phytate P was 0.22 , 0.35 , 0.38 , 0.32 , and 0.44 % in CM , PKE-IN , PKE-CR , PKM , and SBM , respectively . Addition of phytase increased ( P < 0.05 ) the apparent total tract digestibility ( ATTD ) of P from 60.6 to 80.8 , 27.3 to 56.5 , 32.6 to 59.9 , 48.9 to 64.1 , and 41.1 to 72.2 % in CM , PKE-IN , PKE-CR , PKM , and SBM , respectively . The ATTD of P in CM was greater ( P < 0.05 ) than in any of the other ingredients . The ATTD of P in SBM and PKM was greater ( P < 0.05 ) than in PKE-IN , with PKE-CR being intermediate . The STTD of P increased ( P < 0.05 ) from 70.6 to 90.3 , 37.6 to 66.4 , 43.2 to 69.9 , 57.9 to 73.5 , and 49.6 to 81.1 % in CM , PKE-IN , PKE-CR , PKM , and SBM , respectively , when microbial phytase was added to the diets . When expressed as a percentage of total P , phytate P concentration in the ingredient negatively affected ( P < 0.05 ) the ATTD of P ( 107.09 - 1.0564 × % phytate P ; R(2 ) = 87.1 ) and the STTD of P ( 116.3 - 1.0487 × % phytate P ; R(2 ) = 89.4 ) . In conclusion , microbial phytase increased P digestibility of CM , PKM , PKE-CR , PKE-IN , and SBM when fed to growing pigs , and the concentration of phytate P affects the response to microbial phytase It is well known that the intestinal availability of Ca from Ca-rich mineral waters is equivalent to that of milk Ca . However , the effect of associated anions on Ca urinary loss needs to be addressed . The aim of the current study was to compare , under ordinary conditions of consumption , milk and a SO4-rich mineral water as the Ca provider in a large number of subjects consuming the same quantity of Ca from the two sources in a crossover study lasting for an extended period . Thirty-seven healthy women completed a 12-week protocol , divided into four periods of 3 weeks ( W ) . In the first ( W1 - 3 ) and third ( W6 - 9 ) periods , dietary Ca intake was restricted to 600 mg/d . In the second ( W4 - 6 ) and final ( W10 - 12 ) periods , either 400 ml/d medium-fat milk or 1 litre of a Ca- and SO4-rich mineral water , each providing about 480 mg Ca/d , was added to the diet in a r and om manner . Dietary evaluation , blood and urinary measures were performed during the last week ( W6 and W12 ) of each Ca supplementation period . The urinary excretion of Ca was higher ( 0.5 mmol/d more ) with water than with milk ( P<0.001 ) . An examination of all the dietary factors known to influence calciuria suggested that the acidogenic action of SO4 was responsible for this increased calciuria . Thus , despite an equal Ca intake and assuming an unchanged intestinal absorption , these results suggest that Ca balance is better with milk consumption than with CaSO4-rich water Context Clinicians rely on systematic review s for current , evidence -based information . Contribution This survival analysis of 100 meta-analyses indexed in ACP Journal Club from 1995 to 2005 found that new evidence that substantively changed conclusions about the effectiveness or harms of therapies arose frequently and within relatively short time periods . The median survival time without substantive new evidence for the meta-analyses was 5.5 years . Significant new evidence was already available for 7 % of the review s at the time of publication and became available for 23 % within 2 years . Implication Clinical ly important evidence that alters conclusions about the effectiveness and harms of treatments can accumulate rapidly . The Editors Systematic review s have become increasingly common in recent years ( 1 ) and are recommended by many as the best sources of evidence to guide both clinical decisions ( 2 ) and health care policy ( 3 ) . For systematic review s to fulfill these roles , their findings must remain relatively stable for at least several years or effective mechanisms must exist for alerting end users to important changes in evidence . Yet , surprisingly little research has assessed the extent to which systematic review s become out of date or the rate at which this occurs ( 47 ) . Some organizations , such as the Cochrane Collaboration , recommend updating systematic review s every 2 years , but few empirical data guide this or other recommendations about updating . We sought to determine how quickly systematic review s meet explicitly defined criteria for changes in evidence of sufficient importance to warrant updating . We also sought to identify predictors of survival time , the time to such important changes in evidence . Survival time might vary depending on many factors , including the type of question posed by the original review ( for example , therapeutic or diagnostic ) , the types of studies included ( for example , r and omized trials or observational studies ) , and whether the systematic review provided quantitative synthesis . To limit such variation , we focused on systematic review s of r and omized , controlled trials that evaluated therapeutic benefit or harm by providing quantitative synthesis ( meta- analysis ) for at least 1 outcome . Methods Study Design and Sample We used a quasi-r and om process ( alphabetical sort order by author ) to select 100 systematic review s that were indexed in ACP Journal Club with an accompanying commentary between January 1995 and December 2005 ( with a search date no later than 31 December 2004 to ensure at least 1 full year for new evidence to appear ) . We chose this sampling frame because ACP Journal Club selects systematic review s that meet explicit quality st and ards and are deemed directly relevant to clinical practice ( 8) . We regarded the sample size of 100 as sufficiently large to achieve suitably narrow confidence intervals and to permit evaluation of up to 5 potential predictors of survival . Eligibility Criteria Eligible review s evaluated the benefit or harm of a specific drug , class of drug , device , or procedure ( invasive procedure or surgery ) and included r and omized or quasi-r and omized , controlled trials . We excluded evaluations of alternative and complementary medicines because the stability of review s of such therapies might differ substantially from review s of conventional therapies . We required that review s provide a point estimate and 95 % confidence interval for at least 1 outcome in the form of a relative risk , odds ratio , or absolute risk difference for binary outcomes and weighted mean differences for continuous outcomes . We excluded meta-analyses of individual-patient data , meta-regressions , and indirect meta-analyses because of the difficulty of determining whether new data would alter previous quantitative results . Two team members independently assessed eligibility , with disagreements resolved by consensus involving a third review er . When more than 1 review on the same topic was identified , only the earliest was included . Search ing For each review , search es for new trials included identifying new systematic review s on the same topic , su bmi tting relevant content terms to the Clinical Queries function in Ovid , applying the Related Articles function in PubMed to the 3 largest and the 3 most recent trials in the original review ( up to 6 trials in total ) , and using Scopus ( www . scopus .com/ scopus /home.url ) to identify new r and omized trials that cited the original review . When these search strategies yielded no eligible new trials , we conducted more comprehensive electronic search es and review ed relevant chapters in such sources as Clinical Evidence and UpTo Date to ensure that we had not missed new trials . Team members who had background s in both medicine and clinical research screened citations retrieved by the preceding methods to identify trials that would have met the inclusion criteria in the original review . Retrieved articles were screened in chronological order to ascertain quantitative or qualitative signals for the need for updating . The review protocol stopped when any criteria for updating were met . Each systematic review was discussed in detail , with the final statussignal for updating was or was not detectedadjudicated by consensus ( Figure 1 ) . Figure 1 . Overall process for determining updating status . ACP Journal Club Signals for the Need to Up date Systematic Review s In design ing criteria for comparing new findings with those in a previous review , we adapted methods used by other investigators to address similar problems with comparing 2 sets of results relating to the same question ( 913 ) , such as r and omized and nonr and omized studies of the same intervention . These investigators identified conflicting findings among different publications using a combination of quantitative thresholds for differences in effect magnitude and qualitative judgments about the language used to describe the results . We have similarly conceptualized quantitative and qualitative signals of potential changes in evidence that are sufficiently important to warrant updating previous systematic review s. Quantitative Signals Quantitative signals consisted of a change in statistical significance or relative change in effect magnitude of at least 50 % . We restricted these changes to those involving 1 of the primary outcomes of the original review or any mortality outcome . We also ignored trivial changes in statistical significance when the original and up date d meta-analytic results both had P values between 0.04 and 0.06so that quantitative signals of changes in evidence would represent robust indicators of the need to up date previous review s. Quantitative signals were detected by combining data from eligible new trials with the previous results using a fixed-effects approach . Use of fixed-effect models allowed pooling of the new trials with the previous meta-analytic result , as opposed to having to obtain original data from all of the included trials in each of 100 systematic review s. Although r and om-effects models are usually preferred to avoid spurious precision in the face of heterogeneity , our goal was to detect potential changes in evidence that would warrant a formal up date , not produce exact estimates of the up date d results . Qualitative Signals Qualitative signals included new information about harm sufficient to affect clinical decision making , important caveats to the original results , emergence of a superior alternate therapy , and important changes in certainty or direction of effect . Qualitative signals were detected by using explicit criteria for comparing the language in the original review with descriptions of findings in new systematic review s that addressed the same topic , pivotal trials , clinical practice guidelines , or recent editions of major textbooks ( for example , UpTo Date ) . Pivotal trials were defined as trials that had a sample size at least 3 times larger than that of the previous largest trial or were published in 1 of the 5 highest-impact general medical journals ( The New Engl and Journal of Medicine , Lancet , Journal of the American Medical Association , Annals of Internal Medicine , and the British Medical Journal ) . We defined 2 levels of importance for qualitative signals : potentially invalidating changes in evidence , which would make one no longer want clinicians or policymakers to base decisions on the original findings ( such as a pivotal trial that characterized treatment effectiveness in terms opposite of those in the original systematic review ) , and major changes in evidence , which would affect clinical decision making in important ways without invalidating the previous results ( such as the identification of patient population s for whom treatment is more or less beneficial ) . Major changes also included differing characterizations of effectiveness that were less extreme than those for potentially invalidating signals but that would still affect clinical decision making ( for example , a change from possibly beneficial to definitely beneficial ) . Of importance , such characterizations as possibly effective , probably effective , and promising , were all categorized as possibly effective . Thus , qualitative signals for changes in evidence captured substantive differences in the characterization of treatment effects , not merely semantic differences . Full definitions for each of the specific signals can be found at www.ohri.ca/UpdatingSystRevs . Data Collection For each review , we characterized the clinical content area , eligibility criteria for included trials , definitions of reported outcomes , number of included trials and participants , meta-analytic result for each outcome , identification of statistical heterogeneity , and excerpted quotations of the authors ' characterizations of the main results . We also abstract ed whether a given outcome was explicitly identified as 1 of the primary or main outcomes . We discounted identification of more than 3 such outcomes as inconsistent with the Systematic review s are increasingly used to answer clinical questions . Their popularity is partly attributable to their apparent clinical superiority in providing quick summaries of evidence from the ever-growing medical literature ( more than 750,000 items annually [ 1 ] ) , but also thanks to the great impact of the Cochrane Collaboration in promoting the use of the systematic review [ 2 ] . We also note that many scientific journals favour systematic review s because they tend to contribute to higher journal impact factors . However , the rise of systematic review s should give cause for concern ; more than 8000 are being indexed in MEDLINE annually , reflecting a three-fold increase over the last decade [ 3 ] . We write ‘ concern ’ , because many of these review s across healthcare seem to fall short of essential requirements such as incorporating risk of bias assessment in meta-analyses ( only 16 % ) , search ing for unpublished data ( only 7 % ) , or not fully following a protocol ( only one-third [ 3 ] ) . A recent study of review s published in anaesthetic journals revealed similar shortfalls [ 4 ] . Further more , the quality of reporting is lower in some countries and in journals with lower impact factors [ 5 , 6 ] . The apparent poor quality of many published systematic review s greatly increases the risk of misleading conclusions , which ultimately could harm our patients [ 7 ] . Despite their veneer of sophistication , one has to bear in mind that systematic review s are , in essence , retrospective appraisal s of the evidence . Editors , writers and readers should exercise great caution when interpreting conclusions of review s that only include very few trials , even when they fulfill the required st and ards [ 3 ] . Despite great efforts to promote adequate quality of review s through international guidelines such as PRISMA , GRADE and the Cochrane H and book [ 8 ] , the majority of review s may suffer from threats to the validity of their findings due to risk of systematic errors ( bias ) , design errors ( i.e. , erroneous selection of patients , doses of medication , comparators , analyses , outcomes ) and r and om error ( play of chance ) [ 9 ] . In a previous publication in this journal , some of the method ological issues and requirements for authors and editors were thoroughly discussed [ 10 ] . But we believe that other issues need to be addressed , in particular the amount of information included in meta-analyses from systematic review s , with the power this brings The effect of small calcium and vitamin D supplements on mineral metabolism in normal persons is unclear . To investigate the biochemical response to these medications , we administered 1000 mg Ca and 25 micrograms cholecalciferol per day or a placebo to 92 normal men for 1 y. The Ca and cholecalciferol were tolerated well . 25-Hydroxycholecalciferol [ 25-(OH)D ] and 24,25-dihydroxycholecalciferol [ 24,25-(OH)2D ] levels rose in treated subjects ; there was no definite change in 1,25-(OH)2D concentrations . The average difference in 25-(OH)D levels between treated and untreated subjects was 30 nmol/L at 1 y. Fasting serum Ca , alkaline phosphatase , creatinine , and parathyroid hormone levels and the fasting urinary excretion of Ca , phosphorus and cAMP , were not affected . However , 24-h urinary Ca excretion was higher in the supplemented group ( 3.5 + /- 1.9 vs 4.7 + /- 1.7 mmol/d , p = 0.006 ) . Serum P concentrations were slightly higher in the supplemented group at 1 y. In normal men  small calcium and cholecalciferol supplements are safe , provide adequate vitamin D nutrition and apparently increase net gastrointestinal Ca absorption Background : Evidence suggests that dietary calcium intake may be inversely related to body weight . One explanatory mechanism is that dietary calcium increases fecal fat excretion , due to either calcium soap formation and /or binding of bile acids ( BAs ) in the intestine . Objective : To examine the effect of calcium from low-fat dairy products on fecal fat excretion . Design : A r and omized crossover study with 11 subjects , comparing two 7-d diets : one high in calcium from low-fat dairy products ( high-Ca ; 2300 mg Ca per d ) and one low in calcium ( low-Ca ; 700 mg Ca per d ) . Measurements : All feces were collected during the last 5 days of each diet period and analyzed for fat , energy and calcium content and fatty acid ( FA ) and BA composition . Results : Dairy calcium significantly increased the total fecal fat excretion from 5.4±0.5 g d−1 on the low-Ca diet to 11.5±1.4 g d−1 on the high-Ca diet ( P<0.001 ) . The fecal energy excretion increased almost correspondingly . Saturated , monounsaturated and polyunsaturated FAs were all excreted in larger amounts on the high-Ca diet ( P<0.001 for all ) , with the effect of calcium being greater for monounsaturated than for saturated FAs . The fecal excretion of BAs was unaffected of calcium intakes . Conclusions : Increasing the intake of calcium from low-fat dairy products by 1600 mg d−1 for 7 days doubled total fecal fat excretion , but did not affect the excretion of BAs . The results may partially explain why a high-calcium diet can produce weight loss In many areas of medicine the amount of published information is increasing at an exponential rate , making it difficult for the clinician to condense the data to a manageable amount of valuable and useful information . Systematic review s have been suggested as a remedy for this information overload . Such review s are regarded as the highest level of evidence . Certain statistical methods , e.g. , meta- analysis , have also been introduced for the calculation of a more comprehensive summation of the compiled results from studies with small sample sizes . These findings would then serve as an authoritarian guide for evidence -based practice . Endodontists have lately jumped on the b and wagon of systematic review s and meta-analyses , and papers on various topics are being published . Well done , such comprehensive information would be very useful and authoritative for the practitioner . Alarmingly , the quality of these recent publications is negatively correlated to the frequency . This can have serious consequences in the clinical arena if spurious information is given a seal of approval when communicated as facts in refereed journals . A systematic literature review is design ed to focus on a single question and to synthesize all high- quality research reports relevant to the question . In these studies , however , sources of bias are often not controlled . Therefore , even the best review and meta- analysis becomes useless if it is based on poorly design ed research . Furthermore , these review s are mostly based on published data which are too often biased toward studies that show significant differences in results and /or outcome . “ Uninteresting ” conclusions tend not to be published . Endodontic literature , thus far , is short on well design ed and executed r and omized clinical trials . Furthermore , clinical protocol s often have many important “ proprietary ” modifications that make comparison difficult . This makes it very hard to undertake a systematic review to answer a narrow question . Such GIGO ( garbage in , garbage out ) can easily lead to biased conclusions and reinforce already existing biased comclusions . An example of such bias can be illustrated by a meta- analysis recently published . The study focused on assessing if there were differences in outcome between 1 and 2 treatment visits when treating teeth with apical periodontitis . Relevant publications on this topic are rare , and with the narrow inclusion criteria only 3 investigations were available for the review . However , the only factors connecting these 3 studies was the words “ single ” and “ two visits ” in the title . Beyond that , the selected studies are too different and inadequate for the study . Only 1 study is somewhat demonstrably r and omized , and outcome assessment s are based on 3 vastly different criteria . Two of the studies use calcium hydroxide as intracanal dressing , whereas the third uses no intervisit medication . Complexity of initial pathology and healing time are also clearly factors of great importance but not controlled . In addition , sample sizes in the component studies as well as the final cohort are all too small for the conclusions that there was no significant difference between 1or 2-visit treatment protocol s. To undertake and publish a meta- analysis on such an incomplete sample is counterproductive . Although the publication noted its numerous limitations , it will still communicate erroneous conclusions with a poor scientific foundation to the less informed reader . There are other examples of recently published systematic review s that are very ambiguous and tend to communicate spurious facts . One of these studies looks at the effect of smear-layer removal on sealing ability of root canal obturation . The study is entirely limited to laboratory experiments , with the majority of evaluations using dye leakage which is generally considered to be unreliable . This is an example of review ers lacking content expertise . The authors draw the conclusion , using defective review material , that removal of smear layer enhances the seal of the root filling . We may generally believe that this is the truth BACKGROUND Prenatal calcium and iron supplements are recommended in setting s of low dietary calcium intake and high prevalence of anemia . However , calcium administration may inhibit iron absorption . To overcome calcium-iron interactions , we developed a multi-micronutrient powder containing iron ( 60 mg ) , folic acid ( 400 μg ) , and calcium carbonate granules microencapsulated with a pH-sensitive enteric coating to delay intestinal release . OBJECTIVES We aim ed to establish in vivo evidence that enteric-coated ( EC ) calcium is bioavailable in pregnant women and to explore the dose-responsiveness of fractional calcium absorption ( FCA ) in pregnancy . DESIGN This was a r and omized crossover trial in pregnant women ( 26 - 28 wk of gestation ) in Dhaka , Bangladesh . Participants were allocated to 1 of 3 dose groups ( 500 , 1000 , or 1500 mg elemental Ca ) . FCA was estimated in r and om order for EC and non-EC ( control ) granules by a dual-stable-isotope method ( (44)Ca-labeled granules and intravenous (42)Ca ) on the basis of the relative recovery of (44)Ca compared with (42)Ca in urine over 48 h. RESULTS Forty-nine participants with FCA for both EC and non-EC granules were included in the primary analyses . FCA geometric means were as follows : 21.8 % ( 500 mg ) , 9.2 % ( 1000 mg ) , and 11.7 % ( 1500 mg ) for non-EC granules compared with 3.3 % ( 500 mg ) , 1.2 % ( 1000 mg ) , and 2.1 % for EC granules . Cumulative 48-h FCA of EC calcium was 85 % lower ( P < 0.001 ) than that of non-EC calcium , after adjustment for dose . In comparison to 500 mg , the FCA for the 1000-mg dose was 61 % lower ( P < 0.001 ) and was 42 % lower ( P = 0.002 ) for the 1500-mg dose , after adjustment for formulation . CONCLUSIONS A pH-sensitive enteric coating substantially reduced calcium absorption from a prenatal multi-micronutrient powder . In its current formulation , this novel supplement is not suitable for clinical use . FCA was highly dose-dependent , such that doses of 1000 and 1500 mg delivered only negligibly more bioavailable calcium than the 500-mg dose . This trial was registered at clinical trials.gov as NCT01678079
These outcomes advance the current underst and ing 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
Ca digestibility and utilisation in growing pigs are not well understood , and are usually neglected in diet formulation .
This has implication s 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 .