human
***TASK*** the task is to summarize an input biomedical literature in six sentences 
    ***INPUT*** the input is a biomedical literature 
    ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences 
    ***DOCUMENTATION*** 
    ***EXAMPLES*** 
    Input: To comprehend the results of a r and omised controlled trial ( RCT ) , readers must underst and its design , conduct , analysis , and interpretation . That goal can be achieved only through total transparency from authors . Despite several decades of educational efforts , the reporting of RCTs needs improvement . Investigators and editors developed the original CONSORT ( Consoli date d St and ards of Reporting Trials ) statement to help authors improve reporting by use of a checklist and flow diagram . The revised CONSORT statement presented here incorporates new evidence and addresses some criticisms of the original statement . The checklist items pertain to the content of the Title , Abstract , Introduction , Methods , Results , and Discussion . The revised checklist includes 22 items selected because empirical evidence indicates that not reporting this information is associated with biased estimates of treatment effect , or because the information is essential to judge the reliability or relevance of the findings . We intended the flow diagram to depict the passage of participants through an RCT . The revised flow diagram depicts information from four stages of a trial ( enrolment , intervention allocation , follow- up , and analysis ) . The diagram explicitly shows the number of participants , for each intervention group , included in the primary data analysis . Inclusion of these numbers allows the reader to judge whether the authors have done an intention- to-treat analysis . In sum , the CONSORT statement is intended to improve the reporting of an RCT , enabling readers to underst and a trial 's conduct and to assess the validity of its results PURPOSE As clinical diagnosis of secondary caries is the most common reason for restoration replacement , fluoride-releasing restorative material s have been developed to address this problem . The purpose s of this study were to verify demineralization inhibition produced by 5 restorative material s su bmi tted to two methods of in vitro cariogenic challenge and verify whether these methods influence material behavior by means of polarized light microscopy and microhardness . METHODS Class V cavities were prepared on buccal surfaces of 100 extracted primary molars and r and omly restored with 1 of the 4 fluoride-releasing material s , Fuji IX , Vitremer , Dyract , Tetric Ceram , and Filtek Z250 as control material ( N=10 ) . Specimens were su bmi tted to in vitro caries induction by two different methods , acid gel immersion , and pH cycling . Teeth su bmi tted to gel were then sectioned and prepared for polarized light microscopy in water , while teeth cycled were prepared for microhardness evaluation . RESULTS Polarized light microscopy : Means of demineralization areas ( microm(2 ) ) differed significantly , depending on the restorative material . Tukey 's test revealed the smallest demineralization areas adjacent to Fuji IX and Vitremer restorations , with no difference between them ( P>.05 ) . The greatest demineralization area mean values were verified using Dyract and Filtek Z250 , without differences between them ( P>.05 ) . Microhardness : Glass ionomer cements ( GICs ) performed better on the area of great cariogenic challenge , closer to the surface , than other material s indicating minor mineral loss during pH cycling . The compomer Dyract presented similar performance to GICs and composite resin Tetric Ceram , but it was better than Filtek Z250 . CONCLUSION The experimental model of caries lesion induction may influence material performance . GICs , however , are superior in preventing in vitro demineralization independently of the method Previous papers in this series on evidence -based dentistry have discussed the first 2 steps in seeking answers to clinical problems formulating a clear question and strategically search ing for evidence . The next step , critical appraisal of the evidence , is made easier if one underst and s the basic concepts of clinical research design . The strongest design , especially for questions related to therapeutic or preventive interventions , is the r and omized , controlled trial . Questions relating to diagnosis , prognosis and causation are often studied with observational , rather than experimental , research design s. The strongest study design should be used whenever possible . Rules have been established to grade research evidence . This paper , the fourth in the series , presents an overview of research methodology most commonly used in the dental literature OBJECTIVE The aim of this in vitro study was to evaluate the interaction between two sources of fluoride ( restorative systems and dentifrices ) in inhibiting artificial root caries development . METHODS One hundred and eighty tooth segments were embedded in polyester resin , and s and ed flat . Cylindrical cavities 1.0mm-deep and 1.5mm-diameter were prepared in root dentin and r and omly restored by fluoride-containing restorative systems : Ketac-fil/Espe ( Ke ) , Fuji II LC/GC Corp ( Fj ) , F2000/3 M ( F2 ) , Surefil/Dentsply ( Su ) or a control : Filtek Z250/3 M ( Z2 ) . Ten experimental groups were made to test the association among the five restorative systems and two dentifrices : with F(- ) ( Sensodyne Baking Soda ) or without F(- ) ( Sensodyne Original ) ( n=18 ) . After surface polishing , a 1mm-wide margin around the restorations was demarcated and initial dentin surface Knoop microhardness values ( KHN(i ) ) were obtained . The specimens were su bmi tted to a pH-cycling model , and to applications of slurries of dentifrice . Afterwards the final dentin surface Knoop microhardness values ( KHN(f ) ) were measured . RESULTS The differences between KHN(i ) and KHN(f ) , and the covariate KHN(i ) were considered by the ANCOVA and Tukey 's test ( alpha=0.05 ) . The interaction between restorative system and dentifrice was statistically significant ( p=0.0026 ) . All restorative systems provided some protection against artificial caries challenge when associated with the fluoride-containing dentifrice treatment . The means ( st and ard deviation ) of reductions in Knoop hardness values for systems associated with the fluoride-containing dentifrice were : Ke : 40.0(1.02)(a ) , Fj : 41.9(1.02)(b ) , F2 : 43.3(1.04)(c ) , Su : 43.5(1.00)(c ) , Z2 : 44.0(1.02)(c ) ; and with the non-fluoride-containing dentifrice were : Ke : 42.9(1.02)(a ) , Fj : 44.7(1.01)(b ) , F2 : 45.2(1.09)(bc ) , Su : 46.0(0.99)(c ) , Z2 : 46.6(0.99)(c ) ( statistical differences were expressed by different letters ) . CONCLUSION The cariostatic effect shown by the fluoride-containing dentifrice could enhance that shown by Ketac-fil and Fuji II LC , and could mask that shown by F2000 There is no consensus about an association between microleakage and secondary caries , especially considering the presence of fluoride ( F ) at the tooth/restoration interface . Thus , a r and omized , double-blind , crossover study was carried out to evaluate in situ the effect of microleakage on caries around enamel-dentine restorations in the presence of F from dental material s or dentifrice , either alone or in combination . In 4 phases of 14 days each , 14 volunteers wore palatal devices containing dental slabs restored with composite resin ( CR ) or resin-modified glass ionomer cement ( GI ) . Restorations were made without leakage ( L– ) , following the recommended adhesive procedures , or with leakage ( L+ ) , in the absence of adhesive procedures . Plaque-like biofilm ( PLB ) was left to accumulate on the restored slabs , which were exposed extraorally to a 20 % sucrose solution 10 × /day . The volunteers used a non-F ( NF ) or an F ( FD ) dentifrice 3 × /day , depending on the experimental phase . No differences were found between L+ or L– restorations ( p > 0.05 ) . Higher demineralization in both enamel and dentine around CR restorations was observed under NF ( p < 0.05 ) . F concentration was higher in the fluid of PLB exposed to FD or formed onto GI restoration ( p < 0.05 ) . These results suggest that while microleakage does not affect caries development , GI or FD may maintain increased F levels in the PLB , thereby decreasing caries progression Since the last comprehensive review of anticoagulation in acute myocardial infa rct ion four additional r and omized control trials have been reported . The overwhelming majority of all trials favored anticoagulation .  Rates of thromboembolism were higher in the control , and hemorrhagic complications in the anticoagulated group . Pooling of all r and omized control trials gives mean case fatality rates of 19.6 % for the control and 15.4 % for the anticoagulated group , a relative reduction of 21 % ( P less than 0.05 or less than 0.001 , depending on the analytic method ) . Five of six r and omized control trials reported " no effect " because the difference favoring anticoagulation was not statistically significant . However , sample sizes in these " negative " papers were too small to protect against missing a 21 % reduction in true case fatality rate due to anticoagulation ( beta greater than 0.10 ) . All patients who present no specific contraindication should receive  anticoagulants  during hospitalization for infa rct ion Previous reports have shown a release of fluoride from glass-ionomer cement ( GIC ) restorations into the oral fluids . Fluoride in the ambient fluids has a caries-preventive effect by enhancing remineralization and inhibiting demineralization of the dental hard tissues . Therefore , the current investigation was undertaken to determine whether GIC fillings could contribute to the remineralization of caries lesions in dentin . Small circular preparations were made in disks of dentin which had incipient caries-like lesions in the remaining tissue . The preparations were filled with amalgam or composite material s ( as controls ) or with GIC . The specimens thus contained a restoration close to a dentinal caries-like lesion . The specimens were placed contralaterally in the buccal surfaces of removable partial dentures and were worn intra-orally by volunteers for a 12-week experimental period , after which the specimens were sectioned and analyzed by microradiography . All specimens with GIC restorations exhibited hypermineralization in the tissue bordering the filling and in the wall of the preparation which had been in contact with the restoration . The ( caries-like ) lesions were remineralized , even under conditions of heavy plaque formation . In contrast , specimens with amalgam or composite restorations showed further extensive demineralization . This study demonstrates a significant remineralization potential exerted by the fluoride-releasing GIC restorative material . Consequently , the choice of the restorative material might be crucial for the occurrence or prevention of recurrent caries around restorations PURPOSE Enamel demineralization adjacent to orthodontic brackets is one of the risks associated with orthodontic treatment . Glass ionomer cements have been shown to decrease enamel demineralization adjacent to brackets and b and s but do not exhibit bond strengths comparable to resin composites . The purpose of this in vitro study was to compare a fluoride-releasing resin composite versus a resin-modified glass ionomer cement for inhibition of enamel demineralization surrounding orthodontic brackets . METHODS Forty-five teeth were r and omly assigned to 3 groups of 15 teeth . Fifteen were bonded with Concise ( 3 M ) , a non-fluoride-releasing resin composite ( control ) ; 15 teeth were bonded with Light Bond ( Reliance ) , a fluoride-releasing resin composite ; and 15 teeth were bonded with Fuji Ortho LC ( GC Corporation ) , a resin-modified glass ionomer cement . The teeth were placed in an artificial caries solution to create lesions . Following sectioning of the teeth in a buccolingual direction , polarized light microscopy was utilized to evaluate enamel demineralization adjacent to the orthodontic bracket . The area of the lesion was measured 100 microns from the orthodontic bracket and bonding agent . RESULTS MANOVA ( P < .0001 ) and Duncan 's test ( P < .05 ) indicated the resin-modified glass ionomer cement ( Fuji Ortho LC ) and the fluoride-releasing resin composite ( Light Bond ) had significantly less adjacent enamel demineralization than the non-fluoride-releasing resin composite control . However , there was no significant difference between the resin-modified glass ionomer cement and the fluoride-releasing resin composite . CONCLUSIONS Based on the results of this in vitro study , it can be concluded that Fuji Ortho LC and Light Bond exhibit significant inhibition of adjacent demineralization compared to the non-fluoride-releasing control The aim was to study the effect of three fluoride – releasing restorative material s  on sound enamel of approximal teeth under cariogenic conditions intraorally . Bovine enamel slabs were paired with four hemispherical sample s from each of three test material s ( Ketac Molar , ESPE ; Vitremer , F–2000 , both from 3 M ) and one control material ( Pertac II , ESPE ) . Their curved surface touched enamel at a contact point allowing space for plaque accumulation . Pairs were inserted in the buccal flanges of 2 lower dentures for 70 days . Initially and upon dismantling , enamel surface microhardness was measured and the increase in length of indentation in micrometers was recorded at a distance of 0 , 0.4 , 0.8 and 1.2 mm from the contact point . Respective values were : Pert 
    Output:
    
agent
The evidence suggests that RM-GIC is associated with a higher reduction of demineralization in adjacent hard tooth tissue than composite resin without fluoride .
No difference was found when RM-GIC was compared with fluoride-containing composite resin .
RM-GIC showed efficacy in reducing demineralization .
***TASK*** the task is to summarize an input biomedical literature in six sentences 
    ***INPUT*** the input is a biomedical literature 
    ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences 
    ***DOCUMENTATION*** 
    ***EXAMPLES*** 
    Input: To comprehend the results of a r and omised controlled trial ( RCT ) , readers must underst and its design , conduct , analysis , and interpretation . That goal can be achieved only through total transparency from authors . Despite several decades of educational efforts , the reporting of RCTs needs improvement . Investigators and editors developed the original CONSORT ( Consoli date d St and ards of Reporting Trials ) statement to help authors improve reporting by use of a checklist and flow diagram . The revised CONSORT statement presented here incorporates new evidence and addresses some criticisms of the original statement . The checklist items pertain to the content of the Title , Abstract , Introduction , Methods , Results , and Discussion . The revised checklist includes 22 items selected because empirical evidence indicates that not reporting this information is associated with biased estimates of treatment effect , or because the information is essential to judge the reliability or relevance of the findings . We intended the flow diagram to depict the passage of participants through an RCT . The revised flow diagram depicts information from four stages of a trial ( enrolment , intervention allocation , follow- up , and analysis ) . The diagram explicitly shows the number of participants , for each intervention group , included in the primary data analysis . Inclusion of these numbers allows the reader to judge whether the authors have done an intention- to-treat analysis . In sum , the CONSORT statement is intended to improve the reporting of an RCT , enabling readers to underst and a trial 's conduct and to assess the validity of its results PURPOSE As clinical diagnosis of secondary caries is the most common reason for restoration replacement , fluoride-releasing restorative material s have been developed to address this problem . The purpose s of this study were to verify demineralization inhibition produced by 5 restorative material s su bmi tted to two methods of in vitro cariogenic challenge and verify whether these methods influence material behavior by means of polarized light microscopy and microhardness . METHODS Class V cavities were prepared on buccal surfaces of 100 extracted primary molars and r and omly restored with 1 of the 4 fluoride-releasing material s , Fuji IX , Vitremer , Dyract , Tetric Ceram , and Filtek Z250 as control material ( N=10 ) . Specimens were su bmi tted to in vitro caries induction by two different methods , acid gel immersion , and pH cycling . Teeth su bmi tted to gel were then sectioned and prepared for polarized light microscopy in water , while teeth cycled were prepared for microhardness evaluation . RESULTS Polarized light microscopy : Means of demineralization areas ( microm(2 ) ) differed significantly , depending on the restorative material . Tukey 's test revealed the smallest demineralization areas adjacent to Fuji IX and Vitremer restorations , with no difference between them ( P>.05 ) . The greatest demineralization area mean values were verified using Dyract and Filtek Z250 , without differences between them ( P>.05 ) . Microhardness : Glass ionomer cements ( GICs ) performed better on the area of great cariogenic challenge , closer to the surface , than other material s indicating minor mineral loss during pH cycling . The compomer Dyract presented similar performance to GICs and composite resin Tetric Ceram , but it was better than Filtek Z250 . CONCLUSION The experimental model of caries lesion induction may influence material performance . GICs , however , are superior in preventing in vitro demineralization independently of the method Previous papers in this series on evidence -based dentistry have discussed the first 2 steps in seeking answers to clinical problems formulating a clear question and strategically search ing for evidence . The next step , critical appraisal of the evidence , is made easier if one underst and s the basic concepts of clinical research design . The strongest design , especially for questions related to therapeutic or preventive interventions , is the r and omized , controlled trial . Questions relating to diagnosis , prognosis and causation are often studied with observational , rather than experimental , research design s. The strongest study design should be used whenever possible . Rules have been established to grade research evidence . This paper , the fourth in the series , presents an overview of research methodology most commonly used in the dental literature OBJECTIVE The aim of this in vitro study was to evaluate the interaction between two sources of fluoride ( restorative systems and dentifrices ) in inhibiting artificial root caries development . METHODS One hundred and eighty tooth segments were embedded in polyester resin , and s and ed flat . Cylindrical cavities 1.0mm-deep and 1.5mm-diameter were prepared in root dentin and r and omly restored by fluoride-containing restorative systems : Ketac-fil/Espe ( Ke ) , Fuji II LC/GC Corp ( Fj ) , F2000/3 M ( F2 ) , Surefil/Dentsply ( Su ) or a control : Filtek Z250/3 M ( Z2 ) . Ten experimental groups were made to test the association among the five restorative systems and two dentifrices : with F(- ) ( Sensodyne Baking Soda ) or without F(- ) ( Sensodyne Original ) ( n=18 ) . After surface polishing , a 1mm-wide margin around the restorations was demarcated and initial dentin surface Knoop microhardness values ( KHN(i ) ) were obtained . The specimens were su bmi tted to a pH-cycling model , and to applications of slurries of dentifrice . Afterwards the final dentin surface Knoop microhardness values ( KHN(f ) ) were measured . RESULTS The differences between KHN(i ) and KHN(f ) , and the covariate KHN(i ) were considered by the ANCOVA and Tukey 's test ( alpha=0.05 ) . The interaction between restorative system and dentifrice was statistically significant ( p=0.0026 ) . All restorative systems provided some protection against artificial caries challenge when associated with the fluoride-containing dentifrice treatment . The means ( st and ard deviation ) of reductions in Knoop hardness values for systems associated with the fluoride-containing dentifrice were : Ke : 40.0(1.02)(a ) , Fj : 41.9(1.02)(b ) , F2 : 43.3(1.04)(c ) , Su : 43.5(1.00)(c ) , Z2 : 44.0(1.02)(c ) ; and with the non-fluoride-containing dentifrice were : Ke : 42.9(1.02)(a ) , Fj : 44.7(1.01)(b ) , F2 : 45.2(1.09)(bc ) , Su : 46.0(0.99)(c ) , Z2 : 46.6(0.99)(c ) ( statistical differences were expressed by different letters ) . CONCLUSION The cariostatic effect shown by the fluoride-containing dentifrice could enhance that shown by Ketac-fil and Fuji II LC , and could mask that shown by F2000 There is no consensus about an association between microleakage and secondary caries , especially considering the presence of fluoride ( F ) at the tooth/restoration interface . Thus , a r and omized , double-blind , crossover study was carried out to evaluate in situ the effect of microleakage on caries around enamel-dentine restorations in the presence of F from dental material s or dentifrice , either alone or in combination . In 4 phases of 14 days each , 14 volunteers wore palatal devices containing dental slabs restored with composite resin ( CR ) or resin-modified glass ionomer cement ( GI ) . Restorations were made without leakage ( L– ) , following the recommended adhesive procedures , or with leakage ( L+ ) , in the absence of adhesive procedures . Plaque-like biofilm ( PLB ) was left to accumulate on the restored slabs , which were exposed extraorally to a 20 % sucrose solution 10 × /day . The volunteers used a non-F ( NF ) or an F ( FD ) dentifrice 3 × /day , depending on the experimental phase . No differences were found between L+ or L– restorations ( p > 0.05 ) . Higher demineralization in both enamel and dentine around CR restorations was observed under NF ( p < 0.05 ) . F concentration was higher in the fluid of PLB exposed to FD or formed onto GI restoration ( p < 0.05 ) . These results suggest that while microleakage does not affect caries development , GI or FD may maintain increased F levels in the PLB , thereby decreasing caries progression Since the last comprehensive review of anticoagulation in acute myocardial infa rct ion four additional r and omized control trials have been reported . The overwhelming majority of all trials favored anticoagulation .  Rates of thromboembolism were higher in the control , and hemorrhagic complications in the anticoagulated group . Pooling of all r and omized control trials gives mean case fatality rates of 19.6 % for the control and 15.4 % for the anticoagulated group , a relative reduction of 21 % ( P less than 0.05 or less than 0.001 , depending on the analytic method ) . Five of six r and omized control trials reported " no effect " because the difference favoring anticoagulation was not statistically significant . However , sample sizes in these " negative " papers were too small to protect against missing a 21 % reduction in true case fatality rate due to anticoagulation ( beta greater than 0.10 ) . All patients who present no specific contraindication should receive  anticoagulants  during hospitalization for infa rct ion Previous reports have shown a release of fluoride from glass-ionomer cement ( GIC ) restorations into the oral fluids . Fluoride in the ambient fluids has a caries-preventive effect by enhancing remineralization and inhibiting demineralization of the dental hard tissues . Therefore , the current investigation was undertaken to determine whether GIC fillings could contribute to the remineralization of caries lesions in dentin . Small circular preparations were made in disks of dentin which had incipient caries-like lesions in the remaining tissue . The preparations were filled with amalgam or composite material s ( as controls ) or with GIC . The specimens thus contained a restoration close to a dentinal caries-like lesion . The specimens were placed contralaterally in the buccal surfaces of removable partial dentures and were worn intra-orally by volunteers for a 12-week experimental period , after which the specimens were sectioned and analyzed by microradiography . All specimens with GIC restorations exhibited hypermineralization in the tissue bordering the filling and in the wall of the preparation which had been in contact with the restoration . The ( caries-like ) lesions were remineralized , even under conditions of heavy plaque formation . In contrast , specimens with amalgam or composite restorations showed further extensive demineralization . This study demonstrates a significant remineralization potential exerted by the fluoride-releasing GIC restorative material . Consequently , the choice of the restorative material might be crucial for the occurrence or prevention of recurrent caries around restorations PURPOSE Enamel demineralization adjacent to orthodontic brackets is one of the risks associated with orthodontic treatment . Glass ionomer cements have been shown to decrease enamel demineralization adjacent to brackets and b and s but do not exhibit bond strengths comparable to resin composites . The purpose of this in vitro study was to compare a fluoride-releasing resin composite versus a resin-modified glass ionomer cement for inhibition of enamel demineralization surrounding orthodontic brackets . METHODS Forty-five teeth were r and omly assigned to 3 groups of 15 teeth . Fifteen were bonded with Concise ( 3 M ) , a non-fluoride-releasing resin composite ( control ) ; 15 teeth were bonded with Light Bond ( Reliance ) , a fluoride-releasing resin composite ; and 15 teeth were bonded with Fuji Ortho LC ( GC Corporation ) , a resin-modified glass ionomer cement . The teeth were placed in an artificial caries solution to create lesions . Following sectioning of the teeth in a buccolingual direction , polarized light microscopy was utilized to evaluate enamel demineralization adjacent to the orthodontic bracket . The area of the lesion was measured 100 microns from the orthodontic bracket and bonding agent . RESULTS MANOVA ( P < .0001 ) and Duncan 's test ( P < .05 ) indicated the resin-modified glass ionomer cement ( Fuji Ortho LC ) and the fluoride-releasing resin composite ( Light Bond ) had significantly less adjacent enamel demineralization than the non-fluoride-releasing resin composite control . However , there was no significant difference between the resin-modified glass ionomer cement and the fluoride-releasing resin composite . CONCLUSIONS Based on the results of this in vitro study , it can be concluded that Fuji Ortho LC and Light Bond exhibit significant inhibition of adjacent demineralization compared to the non-fluoride-releasing control The aim was to study the effect of three fluoride – releasing restorative material s  on sound enamel of approximal teeth under cariogenic conditions intraorally . Bovine enamel slabs were paired with four hemispherical sample s from each of three test material s ( Ketac Molar , ESPE ; Vitremer , F–2000 , both from 3 M ) and one control material ( Pertac II , ESPE ) . Their curved surface touched enamel at a contact point allowing space for plaque accumulation . Pairs were inserted in the buccal flanges of 2 lower dentures for 70 days . Initially and upon dismantling , enamel surface microhardness was measured and the increase in length of indentation in micrometers was recorded at a distance of 0 , 0.4 , 0.8 and 1.2 mm from the contact point . Respective values were : Pert 
    Output:
    