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: Recombinant human bone morphogenic protein-2 ( rhBMP-2 ) is an osteoinductive protein that is now available for the acute treatment of open tibial fracture . Data from pre clinical and clinical trials support its role in fracture care . This article summarizes data from two r and omized controlled clinical trials investigating the safety and efficacy of rhBMP-2 in patients with open tibial shaft fractures and tibial fractures with bone defects . Also included is a summary of an economic analysis that examined the cost impact of rhBMP-2  from a hospital and payor perspective OBJECTIVE To estimate the utility ( preference for health ) associated with hip fracture and fear of falling among older women . DESIGN Quality of life survey with the time trade off technique . The technique derives an estimate of preference for health states by finding the point at which respondents show no preference between a longer but lower quality of life and a shorter time in full health . SETTING A r and omised trial of external hip protectors for older women at risk of hip fracture . PARTICIPANTS 194 women aged > /= 75 years enrolled in the r and omised controlled trial or who were eligible for the trial but refused completed a quality of life interview face to face . OUTCOME MEASURES Respondents were asked to rate their own health by using the Euroqol instrument and then rate three health states ( fear of falling , a " good " hip fracture , and a " bad " hip fracture ) by using time trade off technique . RESULTS On an interval scale between 0 ( death ) and 1 ( full health ) , a " bad " hip fracture ( which results in admission to a nursing home ) was valued at 0.05 ; a " good " hip fracture ( maintaining independent living in the community ) 0.31 , and fear of falling 0.67 . Of women surveyed , 80 % would rather be dead ( utility=0 ) than experience the loss of independence and quality of life that results from a bad hip fracture and subsequent admission to a nursing home . The differences in mean utility weights between the trial groups and the refusers were not significant . A test-retest study on 36 women found that the results were reliable with correlation coefficients within classes ranging from 0.61 to 0.88 . CONCLUSIONS Among older women who have exceeded average life expectancy , quality of life is profoundly threatened by falls and hip fractures . Older women place a very high marginal value on their health . Any loss of ability to live independently in the community has a considerable detrimental effect on their quality of life Osteogenic proteins ( OP ) are elements of a class of natural growth factors called Bone Morphogenetic Proteins ( BMP ) . A specific member of this class is OP-1 , a human recombinant protein that has osteogenic properties . The osteoinductive and osteoconductive properties of OP-1 , with its specific collagen matrix , promote the generation of new functionally active , biologically and biomechanically mature bone . We carried out a clinical study to verify the potential of this protein in fresh tibial closed fractures , using OP-1 associated with osteo synthesis by means of a monolateral external fixator CONTEXT Noninferiority and equivalence trials aim to show that the experimental treatment is not clinical ly worse than ( noninferior ) or clinical ly similar to ( equivalent ) a control active treatment . These study objectives imply particular planning and analysis . OBJECTIVE To assess the method ologic quality of reports of r and omized controlled trials of noninferiority and equivalence . DESIGN We search ed MEDLINE and the Cochrane Central Register of Controlled Trials for reports of r and omized controlled trials of noninferiority and equivalence hypotheses published between January 1 , 2003 , and December 31 , 2004 . MAIN OUTCOME MEASURES Data extracted by use of a st and ardized form involved assessment of choice of noninferiority or equivalence margins , sample size calculation , sets of patients analyzed , method of statistical testing and reporting results , and conclusions . RESULTS A total of 162 reports were included in the analysis ( 116 reports of noninferiority and 46 of equivalence ) . The margin defining noninferiority or equivalence was described in most reports ( 156 [ 96.3 % ] ) , with justification of the margin in only 33 ( 20.4 % ) . Almost one quarter of the reports ( 35 [ 21.6 % ] ) did not describe a sample size calculation , and an additional 11 ( 6.8 % ) did not take into account a prespecified noninferiority or equivalence margin . Less than half of the reports ( 69 [ 42.6 % ] ) described both an intent-to-treat ( ITT ; all r and omized patients are included in the analysis ) or modified ITT ( patients who never received treatment are excluded ) and per- protocol ( patients who did not complete the treatment are excluded ) analysis , and only about half of those ( 39 [ 56.5 % ] ) described both types of results . Results were displayed with confidence intervals in 136 reports ( 84.0 % ) . Only 33 articles ( 20.3 % ) fulfilled reporting requirements specific to noninferiority and equivalence trials , 4 of them ( 12.1 % ) with misleading conclusions . CONCLUSIONS Reporting of noninferiority and equivalence trials has important deficiencies : absence of noninferiority or equivalence margin , only an ITT ( or a per- protocol ) analysis performed , and results not adequately reported . Moreover , even for articles fulfilling these requirements , conclusions are sometimes misleading Treatment of long bone non-union ( NU ) continues to be a challenging task for the trauma surgeon often result ing in unsatisfactory results and long-term morbidity . Whilst autologous bone grafting remains the gold st and ard of treatment of these difficult cases , recently , due to the advances made in tissue engineering techniques , other alternatives have become available . In this study we report our preliminary results of treating long bone non-unions using either bone morphogenetic protein-7 ( BMP-7 ) or platelet rich plasma ( PRP ) concentrations .  Twenty-nine cases have entered this study thus far . Preliminary results indicate that  BMP-7 is more efficacious that PRP as there was a significant failure rate of 6.2 % versus 38.5 % between BMP-7 and PRP , respectively Study Design . A prospect i ve study was conducted to examine bone graft donor site morbidity in 106 consecutive patients undergoing posterior spinal fusion . Objectives . To perform a prospect i ve analysis of donor site morbidity , to document the incidence of major complications , and to collect information on the impact of autologous bone graft harvesting from the posterior iliac crest on the overall outcome of spinal surgery . Summary of Background . Bone graft harvesting from the posterior iliac crest for spinal fusion is a source of significant morbidity . Previous retrospective case studies indicate that minor complications are common , but they do not define the natural history and complications of posterior iliac crest bone graft harvesting . Methods . A st and ardized harvesting technique was used . At 3 , 6 , and 12 months after surgery , the patients completed a proforma question naire rating symptoms on a visual analog scale and underwent a postoperative examination by the surgeon . Finally , overall surgical outcome was assessed at 12 months . Results . The major component of morbidity is donor site pain . Mean pain scores were 1.640 at 3 months , 1.812 at 6 months , and 1.207 at 12 months . The pain at 12 months was significantly less than at 3 and 6 months ( P = 0.005 ) , with a trend toward the highest scores at 6 months . A pain score of 0 was reported by 55 % of the patients . Local sensory loss was found in 10 % of the patients . Outcome assessment showed significant differences in morbidity for surgery performed at different spinal levels ( P = 0.001 ) , with lumbosacral surgery result ing in worse outcomes than either cervical ( P < 0.05 ) or thoracolumbar ( P < 0.05 ) surgery . Significantly higher visual analog scores were observed at 6 months in patients with poorer overall outcomes . Conclusions . According to this study , it is reasonable to reassure patients that a good result from spinal surgery will not be compromised by severe symptoms or major morbidity secondary to posterior iliac crest bone graft donation . Before surgery , patients may be advised concerning the risks of donor site pain , which improves significantly by 12 months , local tenderness , and uncommonly localized sensory loss OBJECTIVE To assess the efficacy of osteogenic protein-1 ( OP-1 ) for long bone nonunion . CLINICAL NEED Although most fractures heal within a normal period , about 5 % to 10 % do not heal and are classified as delayed or nonunion fractures . Nonunion and segmental bone loss after fracture , reconstructive surgery , or lesion excision can present complex orthopedic problems , and the multiple surgical procedures often needed are associated with patient morbidity and reduced quality of life . Many factors contribute to the pathogenesis of a delayed union or nonunion fractures , including deficiencies of calcium , vitamin D , or vitamin C , and side effects of medications such as anticoagulants , steroids , some anti-inflammatory drugs , and radiation . It has been shown that smoking interferes with bone repair in several ways . INCIDENCE OF NONUNION AND DELAYED UNION CASES : An estimated 5 % to 10 % of fractures do not heal properly and go on to delayed union or nonunion . If this overall estimate of incidence were applied to the Ontario population , the estimated number of  delayed union or nonunion in the province would be between 3,863 and 7,725 . TREATMENT OF NONUNION CASES : The treatment of nonunion cases is a challenge to orthopedic surgeons . However , the basic principle behind treatment is to provide both mechanical and biological support to the nonunion site . Fracture stabilization and immobilization is frequently used with the other treatment modalities that provide biological support to the fractured bone . Biological support includes material s that could be served as a source of osteogenic cells ( osteogenesis ) , a stimulator of mesenchymal cells ( osteoinduction ) , or a scaffold-like structure ( osteoconduction ) . The capacity to heal a fracture is a latent potential of the stromal stem cells , which synthesize new bone . This process has been defined as osteogenesis . Activation of the stem cells to initiate osteogenic response and to differentiate into bone-forming osteoblasts is called osteoinduction . These 2 properties accelerate the rate of fracture healing or reactivate the ineffective healing process . Osteoconduction occurs when passive structures facilitate the migration of osteoprogenitor cells , the perivascular tissue , and capillaries into these structures . BONE GRAFTS AND BONE GRAFT SUBSTITUTES : Bone graft and bone graft substitutes have one or more of the following components : Undifferentiated stem cellsGrowth factorsStructural latticeUndifferentiated stem cells are unspecialized , multipotential cells that can differentiate into a variety of specialized cells . They can also replicate themselves . The role of stem cells is to maintain and repair the tissue in which they are residing . A single stem cell can generate all cell types of that tissue . Bone marrow is a source of at least 2 kinds of stem cells . Hematopoietic stem cells that form all types of blood cells , and bone marrow stromal stem cells that have osteogenic properties and can generate bone , cartilage , and fibrous tissue . Bone marrow has been used to stimulate bone formation in bone defects and cases of nonunion fractures . Bone marrow can be aspirated from the iliac crest and injected percutaneously with fluoroscopic guidance into the site of the nonunion fracture . The effectiveness of this technique depends on the number and activity of stem cells in the aspirated bone marrow . It may be possible to increase the proliferation and speed differentiation of stem cells by exposing them to growth factor or by combining them with collagen . Many growth factors and cytokines induced in response to injury are believed to have a considerable role in the process of repair . Of the many bone growth factors studied , bone morphogenetics ( BMPs ) have generated the greatest attention because of their osteoinductive potential . The BMPs that have been most widely studied for their ability to induce bone regeneration in humans include BMP-2 and BMP-7 ( osteogenic protein ) . Human osteogenic protein-1 ( OP-1 ) has been cloned and produced with recombinant technology and is free from the risk of infection or allergic reaction . The structural lattice is osteoconductive ; it supports the ingrowth of developing capillaries and perivascular tissues . Three distinct groups of structural lattice have been identified : collagen , calcium sulphate , and calcium phosphate . These material s can be used to replace a lost segment of bone . GRAFTS USED FOR NONUNION : Autologous bone graft is generally considered the gold st and ard and the best material for grafting because it contains several elements that are critical in promoting bone formation , including osteoprogenitor cells , the matrix , and bone morphogenetic proteins . The osteoconductive property of cancellous autograft is related to the porosity of bone . The highly porous , scaffold-like structure of the graft allows host osteoblasts and host osteoprogenitor cells to migrate easily into the area of the defect and to begin regeneration of bone . Sources of cancellous bone are the iliac crest , the distal femur , the greater trochanter , and the proximal tibia . However , harvesting the autologous bone graft is associated with postoperative pain at the donor site , potential injury to the surrounding arteries , nerves , and tissues , and the risk of infection . Thus the development of synthetic material s with osteoconduct 
    Output:
    
agent
***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: Recombinant human bone morphogenic protein-2 ( rhBMP-2 ) is an osteoinductive protein that is now available for the acute treatment of open tibial fracture . Data from pre clinical and clinical trials support its role in fracture care . This article summarizes data from two r and omized controlled clinical trials investigating the safety and efficacy of rhBMP-2 in patients with open tibial shaft fractures and tibial fractures with bone defects . Also included is a summary of an economic analysis that examined the cost impact of rhBMP-2  from a hospital and payor perspective OBJECTIVE To estimate the utility ( preference for health ) associated with hip fracture and fear of falling among older women . DESIGN Quality of life survey with the time trade off technique . The technique derives an estimate of preference for health states by finding the point at which respondents show no preference between a longer but lower quality of life and a shorter time in full health . SETTING A r and omised trial of external hip protectors for older women at risk of hip fracture . PARTICIPANTS 194 women aged > /= 75 years enrolled in the r and omised controlled trial or who were eligible for the trial but refused completed a quality of life interview face to face . OUTCOME MEASURES Respondents were asked to rate their own health by using the Euroqol instrument and then rate three health states ( fear of falling , a " good " hip fracture , and a " bad " hip fracture ) by using time trade off technique . RESULTS On an interval scale between 0 ( death ) and 1 ( full health ) , a " bad " hip fracture ( which results in admission to a nursing home ) was valued at 0.05 ; a " good " hip fracture ( maintaining independent living in the community ) 0.31 , and fear of falling 0.67 . Of women surveyed , 80 % would rather be dead ( utility=0 ) than experience the loss of independence and quality of life that results from a bad hip fracture and subsequent admission to a nursing home . The differences in mean utility weights between the trial groups and the refusers were not significant . A test-retest study on 36 women found that the results were reliable with correlation coefficients within classes ranging from 0.61 to 0.88 . CONCLUSIONS Among older women who have exceeded average life expectancy , quality of life is profoundly threatened by falls and hip fractures . Older women place a very high marginal value on their health . Any loss of ability to live independently in the community has a considerable detrimental effect on their quality of life Osteogenic proteins ( OP ) are elements of a class of natural growth factors called Bone Morphogenetic Proteins ( BMP ) . A specific member of this class is OP-1 , a human recombinant protein that has osteogenic properties . The osteoinductive and osteoconductive properties of OP-1 , with its specific collagen matrix , promote the generation of new functionally active , biologically and biomechanically mature bone . We carried out a clinical study to verify the potential of this protein in fresh tibial closed fractures , using OP-1 associated with osteo synthesis by means of a monolateral external fixator CONTEXT Noninferiority and equivalence trials aim to show that the experimental treatment is not clinical ly worse than ( noninferior ) or clinical ly similar to ( equivalent ) a control active treatment . These study objectives imply particular planning and analysis . OBJECTIVE To assess the method ologic quality of reports of r and omized controlled trials of noninferiority and equivalence . DESIGN We search ed MEDLINE and the Cochrane Central Register of Controlled Trials for reports of r and omized controlled trials of noninferiority and equivalence hypotheses published between January 1 , 2003 , and December 31 , 2004 . MAIN OUTCOME MEASURES Data extracted by use of a st and ardized form involved assessment of choice of noninferiority or equivalence margins , sample size calculation , sets of patients analyzed , method of statistical testing and reporting results , and conclusions . RESULTS A total of 162 reports were included in the analysis ( 116 reports of noninferiority and 46 of equivalence ) . The margin defining noninferiority or equivalence was described in most reports ( 156 [ 96.3 % ] ) , with justification of the margin in only 33 ( 20.4 % ) . Almost one quarter of the reports ( 35 [ 21.6 % ] ) did not describe a sample size calculation , and an additional 11 ( 6.8 % ) did not take into account a prespecified noninferiority or equivalence margin . Less than half of the reports ( 69 [ 42.6 % ] ) described both an intent-to-treat ( ITT ; all r and omized patients are included in the analysis ) or modified ITT ( patients who never received treatment are excluded ) and per- protocol ( patients who did not complete the treatment are excluded ) analysis , and only about half of those ( 39 [ 56.5 % ] ) described both types of results . Results were displayed with confidence intervals in 136 reports ( 84.0 % ) . Only 33 articles ( 20.3 % ) fulfilled reporting requirements specific to noninferiority and equivalence trials , 4 of them ( 12.1 % ) with misleading conclusions . CONCLUSIONS Reporting of noninferiority and equivalence trials has important deficiencies : absence of noninferiority or equivalence margin , only an ITT ( or a per- protocol ) analysis performed , and results not adequately reported . Moreover , even for articles fulfilling these requirements , conclusions are sometimes misleading Treatment of long bone non-union ( NU ) continues to be a challenging task for the trauma surgeon often result ing in unsatisfactory results and long-term morbidity . Whilst autologous bone grafting remains the gold st and ard of treatment of these difficult cases , recently , due to the advances made in tissue engineering techniques , other alternatives have become available . In this study we report our preliminary results of treating long bone non-unions using either bone morphogenetic protein-7 ( BMP-7 ) or platelet rich plasma ( PRP ) concentrations .  Twenty-nine cases have entered this study thus far . Preliminary results indicate that  BMP-7 is more efficacious that PRP as there was a significant failure rate of 6.2 % versus 38.5 % between BMP-7 and PRP , respectively Study Design . A prospect i ve study was conducted to examine bone graft donor site morbidity in 106 consecutive patients undergoing posterior spinal fusion . Objectives . To perform a prospect i ve analysis of donor site morbidity , to document the incidence of major complications , and to collect information on the impact of autologous bone graft harvesting from the posterior iliac crest on the overall outcome of spinal surgery . Summary of Background . Bone graft harvesting from the posterior iliac crest for spinal fusion is a source of significant morbidity . Previous retrospective case studies indicate that minor complications are common , but they do not define the natural history and complications of posterior iliac crest bone graft harvesting . Methods . A st and ardized harvesting technique was used . At 3 , 6 , and 12 months after surgery , the patients completed a proforma question naire rating symptoms on a visual analog scale and underwent a postoperative examination by the surgeon . Finally , overall surgical outcome was assessed at 12 months . Results . The major component of morbidity is donor site pain . Mean pain scores were 1.640 at 3 months , 1.812 at 6 months , and 1.207 at 12 months . The pain at 12 months was significantly less than at 3 and 6 months ( P = 0.005 ) , with a trend toward the highest scores at 6 months . A pain score of 0 was reported by 55 % of the patients . Local sensory loss was found in 10 % of the patients . Outcome assessment showed significant differences in morbidity for surgery performed at different spinal levels ( P = 0.001 ) , with lumbosacral surgery result ing in worse outcomes than either cervical ( P < 0.05 ) or thoracolumbar ( P < 0.05 ) surgery . Significantly higher visual analog scores were observed at 6 months in patients with poorer overall outcomes . Conclusions . According to this study , it is reasonable to reassure patients that a good result from spinal surgery will not be compromised by severe symptoms or major morbidity secondary to posterior iliac crest bone graft donation . Before surgery , patients may be advised concerning the risks of donor site pain , which improves significantly by 12 months , local tenderness , and uncommonly localized sensory loss OBJECTIVE To assess the efficacy of osteogenic protein-1 ( OP-1 ) for long bone nonunion . CLINICAL NEED Although most fractures heal within a normal period , about 5 % to 10 % do not heal and are classified as delayed or nonunion fractures . Nonunion and segmental bone loss after fracture , reconstructive surgery , or lesion excision can present complex orthopedic problems , and the multiple surgical procedures often needed are associated with patient morbidity and reduced quality of life . Many factors contribute to the pathogenesis of a delayed union or nonunion fractures , including deficiencies of calcium , vitamin D , or vitamin C , and side effects of medications such as anticoagulants , steroids , some anti-inflammatory drugs , and radiation . It has been shown that smoking interferes with bone repair in several ways . INCIDENCE OF NONUNION AND DELAYED UNION CASES : An estimated 5 % to 10 % of fractures do not heal properly and go on to delayed union or nonunion . If this overall estimate of incidence were applied to the Ontario population , the estimated number of  delayed union or nonunion in the province would be between 3,863 and 7,725 . TREATMENT OF NONUNION CASES : The treatment of nonunion cases is a challenge to orthopedic surgeons . However , the basic principle behind treatment is to provide both mechanical and biological support to the nonunion site . Fracture stabilization and immobilization is frequently used with the other treatment modalities that provide biological support to the fractured bone . Biological support includes material s that could be served as a source of osteogenic cells ( osteogenesis ) , a stimulator of mesenchymal cells ( osteoinduction ) , or a scaffold-like structure ( osteoconduction ) . The capacity to heal a fracture is a latent potential of the stromal stem cells , which synthesize new bone . This process has been defined as osteogenesis . Activation of the stem cells to initiate osteogenic response and to differentiate into bone-forming osteoblasts is called osteoinduction . These 2 properties accelerate the rate of fracture healing or reactivate the ineffective healing process . Osteoconduction occurs when passive structures facilitate the migration of osteoprogenitor cells , the perivascular tissue , and capillaries into these structures . BONE GRAFTS AND BONE GRAFT SUBSTITUTES : Bone graft and bone graft substitutes have one or more of the following components : Undifferentiated stem cellsGrowth factorsStructural latticeUndifferentiated stem cells are unspecialized , multipotential cells that can differentiate into a variety of specialized cells . They can also replicate themselves . The role of stem cells is to maintain and repair the tissue in which they are residing . A single stem cell can generate all cell types of that tissue . Bone marrow is a source of at least 2 kinds of stem cells . Hematopoietic stem cells that form all types of blood cells , and bone marrow stromal stem cells that have osteogenic properties and can generate bone , cartilage , and fibrous tissue . Bone marrow has been used to stimulate bone formation in bone defects and cases of nonunion fractures . Bone marrow can be aspirated from the iliac crest and injected percutaneously with fluoroscopic guidance into the site of the nonunion fracture . The effectiveness of this technique depends on the number and activity of stem cells in the aspirated bone marrow . It may be possible to increase the proliferation and speed differentiation of stem cells by exposing them to growth factor or by combining them with collagen . Many growth factors and cytokines induced in response to injury are believed to have a considerable role in the process of repair . Of the many bone growth factors studied , bone morphogenetics ( BMPs ) have generated the greatest attention because of their osteoinductive potential . The BMPs that have been most widely studied for their ability to induce bone regeneration in humans include BMP-2 and BMP-7 ( osteogenic protein ) . Human osteogenic protein-1 ( OP-1 ) has been cloned and produced with recombinant technology and is free from the risk of infection or allergic reaction . The structural lattice is osteoconductive ; it supports the ingrowth of developing capillaries and perivascular tissues . Three distinct groups of structural lattice have been identified : collagen , calcium sulphate , and calcium phosphate . These material s can be used to replace a lost segment of bone . GRAFTS USED FOR NONUNION : Autologous bone graft is generally considered the gold st and ard and the best material for grafting because it contains several elements that are critical in promoting bone formation , including osteoprogenitor cells , the matrix , and bone morphogenetic proteins . The osteoconductive property of cancellous autograft is related to the porosity of bone . The highly porous , scaffold-like structure of the graft allows host osteoblasts and host osteoprogenitor cells to migrate easily into the area of the defect and to begin regeneration of bone . Sources of cancellous bone are the iliac crest , the distal femur , the greater trochanter , and the proximal tibia . However , harvesting the autologous bone graft is associated with postoperative pain at the donor site , potential injury to the surrounding arteries , nerves , and tissues , and the risk of infection . Thus the development of synthetic material s with osteoconduct 
    Output:
    